FUBP3 mediates the amyloid-ß-induced neuronal NLRP3 expression.

JOURNAL/nrgr/04.03/01300535-202507000-00028/figure1/v/2024-09-09T124005Z/r/image-tiff Alzheimer's disease is characterized by deposition of amyloid-ß, which forms extracellular neuritic plaques, and accumulation of hyperphosphorylated tau, which aggregates to form intraneuronal neurofibrillary tangles, in the brain. The NLRP3 inflammasome may play a role in the transition from amyloid-ß deposition to tau phosphorylation and aggregation. Because NLRP3 is primarily found in brain microglia, and tau is predominantly located in neurons, it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory cytokines. Here, we found that neurons also express NLRP3 in vitro and in vivo, and that neuronal NLRP3 regulates tau phosphorylation. Using biochemical methods, we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in neurons. In primary neurons and the neuroblastoma cell line Neuro2A, FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-ß is present. In the brains of aged wild-type mice and a mouse model of Alzheimer's disease, FUBP3 expression was markedly increased in cortical neurons. Transcriptome analysis suggested that FUBP3 plays a role in neuron-mediated immune responses. We also found that FUBP3 trimmed the 5' end of DNA fragments that it bound, implying that FUBP3 functions in stress-induced responses. These findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-ß-to-phospho-tau transition than microglial NLRP3, and that amyloid-ß fundamentally alters the regulatory mechanism of NLRP3 expression in neurons. Given that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice, FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.

Research progress on the environmental risk assessment and remediation technologies of heavy metal pollution in agricultural soil.

Controlling heavy metal pollution in agricultural soil has been a significant challenge. These heavy metals seriously threaten the surrounding ecological environment and human health. The effective assessment and remediation of heavy metals in agricultural soils are crucial. These two aspects support each other, forming a close and complete decision-making chain. Therefore, this review systematically summarizes the distribution characteristics of soil heavy metal pollution, the correlation between soil and crop heavy metal contents, the presence pattern and migration and transformation mode of heavy metals in the soil-crop system. The advantages and disadvantages of the risk evaluation tools and models of heavy metal pollution in farmland are further outlined, which provides important guidance for an in-depth understanding of the characteristics of heavy metal pollution in farmland soils and the assessment of the environmental risk. Soil remediation strategies involve multiple physical, chemical, biological and even combined technologies, and this paper compares the potential and effect of the above current remediation technologies in heavy metal polluted farmland soils. Finally, the main problems and possible research directions of future heavy metal risk assessment and remediation technologies in agricultural soils are prospected. This review provides new ideas for effective assessment and selection of remediation technologies based on the characterization of soil heavy metals.

Helicobacter pylori CagA mediated mitophagy to attenuate the NLRP3 inflammasome activation and enhance the survival of infected cells.

Helicobacter pylori (H. pylori) is one of the most common bacterial infections in the world, and its key virulence component CagA is the leading cause of gastric cancer. Mitophagy is a form of selective autophagy that eliminates damaged mitochondria and is essential for some viruses and bacteria to evade the immune system. However, the mechanisms by which CagA mediates H. pylori-induced mitophagy and NLRP3 inflammasome activation remain elusive. In this study, we reported that H. pylori primarily uses its CagA to induce mitochondrial oxidative damage, mitochondrial dysfunction, dynamic imbalance, and to block autophagic flux. Inhibition of mitophagy led to an increase in NLRP3 inflammasome activation and apoptosis and a decrease in the viability of H. pylori-infected cells. Our findings suggested that H. pylori induces mitochondrial dysfunction and mitophagy primarily via CagA. It reduces NLRP3 inflammasome activation to evade host immune surveillance and increases the survival and viability of infected cells, potentially leading to gastric cancer initiation and development. Our findings provide new insights into the pathogenesis of H. pylori-induced gastric cancer, and inhibition of mitophagy may be one of the novel techniques for the prevention and treatment of this disease.

Two-dimensional crystalline platinum oxide.

Platinum (Pt) oxides are vital catalysts in numerous reactions, but research indicates that they decompose at high temperatures, limiting their use in high-temperature applications. In this study, we identify a two-dimensional (2D) crystalline Pt oxide with remarkable thermal stability (1,200 K under nitrogen dioxide) using a suite of in situ methods. This 2D Pt oxide, characterized by a honeycomb lattice of Pt atoms encased between dual oxygen layers forming a six-pointed star structure, exhibits minimized in-plane stress and enhanced vertical bonding due to its unique structure, as revealed by theoretical simulations. These features contribute to its high thermal stability. Multiscale in situ observations trace the formation of this 2D Pt oxide from α-PtO2, providing insights into its formation mechanism from the atomic to the millimetre scale. This 2D Pt oxide with outstanding thermal stability and distinct surface electronic structure subverts the previously held notion that Pt oxides do not exist at high temperatures and can also present unique catalytic capabilities. This work expands our understanding of Pt oxidation species and sheds light on the oxidative and catalytic behaviours of Pt oxide in high-temperature settings.

Rapid one-pot human single nucleotide polymorphism genotyping platform with Cas13a nuclease.

Single nucleotide polymorphism (SNP), as one of the key components of the genetic factors, is important for disease detection and early screening of hereditary diseases. Current SNP genotyping methods require laboratory instruments or long operating times. To facilitate the diagnosis of hereditary diseases, we developed a new method referred to as the LwaCas13a-based SNP genotyping platform (Cas13a platform), which is useful for detecting disease-related SNPs. We report a CRISPR/Cas13a-based SNP genotyping platform that couples recombinase-aided amplification (RAA), T7 transcription, and Leptotrichia wadei Cas13a (LwaCas13a) detection for simple and fast genotyping of human disease-related SNPs. We used this Cas13a platform to identify 17 disease-related SNPs, demonstrating that position 2 in gRNA is suitable for the introduction of additional mismatches to achieve high discrimination in genotyping across a wide range of SNP targets. The discrimination specificity of 17 SNPs was improved 3.0-35.1-fold after introducing additional mismatches at position 2 from the 5'-end. We developed a method, which has a lower risk of cross-contamination and operational complexity, for genotyping SNPs using human saliva samples in an one-pot testing that delivers results within 60 min. Compared to TaqMan probe qPCR, RFLP, AS-PCR and other SNP genotyping methods, the Cas13a platform is simple, rapid and reliable, expanding the applications of the CRISPR/Cas system in nucleic acid detection and SNP genotyping.

A Nile red dye cathode with an asymmetric redox unit for lithium organic batteries.

A Nile red (NR) dye cathode with an asymmetric redox structure of para CN and CO bonds was developed for use in an efficient lithium organic battery with a good capacity of 125 mA h g-1 and two visible discharge/charge voltage plateaus (≈2.0 V and ≈1.7 V). The NR cathode demonstrated the advantages of employing cost-effective dyes to achieve multigradient voltage platform regulation.

Objective performance indicators versus GEARS: an opportunity for more accurate assessment of surgical skill.

PURPOSE: Surgical skill evaluation that relies on subjective scoring of surgical videos can be time-consuming and inconsistent across raters. We demonstrate differentiated opportunities for objective evaluation to improve surgeon training and performance. METHODS: Subjective evaluation was performed using the Global evaluative assessment of robotic skills (GEARS) from both expert and crowd raters; whereas, objective evaluation used objective performance indicators (OPIs) derived from da Vinci surgical systems. Classifiers were trained for each evaluation method to distinguish between surgical expertise levels. This study includes one clinical task from a case series of robotic-assisted sleeve gastrectomy procedures performed by a single surgeon, and two training tasks performed by novice and expert surgeons, i.e., surgeons with no experience in robotic-assisted surgery (RAS) and those with more than 500 RAS procedures. RESULTS: When comparing expert and novice skill levels, OPI-based classifier showed significantly higher accuracy than GEARS-based classifier on the more complex dissection task (OPI 0.93 ± 0.08 vs. GEARS 0.67 ± 0.18; 95% CI, 0.16-0.37; p = 0.02), but no significant difference was shown on the simpler suturing task. For the single-surgeon case series, both classifiers performed well when differentiating between early and late group cases with smaller group sizes and larger intervals between groups (OPI 0.9 ± 0.08; GEARS 0.87 ± 0.12; 95% CI, 0.02-0.04; p = 0.67). When increasing the group size to include more cases, thereby having smaller intervals between groups, OPIs demonstrated significantly higher accuracy (OPI 0.97 ± 0.06; GEARS 0.76 ± 0.07; 95% CI, 0.12-0.28; p = 0.004) in differentiating between the early/late cases. CONCLUSIONS: Objective methods for skill evaluation in RAS outperform subjective methods when (1) differentiating expertise in a technically challenging training task, and (2) identifying more granular differences along early versus late phases of a surgeon learning curve within a clinical task. Objective methods offer an opportunity for more accessible and scalable skill evaluation in RAS.

Targeting METTL3 enhances the chemosensitivity of non-small cell lung cancer cells by decreasing ABCC2 expression in an m6A-YTHDF1-dependent manner.

Patients with non-small cell lung cancer (NSCLC) are easily resistant to first-line chemotherapy with paclitaxel (PTX) or carboplatin (CBP). N6-methyladenosine (m6A) methyltransferase-like 3 (METTL3) has crucial functions in m6A modification and tumorigenesis. However, its role in chemoresistance of NSCLC is still elusive. Here, we demonstrated that METTL3 inhibitor STM2457 significantly reduced the IC50 values of PTX or CBP in NSCLC cells, and they showed a synergistic effect. Comparing with monotherapy, a combination of STM2457 and PTX or CBP exhibited more potent in vitro and in vivo anti-tumor efficacy. In addition, we found that ATP binding cassette subfamily C member 2 (ABCC2) was responsively elevated in cytomembrane after PTX or CBP treatment, and targeting METTL3 could reverse this effect. Mechanistically, targeting METTL3 decreased the m6A modification of ABCC2 mRNA and accelerated its mRNA degradation. Further studies revealed that YTHDF1 could bind and stabilize the m6A-modified mRNA of ABCC2, while YTHDF1 knockdown promoted it mRNA degradation. These results, taken together, demonstrate that targeting METTL3 enhances the sensitivity of NSCLC cells to PTX or CBP by decreasing the cytomembrane-localized ABCC2 in an m6A-YTHDF1-dependent manner, and suggest that METTL3 may be a potential therapeutic target for acquired resistance to PTX or CBP in NSCLC.

Rational Design of an Artificial Metalloenzyme by Constructing a Metal-Binding Site Close to the Heme Cofactor in Myoglobin.

In this study, we constructed a metal-binding site close to the heme cofactor in myoglobin (Mb) by covalently attaching a nonnative metal-binding ligand of bipyridine to Cys46 through the F46C mutation in the heme distal site. The X-ray structure of the designed enzyme, termed F46C-mBpy Mb, was solved in the Cu(II)-bound form, which revealed the formation of a heterodinuclear center of Cu-His-H2O-heme. Cu(II)-F46C-mBpy Mb exhibits not only nitrite reductase reactivity but also cascade reaction activity involving both hydrolysis and oxidation. Furthermore, F46C-mBpy Mb displays Mn-peroxidase activity by the oxidation of Mn2+ to Mn3+ using H2O2 as an oxidant. This study shows that the construction of a nonnative metal-binding site close to the heme cofactor is a convenient approach to creating an artificial metalloenzyme with a heterodinuclear center that confers multiple functions.

Wireless and Opto-Stimulated Flexible Implants: Artificial Retina Constructed by Ferroelectric BiFeO3-BaTiO3/P(VDF-TrFE) Composites.

The degeneration of retinal photoreceptors is one of the primary causes of blindness, and the implantation of retinal prostheses offers hope for vision restoration in individuals who are completely blind. Flexible bioelectronic devices present a promising avenue for the next generation of retinal prostheses owing to their soft mechanical properties and tissue friendliness. In this study, we developed flexible composite films of ferroelectric BiFeO3-BaTiO3 (BFO-BTO) particles synthesized by the hydrothermal method and ferroelectric poly(vinyldene difluoride-trifluoroethylene) (P(VDF-TrFE)) polymer and investigated their applications in artificial retinas. Owing to the coupling of the photothermal effect of BFO-BTO particles and the pyroelectric effect of the P(VDF-TrFE) polymer, the composite films demonstrate a strong photoelectric response (a maximum peak-to-peak photovoltage > 80 V under blue light of 100 mW/cm2) in a wide wavelength range of light (from visible to infrared) with the inherent flexibility and ease of preparation, making it an attractive candidate for artificial retinal applications. Experimental results showed that blind rats implanted with artificial retinas of the composites display light-responsive behavior, showcasing the effectiveness of vision restoration. This study demonstrates a novel approach for employing ferroelectric materials in vision restoration and offers insights into future artificial retina design.

An organic cathode for low-temperature processed, flexible ternary organic solar cells with high-performance.

In this study, we developed a flexible cathode for fabricating high-performance ternary organic solar cells (OSCs). With solvent engineering and acid treatment, the conductivity of the poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) electrode was significantly enhanced with the sheet resistance reduced from 1081 to 83 Ω sq-1. After being coated with polyethylenimine, work function of the PEDOT:PSS electrode was tuned from -5.07 to -4.12 eV, which is beneficial for electron collection in OSCs. With this technique, the OSCs (on glass) showed an average power conversion efficiency (PCE) of 16.3%, which is comparable to that of conventional inverted OSCs with commonly used indium-tin oxide and sol-gel-processed zinc oxide. However, the processing temperature of the inverted OSCs was dramatically lowered from 200 to 120 °C. The flexible OSCs (on polyethylene naphthalate/PEDOT:PSS/PEIE) exhibited a high PCE of 14.1%. After being bended for 300 cycles, the PCE was only degraded by 8.5%, indicating the excellent bendability of the flexible OSCs with the organic cathode.

Biologicals for the treatment of lupus nephritis: a Bayesian network meta-regression analysis.

Background: Previous studies comparing the efficacy and safety of different treatment regimens for lupus nephritis are scarce. Moreover, confounding factors such as the duration of follow-up were hardly adjusted in those studies, potentially compromising the results and their extents to clinical settings. Objective: To rigorously investigate the efficacy and safety of biologics in patients with lupus nephritis using Bayesian network meta-regression analyses that adjust for the follow-up period, in order to provide more robust evidence for clinicians. Methods: Databases comprising PubMed, Embase, MedlinePlus, Cochrane Library, Google Scholars, and Scopus were retrieved for eligible articles from inception to February 29, 2024. The primary endpoint was the complete response rate, the secondary endpoint was the partial response rate, the tertiary endpoints were the adverse events, and infection-related adverse events. Napierian Logarithm of hazard ratio (lnHR) and the standard error of lnHR (selnHR) were generated for dichotomous variants by STATA 18.0 MP and then put into Rstudio 4.3.2 to conduct Bayesian network meta-analysis as well as network meta-regression analysis to yield hazard ratio (HR) as pairwise effect size. Results: Ten studies involving 2138 patients and 11 treatment regimens were ultimately included. In the original analysis, for the primary endpoint, compared to the control group, obinutuzumab (22.6 months), abatacept-30mg (20.5 months), abatacept-10mg (17.8 months), and belimumab (23.3 months) demonstrated significant superiority (HR ranged from 1.6 to 2.5), more ever, their significance regarding relative efficacy was correlated with follow up period, namely "time window" (shown in parentheses above). For the secondary endpoint, compared to the control group, obinutuzumab and abatacept-30mg showed conspicuous preponderance (HR ranged from 1.6 to 2.4), "time window" was also detected in abatacept-30mg (20.5 months), whereas obinutuzumab remained consistently obviously effective regardless of the follow-up period (shown in parentheses above). For the tertiary endpoint, there were no differences among active regimens and control. Conclusions: Considering the efficacy and safety and "time window" phenomenon, we recommend obinutuzumab as the preferred treatment for LN. Certainly, more rigorous head-to-head clinical trials are warranted to validate those findings.

Macular vascular density alteration patterns in paediatric optic neuritis patients with serum MOG antibody positivity detected by optic coherence tomography angiography.

PURPOSE: The retinal microvascular network plays a crucial role in inflammatory injury in paediatric optic neuritis (PON) with serum MOG antibody positivity (MOG + PON). This study compared retinal microvascular densities and structural alterations in MOG + PON eyes with paediatric isolated optic neuritis (PION) eyes and followed up with the final best-corrected visual acuity (BCVA) after 6 months. METHODS: A total of 29 children (52 eyes) with PON, including 15 MOG + PON cases (28 eyes), 6 PION cases (10 eyes), 2 neuromyelitis optica spectrum disorders associated PON(NMOSD-PON) cases (4 eyes), 6 MOG-associated disease (MOGAD) patients without ON-affected eyes (MOG + NPON) cases (10 eyes) and age- and gender-matched healthy controls (HCs) underwent superficial/deep retinal angiography density (SAD/DAD) by optical coherence tomography angiography (OCTA). Their BCVAs were followed up until 6 months after PON onsets. RESULTS: MOG + PON cases had better final BCVAs than PION and NMOSD-ON. MOG + PON (35.7 ± 10.3 %) and PION (40.1 ± 10.3 %) eyes experienced severe SAD reductions in contrast to MOGAD+NPON (48.7 ± 5.2 %) and HCs eyes (55.6 ± 8.2 %). However, DAD in MOG + PON eyes (48.5 ± 9.2 %) and MOG + NPON eyes (53.1 ± 3.3 %) increased compared to HC eyes (45.7 ± 9.6 %; p = 0.028 and 0.009, respectively). SAD reduction occurred in acute PON and was detected as early as 2 weeks after PON onset. CONCLUSIONS: MOG + PON eyes had better final BCVAs than PION eyes, which displayed superficial retinal microvascular perfusion reductions and deep microvascular perfusion increases. SAD could be a sensitive surrogate for PON attacks in children with MOGAD.

Characterization of a novel phage SPX1 and biological control for biofilm of Shewanella in shrimp and food contact surfaces.

Shewanella putrefaciens, commonly found in seafood, forms tenacious biofilms on various surfaces, contributing to spoilage and cross-contamination. Bacteriophages, owing to their potent lytic capabilities, have emerged as novel and safe options for preventing and eliminating contaminants across various foods and food processing environments. In this study, a novel phage SPX1 was isolated, characterized by a high burst size (43.81 ± 3.01 PFU/CFU) and a short latent period (10 min). SPX1 belongs to the Caudoviricetes class, exhibits resistance to chloroform, and sensitivity to ultraviolet. It shows stability over a wide range of temperatures (30-50 °C) and pH levels (3-11). The genome of phage SPX1 consists of 53,428 bp with 49.72 % G + C composition, and lacks tRNAs or virulence factors. Genome analysis revealed the presence of two endolysins, confirming its biofilm-removal capacity. Following the treatment of shrimp surface biofilm with the optimal MOI of 0.001 of phage SPX1 for 5 h, the bacterial count decreased by 1.84 ± 0.1 log10 CFU/cm2 (> 98.5 %). Biofilms on the surfaces of the three common materials used in shrimp processing and transportation also showed varying degrees of reduction: glass (1.98 ± 0.01 log10 CFU/cm2), stainless steel (1.93 ± 0.05 log10 CFU/cm2), and polyethylene (1.38 ± 0.1 log10 CFU/cm2). The study will contribute to phage as a novel and potent biocontrol agent for effectively managing S. putrefaciens and its biofilm, ensuring a reduction in spoilage bacteria contamination during the aquaculture, processing, and transportation of seafood products.

A Nomogram Based on Features of Ultrasonography and Contrast-Enhanced CT to Predict Vessels Encapsulating Tumor Clusters Pattern of Hepatocellular Carcinoma.

OBJECTIVE: This study aimed to establish a clinical prediction model for vessels encapsulating tumor clusters (VETC) based on preoperative ultrasonography (US) and contrast-enhanced computed tomography (CECT) imaging in patients with hepatocellular carcinoma (HCC). METHODS: Data were retrospectively collected from 215 patients who underwent hepatectomy for solitary HCC lesions. They were divided into training and validation cohorts at a ratio of 6:4. Preoperative imaging features were extracted (seven from US and nine from CECT imaging) to explore their relationship with VETC. A VETC prediction model was constructed and graphically depicted as a nomogram. Its performance was evaluated via the receiver operating characteristic (ROC) curve, the calibration curve, and decision curve analysis (DCA). RESULTS: The VETC incidence for all the lesions was 37.7%. The final variables included in the nomogram were "peritumoral enhancement in CECT", "alpha-fetoprotein level > 200 ng/Ml," "halo in US," "capsule enhancement in CECT," and "posterior acoustic enhancement in US." The area under the curve (AUC) values for the training and validation cohorts were 0.824 and 0.725, respectively. The Hosmer-Lemeshow fit test showed no statistical difference (p = 0.369 and p = 0.067 for the training and validation cohorts, respectively). DCA demonstrated that our nomogram provided clinical benefits to a wide range of patients. According to the nomogram score, the VETC-positive and -negative groups demonstrated significant differences in both the training (p < 0.001) and validation (p = 0.001) cohorts. CONCLUSION: Our prediction model based on US and CECT imaging features can accurately predict VETC in HCC.

Smart Ship Draft Reading by Dual-Flow Deep Learning Architecture and Multispectral Information.

In maritime transportation, a ship's draft survey serves as a primary method for weighing bulk cargo. The accuracy of the ship's draft reading determines the fairness of bulk cargo transactions. Human visual-based draft reading methods face issues such as safety concerns, high labor costs, and subjective interpretation. Therefore, some image processing methods are utilized to achieve automatic draft reading. However, due to the limitations in the spectral characteristics of RGB images, existing image processing methods are susceptible to water surface environmental interference, such as reflections. To solve this issue, we obtained and annotated 524 multispectral images of a ship's draft as the research dataset, marking the first application of integrating NIR information and RGB images for automatic draft reading tasks. Additionally, a dual-branch backbone named BIF is proposed to extract and combine spectral information from RGB and NIR images. The backbone network can be combined with the existing segmentation head and detection head to perform waterline segmentation and draft detection. By replacing the original ResNet-50 backbone of YOLOv8, we reached a mAP of 99.2% in the draft detection task. Similarly, combining UPerNet with our dual-branch backbone, the mIoU of the waterline segmentation task was improved from 98.9% to 99.3%. The inaccuracy of the draft reading is less than ±0.01 m, confirming the efficacy of our method for automatic draft reading tasks.

Methadone Conversion Using a 3-Day Switch Strategy in Patients with Cancer on High-Dose Opioids: A Retrospective Study.

INTRODUCTION: Methadone has shown effectiveness in pain control in patients with cancer who are intolerant to other opioids in China. However, the optimal strategy for methadone conversion from previous high doses of opioids in refractory cancer pain remains debatable. This study aimed to describe the efficacy and safety of a 3-day switch (3DS) strategy for methadone conversion in patients with refractory cancer pain on high doses of opioids. METHODS: We retrospectively reviewed 30-day medical records of 70 patients with refractory cancer pain who used a 3DS strategy for methadone conversion from previous high doses of opioids from July 2018 to December 2022. The 3DS strategy indicated that the methadone dose was increased by one third every day for 3 days. Data on the rate of successful conversion, the time to stable analgesia after conversion, the conversion efficiency, the corrected QT (QTc) interval, the actual conversion ratios, adverse events (AEs), and quality of life were analyzed. RESULTS: Seventy patients received 3DS methadone conversion and 64 patients were eligible for analysis. Fifty patients (78%) achieved stable analgesia, and the median time to stable analgesia was 8.14 ± 2.70 (range 6-14) days. The average dose of methadone was 77.94 ± 42.74 mg. The most common AEs (≥ 10%) included constipation, dry mouth, nausea, and cold sweats. The incidence of constipation was reduced post-methadone conversion, and a statistically significant but asymptomatic prolongation of the QTc interval was observed. Additionally, the actual conversion ratios were lower than Ayonrinde's recommended ratios. CONCLUSIONS: The 3DS strategy for methadone conversion is applicable in Chinese patients with refractory cancer pain on high doses of opioids.

Heterologous Expression of Sunflower HaHPT and HaTMT Genes Enhances Rice-Grain Vitamin E Content.

Insufficient dietary vitamin intake can lead to severe health conditions in humans. Improving the vitamin E (VE) content of food crops such as rice through breeding is an economical and effective means to alleviate this problem. In this study, Homogentisate phytyltransferase (HPT) and γ-tocopherol methyltransferase (γ-TMT), two genes derived from sunflower (Helianthus annuus L., a high VE species), were introduced into an elite rice (Oryza sativa L.) cultivar "Ningjing 7" for biofortification. We verified the successful expression of the two genes in multiple transformation events. High-performance liquid chromatography revealed that transgenic plants expressing either HaHPT alone or HaHPT and HaTMT accumulate more VE compared with the wild type. We also revealed that the level of α-tocopherol, the form of VE with the highest biological activity, had increased to 2.33 times in transgenic HaTMT plants compared with the wild type. Transcriptome analysis revealed that the expression levels of some chlorophyll synthesis pathway genes related to VE precursor synthesis significantly increased during grain filling in transgenic rice grains. No difference in agronomic traits was observed between the transgenic plants and their wild type except for a slightly reduced plant height associated with the transgenic plants. These data demonstrate that the heterologous expression of HaHPT gene is effective in increasing the total VE content, while HaTMT plays an important role in the relative abundance of α-tocopherol in rice grains. This study demonstrates a promising strategy for breeding rice with elevated VE content via metabolic engineering.

Progress of the Impact of Terahertz Radiation on Ion Channel Kinetics in Neuronal Cells.

In neurons and myocytes, selective ion channels in the plasma membrane play a pivotal role in transducing chemical or sensory stimuli into electrical signals, underpinning neural and cardiac functionality. Recent advancements in biomedical research have increasingly spotlighted the interaction between ion channels and electromagnetic fields, especially terahertz (THz) radiation. This review synthesizes current findings on the impact of THz radiation, known for its deep penetration and non-ionizing properties, on ion channel kinetics and membrane fluid dynamics. It is organized into three parts: the biophysical effects of THz exposure on cells, the specific modulation of ion channels by THz radiation, and the potential pathophysiological consequences of THz exposure. Understanding the biophysical mechanisms underlying these effects could lead to new therapeutic strategies for diseases.

Glycemic Control in Diabetic Patients Improved Overall Lung Cancer Survival across Diverse Populations.

BACKGROUND: The consequence of diabetes on lung cancer overall survival (OS) is debated. This retrospective study used two large lung cancer databases to assess comprehensively diabetes effects on lung cancer OS in diverse demographic populations, including health disparity. METHODS: The University of Texas MD Anderson Cancer Center database (32,643 lung cancer cases with 11,973 diabetics) was extracted from electronic health records (EHRs) using natural language processing (NLP). Associations were between diabetes and lung cancer prognostic features [age, sex, race, body mass index (BMI), insurance status, smoking, stage, and histopathology]. Hemoglobin A1C (HgbA1c) and glucose levels assessed glycemic control. Validation was with a Louisiana cohort (17,768 lung cancer cases with 4,746 diabetics) enriched for health disparity cases. Kaplan-Meier analysis, log-rank test, multivariable Cox proportional hazard models, and survival tree analyses were employed. RESULTS: Lung cancer patients with diabetes exhibited marginally elevated OS or no statistically-significant difference versus non-diabetic patients. When examining OS for two glycemic levels (HgbA1c > 7.0 or glucose > 154 mg/dL versus HgbA1c > 9.0 or glucose > 215 mg/dL), a statistically significant improvement in OS occurred in lung cancers with controlled versus uncontrolled glycemia (P < 0.0001). This improvement spanned gender, age, smoking status, insurance status, stage, race, BMI, histopathology and therapy. Survival tree analysis revealed that obese and morbidly obese patients with controlled glycemia or no known diabetes had higher lung cancer OS than comparison groups. CONCLUSION: These findings indicate a need for optimal glycemic control to improve lung cancer OS in diverse populations with diabetes.