Effects of cooking with solid fuel on hearing loss in Chinese adults-Based on two cohort studies.

The association between cooking fuel and hearing loss still needs more research to clarify, and two longitudinal cohort studies were explored to find if solid fuel use for cooking affected hearing in Chinese adults. The data from Chinese Health and Retirement Longitudinal Survey (CHARLS) and Chinese Longitudinal Healthy Longevity Survey (CLHLS) were analyzed. Participants (older than 18) without hearing loss at baseline and follow-up visits were included, which were divided into clean fuel and solid fuel groups. Hearing loss rate was from follow-up visits (both in year 2011) until the recent one (year 2018 in CHARLS and 2019 in CLHLS). Cox regressions were applied to examine the associations with adjustment for potential confounders. Fixed-effect meta-analysis was used to pool the results. A total of 9049 participants (average age 8.34 ± 9.12 [mean ± SD] years; 4247 [46.93%] males) were included in CHARLS cohort study and 2265 participants (average age, 78.75 ± 9.23 [mean ± SD] years; 1148 [49.32%] males) in CLHLS cohort study. There were 1518 (16.78%) participants in CHARLS cohort and 451 (19.91%) participants in CLHLS cohort who developed hearing loss. The group of using solid fuel for cooking had a higher risk of hearing loss (CHARLS: HR, 1.16; 95% CI 1.03-1.30; CLHLS: HR, 1.43; 95% CI 1.11-1.84) compared with the one of using clean fuel. Pooled hazard ratio showed the incidence of hearing loss in the solid fuel users was 1.17 (1.03, 1.29) times higher than that of clean fuel users. Hearing loss was associated with solid fuel use and older people were at higher risk. It is advised to replace solid fuel by clean fuel that may promote health equity.

Exercise ameliorates muscular excessive mitochondrial fission, insulin resistance and inflammation in diabetic rats via irisin/AMPK activation.

This study aimed to investigate the effects of exercise on excessive mitochondrial fission, insulin resistance, and inflammation in the muscles of diabetic rats. The role of the irisin/AMPK pathway in regulating exercise effects was also determined. Thirty-two 8-week-old male Wistar rats were randomly divided into four groups (n = 8 per group): one control group (Con) and three experimental groups. Type 2 diabetes mellitus (T2DM) was induced in the experimental groups via a high-fat diet followed by a single intraperitoneal injection of streptozotocin (STZ) at a dosage of 30 mg/kg body weight. After T2DM induction, groups were assigned as sedentary (DM), subjected to 8 weeks of treadmill exercise training (Ex), or exercise training combined with 8-week cycloRGDyk treatment (ExRg). Upon completion of the last training session, all rats were euthanized and samples of fasting blood and soleus muscle were collected for analysis using ELISA, immunofluorescence, RT-qPCR, and Western blotting. Statistical differences between groups were analyzed using one-way ANOVA, and differences between two groups were assessed using t-tests. Our findings demonstrate that exercise training markedly ameliorated hyperglycaemia, hyperlipidaemia, and insulin resistance in diabetic rats (p < 0.05). It also mitigated the disarranged morphology and inflammation of skeletal muscle associated with T2DM (p < 0.05). Crucially, exercise training suppressed muscular excessive mitochondrial fission in the soleus muscle of diabetic rats (p < 0.05), and enhanced irisin and p-AMPK levels significantly (p < 0.05). However, exercise-induced irisin and p-AMPK expression were inhibited by cycloRGDyk treatment (p < 0.05). Furthermore, the administration of CycloRGDyk blocked the effects of exercise training in reducing excessive mitochondrial fission and inflammation in the soleus muscle of diabetic rats, as well as the positive effects of exercise training on improving hyperlipidemia and insulin sensitivity in diabetic rats (p < 0.05). These results indicate that regular exercise training effectively ameliorates insulin resistance and glucolipid metabolic dysfunction, and reduces inflammation in skeletal muscle. These benefits are partially mediated by reductions in mitochondrial fission through the irisin/AMPK signalling pathway.

TolDC Restores the Balance of Th17/Treg via Aryl Hydrocarbon Receptor to Attenuate Colitis.

BACKGROUND: Tolerogenic dendritic cells (TolDCs) have been evidenced to trigger regulatory T cell's (Treg's) differentiation and be involved in the pathogenesis of Crohn's disease (CD). Aryl hydrocarbon receptor (AhR) plays a crucial role in the differentiation of TolDCs, although the mechanism remains vague. This study aimed to evaluate the role of AhR in TolDCs formation, which may affect Th17/Treg balance in CD. METHODS: Colon biopsy specimens were obtained from healthy controls and patients with CD. Wild type (WT) and AhR-/- mice were induced colitis by drinking dextran sulphate sodium (DSS) with or without 6-formylindolo 3,2-b carbazole (FICZ) treatment. Wild type and AhR-/- bone marrow-derived cells (BMDCs) were cultured under TolDCs polarization condition. Ratios of DCs surface markers were determined by flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was performed to quantify the levels of interleukin (IL)-1ß, transforming growth factor (TGF)-ß and IL-10. Tolerogenic dendritic cells differentiated from BMDCs of WT or AhR-/- mice were adoptively transferred to DSS-induced WT colitis mice. RESULTS: Patients with CD showed less AhR expression and activation in their inflamed colon regions. Compared with WT mice, AhR-/- mice experienced more severe colitis. Tolerogenic dendritic cells and Tregs were both decreased in the colon of AhR-/- colitis mice, while Th17 cells were upregulated. In vitro, compared with WT DCs, AhR-deficient DCs led to less TolDC formation. Furthermore, intestinal inflammation in WT colitis mice, which transferred with AhR-/- TolDCs, showed no obvious improvement compared with those transferred with WT TolDCs, as evidenced by no rescues of Th17/Treg balance. CONCLUSIONS: Activation of AhR attenuates experimental colitis by modulating the balance of TolDCs and Th17/Treg. The AhR modulation of TolDCs may be a viable therapeutic approach for CD.

Deletion of AhR aggravated colitis in mice, while AhR activation ameliorated colitis by promoting TolDCs formation which in turn restored Th17/Treg balance in colons. Thus, induction of TolDCs via regulating AhR may supply a therapeutic target for CD.

Low cycle number multiplex PCR: A novel strategy for the construction of amplicon libraries for next-generation sequencing.

Multiplex PCR is a critical step when preparing amplicon library for next-generation sequencing. However, there are several challenges related to multiplex PCR including poor uniformity, nonspecific amplification, and primer-dimers. To address these issues, we propose a novel solution strategy that involves using a low cycle number (<10 cycles) in multiplex PCR and then employing carrier DNAs and magnetic beads for the selection of targeted products. This technique improves the amplicon uniformity while also reducing primer-dimers and PCR artifacts. To evaluate our technique, we initially utilized 120 DNA fragments from mouse genome containing single nucleotide polymorphism (SNP) sites. Sequencing results demonstrated that with only 7 cycles of multiplex PCR, 95.8% of the targeted SNP sites were mapped, with a coverage of at least 1×. The average sequencing depth of all amplicons was 1705.79 ± 1205.30×; 87% of them reached a coverage depth that exceeded 0.2-fold of the average sequencing depth. Our method had a greater uniformity (87%) when compared to Hi-Plex PCR (53.3%). Furthermore, we validated our strategy by randomly selecting 90 primer pairs twice from the initial set of 120 primer-pairs. Next, we used the same protocol to prepare amplicon libraries. The two groups had an average sequencing depth of 1013.30 ± 585.57× and 219.10 ± 158.27×, respectively; over 84% of the amplicons had a sequencing depth that exceeded 0.2-fold of average depth. These results suggest that the use of a low cycle number in multiplex PCR is a cost-effective and efficient approach for the preparation of amplicon libraries.

Resveratrol Enhances Anticancer Effects of Silybin on HepG2 Cells and H22 Tumor-bearing Mice via Inducing G2/M Phase Arrest and Increasing Bax/Bcl-2 Ratio.

BACKGROUND: Silybin, a major flavonoid extracted from the seeds of milk thistle, has a strong hepatoprotective but weak anti-hepatoma activity. Screening another natural ingredient and combining it with silybin is expected to improve the anti-hepatoma efficacy of silybin. OBJECTIVE: The objective of this study was to investigate the synergistic anti-hepatoma effect of resveratrol and silybin on HepG2 cells and H22 tumor-bearing mice in hepatocellular carcinoma (HCC) in vitro and in vivo, respectively. METHODS: Cell viability, scratch wound, clone formation, cell apoptosis, cell cycle, and western blot analysis of HepG2 cells were used to investigate the synergistic effects in vitro of the combination resveratrol with silybin. Growth rates, tumor weights, organ indexes, and histological pathological examination in H22 tumor-bearing mice were used to investigate the synergistic effects in vivo. RESULTS: The combination of resveratrol (50 µg/mL) and silybin (100 µg/mL) significantly suppressed cell viability, whose combination index (CI) was 1.63 (>1.15), indicating the best synergism. The combination exhibited the synergistic effect in blocking the migration and proliferative capacity of HepG2 cells in the measurement in vitro. In particular, resveratrol enhanced the upregulation of Bcl-2 expression and the downregulation of Bax expression with a concurrent increase in the Bax/Bcl-2 ratio. The combination of resveratrol (50 mg/kg) and silybin (100 mg/kg) reduced the tumor weight, inhibited the growth rate, increased the organ indexes, and destroyed the tumor tissue morphology in H22 tumor-bearing mice. CONCLUSION: Resveratrol was found to exhibit synergistic anti-cancer effects with silybin on HepG2 cells and H22 tumor-bearing mice.

Highly efficient activation of peroxymonosulfate by ZIF-67 anchored cotton derived for ciprofloxacin degradation.

Metal-organic framework (MOF) and MOF-derived materials have attracted extensive research interest as environmental catalysts. In this study, a composite material (ZIF-67/CCot-8) was successfully prepared using cotton fiber as a substrate and growing ZIF-67 in situ. This material exhibited excellent catalytic performance and significantly improved the efficiency of antibiotics degradation. ZIF-67/CCot-8 at a concentration of 0.05 g/L, combined with 0.2 mM peroxymonosulfate (PMS), removed approximately 97% of ciprofloxacin (CIP) and 99% of tetracycline and sulfamethoxazole within 15 min. The high catalytic efficiency of this catalyst is mainly attributed to the uniform distribution of ZIF-67-derived nanoparticles on the surface of the cotton fibers, providing abundant active sites and thereby significantly enhancing the efficiency of antibiotics degradation. Radical quenching experiments and electron paramagnetic resonance (EPR) analyses revealed that sulfate radicals (SO4•-) and singlet oxygen (1O2) were the main active species. Mass spectrometry (MS) was used to elucidate the CIP degradation pathway. The growth of the roots and stems of soybean sprouts in different water environments (tap water, treated water, and untreated water) was also observed. The results demonstrated a significant improvement in the inhibition of plant growth in the post-degradation CIP solution, indicating a substantial reduction in the toxicity of the degraded aqueous solution. To validate the practicality of the ZIF-67/CCot-8/PMS system, a continuous-flow water-treatment device was designed. This system removed 98% of the CIP solution within 180 min, demonstrating its excellent durability. This study presents a potential pathway for effective antibiotics removal using MOF-derived materials.

Exercise ameliorating myocardial injury in type 2 diabetic rats by inhibiting excessive mitochondrial fission involving increased irisin expression and AMP-activated protein kinase phosphorylation.

PURPOSE: Though exercise generates beneficial effects on diabetes-associated cardiac damage, the underlying mechanism is largely unclear. Therefore, we prescribed a program of 8-week treadmill training for type 2 diabetes mellitus (T2DM) rats and determined the role of irisin signaling, via interacting with AMP-activated protein kinase (AMPK), in mediating the effects of exercise on myocardial injuries and mitochondrial fission. METHODS: Forty 8-week-old male Wistar rats were randomly divided into groups of control (Con), diabetes mellitus (DM), diabetes plus exercise (Ex), and diabetes plus exercise and Cyclo RGDyk (ExRg). Ex and ExRg rats received 8 weeks of treadmill running, and the rats in the ExRg group additionally were treated with a twice weekly injection of Cyclo RGDyk, an irisin receptor-αV/ß5 antagonist. At the end of the experiment, murine blood samples and heart tissues were collected and analyzed with methods of ELISA, Western blot, real-time quantitative polymerase chain reaction, as well as immunofluorescence staining. RESULTS: Exercise effectively mitigated T2DM-related hyperglycemia, hyperinsulinemia, lipid dysmetabolism, and inflammation, which could be diminished by Cyclo RGDyk treatment. Additionally, exercise alleviated T2DM-induced myocardial injury and excessive mitochondrial fission, whereas the beneficial effects were blocked by the administration of Cyclo RGDyk. T2DM significantly decreased serum irisin concentrations and fibronectin type III domain-containing protein 5 (FNDC5)/irisin gene and protein expression levels in the rat heart, whereas exercise could rescue T2DM-reduced FNDC5/irisin expression. Blocking irisin receptor signaling diminished the exercise-alleviated mitochondrial fission protein expression and elevated AMPK phosphorylation. CONCLUSION: Exercise is effective in mitigating diabetes-related insulin resistance, metabolic dysfunction, and inflammation. Irisin signaling engages in exercise-associated beneficial effects on myocardial injury and excessive mitochondrial fission in diabetes rats involving elevated AMPK phosphorylation.

Enhanced Light-Harvesting and Energy Transfer in Carbon Dots Embedded Thylakoids for Photonic Hybrid Capacitor Applications.

Nanohybrid photosystems have advantages in converting solar energy into electricity, while natural photosystems based solar-powered energy-storage device is still under developed. Here, we fabricate a new kind of photo-rechargeable zinc-ion hybrid capacitor (ZHC) benefiting from light-harvesting carbon dots (CDs) and natural thylakoids for realizing solar energy harvesting and storage simultaneously. Under solar light irradiation, the embedded CDs in thylakoids (CDs/Thy) can convert the less absorbed green light into highly absorbed red light for thylakoids, besides, Förster resonance energy transfer (FRET) between CDs and Thy also occurs, which facilitates the photoelectrons generation during thylakoids photosynthesis, thereby resulting in 6-fold photocurrent output in CDs/Thy hybrid photosystem, compared to pristine thylakoids. Using CDs/Thy as the photocathode in ZHCs, the photonic hybrid capacitor shows photoelectric conversion and storage features. CDs can improve the photo-charging voltage response of ZHCs to ≈1.2 V with a remarkable capacitance enhancement of 144 % under solar light. This study provides a promising strategy for designing plant-based photonic and electric device for solar energy harvesting and storage.

Combined exposure to manganese and iron decreases oxidative stress-induced nerve damage by increasing Nrf2/HO-1/NQO1 expression.

BACKGROUND: Manganese (Mn) and iron (Fe) are essential trace elements for humans, yet excessive exposure to Mn or Fe can accumulate in the central nervous system (CNS) and cause neurotoxicity. The purpose of this study was to investigate the effects of Mn and Fe exposure, alone or in combination, on inducing oxidative stress-induced neurological damage in rat cortical and SH-SY5Y cells, and to determine whether combined exposure to these metals increases their individual toxicity. METHODS: SH-SY5Y cells and male Sprague-Dawley rats were used to observe the effects of oxidative stress-induced neurological damage induced by exposure to manganese and iron alone or in combination. To detect the expression of anti-oxidative stress-related proteins, Nrf2, HO-1, and NQO1, and the apoptosis-related proteins, Bcl2 and Bax, and the neurological damage-related protein, α-syn. To detect reactive oxygen species generation and apoptosis. To detect the expression of the rat cortical protein Nrf2. To detect the production of proinflammatory cytokines. RESULTS: We demonstrate that juvenile developmental exposure to Mn and Fe and their combination impairs cognitive performance in rats by inducing oxidative stress causing neurodegeneration in the cortex. Mn, Fe, and their combined exposure increased the expression of ROS, Bcl2, Bax, and α-syn, activated the inflammatory factors IL-6 and IL-12, inhibited the activities of SOD and GSH, and induced oxidative stress-induced neurodegeneration both in rats and SH-SY5Y cells. Combined Mn-Fe exposure attenuated the oxidative stress induced by Mn and Fe exposure alone by increasing the expression of antioxidant factors Nrf2, HO-1, and NQO1. CONCLUSION: In both in vivo and in vitro studies, manganese and iron alone or in combination induced oxidative stress, leading to neuronal damage. In contrast, combined exposure to manganese and iron mitigated the oxidative stress induced by exposure to manganese and iron alone by increasing the expression of antioxidant factors. Therefore, studies to elucidate the main causes of toxicity and establish the molecular mechanisms of toxicity should help to develop more effective therapeutic modalities in the future.

Long-term impact of PM2.5 exposure on frailty, chronic diseases, and multimorbidity among middle-aged and older adults: insights from a national population-based longitudinal study.

Particulate Matter 2.5 (PM2.5) is a significant risk factor for frailty and chronic diseases. Studies on the associations between PM2.5 and frailty, chronic diseases, and multimorbidity are scarce, especially from large cohort studies. We aimed to explore the potential association between PM2.5 exposure and the risk of frailty, chronic diseases, and multimorbidity. We collected data from a national cohort (CHARLS) with a follow-up period of 11-18 years, totaling 13,366 participants. We obtained PM2.5 concentration data from the Atmospheric Composition Analysis Group at Dalhousie University. PM2.5 exposure is based on the average annual concentration in the prefecture-level city where residents live. We define frailty as the comprehensive manifestation of declining various body functions, characterized by a frailty index of 0.25 or greater, and multimorbidity as the presence of at least two or more chronic conditions. Cox proportional hazards regression was used to estimate the hazard ratio (HR) with its 95% confidence interval (95%CI). A 10-µg/m3 increase for PM2.5 was significantly associated with an increased risk of frailty (HR = 1.289, 95%CI = 1.257-1.322, P < 0.001). A 10-µg/m3 increase for PM2.5 was significantly associated with the elevated risk for most chronic diseases. Compared to those with no morbidity or only single morbidity, a 10-µg/m3 increase for PM2.5 was significantly associated with the elevated risk for multimorbidity (HR = 1.220, 95%CI = 1.181-1.260, P < 0.001). Ambient PM2.5 exposure is a significant risk factor for frailty, chronic diseases, and multimorbidity, and some measures need to be taken to reduce PM2.5 concentration and prevent frailty and chronic diseases.

Signal Transduction Associated with Mn-induced Neurological Dysfunction.

Manganese (Mn) is a heavy metal that occurs widely in nature and has a vital physiological role in growth and development. However, excessive exposure to Mn can cause neurological damage, especially cognitive dysfunction, such as learning disability and memory loss. Numerous studies on the mechanisms of Mn-induced nervous system damage found that this metal targets a variety of metabolic pathways, for example, endoplasmic reticulum stress, apoptosis, neuroinflammation, cellular signaling pathway changes, and neurotransmitter metabolism interference. This article reviews the latest research progress on multiple signaling pathways related to Mn-induced neurological dysfunction.

Frailty index trajectories in Chinese older adults with diverse levels of social participation: findings from a national population-based longitudinal study.

BACKGROUND: Aging and frailty pose significant challenges globally, placing a substantial burden on healthcare and social services due to their adverse consequences. AIM: The primary objective of this study was to investigate the relationship between social participation and development of frailty transition and trajectory. METHODS: This study utilized data from the CLHLS Cohort, a 10-year follow-up study involving 6713 participants, to investigate the association between social participation and development of frailty. Frailty reflects a comprehensive decline in various body functions. The study employed a group-based trajectory model to analyze the development trajectory of the frailty index and used logistic regression to assess the odds ratio (OR) of frailty risk. RESULTS: We identified two distinct groups of frailty progression trajectories: the "stable development group" and the "rapid growth group." Individuals who engaged in social activities at least once a month, but not daily, exhibited a significant association with an increased risk of transitioning into the "rapid growth group" (OR 1.305, 95% CI 1.032-1.649). Those with social participation less than once a month had an even greater risk (OR 1.872, 95% CI 1.423-2.463). Moreover, low social participation frequency (occasionally/never) has a more pronounced impact on frailty progression in males. CONCLUSION: A higher frequency of social participation is associated with a lower risk of being classified into the "rapid growth group" and a slower rate of frailty index progression. Preventing the progression of frailty can contribute to enhanced support for healthy aging among older adults.

Multifunctional actuators integrated with the function of self-powered temperature sensing made with Ti3C2Tx-bamboo nanofiber composites.

In recent years, multifunctional actuators have received increasing attention and development. In particular, researchers have conducted extensive research on intelligent actuators with integrated sensing functions. Temperature is an important parameter for the deformation of bilayer thermal actuators. By obtaining the temperature information of a bilayer thermal actuator, the deformation amplitude and its state can be judged. Thus, there is an urgent need to develop a type of intelligent actuator with a self-powered temperature sensing function. Herein, Ti3C2Tx-based composites modified with bamboo nanofibers have been proposed and applied to intelligent actuators integrated with a self-powered temperature sensing function. By utilizing the coefficients of thermal expansion between Ti3C2Tx-bamboo nanofiber composites and a polyimide film, a bilayer photo/electro-driven thermal actuator is designed which shows a bending curvature as large as 1.9 cm-1. In addition, Ti3C2Tx-bamboo nanofiber composites have a Seebeck coefficient of -9.15 µV K-1, and are N-type thermoelectric materials and can be used as the component of self-powered temperature sensors. Finally, a series of practical applications were designed, including a light-driven floating actuator (with a moving speed of 5 mm s-1), biomimetic sunflowers, bionic tentacles, and a multifunctional gripper integrated with a self-powered temperature sensing function. In particular, the multifunctional grippers can output voltage signals carrying their temperature information without external complex power sources, demonstrating their potential for remote monitoring. The above results demonstrate that Ti3C2Tx-bamboo nanofiber composites have extensive practical applications in fields such as self-powered sensors, flexible thermoelectric generators, and soft actuators.

Population genomics provides insights into the genetic diversity and adaptation of the Pieris rapae in China.

The cabbage white butterfly (Pieris rapae), a major agricultural pest, has become one of the most abundant and destructive butterflies in the world. It is widely distributed in a large variety of climates and terrains of China due to its strong adaptability. To gain insight into the population genetic characteristics of P. rapae in China, we resequenced the genome of 51 individuals from 19 areas throughout China. Using population genomics approaches, a dense variant map of P. rapae was observed, indicating a high level of polymorphism that could result in adaptation to a changing environment. The feature of the genetic structure suggested considerable genetic admixture in different geographical groups. Additionally, our analyses suggest that physical barriers may have played a more important role than geographic distance in driving genetic differentiation. Population history showed the effective population size of P. rapae was greatly affected by global temperature changes, with mild periods (i.e., temperatures warmer than those during glaciation but not excessively hot) leading to an increase in population size. Furthermore, by comparing populations from south and north China, we have identified selected genes related to sensing temperature, growth, neuromodulation and immune response, which may reveal the genetic basis of adaptation to different environments. Our study is the first to illustrate the genetic signatures of P. rapae in China at the population genomic level, providing fundamental knowledge of the genetic diversity and adaptation of P. rapae.

Regulation of the physiology and virulence of Ralstonia solanacearum by the second messenger 2',3'-cyclic guanosine monophosphate.

Previous studies have demonstrated that bis-(3',5')-cyclic diguanosine monophosphate (bis-3',5'-c-di-GMP) is a ubiquitous second messenger employed by bacteria. Here, we report that 2',3'-cyclic guanosine monophosphate (2',3'-cGMP) controls the important biological functions, quorum sensing (QS) signaling systems and virulence in Ralstonia solanacearum through the transcriptional regulator RSp0980. This signal specifically binds to RSp0980 with high affinity and thus abolishes the interaction between RSp0980 and the promoters of target genes. In-frame deletion of RSp0334, which contains an evolved GGDEF domain with a LLARLGGDQF motif required to catalyze 2',3'-cGMP to (2',5')(3',5')-cyclic diguanosine monophosphate (2',3'-c-di-GMP), altered the abovementioned important phenotypes through increasing the intracellular 2',3'-cGMP levels. Furthermore, we found that 2',3'-cGMP, its receptor and the evolved GGDEF domain with a LLARLGGDEF motif also exist in the human pathogen Salmonella typhimurium. Together, our work provides insights into the unusual function of the GGDEF domain of RSp0334 and the special regulatory mechanism of 2',3'-cGMP signal in bacteria.

Preparation and Kokumi Properties of N-Acetyl-Val/Leu/Ile/Met/Phe in the Presence of Acetic Acid and Amino Acid: A Commercially Available Transglutaminase and Protease A 2SD.

Kokumi is a beneficial feeling for the evaluation of food quality, and thus, preparing and understanding the taste properties of kokumi compounds are important for the flavor of food. N-acetyl-Val/Leu/Ile/Met/Phe/Trp/Tyr is a type of kokumi compound found in food and usually prepared by chemical reagents. In this study, we first prepared these six kokumi compounds using transglutaminase and protease A2SD in aqueous solution by using amino acids and acetic acid as substrates and evaluated their kokumi characteristics. HPLC and LC-MS were used to identify quantitative N-acetyl amino acids. Using Phe and acetic acid as substrates, transglutaminase and protease A2SD showed the highest yields for N-acetyl-Phe of 22.75 and 42.21%, respectively, under the optimal conditions. For N-acetyl-Val/Leu/Ile/Met/Trp/Tyr, these two enzymes showed the synthesis yield in the ranges of 2.22-20.12 and 0.75-12.91%, respectively. Six N-acetyl-amino acids were succesully enriched by ethyl acetate with a recovery over 50% and purity over 95%. Sensory evaluation found that N-acetyl-Val/Leu/Ile/Met/Phe are kokumi compounds that enhance sweet, umami, and salt tastes in 5% sucrose, 0.3% NaCl, and 0.5% sodium glutamate, especially N-acetyl-Val, with the salt- and umami-enhancing threshold values of 0.63 and 1.25 g/L, respectively. Therefore, transglutaminase and protease A2SD for the synthesis of partial N-acetyl amino acid might have the potential to be applied in food as a kokumi compound.

Mechanism of LEF1-AS1 regulating HUVEC cells by targeting miR-489-3p/S100A11 axis.

Background: The venous malformation is the most common congenital vascular malformation and exhibits the characteristics of local invasion and lifelong progressive development. Long noncoding RNA (lncRNA) regulates endothelial cells, vascular smooth muscle cells, macrophages, vascular inflammation, and metabolism and also affects the development of venous malformations. This study aimed to elucidate the role of the lncRNA LEF1-AS1 in the development of venous malformations and examine the interaction among LEF1-AS1, miR-489-3p, and S100A11 in HUVEC cells. Methods: Venous malformation tissues, corresponding normal venous tissues, and HUVEC cells were used. Agilent human lncRNA microarray gene chip was used to screen differential genes, RNA expression was detected using quantitative reverse transcription PCR, and protein expression was detected using Western blotting. The proliferation, migration, and angiogenesis of HUVEC cells were assessed using CCK8, transwell, and in vitro angiogenesis tests. Results: A total of 1,651 lncRNAs were screened using gene chip analysis, of which 1015 were upregulated and 636 were downregulated. The lncRNA LEF1-AS1 was upregulated with an obvious difference multiple, and the fold-change value was 11.03273. The results of the analysis performed using the StarBase bioinformatics prediction website showed that LEF1-AS1 and miR-489-3p possessed complementary binding sites and that miR-489-3p and S100A11 also had complementary binding sites. The findings of tissue experiments revealed that the expressions of LEF1-AS1 and S100A11 were higher in tissues with venous malformations than in normal tissues, whereas the expression of miR-489-3p was lower in venous malformations than in normal tissues. Cell culture experiments indicated that LEF1-AS1 promoted the proliferation, migration, and angiogenesis of HUVEC cells. In these cells, LEF1-AS1 targeted miR-489-3p, which in turn targeted S100A11. LEF1-AS1 acted as a competitive endogenous RNA and promoted the expression of S100A11 by competitively binding to miR-489-3p and enhancing the proliferation, migration, and angiogenesis of HUVEC cells. Thus, LEF1-AS1 participated in the occurrence and development of venous malformation. Conclusions: The expression of LEF1-AS1 was upregulated in venous malformations, and the expression of S100A11 was increased by the adsorption of miR-489-3p to venous endothelial cells, thus enhancing the proliferation, migration, and angiogenesis of HUVEC cells. In conclusion, LEF1-AS1 is involved in the occurrence and development of venous malformations by regulating the miR-489-3p/S100A11 axis, which provides valuable insights into the pathogenesis of this disease and opens new avenues for its treatment.

Advances in pixel driving technology for micro-LED displays.

Micro-LED displays have been recognized as the next-generation display technology. This review focuses on the pixel-driving technology of micro-LED displays. The performance of pixel driving on micro-LED displays is discussed in terms of brightness uniformity, driving speed, grayscale, and frame rate under various driving architectures. Since the memristors possess characteristics similar to those of biological synaptic neurons due to the ion migration mechanism, the neural network approach which combines the memristor arrays with the pixel driving circuit of micro-LEDs could promote the development of smart and efficient displays.

Progress and prospect: Biosynthesis of plant natural products based on plant chassis.

Plant-derived natural products are a specific class of active substances with numerous applications in the medical, energy, and industrial fields. Many of these substances are in high demand and have become the fundamental materials for various purposes. Recently, the use of synthetic biology to produce plant-derived natural products has become a significant trend. Plant chassis, in particular, offer unique advantages over microbial chassis in terms of cell structure, product affinity, safety, and storage. The development of the plant hairy root tissue culture system has accelerated the commercialization and industrialization of synthetic biology in the production of plant-derived natural products. This paper will present recent progress in the synthesis of various plant natural products using plant chassis, organized by the types of different structures. Additionally, we will summarize the four primary types of plant chassis used for synthesizing natural products from plant sources and review the enabling technologies that have contributed to the development of synthetic biology in recent years. Finally, we will present the role of isolated and combined use of different optimization strategies in breaking the upper limit of natural product production in plant chassis. This review aims to provide practical references for synthetic biologists and highlight the great commercial potential of plant chassis biosynthesis, such as hairy roots.

PtrA regulates prodigiosin synthesis and biological functions in Serratia marcescens FZSF02.

Serratia marcescens is a gram-negative bacterium that is able to produce many secondary metabolites, such as the prominent red pigment prodigiosin (PG). In this work, a ptrA-disrupted mutant strain with reduced PG production was selected from Tn5 transposon mutants. RT-qPCR results indicated that ptrA promoted elevated transcription of the pig gene cluster in S. marcescens FZSF02. Furthermore, we found that ptrA also controls several other important biological functions of S. marcescens, including swimming and swarming motilities, biofilm formation, hemolytic activity, and stress tolerance. In conclusion, this study demonstrates that ptrA is a PG synthesis-promoting factor in S. marcescens and provides a brief understanding of the regulatory mechanism of ptrA in S. marcescens cell motility and hemolytic activity.