Emerging microglial biology highlights potential therapeutic targets for Alzheimer's disease.

Alzheimer's disease is a chronic degenerative disease of the central nervous system, which primarily affects elderly people and accounts for 70-80 % of dementia cases. The current prevailing amyloid cascade hypothesis suggests that Alzheimer's disease begins with the deposition of amyloid ß (Aß) in the brain. Major therapeutic strategies target Aß production, aggregation, and clearance, although many clinical trials have shown that these therapeutic strategies are not sufficient to completely improve cognitive deficits in AD patients. Recent genome-wide association studies have identified that multiple important regulators are the most significant genetic risk factors for Alzheimer's disease, especially in the innate immune pathways. These genetic risk factors suggest a critical role for microglia, highlighting their therapeutic potential in treating neurodegenerative diseases. In this review, we discuss how these recently documented AD risk genes affect microglial function and AD pathology and how they can be further targeted to regulate microglial states and slow AD progression, especially the highly anticipated APOE and TREM2 targets. We focused on recent findings that modulation of innate and adaptive neuroimmune microenvironment crosstalk reverses cognitive deficits in AD patients. We also considered novel strategies for microglia in AD patients.

Electrical Kinetic Model of a Hydroxylated Graphene FET Gas Sensor.

Graphene transistor sensors, with advantages such as facile surface functionalization and high sensitivity, have gained extensive research interest in gas detection applications. This study fabricated back-gated graphene transistors and employed a hydroxylation scheme for the surface functionalization of graphene. On the basis of the interaction mechanisms between gas molecules and graphene's electrical properties, a compact electrical kinetics model considering the gas-solid surface reaction of graphene transistors is proposed. The model can accurately predict the electrical kinetic performance and can be used to optimize sensor characteristics. The bias condition of a higher response can be rapidly determined. In addition, the density of hydroxyl groups on graphene is revealed to be the direction of improvement and a key factor of response. Hence, the gas detection capacity of sensors with varying densities of hydroxyl groups was assessed concerning ammonia gas, and design technology co-optimization (DTCO) is realized. Measurement results show that the sensor with 70 s of hydroxylation time has a 7.7% response under 22 ppm ammonia gas.

Hot Workability and Microstructure Evolution of Homogenized 2050 Al-Cu-Li Alloy during Hot Deformation.

For this article, hot compression tests were carried out on homogenized 2050 Al-Cu-Li alloys under different deformation temperatures and strain rates, and an Arrhenius-type constitutive model with strain compensation was established to accurately describe the alloy flow behavior. Furthermore, thermal processing maps were created and the deformation mechanisms in different working regions were revealed by microstructural characterization. The results showed that most of the deformed grains orientated toward <101>//CD (CD: compression direction) during the hot compression process, and, together with some dynamic recovery (DRV), dynamic recrystallization (DRX) occurred. The appearance of large-scale DRX grains at low temperatures rather than in high-temperature conditions is related to the particle-stimulated nucleation mechanism, due to the dynamic precipitation that occurs during the deformation process. The hot-working diagrams with a true strain of 0.8 indicated that the high strain-rate regions C (300 °C-400 °C, 0.1-1 s-1) and D (440 °C-500 °C, 0.1-1 s-1) are unfavorable for the processing of 2050 Al-Li alloys, owing to the flow instability caused by local deformation banding, microcracks, and micro-voids. The optimum processing region was considered to be 430 °C-500 °C and 0.1 s-1-0.001 s-1, with a dissipation efficiency of more than 30%, dominated by DRV and DRX; the DRX mechanisms are DDRX and CDRX.

Optimizing tomato waste hydrolysate for enhanced fucoxanthin biosynthesis in mixotrophic cultivation of Isochrysis galbana.

Vegetable waste, rich in bioactive compounds, offers a promising resource for producing value-added products. This study explored the use of tomato waste, containing glucose (40 mg/g), lycopene (95.12 µg/g), and ß-carotene (24.31 µg/g), for cultivating fucoxanthin-rich Isochrysis galbana. Water-soluble lycopene (2.0 µg/mL) and ß-carotene (0.4 µg/mL) effectively upregulated key carotenoid synthesis genes and boosted cell growth and fucoxanthin production (3.64 and 3.60 pg/cell, respectively) within 10 days in a mixotrophic culture. Optimized tomato waste hydrolysate achieved a high cell density of 1.21 × 107 cells/mL, 2.13 g/L biomass, and 21.02 mg/g fucoxanthin. This study highlights the potential of combining tomato waste with microalgae for a novel and innovative approach towards waste management and resource utilization.

An updated and comprehensive review of the morphology, ethnomedicinal uses, phytochemistry, and pharmacological activity of Aster tataricus L. f.

Ethnopharmacological relevance: Aster tataricus L.f., an extensively used herb in traditional Chinese medicine for more than 2000 years, is known as "Zi wan" or "Fan huncao". Its dried root and rhizome hold great promise in the treatment of cough, asthma, tumor, inflammation, etc.Aim of the study: This literature review summarizes the morphology characteristics, ethnopharmacological use, phytochemical properties, pharmacological effects, and potential applications of Aster tataricus. Furthermore, this review will discuss the future research trends and development prospects of this plant. Materials and methods: Using "Aster tataricus L.f.", "Traditional medicinal usage", "Phytochemistry", "Pharmacological effects" as the keywords and gathered relevant data on Aster tataricus L.f. using electronic databases (Elsevier, PubMed, ACS, CNKI, Google Scholar, Baidu Scholar, Web of Science), relevant books, and classic literature about Chinese herb. Result: A total of 186 compounds have been isolated and identified from Aster tataricus, including terpenes, organic acids, peptides, and flavonoids. And Aster tataricus has been widely used as a natural cough suppressant and has anti-oxidative, anti-inflammatory, anti-depressive, and anti-tumor effects. In addition, Aster tataricus has also been reported to have damaging effects on the liver as well as other toxicities were discussed in this review. Conclusions: Aster tataricus is an ancient herbal medicine with a broad spectrum of pharmaco logical activities that has been used for thousands of years in China, and has shown remarkable effectiveness in the treatment of various diseases, especially cough, asthma, inflammation. Although its rich chemical constituents have various pharmacological activities, the underlying mechanisms, as well as its toxicity and safety, remains unclear and warrant further investigation.

[Orthopedic robot-assisted endoscopic transforaminal lumbar interbody fusion for lumbar disc herniation with lumbar instability].

OBJECTIVE: To explore the safety and effectiveness of the robot-assisted system for transforaminal percutaneous endoscopic in the treatment of lumbar disc herniation with lumbar instability. METHODS: From October 2021 to March 2023, 26 patients with single-segment lumbar disc herniation and lumbar spinal instability were treated with robot-assisted system for transforaminal percutaneous endoscopic. The operation time, intraoperative blood loss, incision length, postoperative drainage volume, postoperative ambulation activity time, postoperative hospitalization time were record. The intervertebral space height and the lumbar lordosis angle before and after surgery were observed and compared. Pain level was evaluated using the visual analogue scale(VAS). The clinical efficacy was evaluated by Oswestry disability index(ODI). The interbody fusion was evaluated by Brantigan Steffee criteria. RESULTS: All patients successfully completed the operation, the operation time ranged form 105 to 109 min with an average of (150.8±24.1) min. Intraoperative blood loss ranged form 35 to 88 ml with an average of (55.5±16.4) ml. Incision length ranged form 1.4 to 3.5 cm with an average of (2.3±0.8) cm. Postoperative drainage volume ranged form 15 to 40 ml with an average of (28.5±7.8) ml. Postoperative ambulation time ranged form 15 to 30 h with an average of (22.8±4.5) h. Postoperative hospitalization time was 3 to 7 d with an average of (4.2±1.3) d. Total of 26 patients were followed up, the duration ranged from 12 to 16 months with an average of (14.0±1.3) months. The VAS and ODI at 1 week [(2.96±0.72) points, (41.63±4.79)%] and 12 months[(1.27±0.60) points, (13.11±2.45)%] were significantly different from those before surgery[(6.69±0.93) points, (59.12±5.92)%], P<0.01. The height of the intervertebral space (11.95±1.47) mm and lumbar lordosis (57.46±7.59)° at 12 months were significantly different from those before surgery [(6.67±1.20) mm, (44.08±7.79)°], P<0.01. At 12 months after surgery, all patients had no pedicle screw rupture or dislocation of the fusion cage, and the intervertebral fusion was successful. According to Brantigan-Steffee classification, 17 cases were grade D and 9 cases were grade E. CONCLUSION: Robot-assisted system for transforaminal percutaneous endoscopic for the treatment of single-segment lumbar disc herniation with lumbar instability improved the accuracy and safety of the operation, and the clinical effect of early follow-up is accurate.

Efficient and stable semitransparent perovskite photovoltaics via a Lewis base incorporation.

Semitransparent perovskite solar cells (ST-PSCs) have great potential in building integrated photovoltaics. However, semitransparent devices suffer from a low electron mobility and an imbalanced charge-carrier transport, leading to an unsatisfactory power conversion efficiency (PCE) and limited stability. Herein, we report a high-performance ST-PSC via the incorporation of a special Lewis base. A better perovskite with an improved crystallinity and less defects was achieved, and a matched energy level alignment between the perovskite and [6,6]-phenyl-C61-butyric acid methyl ester was also induced, thereby leading to a high electron mobility and an exceptional balance of hole and electron mobility approaching 1 : 1. The prepared ST-PSC exhibited a PCE of 20.22% at average visible transmittance (AVT) of 4.93%, 18.32% at AVT of 14.38%, and 15.00% at AVT of 25.65%. These PCEs are the highest values among those ST-PSCs based on top metallic electrodes at a close AVT. The ST-PSCs maintained 92% of the initial PCE in storage for 1000 h, and they held 84% of the initial PCE under the continuous maximum power point tracking measurement for 530 hours. The work paves the way to realize ST-PSCs with a high PCE, high light utilization efficiency and substantially enhanced stability.

23.81%-Efficiency Flexible Inverted Perovskite Solar Cells with Enhanced Stability and Flexibility via a Lewis Base Passivation.

Lewis base molecules bind the undercoordinated lead atoms at interfaces and grain boundaries, leading to the high efficiency and stability of flexible perovskite solar cells (PSCs). We demonstrated a highly efficient, stable, and flexible PSC via interface passivation using a Lewis base of tri(o-tolyl)phosphine (TTP). It not only induced an intimate interface contact and a complete deposition of the perovskite thin layers on hole transport layers (HTLs) but also led to a better perovskite with a raised crystallinity, fewer defects, and a better morphology, including fewer gullies, high uniformity, and low roughness. Furthermore, the TTP treatments induced a good alignment of energy levels among the perovskites, HTLs, and C60. The resultant flexible inverted PSCs exhibited a high power conversion efficiency (PCE) of 23.81%, which is one of the highest PCEs among these flexible inverted PSCs. Moreover, the optimized flexible PSCs exhibited high storage stability, superior operation stability, and enhanced mechanical flexibility. This study presents an effective method to substantially raise the PCE, stability, and mechanical flexibility of the flexible inverted perovskite photovoltaics.

Integrating Polyoxometalates and Silver Clusters into Atomically Precise Molecular Heterojunction.

The Ag cluster-POM assemblies have been shown to possess interesting and potentially useful properties. However, there is no precedent example of atomically precise Ag cluster-POM assemblies showing heterojunction effects in photocatalysis. Herein, the synthesis and total structure determination of the periodically distributed molecular heterojunction [Ag12(SCy)6(CH3CN)12(PW12O40)]n (Ag12-PW12) are reported. The assembly of Ag/W clusters into 3D network can endow the resulting binary structure with an aesthetic topology and unique physicochemical properties. More remarkably, the incorporation of Ag12 cluster with PW12 can efficiently facilitate the separation of photogenerated electrons and holes, thus significantly promoting the catalytic efficiency in selective oxidation of sulfides. The Ag12-PW12 heterojunction can be recovered and reused five times with no drastic change in the catalytic performance. This research is expected to assist in the rational design of cluster-based heterojunction catalysts. The increase of catalytic activity of the Ag12-PW12 assembly in comparison with the unassembled Ag12 and PW12 clusters is attributed to the synergistic effect of Ag12 and PW12 clusters, offering the splendid opportunity for deciphering structure-reactivity relationship of heterostructure-coupled photosystem.

A Double Network Composite Hydrogel with Self-Regulating Cu2+/Luteolin Release and Mechanical Modulation for Enhanced Wound Healing.

Designing adaptive and smart hydrogel wound dressings to meet specific needs across different stages of wound healing is crucial. Here, we present a composite hydrogel, GSC/PBE@Lut, that offers self-regulating release of cupric ions and luteolin and modulates mechanical properties to promote chronic wound healing. The double network hydrogel, GSC, is fabricated through photo-cross-linking of gelatin methacrylate, followed by Cu2+-alginate coordination cross-linking. On one hand, GSC allows for rapid Cu2+ release to eliminate bacteria in the acidic pH environment during inflammation and reduces the hydrogel's mechanical strength to minimize tissue trauma during early dressing changes. On the other hand, GSC enables slow Cu2+ release during the proliferation stage, promoting angiogenesis and biocompatibility. Furthermore, the inclusion of pH- and reactive oxygen species (ROS)-responsive luteolin nanoparticles (PBE@Lut) in the hydrogel matrix allows for controlled release of luteolin, offering antioxidant and anti-inflammatory effects and promoting anti-inflammatory macrophage polarization. In a murine model of Staphylococcus aureus infected wounds, GSC/PBE@Lut demonstrates exceptional therapeutic benefits in antibacterial, anti-inflammatory, angiogenic, and tissue regeneration. Overall, our results suggest that smart hydrogels with controlled bioactive agent release and mechanical modulation present a promising solution for treating chronic wounds.

Mechanisms of electroacupuncture relieves uterine smooth muscle spasm in dysmenorrhea rats based on Rho/ROCK signaling pathway. / 基于Rho/ROCKä¿¡å·é€šè·¯æŽ¢è®¨ç”µé’ˆä»»è„‰ã€ç£è„‰ç»ç©´ç¼“è§£ç±»ç—›ç»æ¨¡åž‹å¤§é¼ å­å®«å¹³æ»‘è‚Œç—‰æŒ›çš„æœºåˆ¶.

OBJECTIVES: To investigate the effect of electroacupuncture (EA) on Rho/Rho-associated coiled-coil-forming kinases (ROCK) signaling pathway of uterus tissue in rats with dysmenorrhea, so as to explore the underlying mechanism of EA treating primary dysmenorrhea (PD) and uterine smooth muscle spasm, and to observe whether there is a difference in the effect of meridian acupoints in Conception Vessel (CV) and Governer Vessel (GV). METHODS: Sixty female SD rats were randomly divided into saline, model, CV, GV, and non-acupoint groups, with 12 rats in each group. The dysmenorrhea model was established by subcutaneous injection of estradiol diphenhydrate combined with intraperitoneal injection of oxytocin (OT). EA (2 Hz) was applied to "Qihai" (CV6) and "Zhongji" (CV3) for CV group, "Mingmen" (GV4) and "Yaoshu" (GV2) for GV group, "non-acupoint 1" and "non-acupoint 3" on the left side for non-acupoint group, and manual acupuncture was applied to "Guanyuan" (CV4) for CV group, "Yaoyangguan" (GV3) for GV group, "non-acupoint 2" on the left side for non-acupoint group. The treatment was conducted for 20 min each time, once daily for 10 days. The writhing score was evaluated. The smooth myoelectric signals of rats' uterus in vivo were recorded by multi-channel physiological recorder. The uterine histopathological changes were observed by HE staining. The contents of prostaglandin F2α (PGF2α), OT and calcium ion (Ca2+) in uterine tissue of rats were detected by ELISA. The protein and mRNA expression levels of smooth muscle 22-α (SM22-α), RhoA and ROCKⅡ in uterine tissue were detected by Western blot and fluorescence quantitative PCR, respectively. RESULTS: Compared with the saline group, the writhing score of rats in the model group was increased (P<0.01), the amplitude voltage of uterine smooth muscle in vivo was elevated (P<0.01), the contents of PGF2α, OT and Ca2+, the protein and mRNA expression of SM22-α, RhoA and ROCK Ⅱ in uterine tissue were all increased (P<0.01). Compared with the model and the non-acupoint groups, the writhing scores of the CV and the GV groups were decreased (P<0.01, P<0.05), the amplitude voltage of uterine smooth muscle was decreased (P<0.01), the contents of PGF2α, OT and Ca2+ in uterine tissue were decreased (P<0.01, P<0.05), and the protein expression and mRNA expression of SM22-α, RhoA and ROCKⅡ in uterine tissue were decreased (P<0.01, P<0.05). HE staining showed extensive exfoliation of uterine intima with severe edema and increased glandular secretion in the model group, which was alleviated in the CV and GV groups. CONCLUSIONS: EA at acupoints of CV and GV can significantly reduce the writhing score, uterine smooth muscle amplitude voltage, pathological injury degree of uterus, and relieve spasm of uterine smooth muscle in dysmenorrhea rats, which may be related to its effect in regulating PGF2α and OT contents, inhibiting the Rho/ROCK signaling pathway, and reducing the SM22-α, RhoA, ROCKⅡ protein and mRNA expression, and Ca2+ content in uterine tissue.

A Biodegradable Janus Sponge for Negative Pressure Wound Therapy.

Negative pressure wound therapy (NPWT) is effective in repairing serious skin injury. The dressing used in the NPWT is important for wound healing. In this paper, we develop biodegradable amphiphilic polyurethanes (PUs) and fabricate the PUs into sponges as wound dressings (Bi@e) with Janus pore architectures for NPWT. The Bi@e is adaptive to all the stages of the wound healing process. The Janus Bi@e sponge consists of two layers: the dense hydrophobic upper layer with small pores provides protection and support during negative pressure drainage, and the loose hydrophilic lower layer with large pores absorbs large amounts of wound exudate and maintains a moist environment. Additionally, antibacterial agent silver sulfadiazine (SSD) is loaded into the sponge against Escherichia coli and Staphylococcus aureus with a concentration of 0.50 wt%. The Janus sponge exhibits a super absorbent capacity of 19.53 times its own water weight and remarkable resistance to compression. In a rat skin defect model, the Janus Bi@e sponge not only prevents the conglutination between regenerative skin and dressing but also accelerates wound healing compared to commercially available NPWT dressing. The Janus Bi@e sponge is a promising dressing for the NPWT.

Migraine Duration as a Potential Amplifier of Obesity.

Purpose: Migraine is a complex neurovascular disorder with obesity as a notable risk factor. This study aimed to investigate an under-researched area of the association between migraine duration and body composition. Patients and Methods: Patients with migraine from a neurology outpatient department were enrolled and were categorized into four groups based on illness duration: 1 year, 1-5 years, 5-10 years, and >10 years. Patient demographics, blood biochemistry, and body composition data were collected and analyzed statistically. Results: Patients with migraine were predominantly female, with lower education levels, significant work stress, poor sleep, and limited exercise. Longer migraine duration corresponded to increased obesity metrics. Notably, those patients with under 1 year of illness showed elevated blood lipid and liver function levels, whereas those with >10 years showed increased weight, waist circumference, body mass index, and fat content, despite higher physical activity. Significant positive correlation between obesity metrics and migraine duration was seen in patients who had migraine for >1 year. Conclusion: Our findings indicate that protracted episodes of migraine could amplify obesity tendencies, underscoring the imperative of weight regulation in migraine intervention to diminish ensuing adiposity-associated hazards.

A specific inflammatory suppression fibroblast subpopulation characterized by MHCII expression in human dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a significant cause of heart failure that requires heart transplantation. Fibroblasts play a central role in the fibro-inflammatory microenvironment of DCM. However, their cellular heterogeneity and interaction with immune cells have not been well identified. An integrative analysis was conducted on single-cell RNA sequencing (ScRNA-Seq) data from human left ventricle tissues, which comprised 4 hearts from healthy donors and 6 hearts with DCM. The specific antigen-presenting fibroblast (apFB) was explored as a subtype of fibroblasts characterized by expressing MHCII genes, the existence of which was confirmed by immunofluorescence staining of 3 cardiac tissues from DCM patients with severe heart failure. apFB highly expressed the genes that response to IFN-γ, and it also have a high activity of the JAK-STAT pathway and the transcription factor RFX5. In addition, the analysis of intercellular communication between apFBs and CD4+T cells revealed that the anti-inflammatory ligand-receptor pairs TGFB-TGFR, CLEC2B-KLRB1, and CD46-JAG1 were upregulated in DCM. The apFB signature exhibited a positive correlation with immunosuppression and demonstrated diagnostic and prognostic value when evaluated using a bulk RNA dataset comprising 166 donors and 166 DCM samples. In conclusion, the present study identified a novel subpopulation of fibroblasts that specifically expresses MHCII-encoding genes. This specific apFBs can suppress the inflammation occurring in DCM. Our findings further elucidate the composition of the fibro-inflammatory microenvironment in DCM, and provide a novel therapeutic target.

Moniezia benedeni infection increases IgE+ cells in sheep (Ovis aries) small intestine.

The concentration of immunoglobulin (Ig) E is the lowest among serum Igs, but it can induces type I hypersensitivity and plays an important role in anti-parasitic infection. The present study aimed to explore the residence characteristics of IgE+ cells in the sheep small intestine and the impact of Moniezia benedeni infection on them. The recombinant plasmids pET-28a-IgE were constructed and induced and expressed in Escherichia coli. BL21 (DE3). The rabbit anti-sheep IgE polyclonal antibody was prepared using the obtained recombinant protein as antigen. Finally, the levels of IgE+ cells in the small intestine of healthy (Control group) and naturally M. benedeni-infected (Infected group) sheep were detected analyzed. The results showed that the rabbit anti-sheep IgE polyclonal antibody with good immunogenicity (titer = 1: 128000) could specifically bind to the heavy chain of natural sheep IgE. In the Control group, the IgE+ cells were mainly distributed in lamina propria of the small intestine, and the densities were significantly decreased from duodenum to ileum (P<0.05), with respective values of (4.28 cells / 104 µm2, 1.80 cells / 104 µm2, and 1.44 cells / 104 µm2 in duodenum, jejunum, and ileum. In the Infected group, IgE+ cells density were 6.26 cells / 104 µm2, 3.01 cells / 104 µm2, and 2.09 cells / 104 µm2 in duodenum, jejunum and ileum respectively, which were significantly higher in all segments compared to the Control group (P<0.05), increasing by 46.26%, 67.22% and 45.14%, respectively. In addition, compared with the Control group, the IgE protein levels were significantly increased in all intestinal segments of the Infected group (P<0.01), however, there was no significant differences among the different intestinal segments within the same group (P>0.05). The results demonstrated that M. benedeni infection could significantly increase the content of IgE and the distribution density of its secreting cells in sheep small intestine. The intestinal mucosal immune system of sheep presented obvious specificity against M. benedeni infection. This lays a good foundation for further exploring molecular mechanisms of the intestinal mucosal immune system monitoring and responding to M. benedeni infection.

Polygonum cuspidatum polysaccharide: A review of its extraction and purification, structure analysis, and biological activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum cuspidatum Sieb. et Zucc. is mainly distributed in Shanxi, Gansu, and Sichuan province of China. It is also found in Korea and Japan. Its dried roots and rhizomes are used as medicinal herbs and have been used to treat hyperglycemia and various inflammatory disorders. AIM OF THE REVIEW: This paper aims to provide an up-to-date review of the developments in the studies involving the extraction and purification, structure analysis, pharmacological effects, and potential applications of polysaccharides obtained from Polygonum cuspidatum. Additionally, the possible future research directions of this plant are discussed. MATERIALS AND METHODS: This article used "Polygonum cuspidatum polysaccharide (PCP)" and "Polygonum cuspidatum" as the keywords and gathered relevant data on Polygonum cuspidatum using electronic databases (Elsevier, PubMed, ACS, CNKI, Google Scholar, Baidu Scholar, Web of Science), relevant books, and classic literature about Chinese herb. RESULTS: Excluding irrelevant and repetitive documents, 278 documents were finally included, of which 88 were in Chinese and 190 were in English. The CiteSpace software was used to visualize the trends and keywords in this research field. We concluded that the main extraction methods for Polygonum cuspidatum polysaccharide are water extraction and alcohol precipitation, microwave-assisted extraction, ultrasound-assisted extraction, and microjet extraction. High-performance liquid chromatography and column chromatography are also commonly used in the separation and purification of PCP. PCP has antitumor, immunomodulatory, hypoglycemic, and antioxidant effects. This paper provides an updated and deeper understanding of PCP, serving as a theoretical foundation for the further optimization of polysaccharide structures and the development of PCP as a novel functional material for clinical application.

Unregulated GmAGL82 due to Phosphorus Deficiency Positively Regulates Root Nodule Growth in Soybean.

Nitrogen fixation, occurring through the symbiotic relationship between legumes and rhizobia in root nodules, is crucial in sustainable agriculture. Nodulation and soybean production are influenced by low levels of phosphorus stress. In this study, we discovered a MADS transcription factor, GmAGL82, which is preferentially expressed in nodules and displays significantly increased expression under conditions of phosphate (Pi) deficiency. The overexpression of GmAGL82 in composite transgenic plants resulted in an increased number of nodules, higher fresh weight, and enhanced soluble Pi concentration, which subsequently increased the nitrogen content, phosphorus content, and overall growth of soybean plants. Additionally, transcriptome analysis revealed that the overexpression of GmAGL82 significantly upregulated the expression of genes associated with nodule growth, such as GmENOD100, GmHSP17.1, GmHSP17.9, GmSPX5, and GmPIN9d. Based on these findings, we concluded that GmAGL82 likely participates in the phosphorus signaling pathway and positively regulates nodulation in soybeans. The findings of this research may lay the theoretical groundwork for further studies and candidate gene resources for the genetic improvement of nutrient-efficient soybean varieties in acidic soils.

Examining the molecular mechanisms of topiramate in alleviating insulin resistance: A study on C2C12 myocytes and 3T3L-1 adipocytes.

PURPOSE: Migraine, a severely debilitating condition, may be effectively managed with topiramate, known for its migraine prevention and weight loss properties due to changes in body muscle and fat composition and improved insulin sensitivity. However, the mechanism of topiramate in modulating insulin response in adipocytes and myocytes remains elusive. This study aims to elucidate these molecular mechanisms, offering insights into its role in weight management for migraine sufferers and underpinning its clinical application. METHODS: Insulin resistance improvements were evaluated through glucose uptake measurements in C2C12 muscle cells and 3T3L-1 adipocytes, with Oil red O staining conducted on adipocytes. RNA-seq transcriptome analysis was used to identify the regulatory target genes of topiramate in these cells. The involvement of key genes and pathways was further validated through western blot analysis. RESULTS: Topiramate effectively reduced insulin resistance in C2C12 and 3T3L-1 cells. In C2C12 cells, it significantly lowered SORBS1 gene and protein levels. In 3T3L-1 cells, topiramate upregulated CTGF and downregulated MAPK8 and KPNA1 genes. Changes were notable in nuclear cytoplasmic transport and circadian signaling pathways. Furthermore, it caused downregulation of MKK7, pJNK1/ JNK1, BMAL1, and CLOCK proteins compared to the insulin-resistant model. CONCLUSION: This study provides preliminary insights into the mechanisms through which topiramate modulates insulin resistance in C2C12 myocytes and 3T3L-1 adipocytes, enhancing our understanding of its therapeutic potential in managing weight and insulin sensitivity in migraine patients.

Oxidase-like manganese oxide nanoparticles: a mechanism of organic acids/aldehydes as electron acceptors and potential application in cancer therapy.

Identifying the underlying catalytic mechanisms of synthetic nanocatalysts or nanozymes is important in directing their design and applications. Herein, we revisited the oxidation process of 4,4'-diamino-3,3',5,5'-tetramethylbiphenyl (TMB) by Mn3O4 nanoparticles and revealed that it adopted an organic acid/aldehyde-triggered catalytic mechanism at a weakly acidic or neutral pH, which is O2-independent and inhibited by the pre-addition of H2O2. Importantly, similar organic acid/aldehyde-mediated oxidation was applied to other substrates of peroxidase in the presence of nanoparticulate or commercially available MnO2 and Mn2O3 but not MnO. The selective oxidation of TMB by Mn3O4 over MnO was further supported by density functional theory calculations. Moreover, Mn3O4 nanoparticles enabled the oxidation of indole 3-acetic acid, a substrate that can generate cytotoxic singlet oxygen upon single-electron transfer oxidation, displaying potential in nanocatalytic tumor therapy. Overall, we revealed a general catalytic mechanism of manganese oxides towards the oxidation of peroxidase substrates, which could boost the design and various applications of these manganese-based nanoparticles.

A mitochondria-targeted anticancer copper dithiocarbamate amplifies immunogenic cuproptosis and macrophage polarization.

The way that cancer cells die inspires treatment regimens and cytolytic cuproptosis induced by copper complexes, like copper(II) bis(diethyldithiocarbamate) (CuET), has emerged as a novel therapeutic target. Herein, a triphenylphosphonium-modified CuET (TPP-CuET) is designed to target mitochondrial metabolism, triggering intense immunogenic cuproptosis in breast cancer cells and remodeling tumor-associated macrophages. TPP-CuET enables an enhanced mitochondrial copper accumulation in comparison to CuET (29.0% vs. 19.4%), and severely disrupts the morphology and functions of mitochondria, encompassing the tricarboxylic acid cycle, ATP synthesis, and electron transfer chain. Importantly, it triggers amplified immunogenic death of cancer cells, and the released damage-associated molecular patterns effectively induce M1 polarization and migration of macrophages. Transcriptome analysis further reveals that TPP-CuET promotes antigen processing and presentation in cancer cells through the MHC I pathway, activating the immune response of CD8 T cells and natural killer cells. To the best of our knowledge, TPP-CuET is the first mitochondrial targeted immunogenic cuproptosis inducer and is expected to flourish in antitumor immunotherapy.