Room-Temperature Liquid Crystalline Tetraphenylethylene-Surfactant Complex with Chiral Supramolecular Structure and Tunable Circularly Polarized Luminescence.

A novel room-temperature liquid crystal of tetraphenylethylene derivative (TPE-DHAB) was synthesized using an ionic self-assembly strategy. The TPE-DHAB complex exhibits typical aggregation-induced emission properties and a unique helical supramolecular structure. Moreover, the generation and handedness inversion of circularly polarized luminescence (CPL) can be achieved through further chiral solvation, providing a facile approach to fabricate room-temperature liquid crystalline materials with controllable supramolecular structures and tunable CPL properties through a synergistic strategy of ionic self-assembly and chiral solvation process.

cGAS-activated endothelial cell-T cell cross-talk initiates tertiary lymphoid structure formation.

Aberrant activation of the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway causes autoimmunity in humans and mice; however, the exact mechanism by which the cGAS-STING pathway initiates adaptive immunity and tissue pathology is still not fully understood. Here, we used a cGAS knockin (KI) mouse model that develops systemic autoimmunity. In the lungs of cGAS-KI mice, blood vessels were enclosed by organized lymphoid tissues that resemble tertiary lymphoid structures (TLSs). Cell-intrinsic cGAS induction promoted up-regulation of CCR5 in CD8+ T cells and led to CCL5 production in vascular endothelial cells. Peripheral CD8+ T cells were recruited to the lungs and produced CXCL13 and interferon-γ. The latter triggered endothelial cell death, potentiated CCL5 production, and was essential for TLS establishment. Blocking CCL5 or CCR5, or depleting CD8+ T cells, impaired TLS formation. cGAS-mediated TLS formation also enhanced humoral and antitumor responses. These data demonstrate that cGAS signaling drives a specialized lymphoid structure that underlies autoimmune tissue pathology.

A Mid-Infrared Perfect Metasurface Absorber with Tri-Band Broadband Scalability.

Metasurfaces have emerged as a unique group of two-dimensional ultra-compact subwavelength devices for perfect wave absorption due to their exceptional capabilities of light modulation. Nonetheless, achieving high absorption, particularly with multi-band broadband scalability for specialized scenarios, remains a challenge. As an example, the presence of atmospheric windows, as dictated by special gas molecules in different infrared regions, highly demands such scalable modulation abilities for multi-band absorption and filtration. Herein, by leveraging the hybrid effect of Fabry-Perot resonance, magnetic dipole resonance and electric dipole resonance, we achieved multi-broadband absorptivity in three prominent infrared atmospheric windows concurrently, with an average absorptivity of 87.6% in the short-wave infrared region (1.4-1.7 µm), 92.7% in the mid-wave infrared region (3.2-5 µm) and 92.4% in the long-wave infrared region (8-13 µm), respectively. The well-confirmed absorption spectra along with its adaptation to varied incident angles and polarization angles of radiations reveal great potential for fields like infrared imaging, photodetection and communication.

A case study of a bispecific antibody manufacturability assessment and optimization during discovery stage and its implications.

The manufacturability assessment and optimization of bispecific antibodies (bsAbs) during the discovery stage are crucial for the success of the drug development process, impacting the speed and cost of advancing such therapeutics to the Investigational New Drug (IND) stage and ultimately to the market. The complexity of bsAbs creates challenges in employing effective evaluation methods to detect developability risks in early discovery stage, and poses difficulties in identifying the root causes and implementing subsequent engineering solutions. This study presents a case of engineering a bsAb that displayed a normal solution appearance during the discovery phase but underwent significant precipitation when subjected to agitation stress during 15 L Chemistry, Manufacturing, and Control (CMC) production Leveraging analytical tools, structural analysis, in silico prediction, and wet-lab validations, the key molecular origins responsible for the observed precipitation were identified and addressed. Sequence engineering to reduce protein surface hydrophobicity and enhance conformational stability proved effective in resolving agitation-induced aggregation. The refined bsAb sequences enabled successful mass production in CMC department. The findings of this case study contribute to the understanding of the fundamental mechanism of agitation-induced aggregation and offer a potential protein engineering procedure for addressing similar issues in bsAb. Furthermore, this case study emphasizes the significance of a close partnership between Discovery and CMC teams. Integrating CMC's rigorous evaluation methods with Discovery's engineering capability can facilitate a streamlined development process for bsAb molecules.

Prevalence of thyroid nodule and relationship with physiological and psychosocial factors among adults in Zhejiang Province, China: a baseline survey of a cohort study.

BACKGROUND: Thyroid nodules have attracted much attention due to their high incidence and potential for malignant transformation. Compared with the clinical assessment and diagnosis of thyroid nodules, there are relatively few studies on the epidemiological risk factors for thyroid nodules. The aim of this study was to investigate the prevalence of thyroid nodule among adults in Zhejiang province and to explore their relationship with physiological and psychosocial factors. METHODS: The data used in this study were obtained from the baseline survey of the Zhejiang Provincial Cohort Study on Environment and Health. From June 2022 to December 2023, a total of 21,712 participants from five representative cities in Zhejiang were recruited for the baseline survey. Based on the inclusion and exclusion criteria, 15,595 adults were included in the analysis. The data were collected via self-report questionnaires and physical examinations. Multivariate logistic regression analysis was subsequently performed. RESULTS: The detection rate of thyroid nodules was 50.98% among adults in Zhejiang province. Age, gender, education level, BMI, tea and alcohol consumption all had a statistically significant association with thyroid nodules (p < 0.05). After adjusting for sociodemographic factors, results of logistic regression analysis showed that good life satisfaction (OR = 0.854, 95% CI: 0.780-0.934) had a lower risk of thyroid nodules, however, poor life satisfaction (OR = 1.406, 95% CI: 1.014-1.951), social isolation (OR = 1.294, 95% CI: 1.089-1.538) and a family history of thyroid nodules (OR = 1.334, 95% CI: 1.064-1.672) had a greater risk of thyroid nodules. CONCLUSION: The detection rate of thyroid nodules in adults of Zhejiang province was an increasing trend compared with that in previous years. In addition to the sensitive thyroid nodule screening technology, influencing factors mentioned in this study might also represent credible candidates for this increase. As variable influence factors, weight management, good interpersonal relationships and life satisfaction should be the focus of health interventions.

Dietary Iodine Intake and Sources among Residents in Zhejiang Province 10 Years after Reducing Iodine Concentration in Iodized Salt.

We aimed to assess dietary iodine intake and sources in Zhejiang Province a decade after a reduction in iodine concentration in iodized salt. Three-day 24 h dietary recall and household weighing were used, complemented by "Chinese Food Composition" data. Household water and salt samples were collected from 5890 residents and analyzed. Differences in iodized salt consumption rates were observed across the following regions: inland (84.20%), subcoastal (67.80%), and coastal (37.00%) areas. The median (P25, P75) iodine concentration in water and diet were 2.2 (0.9, 4.0) µg/L and 142.05 (58.94, 237.11) µg/d, respectively, with significant regional differences in dietary concentration (inland [185.61 µg/d], subcoastal [153.42 µg/d], and coastal [75.66 µg/d]). Males (149.99 µg/d) and iodized salt consumers (191.98 µg/d) had a significantly higher dietary iodine intake than their counterparts. Regions were ranked as follows based on the proportions of individuals meeting the recommended dietary iodine intake: inland (69.40%), subcoastal (56.50%), and coastal (34.10%) areas. Dietary sources included salt (48.54%), other foods (32.06%), drinking water (8.84%), laver (4.82%), kelp (3.02%), and other seafood (2.32%). The qualified iodized salt consumption rate was significantly lower than the national standard. Zhejiang Province should continue implementing measures to control iodine deficiency through salt iodization, education efforts, and increasing the qualified iodized salt consumption rate.

A crystal capping layer for formation of black-phase FAPbI3 perovskite in humid air.

Black-phase formamidinium lead iodide (α-FAPbI3) perovskites are the desired phase for photovoltaic applications, but water can trigger formation of photoinactive impurity phases such as δ-FAPbI3. We show that the classic solvent system for perovskite fabrication exacerbates this reproducibility challenge. The conventional coordinative solvent dimethyl sulfoxide (DMSO) promoted δ-FAPbI3 formation under high relative humidity (RH) conditions because of its hygroscopic nature. We introduced chlorine-containing organic molecules to form a capping layer that blocked moisture penetration while preserving DMSO-based complexes to regulate crystal growth. We report power conversion efficiencies of >24.5% for perovskite solar cells fabricated across an RH range of 20 to 60%, and 23.4% at 80% RH. The unencapsulated device retained 96% of its initial performance in air (with 40 to 60% RH) after 500-hour maximum power point operation.

Iron gallic acid biomimetic nanoparticles for targeted magnetic resonance imaging.

Developing T1-weighted magnetic resonance imaging (MRI) contrast agents with enhanced biocompatibility and targeting capabilities is crucial owing to concerns over current agents' potential toxicity and suboptimal performance. Drawing inspiration from "biomimetic camouflage," we isolated cell membranes (CMs) from human glioblastoma (T98G) cell lines via the extrusion method to facilitate homotypic glioma targeting. At an 8:1 mass ratio of ferric chloride hexahydrate to gallic acid (GA), the resulting iron (Fe)-GA nanoparticles (NPs) proved effective as a T1-weighted MRI contrast agent. T98G CM-coated Fe-GA NPs demonstrated improved homotypic glioma targeting, validated through Prussian blue staining and in vitro MRI. This biomimetic camouflage strategy holds promise for the development of targeted theranostic agents in a safe and effective manner.

Comparative evaluation of the diagnostic and prognostic performance of CNSide™ versus standard cytology for leptomeningeal disease.

Background: This retrospective study compares the real-world performance of cerebrospinal fluid (CSF) CNSide™ versus cytology in leptomeningeal disease (LMD). Methods: Consecutive patients with suspected LMD who underwent lumbar punctures for CSF cytology and CNSide™ from January 2020 to December 2022 were reviewed. LMD was classified by EANO criteria. Descriptive statistics, confusion matrix, Kaplan-Meier curves, and Cox proportional regression were used. Results: Median age for 87 evaluable patients was 63 years (range: 23-93); 82 (94%) met EANO criteria for possible/probable/confirmed LMD (EANO/LMD). The commonest primary cancers were breast (36,44.0%) and lung (34,41.5%). Primary lung harbored actionable mutations in 18 (53.0%); primary breast expressed hormone receptors in 27 (75%), and HER2 amplification in 8 (22%). Uncontrolled systemic disease was detected in 35 (40%), while 25 (46%) received systemic therapy with medium/high CNS penetrance at LMD diagnosis. The median time from initial cancer to LMD diagnosis was 31 months (range: 13-73). LMD was confirmed by CSF cytology in 23/82 (28%), all identified by CNSide™. CNSide™ identified 13 additional cases (36/82, 43.9%), increasing diagnostic yield by 56.5%. Median overall survival (mOS) was 31 weeks (95%CI: 21-43), significantly worse for CNSide™ positive versus negative: 4.0 versus 16.0 weeks, respectively (HR = 0.50, P = .010). While survival since LMD diagnosis did not differ by histology, time to LMD diagnosis from initial cancer diagnosis was longer for breast (48.5 months, IQR: 30.0-87.5) versus lung (8 months, IQR:0.5-16.0) cohorts. mOS was longer for patients eligible for intrathecal chemotherapy (HR: 0.189, 95%CI: 0.053-0.672, P = .010). Conclusions: This retrospective, real-world analysis of CNSide™ showed increased sensitivity versus cytology and provided clinically relevant molecular CSF analyses.

Critical Role of Cu Nanoparticle-Loaded Cu(100) Surface Structures on Structured Copper-Based Catalysts in Boosting Ethanol Generation in CO2 Electroreduction.

Presently, realizing high ethanol selectivity in CO2 electroreduction remains challenging due to difficult C-C coupling and fierce product competition. In this work, we report an innovative approach for improving the efficiency of Cu-based electrocatalysts in ethanol generation from electrocatalytic CO2 reduction using a crystal plane modification strategy. These novel Cu-based electrocatalysts were fabricated by electrochemically activating three-dimensional (3D) flower-like CuO micro/nanostructures grown in situ on copper foils and modifying with surfactants. It was demonstrated that the fabricated Cu-based electrocatalyst featured a predominantly exposed Cu(100) surface loaded with high-density Cu nanoparticles (NPs). The optimal Cu-based electrocatalyst displayed considerably improved CO2 electroreduction performance, with a Faraday efficiency of 37.9% for ethanol and a maximum Faraday efficiency of 68.0% for C2+ products at -1.4 V vs RHE in an H-cell, accompanied by a high current density of 69.9 mA·cm-2, much better than the particulate Cu-based electrocatalyst. It was unveiled that the Cu(100)-rich surface of nanoscale petals with abundant under-coordinated copper atoms from CuNPs was conducive to the formation and stabilization of key *CH3CHO and *OC2H5 intermediates, thereby promoting ethanol generation. This study highlighted the critical role of CuNP-loaded Cu(100) surface structures on structured Cu-based electrocatalysts in enhancing ethanol production for the CO2 electroreduction process.

Assessing the predictive value of smoking history for immunotherapy outcomes in bladder cancer patients.

Background: The therapeutic effectiveness of immune checkpoint inhibitors (ICIs) in bladder cancer varies among individuals. Identifying reliable predictors of response to these therapies is crucial for optimizing patient outcomes. Methods: This retrospective study analyzed 348 bladder cancer patients treated with ICIs, with additional validation using data from 248 patients at our institution who underwent PD-L1 immunohistochemical staining. We examined patient smoking history, clinicopathological characteristics, and immune phenotypes. The main focus was the correlation between smoking history and immunotherapy outcomes. Multivariate logistic and Cox proportional hazard regressions were used to adjust for confounders. Results: The study cohort comprised 348 bladder cancer patients receiving ICIs. Among them, 116 (33.3%) were never smokers, 197 (56.6%) were former smokers (median pack-years = 28), and 35 (10.1%) were current smokers (median pack-years = 40). Analysis revealed no statistically significant difference in overall survival across different smoking statuses (objective response rates were 11.4% for current smokers, 17.2% for never smokers, and 22.3% for former smokers; P = 0.142, 0.410, and 0.281, respectively). However, a notable trend indicated a potentially better response to immunotherapy in former smokers compared to current and never smokers. In the validation cohort of 248 patients from our institution, immunohistochemical analysis showed that PD-L1 expression was significantly higher in former smokers (55%) compared to current smokers (37%) and never smokers (47%). This observation underscores the potential influence of smoking history on the tumor microenvironment and its responsiveness to ICIs. Conclusion: In conclusion, our study demonstrates the importance of incorporating smoking history in predicting the response to immunotherapy in bladder cancer patients, highlighting its role in personalized cancer treatment approaches. Further research is suggested to explore the comprehensive impact of lifestyle factors on treatment outcomes.

AcEXPA1, an α-expansin gene, participates in the aluminum tolerance of carpetgrass (Axonopus compressus) through root growth regulation.

KEY MESSAGE: AcEXPA1, an aluminum (Al)-inducible expansin gene, is demonstrated to be involved in carpetgrass (Axonopus compressus) root elongation under Al toxicity through analyzing composite carpetgrass plants overexpressing AcEXPA1. Aluminum (Al) toxicity is a major mineral toxicity that limits plant productivity in acidic soils by inhibiting root growth. Carpetgrass (Axonopus compressus), a dominant warm-season turfgrass widely grown in acidic tropical soils, exhibits superior adaptability to Al toxicity. However, the mechanisms underlying its Al tolerance are largely unclear, and knowledge of the functional genes involved in Al detoxification in this turfgrass is limited. In this study, phenotypic variation in Al tolerance, as indicated by relative root elongation, was observed among seventeen carpetgrass genotypes. Al-responsive genes related to cell wall modification were identified in the roots of the Al-tolerant genotype 'A58' via transcriptome analysis. Among them, a gene encoding α-expansin was cloned and designated AcEXPA1 for functional characterization. Observed Al dose effects and temporal responses revealed that Al induced AcEXPA1 expression in carpetgrass roots. Subsequently, an efficient and convenient Agrobacterium rhizogenes-mediated transformation method was established to generate composite carpetgrass plants with transgenic hairy roots for investigating AcEXPA1 involvement in carpetgrass root growth under Al toxicity. AcEXPA1 was successfully overexpressed in the transgenic hairy roots, and AcEXPA1 overexpression enhanced Al tolerance in composite carpetgrass plants through a decrease in Al-induced root growth inhibition. Taken together, these findings suggest that AcEXPA1 contributes to Al tolerance in carpetgrass via root growth regulation.

Case Report: A rare transthyretin mutation p.D58Y in a Chinese case of transthyretin amyloid cardiomyopathy.

Hereditary transthyretin amyloid (ATTRv) cardiomyopathy (CM) is caused by mutations in the TTR gene. TTR mutations contribute to TTR tetramer destabilization and dissociation, leading to excessive deposition of insoluble amyloid fibrils in the myocardium and finally resulting in cardiac dysfunction. In this article, we report a case of a Chinese patient with transthyretin mutation p.D58Y and provide detailed information on cardiac amyloidosis, including transthoracic echocardiography, cardiac magnetic resonance, and SPECT imaging for the first time. Our report aims to provide a better understanding of ATTR genotypes and phenotypes.

The STING agonist IMSA101 enhances chimeric antigen receptor T cell function by inducing IL-18 secretion.

As a strategy to improve the therapeutic success of chimeric antigen receptor T cells (CART) directed against solid tumors, we here test the combinatorial use of CART and IMSA101, a newly developed stimulator of interferon genes (STING) agonist. In two syngeneic tumor models, improved overall survival is observed when mice are treated with intratumorally administered IMSA101 in addition to intravenous CART infusion. Transcriptomic analyses of CART isolated from tumors show elevated T cell activation, as well as upregulated cytokine pathway signatures, in particular IL-18, in the combination treatment group. Also, higher levels of IL-18 in serum and tumor are detected with IMSA101 treatment. Consistent with this, the use of IL-18 receptor negative CART impair anti-tumor responses in mice receiving combination treatment. In summary, we find that IMSA101 enhances CART function which is facilitated through STING agonist-induced IL-18 secretion.

Network pharmacology-based investigation of the effects of Shenqi Fuzheng injection on glioma proliferation and migration via the SRC/PI3K/AKT signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: In the clinic, Shenqi Fuzheng Injection (SFI) is used as an adjuvant for cancer chemotherapy. However, the molecular mechanism is unclear. AIM OF THE STUDY: We screened potential targets of SFI action on gliomas by network pharmacology and performed experiments to validate possible molecular mechanisms against gliomas. MATERIALS AND METHODS: We consulted relevant reports on the SFI and glioma incidence from PubMed and Web of Science and focused on the mechanism through which the SFI inhibits glioma. According to the literature, two primary SFI components-Codonopsis pilosula (Franch.) Nannf. and Astragalus membranaceus (Fisch.) Bunge-have been found. All plant names have been sourced from "The Plant List" (www.theplantlist.org). The cell lines U87, T98G and GL261 were used in this study. The inhibitory effects of SFI on glioma cells U87 and T98G were detected by CCK-8 assay, EdU, plate cloning assay, scratch assay, Transwell assay, immunofluorescence, flow cytometry and Western blot. A subcutaneous tumor model of C57BL/6 mice was constructed using GL261 cells, and the SFI was evaluated by HE staining and immunohistochemistry. The targets of glioma and the SFI were screened using network pharmacology. RESULTS: A total of 110 targets were enriched, and a total of 26 major active components in the SFI were investigated. There were a total of 3,343 targets for gliomas, of which 79 targets were shared between the SFI and glioma tissues. SFI successfully prevented proliferation and caused cellular S-phase blockage in U87 and T98G cells, thus decreasing their growth. Furthermore, SFI suppressed cell migration by downregulating EMT marker expression. According to the results of the in vivo tests, the SFI dramatically decreased the development of tumors in a transplanted tumour model. Network pharmacological studies revealed that the SRC/PI3K/AKT signaling pathway may be the pathway through which SFI exerts its anti-glioma effects. CONCLUSIONS: The findings revealed that the SRC/PI3K/AKT signaling pathway may be involved in the mechanism through which SFI inhibits the proliferation and migration of glioma cells.

Control of Kinetic Pathways toward Supramolecular Chiral Polymorphs for Tunable Circularly Polarized Luminescence.

An amphiphilic aza-BODIPY dye (S)-1 bearing two chiral hydrophilic side chains with S-stereogenic centers was synthesized. This dye exhibited kinetic-controlled self-assembly pathways and supramolecular chiral polymorphism properties in MeOH/H2O (9/1, v/v) mixed solvent. The (S)-1 monomers first aggregated into a kinetic controlled, off-pathway species Agg. A, which was spontaneously transformed into an on-pathway metastable aggregate (Agg. B) and subsequently into the thermodynamic Agg. C. The three aggregate polymorphs of dye (S)-1 displayed distinct optical properties and nanomorphologies. In particular, chiral J-aggregation characteristics were observed for both Agg. B and Agg. C, such as Davydov-split absorption bands (Agg. B), extremely sharp and intense J-band with large bathochromic shift (Agg. C), non-diminished fluorescence upon aggregation, as well as strong bisignated Cotton effects. Moreover, the AFM and TEM studies revealed that Agg. A had the morphology of nanoparticle while fibril or rod-like helical nanostructures with left-handedness were observed respectively for Agg. B and Agg. C. By controlling the kinetic transformation process from Agg. B to Agg. C, thin films consisting of Agg. B and Agg. C with different ratios were prepared, which displayed tunable CPL with emission maxima at 788-805 nm and g-factors between -4.2×10-2 and -5.1×10-2.

Crown-Assisted CsCu2I3 Growth and Trap Passivation for Perovskite Light-Emitting Diodes.

Copper (Cu)-based perovskites are promising for lead-free perovskite light-emitting diodes (PeLEDs). However, it remains a significant challenge to achieve high performance devices due to the nonradiative loss caused by the disordered crystallization and lack of passivation. Crown ethers are known to form host-guest complexes by the interaction between C-O-C groups and certain cations, and 18-crown-6 (18C6) with an appropriate complementary size can interact with Cs+ and Cu+ cations. Herein, we studied the interaction between CsCu2I3 and two crowns with the same cyclic size, 18C6 and dibenzo-18-crown-6 (D18C6). Particularly, D18C6 can reduce the nonradiative recombination rate of CsCu2I3 film by passivating the defects and optimizing the film morphology effectively. The room mean square (RMS) decreased from 5.06 to 2.95 nm, and the PLQY was promoted from 4.71% to 19.9%. Besides, D18C6 can also decrease the barrier of hole injection. The PeLEDs based on D18C6-modified CsCu2I3 realized noticeable improvement with a maximum luminance and EQE of 583 cd/m2 and 0.662%, respectively.

The feasibility of the posterior tibial nerve-flexor hallucis brevis pathway applied in neuromuscular monitoring: a multicentric, controlled, and prospective clinical trial.

This study aimed to investigate the clinical viability of utilizing the flexor hallucis brevis as an alternative site for neuromuscular monitoring compared to the conventional adductor pollicis. Patients were recruited from three medical centers. Cis-atracurium was administered, and two monitors were employed independently to assess neuromuscular blockade of the adductor pollicis and the ipsilateral flexor hallucis brevis, following a train of four (TOF) pattern until TOF ratios exceeded 0.9 or until the conclusion of surgery. Statistical analysis revealed significant differences in onset time, duration of no-twitch response, spontaneous recovery time, and total monitoring time between the two sites, with mean differences of -53.54 s, -2.49, 3.22, and 5.89 min, respectively (P < 0.001).The posterior tibial nerve-flexor hallucis brevis pathway presents a promising alternative for neuromuscular monitoring during anesthesia maintenance. Further investigation is warranted to explore its utility in anesthesia induction and recovery. Trial registration: The trial was registered at www.chictr.org.cn (20/11/2018, ChiCTR1800019651).

Characterization of SgALMT genes reveals the function of SgALMT2 in conferring aluminum tolerance in Stylosanthes guianensis through the mediation of malate exudation.

Aluminum (Al) toxicity is the major constraint on plant growth and productivity in acidic soils. An adaptive mechanism to enhance Al tolerance in plants is mediated malate exudation from roots through the involvement of ALMT (Al-activated malate transporter) channels. The underlying Al tolerance mechanisms of stylo (Stylosanthes guianensis), an important tropical legume that exhibits superior Al tolerance, remain largely unknown, and knowledge of the potential contribution of ALMT genes to Al detoxification in stylo is limited. In this study, stylo root growth was inhibited by Al toxicity, accompanied by increases in malate and citrate exudation from roots. A total of 11 ALMT genes were subsequently identified in the stylo genome and named SgALMT1 to SgALMT11. Diverse responses to metal stresses were observed for these SgALMT genes in stylo roots. Among them, the expressions of 6 out of the 11 SgALMTs were upregulated by Al toxicity. SgALMT2, a root-specific and Al-activated gene, was selected for functional characterization. Subcellular localization analysis revealed that the SgALMT2 protein is localized to the plasma membrane. The function of SgALMT2 in mediating malate release was confirmed by analysis of the malate exudation rate from transgenic composite stylo plants overexpressing SgALMT2. Furthermore, overexpression of SgALMT2 led to increased root growth in transgenic stylo plants treated with Al through decreased Al accumulation in roots. Taken together, the results of this study suggest that malate secretion mediated by SgALMT2 contributes to the ability of stylo to cope with Al toxicity.

Agrimol B alleviates cisplatin-induced acute kidney injury by activating the Sirt1/Nrf2 signaling pathway in mice.

Cisplatin (CDDP) is a widely used chemotherapeutic agent that has remarkable antineoplastic effects. However, CDDP can cause severe acute kidney injury (AKI), which limits its clinical application. Agrimol B is the main active ingredient found in Agrimonia pilosa Ledeb and has a variety of pharmacological activities. The effect of agrimol B on CDDP-induced renal toxicity has not been determined. To investigate whether agrimol B has a protective effect against CDDP-induced AKI, we first identify Sirtuin 1 (Sirt1) as a critical target protein of agrimol B in regulating AKI through network pharmacology analysis. Subsequently, the AKI mouse model is induced by administering a single dose of CDDP via intraperitoneal injection. By detecting the serum urea nitrogen and creatinine levels, as well as the histopathological changes, we confirm that agrimol B effectively reduces CDDP-induced AKI. In addition, treatment with agrimol B counteracts the increase in renal malondialdehyde level and the decrease in superoxide dismutase (SOD), catalase and glutathione levels induced by CDDP. Moreover, western blot results reveal that agrimol B upregulates the expressions of Sirt1, SOD2, nuclear factor erythroid2-related factor 2, and downstream molecules, including heme oxygenase 1 and NAD(P)H quinone dehydrogenase 1. However, administration of the Sirt1 inhibitor EX527 abolishes the effects of agrimol B. Finally, we establish a tumor-bearing mouse model and find that agrimol B has a synergistic antitumor effect with CDDP. Overall, agrimol B attenuates CDDP-induced AKI by activating the Sirt1/Nrf2 signaling pathway to counteract oxidative stress, suggesting that this compound is a potential therapeutic agent for the treatment of CDDP-induced AKI.