Miniaturized Multi-Cantilever MEMS Resonators with Low Motional Impedance.

Microelectromechanical system (MEMS) cantilever resonators suffer from high motional impedance (Rm). This paper investigates the use of mechanically coupled multi-cantilever piezoelectric MEMS resonators in the resolution of this issue. A double-sided actuating design, which utilizes a resonator with a 2.5 µm thick AlN film as the passive layer, is employed to reduce Rm. The results of experimental and finite element analysis (FEA) show agreement regarding single- to sextuple-cantilever resonators. Compared with a standalone cantilever resonator, the multi-cantilever resonator significantly reduces Rm; meanwhile, the high quality factor (Q) and effective electromechanical coupling coefficient (Kteff2) are maintained. The 30 µm wide quadruple-cantilever resonator achieves a resonance frequency (fs) of 55.8 kHz, a Q value of 10,300, and a series impedance (Rs) as low as 28.6 kΩ at a pressure of 0.02 Pa; meanwhile, the smaller size of this resonator compared to the existing multi-cantilever resonators is preserved. This represents a significant advancement in MEMS resonators for miniaturized ultra-low-power oscillator applications.

Low-Voltage High-Frequency Lamb-Wave-Driven Micromotors.

By leveraging the benefits of a high energy density, miniaturization and integration, acoustic-wave-driven micromotors have recently emerged as powerful tools for microfluidic actuation. In this study, a Lamb-wave-driven micromotor is proposed for the first time. This motor consists of a ring-shaped Lamb wave actuator array with a rotor and a fluid coupling layer in between. On a driving mechanism level, high-frequency Lamb waves of 380 MHz generate strong acoustic streaming effects over an extremely short distance; on a mechanical design level, each Lamb wave actuator incorporates a reflector on one side of the actuator, while an acoustic opening is incorporated on the other side to limit wave energy leakage; and on electrical design level, the electrodes placed on the two sides of the film enhance the capacitance in the vertical direction, which facilitates impedance matching within a smaller area. As a result, the Lamb-wave-driven solution features a much lower driving voltage and a smaller size compared with conventional surface acoustic-wave-driven solutions. For an improved motor performance, actuator array configurations, rotor sizes, and liquid coupling layer thicknesses are examined via simulations and experiments. The results show the micromotor with a rotor with a diameter of 5 mm can achieve a maximum angular velocity of 250 rpm with an input voltage of 6 V. The proposed micromotor is a new prototype for acoustic-wave-driven actuators and demonstrates potential for lab-on-a-chip applications.

Two Mn(II)-Bridged Silverton-Type [UMo12O42]8- Polyoxometalates with Catalytic Activity for the Synthesis of Pyrazoles.

Two Mn(II)-bridged Silverton-type {UMo12O42}-based polyoxomolybdates with different three-dimensional structures, Na6(H2O)12[Mn(UMo12O42)] (NaMn) and (NH4)2[K2Na6(µ4-O)2(H2O)1.2Mn(UMo12O42)]·4.6H2O (KMn), were hydrothermally synthesized and further characterized, demonstrating a feasible strategy for the assembly of Silverton-type polyoxomolybdates. Additionally, NaMn is demonstrated to be a good heterogeneous catalyst in the condensation cyclization reaction of hydrazines and 1,3-diketones, and a range of valuable pyrazoles were produced in up to 99% yield.

The role of PALLD-STAT3 interaction in megakaryocyte differentiation and thrombocytopenia treatment.

Impaired differentiation of megakaryocytes constitutes the principal etiology of thrombocytopenia. The signal transducer and activator of transcription 3 (STAT3) is a crucial transcription factor in regulating megakaryocyte differentiation, yet the precise mechanism of its activation remains unclear. PALLD, an actin-associated protein, has been increasingly recognized for its essential functions in multiple biological processes. This study revealed that megakaryocyte/plateletspecific knockout of PALLD in mice exhibited thrombocytopenia due to diminished platelet biogenesis. In megakaryocytes, PALLD deficiency led to impaired proplatelet formation and polyploidization, ultimately weakening their differentiation for platelet production. Mechanistic studies demonstrated that PALLD bound to STAT3 and interacted with its DNA-binding domain (DBD) and Src homology 2 (SH2) domain via Immunoglobulin domain 3 (Ig3). Moreover, the absence of PALLD attenuated STAT3 Y705 phosphorylation and impeded STAT3 nuclear translocation. Based on the PALLD-STAT3 binding sequence, we designed a peptide C-P3, which can facilitate megakaryocyte differentiation and accelerate platelet production in vivo. In conclusion, this study highlights the pivotal role of PALLD in megakaryocyte differentiation and proposes a novel approach for treating thrombocytopenia by targeting the PALLD-STAT3 interaction.

Correction: Assessment of network structure characteristics and factors of corporate flows in Guangdong Province.

[This corrects the article DOI: 10.1371/journal.pone.0293870.].

Association of longitudinal trajectories of fasting plasma glucose with all-cause and cardiovascular mortality among a Chinese older population: a retrospective cohort study.

The association between fasting plasma glucose (FPG), an important indicator of overall glycemic status, and the risk of cardiovascular mortality has been well investigated. The longitudinal study can repeatedly collect measured results for the variables to be studied and then consider the potential effects of intraindividual changes in measurement. This study aimed to identify long-term FPG trajectories and investigate the association between trajectory groups and cardiovascular and all-cause mortality. A latent class growth mixture modeling (LCGMM) was used to identify FPG trajectories. Cox proportional hazard models were used to estimate associations between FPG trajectories and the risk of all-cause and cardiovascular mortality. A U-shaped relationship between FPG and all-cause and cardiovascular mortality was observed in the restricted cubic spline regression models. Two FPG longitudinal trajectories of low-level (mean FPG = 5.12mmol/L) and high-level (mean FPG = 6.74mmol/L) were identified by LCGMM. After being adjusted for potential confounders, compared with the low-level category, the hazard ratios (HRs) for all-cause and cardiovascular mortality were 1.23(1.16-1.30) and 1.25(1.16-1.35), respectively, for the high-level group. Long-term FPG trajectories are significantly associated with and potentially impact the risk of all-cause and cardiovascular mortality.

Association of the CUN-BAE body adiposity estimator and other obesity indicators with cardiometabolic multimorbidity: a cross-sectional study.

Cardiometabolic multimorbidity (CM), defined as the coexistence of two or three cardiometabolic disorders, is one of the most common and deleterious multimorbidities. This study aimed to investigate the association of Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE), body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) with the prevalence of CM. The data were obtained from the 2021 health checkup database for residents of the Electronic Health Management Center in Xinzheng, Henan Province, China. 81,532 participants aged ≥ 60 years were included in this study. Logistic regression models were used to estimate the odd ratios (ORs) and 95% confidence intervals (CIs) for CUN-BAE, BMI, WC, and WHtR in CM. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminatory ability of different anthropometric indicators for CM. The multivariable-adjusted ORs (95% CIs) (per 1 SD increase) of CM were 1.799 (1.710-1.893) for CUN-BAE, 1.329 (1.295-1.364) for BMI, 1.343 (1.308-1.378) for WC, and 1.314 (1.280-1.349) for WHtR, respectively. Compared with BMI, WC and WHtR, CUN-BAE had the highest AUC in both males and females (AUC: 0.642; 95% CI 0.630-0.653 for males, AUC: 0.614; 95% CI 0.630-0.653 for females). CUN-BAE may be a better measure of the adverse effect of adiposity on the prevalence of CM than BMI, WC, and WHtR.

Comparison of the therapeutic effects of febuxostat combined with a low-purine diet and allopurinol combined with a low-purine diet on the improvement of gout patients.

OBJECTIVE: To compare the clinical efficacy of febuxostat combined with a low-purine diet versus allopurinol combined with a low-purine diet in the treatment of gout. METHODS: In this prospective controlled trial, 98 gout patients admitted to our hospital from February 2021 to December 2022 were enrolled as study subjects. Patients were randomly assigned to the study group (febuxostat combined with a low-purine diet) and the control group (allopurinol combined with a low-purine diet), with 49 patients in each group. The therapeutic effect was evaluated based on joint function and serum uric acid levels after treatment, and classified into three levels: markedly effective, effective, and ineffective. The levels of inflammatory factors, including tumor necrosis factor-a (TNF-a), cytokine interleukin-1beta (IL-1ß), and interleukin (IL)-18 (IL-18), were collected. The Numeric Rating Scale (NRS) was used to assess the degree of pain in patients. Clinical indicators before and 6 months after treatment were compared between the two groups. RESULTS: There was no statistically significant difference in age and gender between the two groups. After 6 months of treatment, the effective rate in the study group (48 cases, 97.96%) was higher than that in the control group (42 cases, 85.71%), with a statistically significant difference (p = .027). At the same time, the study group had significantly lower levels of serum uric acid (162.39 µmol/L ± 17.23 µmol/L vs. S198.32 µmol/L ± 18.34 µmol/L, p < .001), creatinine (87.39 mmol/L ± 9.76 mmol/L vs. 92.18 mmol/L ± 9.27 mmol/L, p = .014), total cholesterol (3.65 mmol/L ± 0.65 mmol/L vs. 4.76 mmol/L ± 0.73 mmol/L, p < .001), and triglycerides (1.76 mmol/L ± 0.32 mmol/L vs. 2.28 mmol/L ± 0.41 mmol/L, p < .001) compared to the control group, with statistically significant differences (p < .05). After treatment, the levels of inflammatory factors and degree of pain in the study group were significantly lower than those in the control group (all p < .05). During the treatment process, the incidence of adverse reactions in the study group (2 cases, 4.08%) was lower than that in the control group (9 cases, 18.37%), with a statistically significant difference (p = .025). CONCLUSION: Febuxostat combined with a low-purine diet can reduce inflammatory factors and alleviate the degree of pain in gout patients, significantly improving their clinical symptoms.

Recent Advances in Radiotracers Targeting Novel Cancer-Specific Biomarkers in China: A Brief Overview.

Radiopharmaceuticals play a critical role in nuclear medicine, providing novel tools for specifically delivering radioisotopes for the diagnosis and treatment of cancers. As the starting point for developing radiopharmaceuticals, cancer-specific biomarkers are important and receive worldwide attention. This field in China is currently experiencing a rapid expansion, with multiple radiotracers targeting novel targets being developed and translated into clinical studies. This review provides a brief overview of the exploration of novel imaging targets, preclinical evaluation of their targeting ligands, and translational research in China from 2020 to 2023, for detecting cancer, guiding targeted therapy, and visualizing the immune microenvironment. We believe that China will play an even more important role in the development of nuclear medicine in the world in the future.

Influence of comorbidity of chronic diseases on basic activities of daily living among older adults in China: a propensity score-matched study.

Rationale: With the accelerating process of population aging, the comorbidity of chronic disease (CCD) has become a major public health problem that threatens the health of older adults. Objective: This study aimed to assess whether CCD is associated with basic activities of daily living (BADL) and explore the factors influencing BADL in older adults. Method: A cross-sectional community health survey with stratified random sampling among older residents (≥60 years old) was conducted in 2022. A questionnaire was used to collect information on BADL, chronic diseases, and other relevant aspects. Propensity score matching (PSM) was used to match the older adults with and without CCD. Univariate and multivariate logistic regression analyses were used to explore the factors influencing BADL. PSM was used to match participants with single-chronic disease (SCD) and CCD. Results: Among the 47,720 participants, those with CCD showed a higher prevalence of BADL disability (13.07%) than those with no CCD (6.33%) and SCD (7.39%). After adjusting for potential confounders with PSM, 6,513 pairs of cases with and without CCD were matched. The univariate analysis found that the older adults with CCD had a significantly higher prevalence of BADL disability (13.07%, 851 of 6,513) than those without CCD (9.83%, 640 of 6,513, P < 0.05). The multivariate logistic regression analysis revealed that CCD was a risk factor for BADL in older adults [OR = 1.496, 95% CI: 1.393-1.750, P < 0.001]. In addition, age, educational level, alcohol intake, social interaction, annual physical examination, retirement benefits, depression, weekly amount of exercise, and years of exercise were related to BADL disability (P < 0.05). PSM matching was performed on participants with CCD and SCD and showed that the older adults with CCD had a significantly higher prevalence of BADL disability (13.07%, 851 of 6,513) than those with SCD (11.39%, 742 of 6,513, P < 0.05). Conclusion: The older adults with CCD are at a higher risk of BADL disability than their counterparts with no CCD or SCD. Therefore, we advocate paying attention to and taking measures to improve the health and quality of life of these individuals.

Myeloid Trem2 ameliorates the progression of metabolic dysfunction-associated steatotic liver disease by regulating macrophage pyroptosis and inflammation resolution.

BACKGROUND: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing year by year and has become one of the leading causes of end-stage liver disease worldwide. Triggering Receptor Expressed on Myeloid Cells 2 (Trem2) has been confirmed to play an essential role in the progression of MASLD, but its specific mechanism still needs to be clarified. This study aims to explore the role and mechanism of Trem2 in MASLD. METHODS: Human liver tissues were obtained from patients with MASLD and controls. Myeloid-specific knockout mice (Trem2mKO) and myeloid-specific overexpression mice (Trem2TdT) were fed a high-fat diet, either AMLN or CDAHFD, to establish the MASLD model. Relevant signaling molecules were assessed through lipidomics and RNA-seq analyses after that. RESULTS: Trem2 is upregulated in human MASLD/MASH-associated macrophages and is associated with hepatic steatosis and inflammation progression. Hepatic steatosis and inflammatory responses are exacerbated with the knockout of myeloid Trem2 in MASLD mice, while mice overexpressing Trem2 exhibit the opposite phenomenon. Mechanistically, Trem2mKO can aggravate macrophage pyroptosis through the PI3K/AKT signaling pathway and amplify the resulting inflammatory response. At the same time, Trem2 promotes the inflammation resolution phenotype transformation of macrophages through TGFß1, thereby promoting tissue repair. CONCLUSIONS: Myeloid Trem2 ameliorates the progression of Metabolic dysfunction-associated steatotic liver disease by regulating macrophage pyroptosis and inflammation resolution. We believe targeting myeloid Trem2 could represent a potential avenue for treating MASLD.

Three Polyoxometalate-Based Ag-Organic Compounds as Heterogeneous Catalysts for the Synthesis of Benzimidazoles.

Three new POM-based compounds, with formulae [Na0.63Ag3(Htba)2.37(tba)0.63(H2O)2(PMo12O40)]·4H2O (Ag3PMo), [Ag4(Htba)4(H2O)2(PMo12O40)](NO3)·H2O (Ag4PMo), and [Ag3(Htba)2(tba)(PW12O40)0.5](NO3)0.5·13H2O (Ag3PW), were prepared with a 3-(4H-1,2,4-triazol-4-yl)benzoic acid (Htba) ligand, Keggin-type anions ([PMo12O40]3-/[PW12O40]3-), and a silver ion (Ag+). The structural features of these compounds are particularly different from the multinuclear subunits, which are [Ag3(tba)3] clusters in Ag3PMo, [Ag4(tba)3] chains in Ag4PMo, and [Ag3(tba)3]2 clusters in Ag3PW, connected by multidonor atom tba ligands and Ag+ ions. Meanwhile, in these compounds, polyanions act as polydentate ligands to link adjacent Ag-tba metal-organic units and expand their spatial dimensions. These compounds, as heterogeneous catalysts, exhibit high stability and excellent catalytic activity to construct benzimidazoles. Ag3PMo could efficiently catalyze the condensation of benzene-1,2-diamines and benzaldehydes and produce benzimidazoles in good yields. In addition, Ag3PMo could be reused up to 7 times and was suitable for gram-scale reactions.

Flavokawain C inhibits proliferation and migration of liver cancer cells through FAK/PI3K/AKT signaling pathway.

PURPOSE: This study investigated the potential applicability and the underlying mechanisms of flavokawain C, a natural compound derived from kava extracts, in liver cancer treatment. METHODS: Drug distribution experiment used to demonstrate the preferential tissues enrichment of flavokawain C. Cell proliferation, apoptosis and migration effect of flavokawain C were determined by MTT, colony formation, EdU staining, cell adhesion, transwell, flow cytometry and western blot assay. The mechanism was explored by comet assay, immunofluorescence assay, RNA-seq-based Kyoto encyclopedia of genes and genomes analysis, molecular dynamics, bioinformatics analysis and western blot assay. The anticancer effect of flavokawain C was further confirmed by xenograft tumor model. RESULTS: The studies first demonstrated the preferential enrichment of flavokawain C within liver tissues in vivo. The findings demonstrated that flavokawain C significantly inhibited proliferation and migration of liver cancer cells, induced cellular apoptosis, and triggered intense DNA damage along with strong DNA damage response. The findings from RNA-seq-based KEGG analysis, molecular dynamics, bioinformatics analysis, and western blot assay mechanistically indicated that treatment with flavokawain C notably suppressed the FAK/PI3K/AKT signaling pathway in liver cancer cells. This effect was attributed to the induction of gene changes and the binding of flavokawain C to the ATP sites of FAK and PI3K, resulting in the inhibition of their phosphorylation. Additionally, flavokawain C also displayed the strong capacity to inhibit Huh-7-derived xenograft tumor growth in mice with minimal adverse effects. CONCLUSIONS: These findings identified that flavokawain C is a promising anticancer agent for liver cancer treatment.

Giant Tunability of Rashba Splitting at Cation-Exchanged Polar Oxide Interfaces by Selective Orbital Hybridization.

The 2D electron gas (2DEG) at oxide interfaces exhibits extraordinary properties, such as 2D superconductivity and ferromagnetism, coupled to strongly correlated electrons in narrow d-bands. In particular, 2DEGs in KTaO3 (KTO) with 5d t2g orbitals exhibit larger atomic spin-orbit coupling and crystal-facet-dependent superconductivity absent for 3d 2DEGs in SrTiO3 (STO). Herein, by tracing the interfacial chemistry, weak anti-localization magneto-transport behavior, and electronic structures of (001), (110), and (111) KTO 2DEGs, unambiguously cation exchange across KTO interfaces is discovered. Therefore, the origin of the 2DEGs at KTO-based interfaces is dramatically different from the electronic reconstruction observed at STO interfaces. More importantly, as the interface polarization grows with the higher order planes in the KTO case, the Rashba spin splitting becomes maximal for the superconducting (111) interfaces approximately twice that of the (001) interface. The larger Rashba spin splitting couples strongly to the asymmetric chiral texture of the orbital angular moment, and results mainly from the enhanced inter-orbital hopping of the t2g bands and more localized wave functions. This finding has profound implications for the search for topological superconductors, as well as the realization of efficient spin-charge interconversion for low-power spin-orbitronics based on (110) and (111) KTO interfaces.

Assessment of network structure characteristics and factors of corporate flows in Guangdong Province.

With the rapid development of the world city network, the traditional location theory has gradually been disproven, and the advantages of the flow space over the traditional vertical organizational structure are gradually being revealed. Therefore, from corporate branch networks and corporate investment networks, 21 cities in urban agglomerations of Guangdong are taken as case studies for this paper. Furthermore, in this paper, 5 representative types of corporate contact data (catering service, financial service, life service, sports and leisure and accommodation service) are selected, the social network analysis (SNA) method is used to quantitatively analyze the network structure characteristics of urban agglomerations, and a spatial interaction model is constructed to explore the factors influencing. The results indicate that secondary networks have developed in Guangdong. The financial service network is the most complex, followed by the life services, sports and leisure and catering networks. The accommodation service network structure is the simplest. Among all kinds of networks, Guangzhou and Shenzhen have the highest status. The catering and accommodation corporations in Yangjiang in the west have a relatively major external development. Shantou in the east has many branches of various types, while most of the capital exchange in the region is concentrated in Heyuan and Qingyuan in the north. The coefficients of geographical proximity and the urban development level play a significant role in promoting the development of networks. However, administrative capacity limits the attractiveness of origin cities to a certain extent.

Data on Singapore longitudinal early development study (SG-LEADS).

The Singapore Longitudinal Early Development Study (SG-LEADS) seeks to understand factors that can enhance or hinder Singaporean children's early childhood development with an aim to inform public policies that can help each child reach his or her potential. SG-LEADS is a nationally representative household survey that focuses on Singaporean households with children aged 0-6 at the baseline. It adopts a multi-stage probability sampling - clustered and stratified sampling strategy - with an oversample of the low-income households residing in 1-3-room HDB (Housing Development Board) public housing units. In-home face-to-face interviews were conducted on the computer-assisted personal interviewing (CAPI) systems. The baseline survey was conducted between 2018 and 2019. Up to two eligible children and their primary caregivers were interviewed in each household. In total, 5,005 Singaporean children aged 0-6 in 3,476 households and their primary caregivers were successfully interviewed. In 2021, 4,351 children in 3,017 households were successfully re-interviewed. The contents of SG-LEADS are designed based on theories in multiple disciplines including sociology, psychology and economics about how multiple contexts (home, out-of-home care institution, community and state) interact to shape the multiple domains of child development. The survey includes assessments of children's motor, social-emotional well-being, language and cognitive skills, and biometric measures. Rich data about the family's socioeconomic, demographic and cultural backgrounds, family structure, family relations, home environment, social support, food security, financial distress, public program participation, and neighborhood characteristics and cohesion were collected. Comprehensive information was obtained about the target child's early childcare and preschool arrangements, children's time use (through time diaries), technology use, enhancement activities, nutrition intake and more. Primary caregivers' social-emotional well-being, cognitive skills, and parenting behavior were also assessed. In Wave 2, a special module about the family's COVID-19 experiences and responses was added. Descriptive statistics were presented on the study website. Multivariate analyses were conducted based on the SG-LEADS dataset with a variety of robust methodologies such as structural equation modeling, fixed effect analysis, lagged dependent variable model, hierarchical regression analyses, mediation analysis, propensity score matching, and so forth. Thus far, 14 journal articles have been published with a dozen or so papers under review. These analyses cover a wide range of topics, including but not limited to, 1) the impact of socioeconomic status on children's development such as infants' vocabulary, children's academic achievement and socio-emotional development, 2) the impact of paternity leave-taking on child outcome (3) how food insecurity affects children's behavior, (4) family experiences and resilience during COVID-19, (6) childcare arrangements and children's behavior and cognitive development, (6) children's ability to delay gratification in early childhood, (7) children in cross-national families, 8) children's time use, (9) family and community social capital and child development. The rich data in this longitudinal study provide many opportunities to research a wide range of topics related to early child development in an Asian context. This dataset holds tremendous potential to uncover valuable insights and inform evidence-based policy interventions to support optimal early childhood development. International comparative studies can also be conducted with similar surveys conducted in other countries.

Distribution and source of heavy metals in Tibetan Plateau topsoil: New insight into the influence of long-range transported sources to the surrounding glaciers.

Heavy metals present a substantial threat to both the environment and human health. Considering the delicate ecological equilibrium of the Tibetan Plateau (TP) and its heightened susceptibility to anthropogenic impacts, scholarly attention has progressively turned toward the examination of heavy metal pollution within the plateau's environment. In this study, we conducted a comprehensive analysis of various heavy metals (As, Cr, Co, Ni, Cu, Mo, Cd, Pb, and Sb), utilizing topsoil samples collected from the TP during the period of 2018-2021. Additionally, snow and cryoconite samples obtained from TP glaciers during the same timeframe were also subjected to analysis. The results indicate elevated concentrations of total heavy metals in the eastern and western TP (328.7 µg/g), as opposed to the central and southern TP (145.7 µg/g). Most heavy metals exhibit a consistent spatial distribution pattern. High Enrichment Factors (EFs) and Geoaccumulation Index (Igeo) values for As and Cd suggest their enrichment in TP topsoil. Receptor modeling identified three primary sources of heavy metals within the topsoil: industrial sources (42.3%), inherent natural sources within the surface soil (20.6%), and vehicular emissions (14.2%). Substantial differences in heavy metal concentrations and spatial distribution were observed between the topsoil and the glacial snow-cryoconite matrix. The prominent presence of Sb in the snow-cryoconite matrix, in contrast to its low abundance in the topsoil, indicates distinct source influences of long-range transported materials between the two environments. Our inference suggests that the influence of heavy metals from distant pollutants undergo mixing and dilution in the topsoil due to the presence of local indigenous heavy metals, although such influence is notably observed on the glacier surface of the TP. Consequently, this underscores the significant impact of long-range transported sources on heavy metals, surpassing the influence of local TP soils, to the alpine glaciers and even other atmospheric sediments in Tibetan Plateau.

Microbial Fermentation as an Efficient Method for Eliminating Pyrethroid Pesticide Residues in Food: A Case Study on Cyfluthrin and Aneurinibacillus aneurinilyticus D-21.

The microbial fermentation of food has emerged as an efficient means to eliminate pesticide residues in agricultural products; however, the specific degradation characteristics and mechanisms remain unclear. In this study, a Gram-positive bacterium, Aneurinibacillus aneurinilyticus D-21, isolated from fermented Pixian Douban samples exhibited the capability to degrade 45 mg/L of cyfluthrin with an efficiency of 90.37%. Product analysis unveiled a novel cyfluthrin degradation pathway, involving the removal of the cyanide group and ammoniation of the ester bond into an amide. Whole genome analysis discovered the enzymes linked to cyfluthrin degradation, including nitrilase, esterase, carbon-nitrogen ligases, and enzymes associated with aromatic degradation. Additionally, metabolome analysis identified 140 benzenoids distributed across various aromatic metabolic pathways, further substantiating D-21's catabolic capability toward aromatics. This study underscores the exceptional pyrethroid degradation prowess of A. aneurinilyticus D-21, positioning it as a promising candidate for the biotreatment of pesticide residues in food systems.

Transforming growth factor-ß1 protects against white matter injury and reactive astrogliosis via the p38 MAPK pathway in rodent demyelinating model.

In central nervous system (CNS), demyelination is a pathological process featured with a loss of myelin sheaths around axons, which is responsible for the diseases of multiple sclerosis, neuromyelitis optica, and so on. Transforming growth factor-beta1 (TGF-ß1) is a multifunctional cytokine participating in abundant physiological and pathological processes in CNS. However, the effects of TGF-ß1 on CNS demyelinating disease and its underlying mechanisms are controversial and not well understood. Herein, we evaluated the protective potential of TGF-ß1 in a rodent demyelinating model established by lysophosphatidylcholine (LPC) injection. It was identified that supplement of TGF-ß1 evidently rescued the cognitive deficit and motor dysfunction in LPC modeling mice assessed by novel object recognition and balance beam behavioral tests. Besides, quantified by luxol fast blue staining, immunofluorescence, and western blot, administration of TGF-ß1 was found to significantly ameliorate the demyelinating lesion and reactive astrogliosis by suppressing p38 MAPK pathway. Mechanistically, the results of in vitro experiments indicated that treatment of TGF-ß1 could directly promote the differentiation and migration of cultured oligodendrocytes. Our study revealed that modulating TGF-ß1 activity might serve as a promising and innovative therapeutic strategy in CNS demyelinating diseases.

Homology-Activated Ultrasensitive Nanomedicines for Precise NIR-II FL/MRI Imaging-Guided "Knock-On" Dynamic Therapy in Rheumatoid Arthritis.

Stimuli-responsive nanomedicines represent a pivotal technology for in situ on-demand drug release and offer multiple advantages over conventional drug delivery systems to combat rheumatoid arthritis(RA). However, the lack of sensitivity to a single-stimuli source or the inability to synchronize multi-stimuli responses can easily lead to challenges in achieving precise-theranostics of RA. Herein, a homology-activated ultrasensitive nanomedicines MnO2-CQ4T-GOx(MCG NMs) is designed for NIR-II fluorescence(NIR-II FL)/magnetic resonance imaging(MRI)-guided effective "knock-on" dynamic anti-RA therapy. Building upon the characteristics of the RA-microenvironment, the MCG innovatively construct a MnO2-Mn2+ system, which can normalized activation sites. The ultrasensitive-responsive degradation is achieved using the multi-stimuli processes in the RA-microenvironment, triggering release of functional small molecules. The produced Mn2+ can exert Fenton-like activity to generate •OH from H2O2, thus providing the effective chemodynamic therapy(CDT). Moreover, the up-regulation of H2O2 by GOx-catalysis not only sensitizes the MnO2-Mn2+ system but also achieves self-enhancing CDT efficacy. The NIR-II FL quenching of CQ4T-BSA in the aggregated state occurs in MCG NMs, which can be rapidly and precisely "turn-on" via the MnO2-Mn2+ system. Meanwhile, the integration of activated Mn2+-based MRI imaging has successfully developed an activatable dual-modal imaging. Feedback imaging-guided precise photodynamic therapy of CQ4T-BSA can achieve efficient "knock-on" dynamic therapy for RA.