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The aim of this study was to explore the effects of different lactic acid bacteria additives (Lactiplantibacillus plantarum or Lentilactobacillus buchneri) on the fermentation quality, chemical composition, in vitro digestibility, bacterial community structure, and predictive function of S. perfoliatum silage feed. Fresh S. perfoliatum was wilted overnight, then its moisture content was adjusted between 65 and 70%. The experiment was performed in three groups as follows: (1) the control group (CK group), which lacked a Lactobacillus preparation; (2) the Lactiplantibacillus plantarum (L. plantarum) group (LP group), which was inoculated with L. plantarum at 5 × 106 cfu/g FW; and (3) the Lentilactobacillus buchneri (L. buchneri) group (LB group), which was inoculated with L. buchneri at 5 × 106 cfu/g FW. The results showed that L. plantarum significantly reduced pH and increased lactic acid (LA) content in S. perfoliatum silage compared with the control. L. buchneri, on the other hand, excelled in reducing ammonia nitrogen (NH3-N) content and significantly increased acetic acid (AA) content. At 60 days of fermentation, the CP content was significantly higher (p < 0.05) in the LP and LB groups than in the CK group (19.29 vs. 15.53 and 15.87). At 60 days of fermentation, the ivCPD was significantly higher (p < 0.05) in the LB group than in the CK and LP groups (57.80 vs. 54.77 and 55.77). The 60-day silage process completely altered the bacterial community of S. perfoliatum silage. In the fresh samples, the dominant genera were Weissella_A and Pantoea_A. Weissella_A and Pantoea_A were gradually replaced by Lentilactobacillus and Lactiplantibacillus after S. perfoliatum ensiling. After 45 days of fermentation, L. buchneri became the dominant strain in CK, LP and LB groups. Inoculation with L. plantarum altered the succession of the bacterial community from 7 to 15 days of fermentation of S. perfoliatum. In contrast, inoculation with L. buchneri affected the succession of the bacterial community from 30 to 60 days of S. perfoliatum fermentation. In S. perfoliatum silage aged 7 to 60 days, the amino acid metabolic pathway in the LB group remained upregulated. The experimental results revealed that inoculation with L. buchneri had a stronger effect on S. perfoliatum silage than inoculation with L. plantarum. Thus, L. buchneri should be selected as an additive for S. perfoliatum silage fermentation in practical production.

Research on the supply–demand relationships of ecosystem services (ESs) in alpine pastoral regions remains relatively scarce, yet it is crucial for regional ecological management and sustainable development. This study focuses on the Sanjiangyuan Region, a typical alpine pastoral area and significant ecological barrier, to quantitatively assess the supply–demand dynamics of key ESs and their spatial heterogeneity from 2000 to 2020. It further aims to elucidate the underlying driving mechanisms, thereby providing a scientific basis for optimizing regional ecological management. Four key ES indicators were selected: water yield (WY), grass yield (GY), soil conservation (SC), and habitat quality (HQ). ES supply and demand were quantified using an integrated approach incorporating the InVEST model, the Revised Universal Soil Loss Equation (RUSLE), and spatial analysis techniques. Building on this, the spatial patterns and temporal evolution characteristics of ES supply–demand relationships were analyzed. Subsequently, the Geographic Detector Model (GDM) and Geographically and Temporally Weighted Regression (GTWR) model were employed to identify key drivers influencing changes in the comprehensive ES supply–demand ratio. The results revealed the following: (1) Spatial Patterns: Overall ES supply capacity exhibited a spatial differentiation characterized by “higher values in the southeast and lower values in the northwest.” Areas of high ES demand were primarily concentrated in the densely populated eastern region. WY, SC, and HQ generally exhibited a surplus state, whereas GY showed supply falling short of demand in the densely populated eastern areas. (2) Temporal Dynamics: Between 2000 and 2020, the supply–demand ratios of WY and SC displayed a fluctuating downward trend. The HQ ratio remained relatively stable, while the GY ratio showed a significant and continuous upward trend, indicating positive outcomes from regional grass–livestock balance policies. (3) Driving Mechanisms: Climate and natural factors were the dominant drivers of changes in the ES supply–demand ratio. Analysis using the Geographical Detector’s q-statistic identified fractional vegetation cover (FVC, q = 0.72), annual precipitation (PR, q = 0.63), and human disturbance intensity (HD, q = 0.38) as the top three most influential factors. This study systematically reveals the spatial heterogeneity characteristics, dynamic evolution patterns, and core driving mechanisms of ES supply and demand in an alpine pastoral region, addressing a significant research gap. The findings not only provide a reference for ES supply–demand assessment in similar regions regarding indicator selection and methodology but also offer direct scientific support for precisely identifying priority areas for ecological conservation and restoration, optimizing grass–livestock balance management, and enhancing ecosystem sustainability within the Sanjiangyuan Region.

Nanozymes are promising for precise cancer treatment, but are typically limited in terms of the low catalytic efficiency and the complexity in tumor microenvironment (TME). Herein, we describe a bimodal type of AgPd plasmonic blackbody (AgPd PB) nanozyme of compact sizes (< 30 nm), which presents not only boosted enzyme efficacy but also efficient photothermal therapy (PTT) for synergized therapy through tissue-penetrating light in the second biological window (1000–1700 nm). The synthesized hyperbranched AgPd PB nanozymes possess intense and broadband localized surface plasmonic resonance absorption of 400–1300 nm, entailing prominent photothermal efficiency ( η  = 45.1% at 1064 nm) for PTT. Importantly, PTT was found to significantly boost the nanozyme efficacy of both catalase (CAT) and peroxidase (POD) processes, which correspondingly decompose H 2 O 2 to into O 2 to relieve tumor hypoxia, and activate H 2 O 2 to generate oxidative •OH radical. While the generated •OH was found to be able to minimize heat shock proteins (HSPs), which plays a vital role to counterbalance PTT effect both in vitro and in vivo. As compared to control ground without treatment, the synergized nanozyme and PTT activities resulted in about 7-fold reduction of tumor volume, thus elevating the survival rate from 0 to 80% at 30 days posttreatment. Besides the synergistic therapy, the AgPd PB nanozyme were shown to own fluorescence, computed tomography (CT), and photoacoustic (PA) imaging abilities, thus having implications for uses in imaging-guided precise cancer therapy. This study provides a paradigm of TME responsive theranostics under NIR-II light irradiation. Graphical Abstract

α1C-tubulin ( TUBA1C ) is a member of the α-tubulin family and has served as a potential biomarker in a variety of cancers in many studies. In this study, the gene expression profile of TUBA1C in The Cancer Genome Atlas (TCGA) was extracted for analysis, and the prognostic value of TUBA1C in breast cancer was comprehensively evaluated. The Wilcoxon signed-rank test, Kruskal-Wallis test, and logistic regression analysis were performed to confirm the correlations between TUBA1C expression and the clinical characteristics of breast cancer patients. The effect of TUBA1C expression on the survival of breast cancer patients was assessed by Kaplan-Meier curve, Cox regression analysis, and the Kaplan-Meier plotter (an online database). The TCGA data set was used for the Gene Set Enrichment Analysis (GSEA). The results confirmed that high TUBA1C expression in breast cancer was closely correlated with survival time, survival status, and tumor size. In addition, elevated TUBA1C expression can predict poor overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS). Univariate and multivariate analyses (Cox regression analyses) confirmed that TUBA1C was an independent prognostic factor for the OS of breast cancer patients. The GSEA identified that the high TUBA1C expression phenotype was differentially enriched in cell cycle, basal transcription factor, P53 signaling pathway, pathways in cancer, TOLL-like receptor signaling pathway, and NOD-like receptor signaling pathway. In summary, high messenger RNA (mRNA) expression of TUBA1C is an independent risk factor for poor prognosis of breast cancer.

The prevalence of Alzheimer's disease (AD) is significantly gender-differentiated, with the number of female AD patients far exceeding that of males, accounting for two-thirds of the total prevalence. Although postmenopausal AD mice have been shown to have more prominent pathologic features and memory impairments than normal AD mice, the relevant molecular mechanisms leading to these outcomes have not been well elucidated. In the present study, we used the disturbance of excitation-inhibition balance in the postmenopausal brain as an entry point to explore the link between estrogen deficiency, disorders of the glutamatergic-GABAergic nervous system, and memory impairment. Wild-type (WT) mice and APP/PS1/tau (3 × Tg-AD) mice (10 months old) were randomly divided into four groups: WT+Sham group, WT+OVX group, 3 × Tg-AD+Sham group and 3 × Tg-AD+OVX group. Ovariectomy (OVX) was performed in the WT+OVX group and the 3 × Tg-AD+OVX group, and sham surgery was performed in the WT+Sham group and the 3 × Tg-AD+Sham group. The learning and memory ability and the anxiety and depression-like behavior changes of mice were evaluated by behavioral experiments, and the association between estrogen-estrogen receptors pathway and glutamatergic/GABAergic nervous system and female AD was evaluated by neurochemical experiments. In WT and 3 × Tg-AD mice, OVX resulted in impaired learning and memory abilities and anxiety and depression-like behaviors; reduced estrogen levels and downregulated the expression of estrogen receptors; upregulated the expression of amyloid-β, amyloid precursor protein, presenilin 1, and p-tau; upregulated the expression of Bcl-2-associated X protein and downregulated the expression of B-cell lymphoma-2, promoting cell apoptosis; reduced the number of neuronal dendrites and downregulated the expression of postsynaptic density protein-95; more importantly, OVX increased brain glutamate levels but downregulated the expression of N-methyl-D-aspartate receptor-2B, excitatory amino acid transporter 1, excitatory amino acid transporter 2, γ-aminobutyric acid receptor-A and γ-aminobutyric acid receptor-B. Our results suggested that OVX-induced estrogen-estrogen receptors pathway disruption caused learning and memory impairment and anxiety and depression-like behaviors, upregulated the expression of AD pathological markers, promoted apoptosis, destroyed neuronal structure, and most importantly, caused glutamatergic/GABAergic nervous system disorders.

Optically responsive composite materials hold significant promise for in vivo diagnostics and targeted therapies. Rare‐earth‐doped upconversion nanoparticles (UCNPs), renowned for their unique luminescence properties, large anti‐Stokes shift, excellent biocompatibility, and deep tissue penetration, have emerged as highly promising candidates for advanced phototherapy in biological systems. This review first explores the fundamental mechanisms of upconversion luminescence, as well as synthesis, surface modification, and design strategies to brighten upconversion. It then highlights recent advances and key applications of UCNPs in biological therapy, including upconversion‐mediated phototherapy, multimodal therapeutic approaches, and image‐guided therapy and surgery. Finally, it discusses the current challenges and opportunities in both fundamental research and clinical translation, providing theoretical insights and practical guidance to support the broader application of UCNPs in biological therapy and clinical medicine. Rare‐earth‐doped upconversion nanoparticles have emerged as anti‐Stokes nanoprobes for advanced phototherapy in biological systems. This review highlights recent advances in their use for therapeutic applications, spanning from fundamental principles to cutting‐edge technologies, and provides insights into their future development for precision medicine.

In this experiment, Lactobacillus plantarum and Lactobacillus buchneri were added individually or in combination to Silphium perfoliatum L. (SP) silage to investigate the effects of different fermentation types of lactobacilli on the fermentation quality, in vitro digestibility, and aerobic stability of SP-silage, with a view to providing a certain scientific basis and technical support for obtaining high-quality SP-silage in production. The experiment comprised a non-additive group (control), an L. plantarum group (LP), an L. buchneri group (LB), and an L. plantarum and L. buchneri mixed treatment group (LPLB). Samples were taken after 60 days of fermentation and analyzed for the fermentation quality, in vitro digestibility, and aerobic stability of the SP-silage. The results showed that the addition of LP, LB, and LPLB significantly reduced the pH and proportion of ammonia nitrogen to total nitrogen and significantly increased the lactic acid, in vitro dry matter digestibility, and in vitro crude protein digestibility in the SP-silage (p < 0.05). Compared to the control group, the dry matter and crude protein contents of the LB and LPLB groups were significantly increased, while the neutral detergent fiber and acid detergent fiber contents were significantly reduced (p < 0.05). The SP-silage supplemented with LPLB had the highest dry matter and crude protein contents. The gross and digestible energies of the SP-silage in the LB and LPLB groups were significantly higher than those in the control and LP groups (p < 0.05). The aerobic stability of the SP-silage was significantly reduced by 24.14% in the LP group and increased by 58.62% and 34.48% in the LB and LPLB groups, respectively, compared to the control group (p < 0.05). It was shown that adding a combination of LP and LB resulted in the best fermentation quality, nutritional value, and in vitro digestibility of the SP-silage. LB was effective in improving the aerobic stability of SP-silage.

In this work, a class of interpolation and smoothing exponential splines with respect to a sixth order differential operator with two parameters is constructed. All the square matrices involved in the construction are proved to be tridiagonal symmetric and diagonally dominant, which results in algorithms for computing this class of exponential splines. The obtained splines have C4 continuity and are the minimum solution of the combination of interpolation and a generalized smoothing energy integral. The performances of the resulting splines in financial data from the S &P500 index and the effect of fitting multi-exponential decay data are given. Numerical experiments show that the resulting splines have more freedom to adjust the shape and control the energy of the curves and perform better than previous methods in fitting multi-exponential decay data. And cross validation and generalized cross validation for determining an appropriate smoothing parameter are also developed.

Background: As antioxidant and anti-inflammatory agents, carbonic anhydrase inhibitors can exert potentially useful therapeutic effects following central nervous system trauma, including intracerebral hemorrhage (ICH). However, the therapeutic efficacy of ethoxyzolamide (ETZ) as a novel carbonic anhydrase inhibitor for ICH has not yet been determined. Methods: An autologous blood injection method was used to establish ICH models, which were then used to establish the effects of intraperitoneal injection of ETZ on ICH. Neuronal damage, apoptotic protein expression, oxidative and inflammatory factor content, microglia marker Iba-1 positivity, hepatic and renal pathological changes, and serum concentrations of hepatic and renal function indices were assessed by Nissl staining, western blotting, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, hematoxylin and eosin (HE) staining, and automatic biochemical analysis in brain tissues. Results: The ICH group showed massive hemorrhagic foci; significant increases in brain water content, modified mouse neurological deficit scoring (mNSS) score, pro-apoptotic protein expression, oxidative factors, pro-inflammatory factors, and Iba-1 positivity; and significant reductions in Nissl body size, anti-apoptotic protein expression, and antioxidant factors, all of which were reversed by ETZ in a dose-dependent manner. ETZ has a good biosafety profile with no significant burden on the human liver or kidneys. The Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway was mildly activated in ICH mice, and was further increased after ETZ injection. Molecular docking experiments revealed that ETZ could dock onto the Nrf2-binding domain of keap1. Conclusions: ETZ, as a novel carbonic anhydrase inhibitor, further activated the Keap1/Nrf2 pathway by docking with the Nrf2-binding domain of keap1, thereby exerting antioxidant, anti-inflammatory, anti-apoptotic, and cerebral neuroprotective effects in ICH mice.

Dynamic regulation of nanoparticles in a controllable manner has great potential in various areas. Compared to the individual nanoparticles, the assembled nanoparticles exhibit superior properties and functions, which can be applied to achieve desirable performances. Here, a pH‐responsive i‐motif DNA‐mediated strategy to tailor the programmable behaviors of erbium‐based rare‐earth nanoparticles (ErNPs) decorated copper doped metal‐organic framework (CPM) nanohybrids (ECPM) under physiological conditions is reported. Within the acidic tumor microenvironment, the i‐motif DNA strands are able to form quadruplex structures, resulting in the assembly of nanohybrids and selective tumor accumulation, which further amplify the ErNPs downconversion emission (1550 nm) signal for imaging. Meanwhile, the ECPM matrix acts as a near‐infrared (NIR) photon‐activated reactive oxygen species (ROS) amplifier through the singlet oxygen generation of the matrix in combination with its ability of intracellular glutathione depletion upon irradiation. In short, this work displays a classical example of engineering of nanoparticles, which will manifest the importance of developing nanohybrids with structural programmability in biomedical applications. “Unity makes strength,” the smart use of MOF‐based nanohybrid (ECPM) for depleting the intracellular GSH and thus increasing the delivery efficiency of the ECPM is reported. The unique acidity‐responsive assembly of ECPM enables in situ clustering of the nanohybrid in the acidic tumor microenvironment (TME), which can achieve NIR‐activated tumor‐specific cancer theranostics with negligible side effects.