A Platinum-Aluminum Bimetallic Salen Complex for Pro-senescence Cancer Therapy.

Cell senescence is defined as irreversible cell cycle arrest, which can be triggered by telomere shortening or by various types of genotoxic stress. Induction of senescence is emerging as a new strategy for the treatment of cancer, especially when sequentially combined with a second senolytic drug capable of killing the resulting senescent cells, however severely suffering from the undesired off-target side effects from the senolytic drugs. Here, we prepare a bimetalic platinum-aluminum salen complex (Alumiplatin) for cancer therapy-a combination of pro-senesence chemotherapy with in situ senotherapy to avoid the side effects. The aluminum salen moiety, as a G-quadruplex stabilizer, enhances the salen's ability to induce cancer cell senescence and this phenotype is in turn sensitive to the cytotoxic activity of the monofunctional platinum moiety. It exhibits an excellent capability for inducing senescence, a potent cytotoxic activity against cancer cells both in vitro and in vivo, and an improved safety profile compared to cisplatin. Therefore, Alumiplatin may be a good candidate to be further developed into safe and effective anticancer agents. This novel combination of cell senescence inducers with genotoxic drugs revolutionizes the therapy options of designing multi-targeting anticancer agents to improve the efficacy of anticancer therapies.

The effect of the Sport Education Model in physical education on student learning attitude: a systematic review.

BACKGROUND: Evidence indicates that the Sport Education Model (SEM) has demonstrated effectiveness in enhancing students' athletic capabilities and fostering their enthusiasm for sports. Nevertheless, there remains a dearth of comprehensive reviews examining the impact of the SEM on students' attitudes toward physical education learning. PURPOSE: The purpose of this review is to elucidate the influence of the SEM on students' attitudes toward physical education learning. METHODS: Employing the preferred reporting items of the Systematic Review and Meta-analysis (PRISMA) statement guidelines, a systematic search of PubMed, SCOPUS, EBSCOhost (SPORTDiscus and CINAHL Plus), and Web of Science databases was conducted in mid-January 2023. A set of keywords associated with the SEM, attitudes toward physical education learning, and students were employed to identify relevant studies. Out of 477 studies, only 13 articles fulfilled all the eligibility criteria and were consequently incorporated into this systematic review. The validated checklist of Downs and Black (1998) was employed for the assessment, and the included studies achieved quality scores ranging from 11 to 13. The ROBINS-I tool was utilized to evaluate the risk of bias in the literature, whereby only one paper exhibited a moderate risk of bias, while the remainder were deemed to have a high risk. RESULTS: The findings unveiled significant disparities in cognitive aspects (n = 8) and affective components (n = 12) between the SEM intervention and the Traditional Teaching (TT) comparison. Existing evidence suggests that the majority of scholars concur that the SEM yields significantly superior effects in terms of students' affective and cognitive aspects compared to the TT. CONCLUSIONS: Nonetheless, several issues persist, including a lack of data regarding junior high school students and gender differences, insufficient frequency of weekly interventions, inadequate control of inter-group atmosphere disparities resulting from the same teaching setting, lack of reasonable testing, model fidelity check and consideration for regulating variables, of course, learning content, and unsuitable tools for measuring learning attitudes. In contrast, the SEM proves more effective than the TT in enhancing students' attitudes toward physical learning. SYSTEMATIC REVIEW REGISTRATION: ( https://inplasy.com/ ) (INPLASY2022100040).

Target proteins-regulated DNA nanomachine-electroactive substance complexes enable separation-free electrochemical detection of clinical exosome.

Simple and reliable profiling of tumor-derived exosomes (TDEs) holds significant promise for the early detection of cancer. Nonetheless, this remains challenging owing to the substantial heterogeneity and low concentration of TDEs. Herein, we devised an accurate and highly sensitive electrochemical sensing strategy for TDEs via simultaneously targeting exosomal mucin 1 (MUC1) and programmed cell death ligand 1 (PD-L1). This approach employs high-affinity aptamers as specific recognition elements, utilizes rolling circle amplification and DNA nanospheres as effective bridges and signal amplifiers, and leverages methylene blue (MB) and doxorubicin (DOX) as robust signal reporters. The crux of this separation- and label-free method is the specific response of MB and DOX to G-quadruplex structures and DNA nanospheres, respectively. Quantifying TDEs using this strategy enabled precise discrimination of lung cancer patients (n = 25) from healthy donors (n = 12), showing 100% specificity (12/12), 92% sensitivity (23/25), and an overall accuracy of 94.6% (35/37), with an area under the receiver operating characteristic curve (AUC) of 0.97. Furthermore, the assay results strongly correlated with findings from computerized tomography and pathological analyses. Our approach could facilitate the early diagnosis of lung cancer through TDEs-based liquid biopsy.

Unveiling the Impact of Metacognition on Academic Achievement in Physical Education and Activity Settings: A Comprehensive Systematic Review and Meta-Analysis of Qualitative Insights.

Purpose: The purpose of this study is to unveil the impact of metacognition on academic achievement in physical education and activity settings by conducting a comprehensive systematic literature review with a meta-analysis of qualitative findings. Patients and Methods: Systematic searches identified English-language, peer-reviewed journal articles reporting the results of qualitative or mixed-methods studies of the emerging themes of metacognition on academic achievement in sports. PubMed, Web of Science, Scopus, ProQuest, and SPORTDiscus were searched from inception to June 2023. Results: Data from 20 studies were included in the review. Thematic meta-analysis identified descriptive themes: 1) Metacognitive performance during the learning process in different sports disciplines; 2) Domains of metacognitive skills related to academic performance; 3) Self-regulation strategies related to academic performance; 4) Influencing factors of metacognition; 5) Metacognitive interventions on motor learning and academic performance. Generate an analytical theme based on five descriptive themes. Conclusion: In-depth descriptions of the emerging themes related to metacognition and academic performance during motor learning were provided by different students and athletes. The conclusions reported in the study align with the theoretical models of metacognition. The research findings will provide strategies for physical education teachers, coaches, and trainers to enhance both physical and academic performance.

Fluorination of porphyrin ß-periphery boosts nickel(II)-catalyzed hydrogen evolution reaction.

Tunichlorin, the naturally occurring chlorophyll cofactor containing Ni(II) ion, sets up a golden standard for designing the electrocatalysts for hydrogen evolution reaction (HER) via ß-peripheral modification. Besides the fine-tuning of the porphyrin ß-periphery such as adjusting the aromatics (the saturated level of tetrapyrrole) or installing hydroxyl group (hydrogen bond network) to enhance the catalytic HER efficiency, here we report that ß-fluorination of porphyrin is also an important approach to increase the reactivity of Ni(II) center. Benefiting the previously reported derivatization of ß-fluorinated porpholactones, we constructed a ß-fluorinated tunichlorin mimic (6). Compared with the non-fluorinated analogs (1, 3, and 5), we found that 2, 4, and 6 exhibit significant electrocatalytic HER reactivity acceleration (in terms of turnover frequencies, TOF, s-1) of ca. 37, 170, 133-fold, respectively. Mechanism studies suggested that ß-fluorination negatively shifts the metal complexes' reduction potentials and accelerates the electron transfer process, both contributing to the boosting of HER reaction. Notably, 6 showed an 890-fold increase of TOFs than 1, demonstrating the combining advantages of the of fluorination, hydrogenation, and hydroxylation at porphyrin ß-periphery.

Unraveling the intricacies of glioblastoma progression and recurrence: insights into the role of NFYB and oxidative phosphorylation at the single-cell level.

Background: Glioblastoma (GBM), with its high recurrence and mortality rates, makes it the deadliest neurological malignancy. Oxidative phosphorylation is a highly active cellular pathway in GBM, and NFYB is a tumor-associated transcription factor. Both are related to mitochondrial function, but studies on their relationship with GBM at the single-cell level are still scarce. Methods: We re-analyzed the single-cell profiles of GBM from patients with different subtypes by single-cell transcriptomic analysis and further subdivided the large population of Glioma cells into different subpopulations, explored the interrelationships and active pathways among cell stages and clinical subtypes of the populations, and investigated the relationship between the transcription factor NFYB of the key subpopulations and GBM, searching for the prognostic genes of GBM related to NFYB, and verified by experiments. Results: Glioma cells and their C5 subpopulation had the highest percentage of G2M staging and rGBM, which we hypothesized might be related to the higher dividing and proliferating ability of both Glioma and C5 subpopulations. Oxidative phosphorylation pathway activity is elevated in both the Glioma and C5 subgroup, and NFYB is a key transcription factor for the C5 subgroup, suggesting its possible involvement in GBM proliferation and recurrence, and its close association with mitochondrial function. We also identified 13 prognostic genes associated with NFYB, of which MEM60 may cause GBM patients to have a poor prognosis by promoting GBM proliferation and drug resistance. Knockdown of the NFYB was found to contribute to the inhibition of proliferation, invasion, and migration of GBM cells. Conclusion: These findings help to elucidate the key mechanisms of mitochondrial function in GBM progression and recurrence, and to establish a new prognostic model and therapeutic target based on NFYB.

Water rights trading planning and its application in water resources management: A water-ecology-food nexus perspective.

Nexus approach provides an effective perspective for implementing synergetic management of water resources. In this study, an interval two-stage chance-constrained water rights trading planning model under water-ecology-food nexus perspective (ITCWR-WEF) is proposed to analyze the interaction between water trading and water-ecology-food (WEF) nexus, which fills in the water resources management gaps from a novel nexus perspective. ITCWR-WEF incorporates hydrological simulation with soil and water assessment tool (SWAT), water rights configuration with interval two-stage chance-constrained programming (ITCP), and multi-criterion analysis with Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS). The developed ITCWR-WEF is applied to a real case of Daguhe watershed, which has characteristics of water scarcity, food producing areas and fragile ecosystem. Initial water rights allocation is addressed before the trading. Mechanisms analysis is designed to reveal mutual effect of water rights trading and WEF nexus. Optimal water management scenario is identified through multi-criterion analysis. Results reveal that the mechanism of water rights trading with WEF nexus under low constraint-violation risk level of water availability and environment capacity is recommended to promote the rational water resources allocation to balance the economic goals, water environment and water supply security, as well as ecological and food water demand guarantees.

Advancements in the study of synaptic plasticity and mitochondrial autophagy relationship.

Synapses serve as the points of communication between neurons, consisting primarily of three components: the presynaptic membrane, synaptic cleft, and postsynaptic membrane. They transmit signals through the release and reception of neurotransmitters. Synaptic plasticity, the ability of synapses to undergo structural and functional changes, is influenced by proteins such as growth-associated proteins, synaptic vesicle proteins, postsynaptic density proteins, and neurotrophic growth factors. Furthermore, maintaining synaptic plasticity consumes more than half of the brain's energy, with a significant portion of this energy originating from ATP generated through mitochondrial energy metabolism. Consequently, the quantity, distribution, transport, and function of mitochondria impact the stability of brain energy metabolism, thereby participating in the regulation of fundamental processes in synaptic plasticity, including neuronal differentiation, neurite outgrowth, synapse formation, and neurotransmitter release. This article provides a comprehensive overview of the proteins associated with presynaptic plasticity, postsynaptic plasticity, and common factors between the two, as well as the relationship between mitochondrial energy metabolism and synaptic plasticity.

The role of dendritic cells in cancer immunity and therapeutic strategies.

Dendritic cells (DCs) are asserted as the most potent antigen-presenting cells (APCs) that orchestrate both innate and adaptive immunity, being extremely effective in the induction of robust anti-cancer T cell responses. Hence, the modulation of DCs function represents an attractive target for improving cancer immunotherapy efficacy. A better understanding of the immunobiology of DCs, the interaction among DCs, immune effector cells and tumor cells in tumor microenvironment (TME) and the latest advances in biomedical engineering technology would be required for the design of optimal DC-based immunotherapy. In this review, we focus on elaborating the immunobiology of DCs in healthy and cancer environments, the recent advances in the development of enhancing endogenous DCs immunocompetence via immunomodulators as well as DC-based vaccines. The rapidly developing field of applying nanotechnology to improve DC-based immunotherapy is also highlighted.

A chromosome-level genome assembly of a deep-sea symbiotic Aplacophora mollusc Chaetoderma sp.

The worm-shaped, shell-less Caudofoveata is one of the least known groups of molluscs. As early-branching molluscs, the lack of high-quality genomes hinders our understanding of their evolution and ecology. Here, we report a high-quality chromosome-scale genome of Chaetoderma sp. combining PacBio, Illumina, and high-resolution chromosome conformation capture sequencing. The final assembly has a size of 2.45 Gb, with a scaffold N50 length of 141.46 Mb, and is anchored to 17 chromosomes. Gene annotations showed a high level of accuracy and completeness, with 23,675 predicted protein-coding genes and 94.44% of the metazoan conserved genes by BUSCO assessment. We further present 16S rRNA gene amplicon sequencing of the gut microbiota in Chaetoderma sp., which was dominated by the chemoautotrophic bacteria (phylum Gammaproteobacteria). This chromosome-level genome assembly presents the first genome for the Caudofoveata, which constitutes an important resource for studies ranging from molluscan evolution, symposium, to deep-sea adaptation.

Impact of Codonopsis decoction on cerebral blood flow and cognitive function in rats with chronic cerebral ischemia.

ETHNOPHARMACOLOGICAL RELEVANCE: Some species of Codonopsis (local name in Shanxi: Ludang) have long demonstrated high medicinal and economic value. Radix Codonopsis, the dried root of Codonopsis pilosula (Franch.) Nannf. (C. pilosula), Codonopsis pilosula var. modesta (Nannf.) L.D.Shen (C. pilosula var. modesta), or Codonopsis pilosula subsp. tangshen (Oliv.) D.Y.Hong (C. pilosula subsp. tangshen), was recorded as a traditional Chinese medicine back in the Qing Dynasty in Ben Cao Cong Xin. Radix Codonopsis, a valuable medicinal herb certified by the Chinese National Geographic Indication, is known for invigorating the spleen, nourishing the lungs, promoting blood circulation, and generating fluid properties. Given that chronic cerebral ischemia (CCI) is often associated with the symptoms of qi and blood deficiencies and fluid depletion, we explored the potential of Codonopsis decoction in the treatment of CCI. STUDY AIMS: We investigated the effects of Codonopsis decoction on cerebral blood flow (CBF) and cognitive function in rats with bilateral carotid artery occlusion after surgery; explored whether Codonopsis decoction alleviates pathological injuries in brain tissue of rats after 2-VO surgery; and assessed the impact of Codonopsis decoction on the expression of chemokines, hypoxia-inducible factors, and inflammatory mediators in rats after 2-VO surgery. MATERIALS AND METHODS: We used a 2-VO rat model to simulate CCI. We used a laser speckle imaging (LSI) system to observe changes in CBF before and after surgery. The goal was to examine variations in CBF at different time points after 2-VO surgery. For 4 weeks, the rats were orally administered Codonopsis decoction at doses of 2.7, 5.4, and 10.8 g/kg/day, or Ginaton at a dose of 43.2 mg/kg/day. To assess the effect of Codonopsis on cerebral hypoperfusion symptoms in rats, we conducted the Morris water maze (MWM), Barnes maze (BM), and forelimb grip strength tests. Additionally, pathological experiments including hematoxylin and eosin, Nissl, and Luxol fast blue staining were conducted. Furthermore, we used western blotting to detect changes in the levels of proteins such as the chemotactic factor CKLF1 and hypoxia-inducible actor 1-alpha (HIF-1α). RESULTS: One week after 2-VO surgery, cerebral arterial blood supply in the rats rapidly reduced to approximately 43.39% ± 3.53% of the preoperative level. Cerebral cortex perfusion reached its nadir within 24 h of surgery, gradually recovering and stabilizing by the fourth week after surgery. An integration of the results from the BM, MWM, and grip strength tests, which assessed cognitive function and forelimb strength in rats after 2-VO surgery, unequivocally revealed that Codonopsis treatment significantly reduced the latency period and increased the number of platform crossings in the MWM test. Ginaton exhibited a comparable effect. Moreover, both Codonopsis and Ginaton decreased the number of errors and the time required to locate the target hole in the BM test. Histopathological staining revealed that Codonopsis and Ginaton could ameliorate pathological damage in rats after CCI and reduce the release of factors such as CKLF1 and HIF-1α. CONCLUSION: Codonopsis decoction exerted its protective effects on CCI rats possibly by modulating the levels of chemokines, hypoxia-inducible factors, and neuroinflammatory mediators.

[Protective effect of Liujing Toutong Tablets on rats with permanent cerebral ischemia via NF-κB signaling pathway].

This study investigated the neuroprotective effects and underlying mechanism of Liujing Toutong Tablets(LJTT) on a rat model of permanent middle cerebral artery occlusion(pMCAO). The pMCAO model was established using the suture method. Eighty-four male SPF-grade SD rats were randomly divided into a sham operation group, a model group, a nimodipine group(0.020 g·kg~(-1)), and high-, medium-, and low-dose LJTT groups(2.8, 1.4, and 0.7 g·kg~(-1)). The Longa score, adhesive removal test and laser speckle contrast imaging technique were used to evaluate the degree of neurological functional impairment and changes in local cerebral blood flow. The survival and mortality of rats in each group were recorded daily. After seven days of continuous administration following the model induction, the rats in each group were euthanized, and brain tissue and blood samples were collected for corresponding parameter measurements. Nissl staining was used to examine pathological changes in brain tissue neurons. The levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-1ß, vascular endothelial growth factor(VEGF), calcitonin gene-related peptide(CGRP), beta-endorphin(ß-EP), and endogenous nitric oxide(NO) in rat serum were measured using specific assay kits. The entropy weight method was used to analyze the weights of various indicators. The protein expression levels of nuclear factor kappa-B(NF-κB), inhibitor kappaB alpha(IκBα), phosphorylated IκBα(p-IκBα), and phosphorylated inhibitor of NF-κB kinase alpha(p-IKKα) in brain tissue were determined using Western blot. Immunohistochemistry was used to detect the protein expression of chemokine-like factor 1(CKLF1) and C-C chemokine receptor 5(CCR5) in rat brain tissue. Compared with the sham operation group, the model group showed significantly higher neurological functional impairment scores, prolonged adhesive removal time, decreased cerebral blood flow, increased neuronal damage, reduced survival rate, significantly increased levels of TNF-α, IL-1ß, IL-6, CGRP, and NO in serum, significantly decreased levels of VEGF and ß-EP, significantly increased expression levels of NF-κB p65, p-IκBα/IκBα, and p-IKKα in rat brain tissue, and significantly upregulated protein expression of CKLF1 and CCR5. Compared with the model group, the high-dose LJTT group significantly improved the neurological functional score of pMCAO rats after oral administration for 7 days. LJTT at all doses significantly reduced adhesive removal time and restored cerebral blood flow. The high-and medium-dose LJTT groups significantly improved neuronal damage. The LJTT groups at all doses showed reduced levels of TNF-α, IL-1ß, IL-6, CGRP, and NO in rat serum, increased VEGF and ß-EP levels, and significantly decreased expression levels of NF-κB p65, p-IκBα/IκBα, p-IKKα, and CCR5 protein in rat brain tissue. The entropy weight analysis revealed that CGRP and ß-EP were significantly affected during the model induction, and LJTT exhibited a strong effect in reducing the release of inflammatory factors such as TNF-α and IL-1ß. LJTT may exert a neuroprotective effect on rats with permanent cerebral ischemia by reducing neuroinflammatory damage, and its mechanism may be related to the inhibition of the NF-κB signaling pathway and the regulation of the CKLF1/CCR5 axis. Additionally, LJTT may exert certain analgesic effects by reducing CGRP and NO levels and increasing ß-EP levels.

Regulation of oxygen-glucose deprivation/reperfusion-induced inflammatory responses and M1-M2 phenotype switch of BV2 microglia by lobetyolin.

To elucidate the protective mechanism of lobetyolin on oxygen-glucose deprivation/reperfusion (OGD/R)-induced damage in BV2 microglial cells. The OGD/R model was established using a chemical modeling method to simulate in vivo brain ischemia in lobetyolin-pretreated BV2 cells. The optimum lobetyolin dosage, chemical concentration, and OGD/R modeling duration were screened. The changes in cell morphology were observed, and the levels of immune response-related factors, including tumor necrosis factor-α (TNF-α), interleukin-6, inducible nitric oxide synthase (iNOS), and cluster of differentiation (CD)206, were detected using the enzyme-linked immunosorbent assay. The expression of chemokine-like-factor-1 (CKLF1), hypoxia-inducible factor (HIF)-1α, TNF-α, and CD206, was detected using western blotting. The gene expression of M1 and M2 BV2 phenotype markers was assessed using quantitative polymerase chain reaction (qPCR). The localization of M1 and M2 BV2 markers was detected using immunofluorescence analysis. The results showed that lobetyolin could protect BV2 cells from OGD/R-induced damage. After OGD/R, CKLF1/C-C chemokine receptor type 4 (CCR4) levels increased in BV2 cells, whereas the CKLF1/CCR4 level was decreased due to lobetyolin pretreatment. Additionally, BV2 cells injured with OGD/R tended to be M1 type, but lobetyolin treatment shifted the phenotype of BV2 cells from M1 type to M2 type. Lobetyolin decreased the expression of TNF-α and HIF-1α but increased the expression of transforming growth factor-ß (TGF-ß) in BV2 cells, indicating a dose-effect relationship. The qPCR results showed that lobetyolin decreased the expression of CD16, CD32, and iNOS at the gene level and increased the expression of C-C-chemokine ligand-22 and TGF-ß. The immunofluorescence analysis showed that lobetyolin decreased CD16/CD32 levels and increased CD206 levels. Lobetyolin can protect BV2 cells from OGD/R-induced damage by regulating the phenotypic polarization of BV2 and decreasing inflammatory responses. Additionally, CKLF1/CCR4 may participate in regulating lobetyolin-induced polarization of BV2 cells via the HIF-1α pathway.

Nickel(II) Phototheranostics: A Case Study in Photoactivated H2O2-Enhanced Immunotherapy.

Phototheranostics have emerged as a promising subset of cancer theranostics owing to their potential to provide precise photoinduced diagnoses and therapeutic outcomes. However, the design of phototheranostics remains challenging due to the nature of tumors and their microenvironment, including limitations to the oxygen supply, high rates of recurrence and metastasis, and the immunosuppressive state of cancer cells. Here we report a dual-functional oxygen-independent phototheranostic agent, Ni-2, rationally designed to provide a near-infrared (NIR) photoactivated thermal- and hydroxyl radical (•OH)-enhanced photoimmunotherapeutic anticancer response. Under 880 nm laser irradiation, Ni-2 exhibited high photostability and excellent photoacoustic and photothermal effects with a photothermal conversion efficacy of 58.0%, as well as novel photoredox features that allowed the catalytic conversion of H2O2 to •OH upon photooxidation of Ni(II) to Ni(III). As a multifunctional photoagent, Ni-2 was found not only to inhibit tumor growth in a CT26 tumor-bearing mouse model but also to activate an immune response via a combination of photothermal- and H2O2-induced effects. When combined with an antiprogrammed death-ligand 1 (aPD-L1), Ni-2 treatment allowed for the suppression of distant tumor growth and cancer metastasis. Collectively, the present results provide support for the proposition that Ni-2 or its analogues could emerge as useful tools for photoimmunotherapy. They also highlight the potential of appropriately designed 3d transition metal complexes as "all- in-one" phototheranostics.

Exploring the application value of pro-gastrin-releasing peptide in the clinical diagnosis and surgical treatment of medullary thyroid carcinoma.

OBJECTIVE: To investigate the relationship between pro-gastrin-releasing peptide (ProGRP) and the clinical characteristics of patients with medullary thyroid carcinoma (MTC) and the value of ProGRP in surgical treatment monitoring. PATIENTS AND METHODS: A total of 347 patients with MTC and non-MTC malignant and benign thyroid diseases were enrolled. The concentrations of neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), calcitonin (CT), and ProGRP were determined by Elecsys® assays. The NSE, CEA, CT, and ProGRP levels in different thyroid disease groups were compared, and ProGRP levels in different clinicopathological feature groups pre and postoperatively were further compared. RESULTS: The CT, CEA, NSE, and ProGRP levels were upregulated in the MTC group compared to those in the non-MTC malignant and benign thyroid disease groups. The area under the receiver operating characteristic curve (AUC) of ProGRP for the diagnosis of MTC was 0.832(0.787-0.871), similar to that of CT and CEA. The sensitivity and specificity were 71.4% and 92.7%, respectively, and the optimal cut-off value was 61.8 pg/mL. The AUC of ProGRP combined with CT or CEA for the diagnosis of MTC was 0.933 (0.900-0.958) and 0.922 (0.886-0.949), respectively, which were higher than those of a single index. ProGRP levels were higher in patients with lymph nodes and distant metastases than in patients without metastases. The postoperative level of ProGRP was lower than that before treatment. CONCLUSION: ProGRP is comparable to CEA and CT as an MTC biomarker with broad prospects. It has potential application value in the progression of MTC assessment and the evaluation of surgical intervention effects.

Fuzi decoction treats chronic heart failure by regulating the gut microbiota, increasing the short-chain fatty acid levels and improving metabolic disorders.

Fuzi decoction (FZD) is clinically used to treat chronic heart failure (CHF) in China, but the mechanism underlying FZD treatment in CHF remains unclear. Here, we investigated the potential mechanism underlying FZD treatment of CHF in rats. First, the compounds in FZD-containing serum of rats were identified, and 16 S rRNA sequencing and GC-MS-based untargeted metabolomics analysis were then performed. The levels of fecal short-chain fatty acids (SCFAs) were determined and compared, and fecal microbiota transplantation (FMT) was used to verify the role of the gut microbiota. Our results identified 27 in FD-containing serum. FZD increased the Firmicutes-to-Bacteroidetes ratio and the Lactobacillus abundance and affected the ß diversity of the gut microbiota in rats with CHF. Differential species analysis showed that Lactobacillus and Prevotella were biomarkers of FZD treatment of CHF. Untargeted metabolomics analysis revealed that FZD affected valine, leucine and isoleucine biosynthesis; galactose metabolism; and aminoacyl-tRNA biosynthesis in rats with CHF. Furthermore, FZD significantly increased the acetic acid, propionic acid, butyric acid and isopentanoic acid levels in the feces of rats with CHF. Correlation analysis showed that the butyric acid and Lactobacillus levels had the strongest correlation in the control, sham and high-dose FZD (HFZD) groups, and many microbiota components were closely related to differentially abundant metabolites. FMT revealed that the fecal microbiota obtained from the HFZD group changed the heart rate; the brain natriuretic peptide (BNP), acetic acid, propionic acid, butyric acid, and metabolite levels; and the gut microbiota in rats with CHF. In summary, our study revealed that the mechanism of action of FZD in CHF treatment may be related to improvements in the gut microbiota, elevations in the SCFA content and the regulation of valine, leucine, and isoleucine biosynthesis; galactose metabolism; and other metabolic pathways.

Effects of Dihuang Yinzi Decoction on Alzheimer's Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this study was to systematically evaluate the therapeutic effects of Dihuang Yinzi decoction on Alzheimer's disease (AD) and provide a medical evidence-based clinical application of traditional Chinese medicine (TCM). METHODS: A comprehensive search was conducted across multiple databases, including PubMed, Embase, Cochrane Library, China National Journals Full-text Database, VIP Database for Chinese Technical Periodicals, Wan Fang database, and SinoMed database, to collect clinical randomized controlled trials of Dihuang Yinzi decoction in the treatment of AD. Strict literature screening was performed based on predefined inclusion and exclusion criteria. The Cochrane Collaboration risk of bias assessment tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system recommendation-level method was used to assess the quality of the included studies. Review Manager 5.4 and Stata 17 software were used for data synthesis and processing, while GRADE Profiler 3.6 software was used to evaluate the quality of evidence for outcome indicators (risk ratio, standardized mean difference, and weighted mean difference). RESULTS: A total of 11 studies involving 798 patients met the inclusion criteria. Dihuang Yinzi decoction, whether used alone or in combination with conventional Western medicine, demonstrated superior efficacy compared to conventional Western medicine alone in improving the clinical effective rate, TCM syndrome score, activity of daily living score, Mini-Mental State Examination score, and Hasegawa Dementia Scale score in AD treatment. Furthermore, it exhibited a favorable safety profile. However, the GRADE evidence quality rating for the included studies was low. CONCLUSIONS: Dihuang Yinzi decoction, either used alone or in combination with conventional Western medicine, shows promising results in enhancing cognitive and memory functions as well as the self-care ability of patients with AD. However, the low GRADE evidence quality rating highlights the need for focused advancements in the planning and execution of clinical randomized controlled trials during future research attempts.Ziel dieser Studie ist es, die therapeutischen Effekte von Dihuang Yinzi-Dekokt auf die Alzheimer-Krankheit systematisch zu bewerten und eine evidenzbasierte klinische Anwendung der traditionellen chinesischen Medizin (TCM) bereitzustellen.Es wurde eine umfassende Suche in mehreren Datenbanken, darunter PubMed, Embase, Cochrane Library, China National Journals Volltext-Datenbank, VIP Database for Chinese Technical Periodicals, Wan Fang Datenbank und SinoMed-Datenbank durchgeführt, um randomisierte, kontrollierte klinische Studien zu Dihuang Yinzi-Dekokt in der Behandlung der Alzheimer-Krankheit zu erfassen. Die strenge Literatursuche erfolgte auf Grundlage von vordefinierten Ein-und Ausschlusskriterien. Zur Bewertung der Qualität der eingeschlossenen Studien wurden das Risk-of-Bias-Tool von Cochrane und das GRADE (Grading of Recommendations Assessment, Development, and Evaluation)-System zur Beurteilung der Empfehlungsgrade herangezogen. Die Datensynthese und -verarbeitung erfolgten mithilfe der Review Manager 5.4- und der Stata 17-Software, während für die Bewertung der Evidenzqualität der Outcome-Indikatoren (Risikoverhältnis, standardisierte Mittelwertdifferenz und gewichtete Mittelwertdifferenz) die Software GRADE Profiler 3.6 verwendet wurde.Insgesamt erfüllten 11 Studien, an denen 798 Patienten teilnahmen, die Einschlusskriterien. Dihuang Yinzi-Dekokt zeigte allein oder in Kombination mit konventioneller westlicher Medizin eine überlegene Wirksamkeit gegenüber der alleinigen Verwendung von konventioneller westlicher Medizin in Bezug auf die klinische Gesamtwirksamkeitsrate, den TCM-Syndrom-Score, den Score für die Alltagsaktivitäten, den Mini-Mental State Examination-Score und den Score der Hasegawa-Demenz-Skala in der Behandlung der Alzheimer-Krankheit. Darüber hinaus wies es ein günstiges Sicherheitsprofil auf. Die Evidenzqualität der eingeschlossenen Studien gemäß GRADE wurde jedoch als gering eingestuft.Dihuang Yinzi-Dekokt zeigt allein oder in Kombination mit konventioneller westlicher Medizin vielversprechende Ergebnisse in Bezug auf die Verbesserung der kognitiven und Gedächtnisfunktionen sowie die Selbstversorgungsfähigkeit von Alzheimer-Patienten. Die niedrige Bewertung der Evidenzqualität gemäß GRADE unterstreicht jedoch die Notwendigkeit von zielgerichteten Weiterentwicklungen bei der Planung und Durchführung von randomisierten, kontrollierten klinischen Studien in zukünftigen Forschungsunternehmungen.

A rapid and visual detection of Staphylococcus haemolyticus in clinical specimens with RPA-LFS.

Staphylococcus haemolyticus (S. haemolyticus), which is highly prevent in the hospital environment, is an etiological factor for nosocomial infections. Point-of-care rapid testing (POCT) of S. haemolyticus is not possible with the currently used detection methods. Recombinase polymerase amplification (RPA) is a novel isothermal amplification technology with high sensitivity and specificity. The combination of RPA and lateral flow strips (LFS) can achieve rapid pathogen detection, enabling POCT. This study developed an RPA-LFS methodology using a specific probe/primer pair to identify S. haemolyticus. A basic RPA reaction was performed to screen the specific primer from 6 primer pairs targeting mvaA gene. The optimal primer pair was selected based on agarose gel electrophoresis, and the probe was designed. To eliminate false-positive results caused by the byproducts, base mismatches were introduced in the primer/probe pair. The improved primer/probe pair could specifically identify the target sequence. To explore the optimal reaction conditions, the effects of reaction temperature and duration of the RPA-LFS method were systematically investigated. The improved system enabled optimal amplification at 37 °C for 8 min, and the results were visualized within 1 min. The S. haemolyticus detection sensitivity of the RPA-LFS method, whose performance was unaffected by contamination with other genomes, was 0.147 CFU/reaction. Furthermore, we analyzed 95 random clinical samples with RPA-LFS, quantitative polymerase chain reaction (qPCR), and traditional bacterial-culture assays and found that the RPA-LFS had 100% and 98.73% compliance rates with the qPCR and traditional culture method, respectively, which confirms its clinical applicability. In this study, we designed an improved RPA-LFS assay based on the specific probe/primer pair for the detection of S. haemolyticus via rapid POCT, free from the limitations of the precision instruments, helping to make diagnoses and treatment decisions as soon as possible.

Characterising baseflow signature variability in the Yellow River Basin.

Baseflow is pivotal in maintaining catchment ecological health and improving sustainable economic development. The Yellow River Basin (YRB) is northern China's most important water supplier. However, it faces water shortage due to synergistic effects between natural conditions and anthropogenic activities. Investigating baseflow characteristics quantitively is, therefore, beneficial to promoting the sustainable development of the YRB. In this study, daily ensemble means baseflow data derived from four revised baseflow separation algorithms (i.e., the United Kingdom Institute of Hydrology (UKIH), Lyne-Hollick, Chapman-Maxwell, and Eckhardt methods) - was obtained from 2001 to 2020. Thirteen baseflow dynamics signatures were extracted to investigate baseflow spatiotemporal variations and their determinants across the YRB. The main findings were: (1) There were significant spatial distribution patterns of baseflow signatures, and most signatures had higher values in upstream and downstream reaches than in the middle reaches. There were also mixing patterns with higher values in middle and downstream reaches simultaneously. (2) The magnitude of temporal variation in baseflow signatures was most strongly correlated with catchment terrain (r = -0.4), vegetation growth (r > 0.3), and cropland coverage (r > 0.4). (3) There was a strong synergistic effect of multiple factors (e.g., soil textures, precipitation and vegetation conditions) on baseflow signature values. This study provided a heuristic evaluation of baseflow characteristics in the YRB, contributing to water resources management in the YRB and similar catchments.

Gallium Triggers Ferroptosis through a Synergistic Mechanism.

The gallium ion (Ga3+ ) has long been believed to disrupt ferric homeostasis in the body by competing with iron cofactors in metalloproteins, ultimately leading to cell death. This study revealed that through an indirect pathway, gallium can trigger ferroptosis, a type of non-apoptotic cell death regulated by iron. This is exemplified by the gallium complex of the salen ligand (Ga-1); we found that Ga-1 acts as an effective anion transporter that can affect the pH gradient and change membrane permeability, leading to mitochondrial dysfunction and the release of ferrous iron from the electron transfer chain (ETC). In addition, Ga-1 also targeted protein disulfide isomerases (PDIs) located in the endoplasmic reticulum (ER) membrane, preventing the repair of the antioxidant glutathione (GSH) system and thus enforcing ferroptosis. Finally, a combination treatment of Ga-1 and dietary polyunsaturated fatty acids (PUFAs), which enhances lipid peroxidation during ferroptosis, showed a synergistic therapeutic effect both in vitro and in vivo. This study provided us with a strategy to synergistically induce Ferroptosis in tumor cells, thereby enhancing the anti-neoplastic effect.