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Alzheimer’s disease (AD) is a major form of senile dementia, characterized by progressive memory and neuronal loss combined with cognitive impairment. AD is the most common neurodegenerative disease worldwide, affecting one-fifth of those aged over 85 years. Recent therapeutic approaches have been strongly influenced by five neuropathological hallmarks of AD: acetylcholine deficiency, glutamate excitotoxicity, extracellular deposition of amyloid-β (Aβ plague), formation of intraneuronal neurofibrillary tangles (NTFs), and neuroinflammation. The lowered concentrations of acetylcholine (ACh) in AD result in a progressive and significant loss of cognitive and behavioral function. Current AD medications, memantine and acetylcholinesterase inhibitors (AChEIs) alleviate some of these symptoms by enhancing cholinergic signaling, but they are not curative. Since 2003, no new drugs have been approved for the treatment of AD. This article focuses on the current research in clinical trials targeting the neuropathological findings of AD including acetylcholine response, glutamate transmission, Aβ clearance, tau protein deposits, and neuroinflammation. These investigations include acetylcholinesterase inhibitors, agonists and antagonists of neurotransmitter receptors, β-secretase (BACE) or γ-secretase inhibitors, vaccines or antibodies targeting Aβ clearance or tau protein, as well as anti-inflammation compounds. Ongoing Phase III clinical trials via passive immunotherapy against Aβ peptides (crenezumab, gantenerumab, and aducanumab) seem to be promising. Using small molecules blocking 5-HT 6 serotonin receptor (intepirdine), inhibiting BACE activity (E2609, AZD3293, and verubecestat), or reducing tau aggregation (TRx0237) are also currently in Phase III clinical trials. We here systemically review the findings from recent clinical trials to provide a comprehensive review of novel therapeutic compounds in the treatment and prevention of AD.

A bstract We study the N-partite coherences of GHZ and W states for free bosonic and fermionic fields when any n observers hover near the event horizon of a Garfinkle-Horowitz-Strominger (GHS) dilaton black hole. We derive the more general analytical expressions for N-partite coherence, encompassing both physically accessible and inaccessible coherences in the context of the dilaton black hole. It has been found that the coherence of the bosonic field is greater than that of the fermionic field, while the entanglement of the fermionic field is greater than that of the bosonic field in dilaton spacetime. Additionally, the coherence of the W state is greater than that of the GHZ state, whereas the entanglement of the GHZ state is greater than that of the W state in curved spacetime. These results suggest that we should utilize suitable quantum resources and different types of particles for relativistic quantum information tasks.

Background This study aimed to assess family function in home care for older adults. Understanding family dynamics is essential for providing quality care to older adults choosing to age in place. Methods In a cross-sectional study, 53 patients aged 65 or older receiving home care were evaluated, along with four home care nurses. The General Function of Family Assessment Device (FAD-GF) was used for self-assessment to examine family resources. Results Only 5.7% of older adults reported good family function. Strong correlations were found between assessments by nurses and older adults. Among the six aspects of family function, “problem solving,” “communication,” “affective responsiveness,” and the overall results showed no disparities between the evaluations of older adults and nurses. Conclusions Home care nurses can effectively assess family function using the FAD-GF, particularly after six months of care. This assessment can help identify family issues and enhance home care quality through nurse training in FAD-GF application.

The ultimate goal of phototherapy based on nanoparticles, such as photothermal therapy (PTT) which generates heat and photodynamic therapy (PDT) which not only generates reactive oxygen species (ROS) but also induces a variety of anti-tumor immunity, is to kill tumors. In addition, due to strong efficacy in clinical treatment with minimal invasion and negligible side effects, it has received extensive attention and research in recent years. In this paper, the generations of nanomaterials in PTT and PDT are described separately. In clinical application, according to the different combination pathway of nanoparticles, it can be used to treat different diseases such as tumors, melanoma, rheumatoid and so on. In this paper, the mechanism of pathological treatment is described in detail in terms of inducing apoptosis of cancer cells by ROS produced by PDT, immunogenic cell death to provoke the maturation of dendritic cells, which in turn activate production of CD4+ T cells, CD8+T cells and memory T cells, as well as inhibiting heat shock protein (HSPs), STAT3 signal pathway and so on.

Bacterial biofilms can be viewed as a specific type of persistent bacterial infection. After initial invasion, microbes can attach to living and non-living surfaces, such as prosthetics and indwelling medical devices, and form a biofilm composed of extracellular polysaccharides, proteins, and other components. In hosts, bioffim formation may trigger drug resistance and inflammation, resulting in persistent infections. The clinical aspects of biofilm formation and leading strategies for hiofilm inhihitors will be discussed in this mini-review.

Mutations in the protein tyrosine phosphatase SHP2 affect cells in the bone marrow environment, which leads to aberrant activation of resident haematopoietic stem cells and thereby contributes to the development of leukaemia. A mutated microenvironment in leukaemia Hereditary mutations in the tyrosine phosphatase SHP2 (encoded by PTPN11 ), part of the Ras signalling pathway, have been linked to a syndrome leading to an increased risk of developing leukaemia. Previous studies in mouse models have shown that the function of haematopoietic stem cells carrying these mutations is defective, which suggests a cell-autonomous effect. Cheng-Kui Qu and colleagues find that the mutations also affect cells in the bone marrow environment, blocking their normal control on haematopoietic stem cells and thereby promoting the development of leukaemia. Administration of CCL3 receptor antagonists effectively reversed oncogenesis driven by the Ptpn11 -mutated bone marrow microenvironment. Germline activating mutations of the protein tyrosine phosphatase SHP2 (encoded by PTPN11 ), a positive regulator of the RAS signalling pathway 1 , are found in 50% of patients with Noonan syndrome 2 . These patients have an increased risk of developing leukaemia 3 , especially juvenile myelomonocytic leukaemia (JMML), a childhood myeloproliferative neoplasm (MPN). Previous studies have demonstrated that mutations in Ptpn11 induce a JMML-like MPN through cell-autonomous mechanisms that are dependent on Shp2 catalytic activity 4 , 5 , 6 , 7 . However, the effect of these mutations in the bone marrow microenvironment remains unclear. Here we report that Ptpn11 activating mutations in the mouse bone marrow microenvironment promote the development and progression of MPN through profound detrimental effects on haematopoietic stem cells (HSCs). Ptpn11 mutations in mesenchymal stem/progenitor cells and osteoprogenitors, but not in differentiated osteoblasts or endothelial cells, cause excessive production of the CC chemokine CCL3 (also known as MIP-1α), which recruits monocytes to the area in which HSCs also reside. Consequently, HSCs are hyperactivated by interleukin-1β and possibly other proinflammatory cytokines produced by monocytes, leading to exacerbated MPN and to donor-cell-derived MPN following stem cell transplantation. Remarkably, administration of CCL3 receptor antagonists effectively reverses MPN development induced by the Ptpn11 -mutated bone marrow microenvironment. This study reveals the critical contribution of Ptpn11 mutations in the bone marrow microenvironment to leukaemogenesis and identifies CCL3 as a potential therapeutic target for controlling leukaemic progression in Noonan syndrome and for improving stem cell transplantation therapy in Noonan-syndrome-associated leukaemias.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases in women of reproductive age and features complex pathological symptoms and mechanisms. Existing medical treatments have, to some extent, alleviated the deterioration of PCOS. However, these strategies only temporarily control symptoms, with a few side effects and no preventive effect. Phytochemicals extracted from medicinal herbs and plants are vital for discovering novel drugs. In recent years, many kinds of research have proven that phytochemicals isolated from traditional Chinese medicine (TCM) and medicinal plants show significant potential in preventing, alleviating, and treating PCOS. Nevertheless, compared to the abundance of experimental literature and minimal specific-topic reviews related to PCOS, there is a lack of systematic reviews to summarize these advancements in this promising field. Under this background, we systematically document the progress of bioactive phytochemicals from TCM and medicinal plants in treating PCOS, including flavonoids, polyphenols, and alkaloids. According to the literature, these valuable phytochemicals demonstrated therapeutic effects on PCOS supported by in vivo and in vitro experiments, mainly depending on anti-inflammatory, antioxidation, improvement of hormone disorder and insulin resistance (IR), and alleviation of hyperinsulinemia. Based on the current progress, future research directions should emphasize 1) exploring bioactive phytochemicals that potentially mediate bone metabolism for the treatment of PCOS; 2) improving unsatisfactory bioavailability by using advanced drug delivery systems such as nanoparticles and antibody-conjugated drugs, as well as a chemical modification; 3) conducting in-depth research on the pathogenesis of PCOS to potentially impact the gut microbiota and its metabolites in the evolution of PCOS; 4) revealing the pharmacological effects of these bioactive phytochemicals on PCOS at the genetic level; and 5) exploring the hypothetical and unprecedented functions in regulating PCOS by serving as proteolysis-targeting chimeras and molecular glues compared with traditional small molecule drugs. In brief, this review aims to provide detailed mechanisms of these bioactive phytochemicals and hopefully practical and reliable insight into clinical applications concerning PCOS.

Metabolic network modeling, especially Flux Balance Analysis (FBA), plays a critical role in systems biology by providing insights into cellular behaviors. Although FBA is the main tool for predicting flux distributions, it can face challenges capturing flux variations under different conditions. Selecting an appropriate objective function is therefore important for accurately representing system performance. To address this, we introduce a novel framework (e.g., TIObjFind ) that imposes Metabolic Pathway Analysis (MPA) with Flux Balance Analysis (FBA) to analyze adaptive shifts in cellular responses throughout different stages of a biological system. This framework determines Coefficients of Importance (CoIs) that quantify each reaction’s contribution to an objective function, aligning optimization results with experimental flux data. By examining Coefficients of Importance, TIObjFind enhances the interpretability of complex metabolic networks and provides insights into adaptive cellular responses.

Agarwood is highly valued for its uses as incense, perfume, and medicine. However, systematic analyses of dynamic changes of secondary metabolites during the process of agarwood formation have not yet been reported. In this study, agarwood was produced by transfusing the agarwood inducer into the trunk of , and changing patterns of chemical constituents, especially 2-(2-phenylethyl)chromones (PECs), in wood samples collected from the 1st to 12th month, were analyzed by GC-EI-MS and UPLC-ESI-MS/MS methods. Aromatic compounds, steroids, fatty acids/esters, sesquiterpenoids, and PECs were detected by GC-MS, in which PECs were the major constituents. Following this, UPLC-MS was used for further comprehensive analysis of PECs, from which we found that 2-(2-phenylethyl)chromones of flindersia type (FTPECs) were the most abundant, while PECs with epoxidated chromone moiety were detected with limited numbers and relatively low content. Speculation on the formation of major FTPECs was fully elucidated in our context. The key step of FTPECs biosynthesis is possibly catalyzed by type III polyketide synthases (PKSs) which condensate dihydro-cinnamoyl-CoA analogues and malonyl-CoA with 2-hydroxy-benzoyl-CoA to produce 2-(2-phenyethyl)chromone scaffold, or with 2,5-dihydroxybenzoyl-CoA to form FTPECS with 6-hydroxy group, which may serve as precursors for further reactions catalyzed by hydroxylase or -methyltransferase (OMT) to produce FTPECs with diverse substitution patterns. It is the first report that systematically analyzed dynamic changes of secondary metabolites during the process of agarwood formation and fully discussed the biosynthetic pathway of PECs.

On the basis of traditional unequal clustering protocol for wireless sensor networks, an energy-balance unequal clustering routing protocol is proposed. In the clustering stage, the entire network is divided into clusters of different sizes based on the remaining energy and the distance from the sink node to the node. In the cluster establishment phase, each node calculates the cluster head selection time based on the relative remaining energy, the position, the average distance between the nodes in the cluster. The cluster head is selected by time series, and non-cluster head nodes are selected to join the cluster based on the distance between cluster heads and the remaining energy of the relay cluster head. In the route establishment phase, an optimal transmission path based on minimum spanning tree is built, based on the distance between cluster heads, the residual energy and the distance from node to the sink node. During data transmission, a single hop within a cluster is adopted, and a minimum spanning tree multi-hop method is used between clusters, and the data is finally transmitted to the sink node. The simulation shows that the routing protocol can effectively balance energy consumption and save energy, and the life cycle of the network is prolonged.