Bibliometric analysis of PTEN in neurodevelopment and neurodegeneration.

Phosphatase and tensin homologue deleted on chromosome ten (PTEN) was initially recognized as a significant regulator of cancer suppression and could impede cancer cell survival, proliferation, and energy metabolism. PTEN is highly expressed in neurons and performs crucial functions in neurogenesis, synaptogenesis, and neuronal survival. Disruption of PTEN activity may also result in abnormal neuronal function and is associated with various neurological disorders, including stroke, seizures, and autism. Although several studies have shown that PTEN is involved in the development and degenerative processes of the nervous system, there is still a lack of in-depth studies that summarize and analyse patterns of cooperation between authors, institutions, countries, and journals, as well as research hotspots and trends in this important field. To identify and further visualize the cooperation and comprehend the development and trends of PTEN in the nervous system, especially in neural development and neurological diseases, we used a bibliometric analysis to identify relevant publications on this topic. We first found that the number of publications displayed a growing trend with time, but this was not stable. Universities, institutions, and authors from the United States are leading in this area of research. In addition, many cutting-edge research results have been discovered, such as key regulatory molecules and cellular mechanisms of PTEN in the nervous system, which may provide novel intervention targets and precise therapeutic strategies for related pathological injuries and diseases. Finally, the literature published within the last 5 years is discussed to identify future research trends regarding PTEN in the nervous system. Taken together, our findings, analysed using bibliometrics, may reflect research hotspots and trends, providing a reference for studying PTEN in the nervous system, especially in neural development and neurological diseases. These findings can assist new researchers in developing their research interests and gaining basic information. Moreover, our findings also may provide precise clinical guidelines and strategies for treating nervous system injuries and diseases caused by PTEN dysfunction.

Half-decomposition of salt-bearing dolomite.

Half-calcined dolomites (HCDs) have been widely used in environmental remediation, medicine, and construction. However, advanced calcination technologies are required to modify their microstructure and thus improve their working performance. Herein, we investigated the effects of a variety of inorganic salts on the decomposition of dolomite based on thermogravimetric, compositional, and morphological analysis. The thermogravimetric data showed that certain salts significantly lowered the half-decomposition temperature of dolomite, which included LiCl, CaCl2, MgCl2, AlCl3, LiNO3, KNO3, K2CO3, Li2CO3, Li2SO4, Na3PO4, and K3PO4. Compositional analysis demonstrated that only half-decomposition occurred when salt-bearing dolomite was calcined at a temperature of 723-923 K, leading to the formation of CaO-free HCDs composed of periclase and Mg-calcite having a Mg level of 2.0-10.5 mol%. Morphological analysis showed that porous HCDs were feasibly obtained by calcining salt-bearing dolomite at 723-923 K. MgO coarsening occurred at a temperature above 873 K, but it could be avoided by controlling the calcination time. The mechanism of salts may be related to the heterovalent doping effect, which may lead to an increase in the concentration of vacancies in the dolomite lattice.

Compact and water flushing resistant mesh biofilms forming at short SRT disappeared naturally under extended SRT in dynamic membrane bioreactor.

Extending the solids retention time (SRT) has been demonstrated to mitigate membrane biofouling. Nevertheless, it remains an intriguing question whether the compact and water flushing resistant mesh biofilms developed at short SRT can undergo biodegradation and be removed with extended SRT. In present study, the bio-fouled mesh filter in the 10d-SRT dynamic membrane bioreactor (DMBR), with mesh surfaces and pores covered by compact and water flushing resistant biofilms exhibiting low water permeability, was reused in the 40d-SRT DMBR without any cleanings. After being reused at 40d-SRT, its flux driven by gravity occurred from the 10th day and recovered to a regular level of 36.7 L m-2·h-1 on the 27th day. Both scanning electron microscope (SEM) and confocal laser scanning microscopy (CLSM) analyses indicated that the compact mesh biofilms formed at10d-SRT biodegraded and were removed at 40d-SRT, with the residual biofilms becoming removable by water flushing. As a result, the hydraulic resistance of the bio-fouled mesh filter decreased from 4.36 × 108 to 6.97 × 107 m-1, and its flux fully recovered. The protein and polysaccharides densities in mesh-biofilms decreased from 24.4 to 9.7 mg/cm2 and from 10.7 to 0.10 mg/cm2, respectively, which probably have contributed to the disappearance of compact biofilms and the decrease in adhesion. Furthermore, the sludge and mesh-biofilms in the 40d-SRT reactor contained a higher relative abundance of dominant quorum quenching bacteria, such as Rhizobium (3.52% and 1.35%), compared to those in the 10d-SRT sludge (0.096%) and mesh biofilms (0.79%), which might have been linked to a decline in extracellular polymeric substances and, consequently, the biodegradation and disappearance of compact biofilms.

Tanshinone IIA induces ER stress and JNK activation to inhibit tumor growth and enhance anti-PD-1 immunotherapy in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) remains at the forefront of new cancer cases, and there is an urgent need to find new treatments or improve the efficacy of existing therapies. In addition to the application in the field of cerebrovascular diseases, recent studies have revealed that tanshinone IIA (Tan IIA) has anticancer activity in a variety of cancers. PURPOSE: To investigate the potential anticancer mechanism of Tan IIA and its impact on immunotherapy in NSCLC. METHODS: Cytotoxicity and colony formation assays were used to detect the Tan IIA inhibitory effect on NSCLC cells. This research clarified the mechanisms of Tan IIA in anti-tumor and programmed death-ligand 1 (PD-L1) regulation by using flow cytometry, transient transfection, western blotting and immunohistochemistry (IHC) methods. Besides, IHC was also used to analyze the nuclear factor of activated T cells 1 (NFAT2) expression in NSCLC clinical samples. Two animal models including xenograft mouse model and Lewis lung cancer model were used for evaluating tumor suppressive efficacy of Tan IIA. We also tested the efficacy of Tan IIA combined with programmed cell death protein 1 (PD-1) inhibitors in Lewis lung cancer model. RESULTS: Tan IIA exhibited good NSCLC inhibitory effect which was accompanied by endoplasmic reticulum (ER) stress response and increasing Ca2+ levels. Moreover, Tan IIA could suppress the NFAT2/ Myc proto oncogene protein (c-Myc) signaling, and it also was able to control the Jun Proto-Oncogene(c-Jun)/PD-L1 axis in NSCLC cells through the c-Jun N-terminal kinase (JNK) pathway. High NFAT2 levels were potential factors for poor prognosis in NSCLC patients. Finally, animal experiments data showed a stronger immune activation phenotype, when we performed treatment of Tan IIA combined with PD-1 monoclonal antibody. CONCLUSION: The findings of our research suggested a novel mechanism for Tan IIA to inhibit NSCLC, which could exert anti-cancer effects through the JNK/NFAT2/c-Myc pathway. Furthermore, Tan IIA could regulate tumor PD-L1 levels and has the potential to improve the efficacy of PD-1 inhibitors.

Recombination and repeat-induced point mutation landscapes reveal trade-offs between the sexual and asexual cycles of Magnaporthe oryzae.

The fungal disease caused by Magnaporthe oryzae is one of the most devastating diseases that endanger many crops worldwide. Evidence shows that sexual reproduction can be advantageous for fungal diseases as hybridization facilitates host-jumping. However, the pervasive clonal lineages of M. oryzae observed in natural fields contradict this expectation. A better understanding of the roles of recombination and the fungi-specific repeat-induced point mutation (RIP) in shaping its evolutionary trajectory is essential to bridge this knowledge gap. Here we systematically investigate the RIP and recombination landscapes in M. oryzae using a whole genome sequencing data from 252 population samples and 92 cross progenies. Our data reveal that the RIP can robustly capture the population history of M. oryzae, and we provide accurate estimations of the recombination and RIP rates across different M. oryzae clades. Significantly, our results highlight a parent-of-origin bias in both recombination and RIP rates, tightly associating with their sexual potential and variations of effector proteins. This bias suggests a critical trade-off between generating novel allelic combinations in the sexual cycle to facilitate host-jumping and stimulating transposon-associated diversification of effectors in the asexual cycle to facilitate host coevolution. These findings provide unique insights into understanding the evolution of blast fungus.

Quercetin promotes ATG5-mediating autophagy-dependent ferroptosis in gastric cancer.

Quercetin has been documented to possess a multitude of pharmacological effects, encompassing antioxidant, antiviral, antimicrobial, and anti-inflammatory properties. Nevertheless, the exact molecular mechanisms responsible for the anti-tumor properties of quercetin remain to be fully explicated. To this end, quercetin was administered to gastric cancer cells (in vitro) AGS and MKN45, as well as BALB/c mice (in vivo). The proliferation ability of cells was evaluated using cholecystokinin octapeptide (CCK-8) and colony formation assays. The evaluation of ferroptosis involved the measurement of iron, malondialdehyde (MDA), and lipid reactive oxygen species. Autophagy and apoptosis were evaluated using immunofluorescence staining, western blotting, and flow cytometry analysis. Our findings indicate that quercetin significantly inhibited cell viability and tumor volume compared to the control group. Additionally, quercetin was found to decrease glutathione (GSH), malondialdehyde, and reactive oxygen species (ROS) levels while suppressing beclin1 and LC3B levels in cancer cells. Remarkably, the utilization of siATG5 was found to reverse all the aforementioned effects of quercetin. Ultimately, the effects of quercetin on gastric cancer were validated. In summary, our findings provide evidence that quercetin facilitates autophagy-mediated ferroptosis in gastric cancer.

Sophoricoside improved Crohn's disease-like colitis by inhibiting intestinal epithelial cell apoptosis through PI3K/AKT signaling.

BACKGROUND AND AIMS: Increased apoptosis of intestinal epithelial cells (IECs) is a significant cause of intestinal barrier dysfunction in Crohn's disease (CD). Sophoricoside (SOP) is an isoflavone glycoside known for its anti-apoptotic properties. The aim of this study was to investigate the effects of SOP on mice with CD-like colitis and to understand the underlying mechanisms. METHODS: Mice treated with 2,4,6-trinitrobenzene sulfonic acid (TNBS) were used to examine the therapeutic effect of SOP on CD-like colitis and intestinal barrier damage. To further explore SOP's impact on IECs apoptosis and intestinal barrier protection, an in vitro colonic organoid apoptosis model induced by TNF-α was utilized. Network pharmacology was employed to predict the relevant pathways and molecular processes associated with SOP in the treatment of CD. RESULTS: Treatment with SOP significantly improved colitis symptoms in TNBS mice, as demonstrated by reductions in the Disease Activity Index (DAI), weight loss, colon shortening, macroscopic scores, colonic tissue inflammatory scores, and the expression of pro-inflammatory factors. Our experiments confirmed that SOP protects the intestinal barrier by counteracting IECs apoptosis. Additionally, this study established that SOP reduced IECs apoptosis by inhibiting the PI3K/AKT signaling pathway. CONCLUSIONS: SOP can reduce IECs apoptosis through the inhibition of the PI3K/AKT signaling pathway, thereby protecting the intestinal barrier. This study is the first to illustrate how SOP ameliorates colitis and protects the intestinal barrier, suggesting SOP has potential clinical application in treating CD.

Personalized treatment of well-differentiated gastric neuroendocrine tumors based on clinicopathological classification and grading: A multicenter retrospective study.

BACKGROUND: The incidence of well-differentiated gastric neuroendocrine tumors (G-NET) is increasing annually, and while they have a good prognosis and low mortality rate, their high recurrence rate makes treatment options controversial. This study aims to determine the relationship between individualized treatment plans and the recurrence of G-NET. METHODS: We performed a multicenter, retrospective study of 94 patients with highly differentiated G-NET and treated at Peking Union Medical College Hospital, Yantai Yuhuangding Hospital, and Beijing Zhong-Neng-Jian Hospital from November 2015 to September 2023. Risk factors for recurrence of G-NETs were investigated using chi-squared test and multifactorial logistic regression analysis. RESULTS: After a median follow-up of 49 months, the overall recurrence rate among the 94 G-NET patients was 14% (13/94). The recurrence rates of endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), somatostatin analog (SSA) therapy, and surgery were 43% (6/14), 10% (5/49), 5% (1/22), and 11% (1/9), respectively. Post-treatment recurrence rates were significantly different ( P = 0.014) among four treatments (EMR, ESD, SSA, and surgery), and further subgroup comparisons revealed lower recurrence rates in the ESD and SSA groups than in the EMR group. From the second month onward, SSA therapy considerably reduced the gastrin levels from 1081.0 (571.5, 2472.8) pg/mL to 461.5 (255.3, 795.0) pg/mL ( Z = -3.521, P <0.001). Both chi-squared test and multifactorial logistic regression analysis suggested that among the clinicopathological parameters studied, only the pre-treatment gastrin level ( P = 0.018 and 0.005) and the type of treatment ( P = 0.014 and 0.017) were significantly associated with G-NET recurrence. CONCLUSIONS: Individualized treatment strategies may reduce the risk of relapse after G-NET treatment. Long-term SSA therapy may be a secure and efficacious treatment option for type 1 G-NET with more than six lesions, and it substantially decreases the incidence of post-treatment recurrence.

[Using Multiple Strategies to Improve the Accuracy of Hemodynamic Monitoring].

BACKGROUND & PROBLEMS: Hemodynamic monitoring is an important part of nursing care in the intensive care unit. Recent advances in medical technology and the diversification of intensive care equipment have increased the variety of instruments used in clinical hemodynamic monitoring. Many nurses who use new hemodynamic monitors are not familiar with instrument care, resulting in patient safety incidents caused by nurses not identifying warnings of hemodynamic data change and notifying doctors to provide treatment. The accuracy of hemodynamic monitoring care in our ward of 74.0% motivated this improvement project. PURPOSE: To improve the accuracy of hemodynamic monitoring care to 98.3%. RESOLUTION: Conduct educational training and plan professional education; establish an audit system to regularly monitor the accuracy of nursing care; provide tips to make the operation manual easier to read and understand; establish mobile learning to make learning immediate and more accessible; hold instrument operation practice sessions to improve nursing staff proficiency; monitor and upload data to the hospital information system. RESULTS: After the improvement project, the accuracy of hemodynamic monitoring care increased to 98.7%. CONCLUSIONS: The impact achieved met expectations, and the improvement project will be extended to other intensive care units in the hospital. Our nurses are now more familiar with the operation methods and the significance of monitoring values and interpretation of data. Also, when a value changes or becomes abnormal, they immediately notify the doctor for further evaluation and interventions to improve patient safety.

Identification of selective dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) inhibitors and their effects on tau and microtubule.

The overexpression of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), commonly observed in neurodegenerative diseases like Alzheimer's disease (AD) and Down syndrome (DS), can induce the formation of neurofibrillary tangles (NFTs) and amyloid plaques. Hence, designing a selective DYRK1A inhibitor would result in a promising small molecule for treating neurodegenerative diseases. Developing selective inhibitors for DYRK1A has been a difficult challenge due to the highly preserved ATP-binding site of protein kinases. In this study, we employed a structure-based virtual screening (SBVS) campaign targeting DYRK1A from a database containing 1.6 million compounds. Enzymatic assays were utilized to verify inhibitory properties, confirming that Y020-3945 and Y020-3957 showed inhibitory activity towards DYRK1A. In particular, the compounds exhibited high selectivity for DYRK1A over a panel of 120 kinases, reduced the phosphorylation of tau, and reversed the tubulin polymerization for microtubule stability. Additionally, treatment with the compounds significantly reduced the secretion of inflammatory cytokines IL-6 and TNF-α activated by DYRK1A-assisted NFTs and Aß oligomers. These identified inhibitors possess promising therapeutic potential for conditions associated with DYRK1A in neurodegenerative diseases. The results showed that Y020-3945 and Y020-3957 demonstrated structural novelty compared to known DYRK1A inhibitors, making them a valuable addition to developing potential treatments for neurodegenerative diseases.

Effect of safety and security equipment on patient and visitor violence towards nurses in multiple public hospitals of China during the COVID-19 pandemic: a retrospective, difference-in-difference analysis.

OBJECTIVES: This study aimed to analyse whether safety and security equipment decreased patient and visitor violence (PVV) towards nurses in the COVID-19 period and quantify to what extent safety and security equipment affects PVV. DESIGN: Controlled before and after study and difference-in-difference (DID) analysis. SETTING: A large hospital medical group, consisting of three public tertiary teaching hospitals, namely, Xinjiekou Branch, Huilongguan Branch and Xinlongze Branch of Beijing Jishuitan Hospital, located in the west and north parts of Beijing, China. PARTICIPANTS: A panel of nine departments recruited using two-step sampling method, administered online surveys in 2021 and 2022. A total of 632 eligible nurses participated in the survey in 2021 and 725 eligible nurses in 2022. MEASURES: We assessed impacts of the safety and security equipment on the PVV. The policy had been enacted in June 2020, and the corresponding measures were established after mid-December 2020, and therefore, we use a DID design to evaluate changes in nurses' PVV incidence. Departments are classified as either department installed or non installed, and nurses are classified based on their department. RESULTS: Within the treatment group, the incidence of physical PVV significantly decreased from 13.8% in 2020 to 2.0% in 2021. In the control group, the incidence of physical PVV increased from 0.6% in 2020 to 2.7% in 2021. The application of the safety and security equipment decreased the incidence of physical PVV by 13.93% (95% CI: -23.52% to -4.34%). In contrast, no difference was observed between the treatment and control groups for the incidence of psychological PVV (6.23%, 95% CI: -11.56% to 24.02%) and overall PVV (0.88, 95% CI: -20.90% to 22.66%). CONCLUSION: The safety and security equipment reduced the incidence of physical PVV towards nurses. For hospital managers in public hospitals, longer-term strategies roadmap for PVV prevention measures are needed to create a more supportive work environment in employees.

Jin-Gui-Shen-Qi Wan alleviates fibrosis in mouse diabetic nephropathy via MHC class II.

ETHNOPHARMACOLOGICAL RELEVANCE: Jin-Gui-Shen-Qi Wan (JGSQW) is a traditional Chinese medicine formula that has been traditionally used to alleviate urinary system ailments such as frequent urination and polyuria. Clinical studies have indicated that when combined with hypoglycaemic drugs, JGSQW exhibits a synergistic effect and can improve diabetic nephropathy (DN), yet its underlying mechanism and targets remain unclear. AIM OF THE STUDY: This study aims to investigate the therapeutic efficacy of JGSQW and its underlying mechanisms using a DN db/db mouse model. MATERIALS AND METHODS: Ultrahigh-performance liquid chromatography coupled with mass spectrometry was utilized to analyse the primary active compounds, blood levels, and pharmacokinetics of JGSQW. Additionally, the therapeutic effects of JGSQW and metformin on blood glucose levels, lipid levels, renal function, and renal pathology in diabetic nephropathy mice were investigated using a db/db mouse model. Proteomic analysis was carried out to identify the primary target of JGSQW in treating DN. The mechanism of action was verified by western blotting, immunohistochemistry, and immunofluorescence. Then, molecular docking and molecular dynamics, transfection, drug affinity responsive target stability (DARTS) assay and cell thermal migration assay (CETSA) further validated the targeted binding effect. RESULTS: JGSQW combined with metformin significantly improved the blood glucose levels, blood lipids, renal function, and renal pathology of DN mice. JGSQW mainly exerted its therapeutic effect on DN by targeting major histocompatibility complex class II (MHC class II) molecules. Immunohistochemistry results showed that JGSQW inhibited the expression of collagen I, fibronectin, and alpha smooth muscle actin (α-SMA) expression. Immunofluorescence and Western blot results showed that JGSQW inhibited the expression of H2-Ab1 and H2-Aa, which are MHC class II molecules, thereby suppressing CD4+ T-cell infiltration and improving diabetic kidney fibrosis. The binding ability of paeoniflorin to H2-Aa was predicted and verified by molecular, DARTS, and CETSA assays. Treatment with 80 µM paeoniflorin effectively alleviated high glucose-induced injury in the MPC-5 injury model. H2-Aa was overexpressed at this model concentration, and Western blotting further confirmed that paeoniflorin reduced glomerular podocyte fibrosis by regulating H2-Aa. CONCLUSIONS: JGSQW combined with metformin may have a synergistic effect to alleviates renal fibrosis in diabetic nephropathy by downregulating immune complex MHC class II molecules and attenuating the antigen presentation effect of MHC class II on CD4.

Deep neural network with self-attention based automated determination system for treatment zone and peripheral steepened zone in Orthokeratology for adolescent myopia.

PURPOSE: The aim of this study is to develop an automatic model based on deep learning techniques for determining the Treatment Zone (TZ) and Peripheral Steepened Zone (PSZ) following Orthokeratology (OK) treatment. METHODS: A total of 1346 corneal topography maps were included in the study. A deep neural network based on the Segformer architecture was constructed to automatically detect TZ and PSZ. The model was optimized and trained multiple times, and the areas of TZ, PSZ, and TZ decentration were calculated based on the segmentation results. RESULTS: The mean Intersection over Union (mIoU) of the overall segmentation results of the model reached over 97% after multiple training with different optimization methods, and the IoU for the TZ and PSZ segmentation tasks were 98.08% and 94.54% in test set, respectively. Moreover, the model demonstrated high consistency with the expert annotation for the TZ segmentation, while a significant difference was found in the PSZ segmentation and expert annotation due to several interference factors. CONCLUSION: This study presents an efficient and repeatable system for clinical research, based on a deep neural network that accurately determines TZ and PSZ after OK treatment using the Segformer architecture. However, further deployment validation may be necessary.

Cell membrane-based biomimetic technology for cancer phototherapy: Mechanisms, recent advances and perspectives.

Despite significant advances in medical technology and antitumour treatments, the diagnosis and treatment of tumours have undergone remarkable transformations. Noninvasive phototherapy methods, such as photodynamic therapy (PDT) and photothermal therapy (PTT), have gained significant interest in antitumour medicine. However, traditional photosensitisers or photothermal agents face challenges like immune system recognition, rapid clearance from the bloodstream, limited tumour accumulation, and phototoxicity concerns. Researchers combine photosensitisers or photothermal agents with natural cell membranes to overcome these obstacles to create a nano biomimetic therapeutic platform. When used to coat nanoparticles, red blood cells, platelets, cancer cells, macrophages, lymphocytes, and bacterial outer membranes could provide prolonged circulation, tumour targeting, immune stimulation, or antigenicity. This article covers the principles of cellular membrane biomimetic nanotechnology and phototherapy, along with recent advancements in applying nano biomimetic technology to PDT, PTT, PCT, and combined diagnosis and treatment. Furthermore, the challenges and issues of using nano biomimetic nanoparticles in phototherapy are discussed. STATEMENT OF SIGNIFICANCE: Currently, there has been significant progress in the field of cell membrane biomimetic technology. Researchers are exploring its potential application in tumor diagnosis and treatment through phototherapy. Scholars have conducted extensive research on combining cell membrane technology and phototherapy in anticancer diagnosis and treatment. This review aims to highlight the mechanisms of phototherapy and the latest advancements in single phototherapy (PTT, PDT) and combination phototherapy (PCT, PRT, and PIT), as well as diagnostic approaches. The review provides an overview of various cell membrane technologies, including RBC membranes, platelet membranes, macrophage cell membranes, tumour cell membranes, bacterial membranes, hybrid membranes, and their potential for anticancer applications under phototherapy. Lastly, the review discusses the challenges and future directions in this field.

Pharmacokinetics and pharmacodynamic evaluation of hyaluronic acid-modified imatinib-loaded PEGylated liposomes in CD44-positive Gist882 tumor-bearing mice.

To develop a PEGylated and CD44-targeted liposomes, enabled by surface coating with hyaluronic acid (HA) via amide bond to improve the efficacy of imatinib mesylate (IM), for tumor-targeted cytoplasmic drug delivery. HA was covalently grafted on DSPE-PEG2000-NH2 polymer. HA-modified or unmodified PEGylated liposomes were prepared with ethanol injection method, and the stability, drug release, and cytotoxicity of these liposomes were studied. Meanwhile, intracellular drug delivery efficiency, antitumor efficacy, and pharmacokinetics were also investigated. Ex vivo fluorescence biodistribution was also detected by small animal imaging. In addition, endocytosis mechanism was also explored HA-coated PEGylated liposomes (137.5 nm ± 10.24) had a negative zeta potential (-29.3 mV ± 5.44) and high drug loading (27.8%, w/w). The liposomes were stable with cumulative drug leakage (<60%) under physiological conditions. Blank liposomes were nontoxic to Gist882 cells, and IM-loaded liposomes had higher cytotoxicity to Gist882 cells. HA-modified PEGylated liposomes were internalized more effectively than non-HA coating via CD44-mediated endocytosis. Besides, the cellular uptake of HA-modified liposomes also partly depends on caveolin-medicated endocytosis and micropinocytosis. In rats, both liposomes produced a prolonged half-life of IM (HA/Lp/IM: 14.97h; Lp/IM: 11.15h) by 3- to 4.5-folds compared with the IM solution (3.61h). HA-decorated PEGylated liposomes encapsulated IM exhibited strong inhibitory effect on tumor growth in Gist882 cell-bearing nude mice and formation of 2D/3D tumor spheroids. The Ki67 immunohistochemistry result was consistent with the above results. IM-loaded PEGylated liposomes modified with HA exerted the excellent anti-tumor effect on tumor-bearing mice and more drugs accumulated into the tumor site.

The structure of cognitive strategies for wayfinding decisions.

Literature proposes five distinct cognitive strategies for wayfinding decisions at intersections. Our study investigates whether those strategies rely on a generalized decision-making process, on two frame-specific processes-one in an egocentric and the other in an allocentric spatial reference frame, and/or on five strategy-specific processes. Participants took six trips along a prescribed route through five virtual mazes, each designed for decision-making by a particular strategy. We found that wayfinding accuracy on trips through a given maze correlated significantly with the accuracy on trips through another maze that was designed for a different reference frame (rbetween-frames = 0.20). Correlations were not significantly higher if the other maze was designed for the same reference frame (rwithin-frames = 0.19). However, correlations between trips through the same maze were significantly higher than those between trips through different mazes that were designed for the same reference frame (rwithin-maze = 0.52). We conclude that wayfinding decisions were based on a generalized cognitive process, as well as on strategy-specific processes, while the role of frame-specific processes-if any-was relatively smaller. Thus, the well-established dichotomy of egocentric versus allocentric spatial representations did not translate into a similar, observable dichotomy of decision-making.

Arjunolic acid protects the intestinal epithelial barrier, ameliorating Crohn's disease-like colitis by restoring gut microbiota composition and inactivating TLR4 signalling.

BACKGROUND AND AIMS: Crohn's disease (CD) is characterized by an overabundance of epithelial cell death and an imbalance in microflora, both of which contribute to the dysfunction of the intestinal barrier. Arjunolic acid (AA) has anti-apoptotic effects and regulates microbiota efficacy. The objective of this study was to assess the impact of the treatment on colitis resembling Crohn's disease, along with exploring the potential underlying mechanism. METHODS: CD animal models were created using Il-10-/- mice, and the impact of AA on colitis in mice was evaluated through disease activity index, weight fluctuations, pathological examination, and assessment of intestinal barrier function. To clarify the direct role of AA on intestinal epithelial cell apoptosis, organoids were induced by LPS, and TUNEL staining was performed. To investigate the potential mechanisms of AA in protecting the intestinal barrier, various methods including bioinformatics analysis and FMT experiments were employed. RESULTS: The treatment for AA enhanced the condition of colitis and the function of the intestinal barrier in Il-10-/- mice. This was demonstrated by the amelioration of weight loss, reduction in tissue inflammation score, and improvement in intestinal permeability. Moreover, AA suppressed the apoptosis of intestinal epithelial cells in Il-10-/- mice and LPS-induced colon organoids, while also reducing the levels of Bax and C-caspase-3. In terms of mechanism, AA suppressed the activation of TLR4 signaling in Il-10-/- mice and colon organoids induced by LPS. In addition, AA increased the abundance of short-chain fatty acid-producing bacteria in the stool of Il-10-/- mice, and transplantation of feces from AA-treated mice improved CD-like colitis. CONCLUSIONS: The results of our study demonstrate that AA has a protective effect on the intestinal barrier in Crohn's disease-like colitis by preventing apoptosis. Additionally, this groundbreaking study reveals the capacity of AA to hinder TLR4 signaling and alter the makeup of the intestinal microbiome. The findings present fresh possibilities for treating individuals diagnosed with Crohn's disease. AA offers a hopeful novel strategy for managing Crohn's disease by obstructing crucial pathways implicated in intestinal inflammation and enhancing the gut microbiota.

Gold-Crowned Bismuth-Based Nanocomposites for Sonodynamic, Photothermal, and Chemotherapeutic Cancer Therapy.

Conventional inorganic semiconductor nanoparticles have emerged as photothermal agents in photothermal therapy and as sonosensitizers in sonodynamic therapy. However, their weak drug-loading capabilities and the deficient techniques for multifunctional inorganic nanoparticles limit their applications. A bismuth-based gold-crowned nanocomposite (BACN) was rationally designed and successfully synthesized and could then be used to prepare nanoplatforms with excellent biocompatibilities for synergistic therapy and real-time imaging. Because of the constituent gold nanoparticles and pyridine, the nanoplatforms functioned as drug delivery vehicles, ultrasonically activated sonosensitizers, and photothermal agents. The BACNs exhibited excellent photothermal conversion efficiency (79.1%) in the second near-infrared biowindow (1064 nm). Cellular and mouse experiments demonstrated that under laser and ultrasound irradiation bufalin-loaded BACNs significantly reduced cancer cell counts and completely eradicated tumors, along with great therapeutic biosafety and no discernible recurrence. Additionally, BACNs were also used as contrast agents in computed tomography-photoacoustic imaging. The versatile BACN nanoplatform with multitreatment effects and trimodal imaging properties shows immense potential as an antitumor nanotherapeutic system.

[Chemical constituents from whole herb of Hedyotis scandens].

This study aimed to investigate the chemical constituents in the water extract of the whole herb of Hedyotis scandens by silica gel, ODS, and MCI column chromatographies together with preparative high-performance liquid chromatography(HPLC). The structures of isolated constituents were identified by NMR, HR-ESI-MS, etc. Thirteen compounds were isolated and identified as methyl 4-benzoyloxy-3-methoxybenzeneacetate(1), 4-benzoyloxy-3-methoxybenzeneacetic acid(2), 3-(4-hydroxy-3-methoxyphenyl)-propanoic acid(3), salicylic acid(4), 3-hydroxy-4-methoxypyridine(5), syringic acid(6), hydroxycinnamic acid(7),(R)-6-methyl-4,6-bis(4-methylpent-3-enyl)cyclohexa-1,3-dienecarbaldehyde(8), 1,2-bis(4-hydroxy-3-methoxyphenyl)-1,3-propanediol(9), 1H-indole-3-carboxaldehyde(10), isoscopoletin(11), syringaresinol(12), and pinoresinol(13). Among them, compounds 1 and 2 were new phenolic acid compounds, compounds 3-5, 8-11, and 13 were isolated from this genus for the first time, and compounds 6, 7, and 12 were obtained from H. scandens for the first time. The activity test showed that compounds 1 and 10 had a certain inhibitory effect on Mycobacterium smegmatis, with MIC_(50) values of 58.5 and 33.3 µg·mL~(-1), respectively.

How Does Visual Temporal Processing Affect Chinese Character Reading in Children With Dyslexia? From the Perspective of Inhibition.

Given that inhibition interacts with visual temporal processing (VTP), the past evidence regarding the influence of VTP on the Chinese character reading of children with dyslexia may not disclose the whole picture without considering inhibition. Thus, the present study is among the first to investigate VTP and cognitive inhibition as well as their relationships to Chinese character reading. We compared the performances of 62 Chinese-speaking children with dyslexia in primary school (n = 62, Mage = 11.36 years) on VTP and inhibition tasks to those in a chronological-age-matched group (CA; n = 62, Mage = 11.57 years) and reading-level-matched group (RL; n = 62, Mage = 8.98 years). The results revealed that children with dyslexia performed worse than both the CA-matched and RL-matched groups in VTP and inhibition after controlling for age, nonverbal intelligence, and attention. Moreover, the relationship between VTP and Chinese character reading was moderated by inhibition in children with dyslexia. VTP is positively related to Chinese character reading, but this relationship is observed only at higher levels of inhibition. Our results suggest that inhibition plays a potential role in VTP and Chinese character reading, especially for those with dyslexia whose proficiency in inhibition is not as intact as that of typically developing children.