Nanomaterials-mediated lysosomal regulation: a robust protein-clearance approach for the treatment of Alzheimer's disease.

Alzheimer's disease is a debilitating, progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins, including amyloid plaques and intracellular tau tangles, primarily within the brain. Lysosomes, crucial intracellular organelles responsible for protein degradation, play a key role in maintaining cellular homeostasis. Some studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases, including Alzheimer's disease. Restoring the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer's disease. Currently, the efficacy of drugs in treating Alzheimer's disease is limited, with major challenges in drug delivery efficiency and targeting. Recently, nanomaterials have gained widespread use in Alzheimer's disease drug research owing to their favorable physical and chemical properties. This review aims to provide a comprehensive overview of recent advances in using nanomaterials (polymeric nanomaterials, nanoemulsions, and carbon-based nanomaterials) to enhance lysosomal function in treating Alzheimer's disease. This review also explores new concepts and potential therapeutic strategies for Alzheimer's disease through the integration of nanomaterials and modulation of lysosomal function. In conclusion, this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer's disease. The application of nanotechnology to the development of Alzheimer's disease drugs brings new ideas and approaches for future treatment of this disease.

Genome-wide association study for cashmere traits in Inner Mongolia cashmere goat population reveals new candidate genes and haplotypes.

BACKGROUND: The cashmere goat industry is one of the main pillars of animal husbandry in Inner Mongolia Autonomous Region, and plays an irreplaceable role in local economic development. With the change in feeding methods and environment, the cashmere produced by Inner Mongolia cashmere goats shows a tendency of coarser, and the cashmere yield can not meet the consumption demand of people. However, the genetic basis behind these changes is not fully understood. We measured cashmere traits, including cashmere yield (CY), cashmere diameter (CD), cashmere thickness (CT), and fleece length (FL) traits for four consecutive years, and utilized Genome-wide association study of four cashmere traits in Inner Mongolia cashmere goats was carried out using new genomics tools to infer genomic regions and functional loci associated with cashmere traits and to construct haplotypes that significantly affect cashmere traits. RESULTS: We estimated the genetic parameters of cashmere traits in Inner Mongolia cashmere goats. The heritability of cashmere yield, cashmere diameter, and fleece length traits of Inner Mongolia cashmere goats were 0.229, 0.359, and 0.250, which belonged to the medium heritability traits (0.2 ~ 0.4). The cashmere thickness trait has a low heritability of 0.053. We detected 151 genome-wide significantly associated SNPs with four cashmere traits on different chromosomes, which were very close to the chromosomes of 392 genes (located within the gene or within ± 500 kb). Notch3, BMPR1B, and CCNA2 have direct functional associations with fibroblasts and follicle stem cells, which play important roles in hair follicle growth and development. Based on GO functional annotation and KEGG enrichment analysis, potential candidate genes were associated with pathways of hair follicle genesis and development (Notch, P13K-Akt, TGF-beta, Cell cycle, Wnt, MAPK). We calculated the effective allele number of the Inner Mongolia cashmere goat population to be 1.109-1.998, the dominant genotypes of most SNPs were wild-type, the polymorphic information content of 57 SNPs were low polymorphism (0 < PIC < 0.25), and the polymorphic information content of 79 SNPs were moderate polymorphism (0.25 < PIC < 0.50). We analyzed the association of SNPs with phenotypes and found that the homozygous mutant type of SNP1 and SNP3 was associated with the highest cashmere yield, the heterozygous mutant type of SNP30 was associated with the lowest cashmere thickness, the wild type of SNP76, SNP77, SNP78, SNP80, and SNP81 was associated with the highest cashmere thickness, and the wild type type of SNP137 was associated with the highest fleece length. 21 haplotype blocks and 68 haplotype combinations were constructed. Haplotypes A2A2, B2B2, C2C2, and D4D4 were associated with increased cashmere yield, haplotypes E2E2, F1F1, G5G5, and G1G5 were associated with decreased cashmere fineness, haplotypes H2H2 was associated with increased cashmere thickness, haplotypes I1I1, I1I2, J1J4, L5L3, N3N2, N3N3, O2O1, P2P2, and Q3Q3 were associated with increased cashmere length. We verified the polymorphism of 8 SNPs by KASP, and found that chr7_g.102631194A > G, chr10_g.82715068 T > C, chr1_g.124483769C > T, chr24_g.12811352C > T, chr6_g.114111249A > G, and chr6_g.115606026 T > C were significantly genotyped in verified populations (P < 0.05). CONCLUSIONS: In conclusion, the genetic effect of single SNP on phenotypes is small, and SNPs are more inclined to be inherited as a whole. By constructing haplotypes from SNPs that are significantly associated with cashmere traits, it will help to reveal the complex and potential causal variations in cashmere traits of Inner Mongolia cashmere goats. This will be a valuable resource for genomics and breeding of the cashmere goat.

Correlates of oral pre-exposure prophylaxis cessation among men who have sex with men in China: implications from a nationally quantitative and qualitative study.

BACKGROUND: Several studies have demonstrated the population-level effectiveness of oral PrEP in reducing the risk of HIV infection. However, oral PrEP utilization among MSM in China remains below 1%. While existing literature has primarily focused on oral PrEP preference and willingness, there is limited exploration of the underlying factors contributing to oral PrEP cessation in China. This study aims to fill this gap by investigating the factors associated with oral PrEP cessation among MSM in China. METHODS: Assisted by MSM community organizations, we collected 6,535 electronic questionnaires from 31 regions across China, excluding Taiwan, Hong Kong, and Macau. The questionnaire focused on investigating MSM's awareness, willingness, usage, and cessation of oral PrEP. Additionally, 40 participants were randomly chosen for key informant interviews. These qualitative interviews aimed to explore the reasons influencing MSM discontinuing oral PrEP. RESULTS: We eventually enrolled 6535 participants. Among the 685 participants who had used oral PrEP, 19.70% (135/685) ceased oral PrEP. The results indicated that individuals spending > ¥1000 on a bottle of PrEP (aOR = 2.999, 95% CI: 1.886-4.771) were more likely to cease oral PrEP compared to those spending ≤ ¥1000. Conversely, individuals opting for on-demand PrEP (aOR = 0.307, 95% CI: 0.194-0.485) and those using both daily and on-demand PrEP (aOR = 0.114, 95% CI: 0.058-0.226) were less likely to cease PrEP compared to those using daily PrEP. The qualitative analysis uncovered eight themes influencing oral PrEP cessation: (i) High cost and low adherence; (ii) Sexual inactivity; (iii) Lack of knowledge about PrEP; (iv) Trust in current prevention strategies; (v) Poor quality of medical service and counseling; (vi) PrEP stigma; (vii) Partner and relationship factors; (viii) Access challenges. CONCLUSIONS: The cessation of oral PrEP among MSM in China is associated with various factors, including the cost of oral PrEP medication, regimens, individual perception of HIV risk, stigma, and the quality of medical services. It is recommended to provide appropriate regimens for eligible MSM and develop tailored combinations of strategies to enhance PrEP awareness and acceptance among individuals, medical staff, and the MSM community. The findings from this study can support the refinement of HIV interventions among MSM in China, contributing to efforts to reduce the burden of HIV in this population.

Breast lesions on MRI in mass and non-mass enhancement: Kaiser score and modified Kaiser score + for readers of variable experience.

OBJECTIVES: To compare the diagnostic performance of three readers using BI-RADS and Kaiser score (KS) based on mass and non-mass enhancement (NME) lesions. METHODS: A total of 630 lesions, 393 malignant and 237 benign, 458 mass and 172 NME, were analyzed. Three radiologists with 3 years, 6 years, and 13 years of experience made diagnoses. 596 cases had diffusion-weighted imaging, and the apparent diffusion coefficient (ADC) was measured. For lesions with ADC > 1.4 × 10-3 mm2/s, the KS was reduced by 4 as the modified KS +, and the benefit was assessed. RESULTS: When using BI-RADS, AUC was 0.878, 0.915, and 0.941 for mass, and 0.771, 0.838, 0.902 for NME for Reader-1, 2, and 3, respectively, better for mass than for NME. The diagnostic accuracy of KS was improved compared to BI-RADS for less experienced readers. For Reader-1, AUC was increased from 0.878 to 0.916 for mass (p = 0.005) and from 0.771 to 0.822 for NME (p = 0.124). Based on the cut-off value of BI-RADS ≥ 4B and KS ≥ 5 as malignant, the sensitivity of KS by Readers-1 and -2 was significantly higher for both Mass and NME. When ADC was considered to change to modified KS +, the AUC and the accuracy for all three readers were improved, showing higher specificity with slightly degraded sensitivity. CONCLUSION: The benefit of KS compared to BI-RADS was most noticeable for the less experienced readers in improving sensitivity. Compared to KS, KS + can improve specificity for all three readers. For NME, the KS and KS + criteria need to be further improved. CLINICAL RELEVANCE STATEMENT: KS provides an intuitive method for diagnosing lesions on breast MRI. BI-RADS and KS face greater difficulties in evaluating NME compared to mass lesions. Adding ADC to the KS can improve specificity with slightly degraded sensitivity. KEY POINTS: KS provides an intuitive method for interpreting breast lesions on MRI, most helpful for novice readers. KS, compared to BI-RADS, improved sensitivity in both mass and NME groups for less experienced readers. NME lesions were considered during the development of the KS flowchart, but may need to be better defined.

ReMAR: a preoperative CT angiography guided metal artifact reduction framework designed for follow-up CTA of endovascular coiling.

Objective. Follow-up computed tomography angiography (CTA) is necessary for ensuring occlusion effect of endovascular coiling. However, the implanted metal coil will introduce artifacts that have a negative spillover into radiologic assessment.Method. A framework named ReMAR is proposed in this paper for metal artifacts reduction (MARs) from follow-up CTA of patients with coiled aneurysms. It employs preoperative CTA to provide the prior knowledge of the aneurysm and the expected position of the coil as a guidance thus balances the metal artifacts removal performance and clinical feasibility. The ReMAR is composed of three modules: segmentation, registration and MAR module. The segmentation and registration modules obtain the metal coil knowledge via implementing aneurysms delineation on preoperative CTA and alignment of follow-up CTA. The MAR module consisting of hybrid convolutional neural network- and transformer- architectures is utilized to restore sinogram and remove the artifact from reconstructed image. Both image quality and vessel rendering effect after metal artifacts removal are assessed in order to responding clinical concerns.Main results. A total of 137 patients undergone endovascular coiling have been enrolled in the study: 13 of them have complete diagnosis/follow-up records for end-to-end validation, while the rest lacked of follow-up records are used for model training. Quantitative metrics show ReMAR significantly reduced the metal-artifact burden in follow-up CTA. Qualitative ranks show ReMAR could preserve the morphology of blood vessels during artifact removal as desired by doctors.Significance. The ReMAR could significantly remove the artifacts caused by implanted metal coil in the follow-up CTA. It can be used to enhance the overall image quality and convince CTA an alternative to invasive follow-up in treated intracranial aneurysm.

A comparative study of acupuncture combined with rehabilitation gymnastics on postoperative anal function of lower rectal cancer.

BACKGROUND: From the anal function, inflammatory response and other indicators, acupuncture combined with rehabilitation gymnastics was applied to patients with cancer undergoing low resection, aiming to improve the prognosis of patients. AIM: To explore the effects of acupuncture combined with rehabilitation gymnastics on anal function after lower rectal cancer surgery. METHODS: From January 2020 to December 2022, 128 patients who underwent rectal cancer surgery in the Department of Oncology of Hebei Provincial Hospital of Traditional Chinese Medicine Hospital were selected and divided into two groups using the random number table method, with 64 patients in each group. Patients in the control group were not treated with acupuncture or rehabilitation gymnastics and served as blank controls. Patients in the study group were treated with acupuncture and rehabilitation gymnastics from the 7th postoperative day. The anal incontinence scores, changes in serum interleukin-4, interleukin-6, and interleukin-10 Levels, and serum motilin, 5-hydroxytryptamine, and vasoactive intestinal peptide levels were compared. RESULTS: There were no significant differences in serum interleukin-4, interleukin-6, and interleukin-10 Levels between the groups before treatment (P > 0.05). After treatment, these levels were better than those of the control group (P < 0.05). There was no significant difference in the anal incontinence scores between the groups before and 7 d after surgery (P > 0.05). Anal incontinence scores in the study group were lower than those in the control group at 14 d, 21 d, and 28 d postoperatively (P < 0.05). There were no significant differences in serum motilin, 5-hydroxytryptamine, or vasoactive intestinal peptide levels between the groups before treatment (P > 0.05). After treatment, these levels were higher in the study group than in the control group, and vasoactive intestinal peptide level was lower in the study group than in the control group (P < 0.05). CONCLUSION: Acupuncture combined with rehabilitation gymnastics can promote the recovery of anal function and reduce the inflammatory response in patients with lower rectal cancer after surgery.

Evaluating the clinical application and effect of acupuncture therapy in anal function rehabilitation after low-tension rectal cancer surgery.

BACKGROUND: According to the indexes of serum and anal function, acupuncture therapy was applied to patients with low rectal cancer in order to avoid the occurrence of anal incontinence and reduce complications. AIM: To explore the clinical application and evaluate the effect of acupuncture therapy for anal function rehabilitation after low-tension rectal cancer surgery. METHODS: From the anorectal surgery cases, we selected 120 patients who underwent colorectal cancer surgery between January 2020 and December 2022 and randomly divided them into a control group (n = 60), observation group (n = 60), and control group after surgery for lifestyle intervention (including smoking cessation and exercise), dietary factor adjustment, anal movement, and oral loperamide treatment. The serum levels of motilin, 5-hydroxytryptamine, and vasoactive intestinal peptide (VIP), Wexner score for anal incontinence, and incidence of complications were compared between groups. RESULTS: After treatment, the VIP and 5-hydroxytryptamine levels in the observation group were lower than those in the control group (P < 0.05). The motilin level was higher than that in the control group (P < 0.05). Postoperative anal incontinence was better in the observation group than in the control group (P < 0.05). The incidence of complications in the observation group was 6.67%, which was significantly lower than that in the control group (21.67%; P < 0.05). CONCLUSION: Acupuncture therapy has a positive effect on the rehabilitation of anal function after low-tension rectal cancer surgery; it can effectively help to improve the serum indices of patients, avoid the occurrence of anal incontinence, and reduce the incidence of complications. Popularizing and applying it will be valuable.

Spatial accumulation of lignin monomers and cellulose underlying stalk strength in maize.

Lodging largely affects yield, quality and mechanical harvesting of maize. Stalk strength is one of the major factors that affect maize lodging. Although plant cell wall components including lignin and cellulose were known to be associated with stalk strength and lodging resistance, spatial accumulation of specific lignin monomers and cellulose in different tissues and their association with stalk strength in maize was not clearly understood. In this study, we found that both G and S lignin monomers accumulate highest in root, stem rind and leaf vein. Consistently, most lignin biosynthetic genes were expressed higher in root and stem than in other tissues. However, cellulose appears to be lowest in root. There are only mild changes of G lignin and cellulose in different internodes. Instead, we noticed a dramatic decrease of S-lignin accumulation and lignin biosynthetic gene expression in 2nd to 4th internodes wherein stem breakage usually occurs, thereby revealing a few candidate lignin biosynthetic genes associated with stalk strength. Moreover, stalk strength is positively correlated with G, S lignin, and cellulose, but negatively correlated with S/G ratio based on data of maize lines with high or low stalk strength. Loss-of-function of a caffeic acid o-methyltransferase (COMT), which is involved in S lignin biosynthesis, in the maize bm3 mutant, leads to lower stalk strength. Our data collectively suggest that stalk strength is determined by tissue-specific accumulation of lignin monomers and cellulose, and manipulation of the cell wall components by genetic engineering is vital to improve maize stalk strength and lodging resistance.

Measurable residual disease testing by next generation sequencing is more accurate compared with multiparameter flow cytometry in adults with B-cell acute lymphoblastic leukemia.

Results of measurable residual disease (MRD)-testing by next-generation sequencing (NGS) correlate with relapse risk in adults with B-cell acute lymphoblastic leukemia (ALL) receiving chemotherapy or an allotransplant from a human leukocyte antigen (HLA)-identical relative or HLA-matched unrelated donor. We studied cumulative incidence of relapse (CIR) and survival prediction accuracy using a NGS-based MRD-assay targeting immunoglobulin genes after 2 courses of consolidation chemotherapy cycles in 93 adults with B-cell ALL most receiving HLA-haplotype-matched related transplants. Prediction accuracy was compared with MRD-testing using multi-parameter flow cytometry (MPFC). NGS-based MRD-testing detected residual leukemia in 28 of 65 subjects with a negative MPFC-based MRD-test. In Cox regression multi-variable analyses subjects with a positive NGS-based MRD-test had a higher 3-year CIR (Hazard Ratio [HR] = 3.37; 95 % Confidence Interval [CI], 1.34-8.5; P = 0.01) and worse survival (HR = 4.87 [1.53-15.53]; P = 0.007). Some data suggest a lower CIR and better survival in NGS-MRD-test-positive transplant recipients but allocation to transplant was not random. Our data indicate MRD-testing by NGS is more accurate compared with testing by MPFC in adults with B-cell ALL in predicting CIR and survival. (Registered in the Beijing Municipal Health Bureau Registration N 2007-1007 and in the Chinese Clinical Trial Registry [ChiCTR-OCH-10000940 and ChiCTROPC-14005546]).

LPS-induced senescence of macrophages aggravates calcification and senescence of vascular smooth muscle cells via IFITM3.

BACKGROUND: Cellular senescence, macrophages infiltration, and vascular smooth muscle cells (VSMCs) osteogenic transdifferentiation participate in the pathophysiology of vascular calcification in chronic kidney disease (CKD). Senescent macrophages are involved in the regulation of inflammation in pathological diseases. In addition, senescent cells spread senescence to neighboring cells via Interferon-induced transmembrane protein3 (IFITM3). However, the role of senescent macrophages and IFITM3 in VSMCs calcification remains unexplored. AIMS: To explore the hypothesis that senescent macrophages contribute to the calcification and senescence of VSMCs via IFITM3. METHODS: Here, the macrophage senescence model was established using Lipopolysaccharides (LPS). The VSMCs were subjected to supernatants from macrophages (MCFS) or LPS-induced macrophages (LPS-MCFS) in the presence or absence of calcifying media (CM). Senescence-associated ß-galactosidase (SA-ß-gal), Alizarin red (AR), immunofluorescent staining, and western blot were used to identify cell senescence and calcification. RESULTS: The expression of IFITM3 was significantly increased in LPS-induced macrophages and the supernatants. The VSMCs transdifferentiated into osteogenic phenotype, expressing higher osteogenic differentiation markers (RUNX2) and lower VSMCs constructive makers (SM22α) when cultured with senescent macrophages supernatants. Also, senescence markers (p16 and p21) in VSMCs were significantly increased by senescent macrophages supernatants treated. However, IFITM3 knockdown inhibited this process. CONCLUSIONS: Our study showed that LPS-induced senescence of macrophages accelerated the calcification of VSMCs via IFITM3. These data provide a new perspective linking VC and aging, which may provide clues for diagnosing and treating accelerated vascular aging in patients with CKD.

Relationship between social participation and depressive symptoms in patients with multimorbidity: the chained mediating role of cognitive function and activities of daily living.

OBJECTIVE: The potential mechanisms linking social participation and depressive symptoms in Chinese individuals with multimorbidity are not yet fully understood. This study aims to explore how cognitive function and activities of daily living (ADLs) mediate the relationship between social participation and depressive symptoms in individuals with multimorbidity. METHODS: We selected 3782 participants with multimorbidity from the 2018 China Health and Retirement Longitudinal Study. Data related to social participation, cognitive function, ADLs, and depressive symptoms were extracted. Regression and Bootstrap analyses were used to explore the sequential mediating effects of social participation, cognitive function, ADLs, and depressive symptoms. RESULTS: (1) There was a significant correlation between social participation, cognitive function, activities of daily living, and depressive symptoms (p < 0.01). (2) Social participation directly affected depressive symptoms (ß = -0.205, p < 0.05). (3) Cognitive function (ß = -0.070, p < 0.01) and activities of daily living (ß = -0.058, p < 0.01) played separate mediating roles in the effect of social participation on depressive symptoms. (4) Cognitive function and activities of daily living had a chain-mediated role in the relationship between social participation and depressive symptoms in patients with multimorbidity (ß = -0.020, p < 0.01). CONCLUSION: A chained mediating effect was found between cognitive function, ADLs, social participation, and depressive symptoms in patients with multimorbidity. Social participation was found to improve the cognitive function of patients with multimorbidity, which in turn enhanced their daily life activities and ultimately alleviated their depressive symptoms.

Metal-Organic Framework-Induced Rh Monocoodination on Diphosphine Ligand Enables Catalytic Hydroformylation of Aliphatic Olefins at Room Temperature and Pressure.

Persistent challenges in hydroformylation of olefins include controlling regioselectivity, particularly for short aliphatic olefins and conducting reactions under ambient conditions.  We report here the synthesis of monophosphine-Rh complexes on a typical chelated diphosphine ligand mediated by a Zr-MOF through isolating a pair of phosphorus atoms. We demonstrate that single-crystal X-ray diffraction can elucidate the structural transformation of the Rh catalyst during olefin hydroformylation, providing valuable information on active site reconstruction during catalysis. The Rh-MOF catalyst demonstrates excellent catalytic and recyclable performance in the hydroformylation of short aliphatic olefins with linear to branched ratios of up to 99:1. Due to the framework's capacity to adsorb and concentrate gases, the catalytic reactions occur under room temperature and pressure, eliminating the need for the high temperature and pressures typically required in homogeneous systems. This study show that Zr-MOF can be a unique platform for synthesizing unusual catalytic species that cannot exist in solutions for meaningful chemical transformations and elucidate valuable structural information pertaining to metal-based catalysis.

Determination of 16 ultraviolet-absorbing compounds in marine invertebrates by using LC-USI-MS/MS coupled with QuEChERS.

In this study, we examined multiple endocrine-disrupting ultraviolet-absorbing compounds (UVACs) in marine invertebrates used in personal care products and packaging. Modified QuEChERS and liquid chromatography UniSpray ionization tandem mass spectrometry were used to identify 16 UVACs in marine invertebrates. Matrix-matched calibration curves revealed high linearity (r ≥ 0.9929), with limits of detection and quantification of 0.006-1.000 and 0.020-3.000 ng/g w.w., respectively. In oysters, intraday and interday analyses revealed acceptable accuracy (93%-120%) and precision (≤18%), except for benzophenone (BP) and ethylhexyl 4-(dimethylamino) benzoate. Analysis of 100 marine invertebrate samples revealed detection frequencies of 100%, 98%, 89%, 64%, and 100% for BP, 4-hydroxybenzophenone, 4-methylbenzophenone, 4-methylbenzylidene camphor, and benzophenone-3 (BP-3), respectively. BP and BP-3 were detected at concentrations of 4.40-27.39 and < 0.020-0.560 ng/g w.w., respectively, indicating their widespread presence. Overall, our proposed method successfully detected UVACs in marine invertebrates, raising concerns regarding their potential environmental and health effects.

Modular Synthesis of High Performance Energetic Biocidal Bicyclic Compounds Derivated from Iodopyrazoles.

Modular synthesis can combine different functional module to flexibly regulate comprehensive properties and study the diversity of compounds. This study established a modular bicyclic synthesis strategy of combining polynitro energetic module with iodine-containing biocidal module. Compounds 1-6 with high iodine content (48.72-69.56%) and high thermal stability (Td: 172-304 ˚C) were synthesized and exhaustively identified. By modular synthesis, the detonation properties and gas-production of 3-6 improved greatly expanding their biocidal efficacy and maintained the iodine atomic utilization of iodine-containing module. Notably, 4,5-diiodo-3,4',5'-trinitro-1,3'-bipyrazole (5) and 3,5-diiodo-4,4',5'-trinitro-1,3'-bipyrazole (6) exhibit high detonation velocities (D: 5903 m s-1, 5769 m s-1, respectively) and highest gas production of 212.85 L mol-1 and 217.66 L mol-1 after decomposition. This study diversifies polyiodio-nitro compounds, and also inspire the implementation of similar synthesis strategies to provide family-level synthetic solutions to energetic biocidal materials.

Metal-Doping Strategy for Carbon-Based Sonosensitizer in Sonodynamic Therapy of Glioblastoma.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor and known for its challenging prognosis. Sonodynamic therapy (SDT) is an innovative therapeutic approach that shows promise in tumor elimination by activating sonosensitizers with low-intensity ultrasound. In this study, a novel sonosensitizer is synthesized using Cu-doped carbon dots (Cu-CDs) for the sonodynamic treatment of GBM. Doping with copper transforms the carbon dots into a p-n type semiconductor having a bandgap of 1.58 eV, a prolonged lifespan of 10.7 µs, and an improved electron- and hole-separation efficiency. The sonodynamic effect is efficiency enhanced. Western blot analysis reveals that the Cu-CDs induces a biological response leading to cell death, termed as cuproptosis. Specifically, Cu-CDs upregulate dihydrosulfanyl transacetylase expression, thereby establishing a synergistic therapeutic effect against tumor cell death when combined with SDT. Furthermore, Cu-CDs exhibit excellent permeability through the blood-brain barrier and potent anti-tumor activity. Importantly, the Cu-CDs effectively impede the growth of glioblastoma tumors and prolong the survival of mice bearing these tumors. This study provides support for the application of carbon-based nanomaterials as sonosensitizers in tumor therapy.

IL-18BP Therapy Ameliorates Reproductive and Metabolic Phenotypes in a PCOS Mouse Model by Relieving Inflammation, Fibrosis and Endoplasmic Reticulum Stress.

There is a chronic inflammation in PCOS patients, which is correlated with the pathogenesis of PCOS. IL-18 and IL-18BP are related with some inflammatory diseases, while less explored in PCOS. Whether IL-18BP could be a potential drug of PCOS remains unknown.IL-18 and testosterone levels were evaluated in serum of 10 non-PCOS control patients and 20 PCOS patients. Female C57/BL6 mice were gavaged with letrozole to induce PCOS mouse model and IL-18 level was evaluated in the serum of PCOS mouse model, and IL-18 is intraperitoneally injected in female mice, IL-18BP is intraperitoneally injected in the PCOS mice models. Then the body weights, estrous cycles, reproductive hormones and morphology of ovaries were analyzed. The level of ovarian chronic inflammation, fibrosis and endoplasmic reticulum (ER) stress are evaluated.IL-18 levels are increased in the serum of PCOS patients and PCOS mice models respectively. The serum DHEAS, iWAT weight and adipocyte size were increased in IL-18 group compared to the control group (P < 0.05). In the PCOS mouse model treated with IL-18BP, the body weight and serum LH/FSH ratio was decreased compared to the PCOS group (P < 0.05). The expression levels of inflammatory factors and fibrosis-related genes, the expression level of endoplasmic reticulum stress-related genes, and the ROS positive area of ovarian tissue was decreased (P < 0.05).IL-18 is involved in inducing PCOS phenotypes, while IL-18BP relieves PCOS phenotypes by alleviating ovarian chronic inflammation, fibrosis and ER stress in PCOS mice.

Dihydroartemisinin inhibits follicular helper T and B cells: implications for systemic lupus erythematosus treatment.

Systemic lupus erythematosus (SLE) is a common autoimmune disease, and its pathogenesis mainly involves the aberrant activation of B cells through follicular helper T (Tfh) cells to produce pathogenic antibodies, which requires more effective and safe treatment methods. Dihydroartemisinin (DHA) is the main active ingredient of artemisinin and has immunosuppressive effects. In this study, in vitro experiments confirmed that DHA inhibited Tfh cell induction and weakened its auxiliary function in B cell differentiation; furthermore, DHA directly inhibited B cell activation, differentiation, and antibody production. Furthermore, a mouse model of SLE was established, and we confirmed that DHA significantly reduced the symptoms of SLE and lupus nephritis, and decreased serum immunoglobulin (Ig)G, IgM, IgA, and anti-dsDNA levels. Moreover, DHA reduced the frequencies of total Tfh cells, activated Tfh cells, and B cell lymphoma 6, and interleukin (IL)-21 levels in Tfh cells from the spleen and lymph nodes, as well as the levels of B cells, germinal center B cells, and plasma cells in the spleen, lymph nodes, and kidneys. Additionally, DHA inhibited Tfh cells by blocking IL-2-inducible T cell kinase (ITK) signaling and its downstream nuclear factor (NF)-κB, nuclear factor of activated T cell, and activating protein-1 pathways, and directly inhibited B cells by blocking Bruton's tyrosine kinase (BTK) signaling and the downstream NF-κB and Myc pathways. Overall, our results demonstrated that DHA inhibited Tfh cells by blocking ITK signaling and also directly inhibited B cells by blocking BTK signaling. Therefore, reducing the production of pathogenic antibodies might effectively treat SLE.

[Corrigendum] P2Y2 receptor promotes the migration and invasion of breast cancer cells via EMT­related genes Snail and E­cadherin.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that there appeared to be two instances of overlapping data panels comparing between the cell migration and invasion assay data shown in Figs. 4 and 6 on p. 143 and 145, respectively, such that data which were intended to represent the results from differently performed experiments had apparently been derived from the same original sources. In addition, the authors themselves realized that incorrect western blotting data for Snail protein in Fig. 10A on p. 147 had been included in the figure.  The authors were able to re­examine their original data files, and realized that the affected data panels in these figures had inadvertently been incorporated into them incorrectly. The revised versions of Figs. 4, 6, and 10, featuring the correct data for the 'NC / Control' panels in Fig. 4B and C and the 'siRNA2 / ATP 12 h' panels in Fig. 4A and B, a replacement data panel for the 'siRNA1 / Control' experiment in Fig. 6, and the correct western blotting data for Snail protein in Fig. 10A (together with a revised histogram for the MCF7 cell line relating to Fig. 10A) are shown on the next three pages. The authors wish to emphasize that the errors made in compiling these figures did not affect the overall conclusions reported in the paper, and they are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this corrigendum. All the authors agree to the publication of this corrigendum, and also apologize to the readership for any inconvenience caused. [Oncology Reports 39: 138­150, 2018; DOI: 10.3892/or.2017.6081].

A review of CDKL: An underestimated protein kinase family.

Cyclin-dependent kinase-like (CDKL) family proteins are serine/threonine protein kinases and is a specific branch of CMGC (including CDK, MAPK, GSK). Its name is due to the sequence similarity with CDK and it consists of 5 members. Their function in protein phosphorylation underpins their important role in cellular activities, including cell cycle, apoptosis, autophagy and microtubule dynamics. CDKL proteins have been demonstrated to regulate the length of primary cilium, which is a dynamic and diverse signaling hub and closely associated with multiple diseases. Furthermore, CDKL proteins have been shown to be involved in the development and progression of several diseases, including cancer, neurodegenerative diseases and kidney disease. In this review, we summarize the structural characteristics and discovered functions of CDKL proteins and their role in diseases, which might be helpful for the development of innovative therapeutic strategies for disease.

Effect of altrenogest treatment before weaning on reproductive performance and production efficiency in primiparous and multiparous sows.

BACKGROUND: Most sows will experience negative energy balance during lactation resulting in impaired follicular development. This study aimed to treat 28-day lactating sows with altrenogest (ALT) to suppress follicle enlargement during lactation, and to assess the estrus and reproductive performance post-weaning. METHODS: In this study, we conducted two trials. In trial 1, we monitored the follicular development of lactating sows including 10 primiparous sows and 10 multiparous sows during the whole lactation to confirm the ALT administration time. In trial 2, a total of 42 primiparous and 111 multiparous sows were allocated to three treatments: Ctrl (control group, n = 51): no treatment; TAI (timed artificial insemination group, n = 51): sows were injected with equine chorionic gonadotropin (eCG) after weaning 24 h and gonadotropin-releasing hormone (GnRH) when they expressed estrus; and AT-TAI (ALT treatment-timed artificial insemination group, n = 51): base on the process of TAI group, the sows were fed with 20 mg ALT per day before weaning 10 days. All sows were artificially inseminated twice at 12 h and 36 h after estrus. The follicle size changes and serum hormone levels were explored in this process. RESULTS: Although the follicle size of multiparous sows was larger than primiparous sows during the whole lactation (P < 0.05), similar change trends of follicle size were observed in primiparous and multiparous sows. Meanwhile, the FSH, LH and E2 levels of multiparous sows were higher than primiparous sows. The ALT treatment significantly inhibits the increase in follicle size (P < 0.05) and reduces the serum levels of FSH, LH and E2 (P > 0.05). Additionally, ALT treatment increases estrus concentration and the preovulatory follicle size (P < 0.05), meanwhile, it delays the weaning-to-estrus interval (WEI, P < 0.001). However, the estrus rate, pregnancy rate, total pigs born and born alive did not differ between treatments (P > 0.05). CONCLUSIONS: There were significant differences in the size of follicles in the lactation between primiparous and multiparous sows. ALT treatment during the last ten days of lactation concentrated estrus expression leading to higher work efficiency of breeder in batch production, however, with no improvement in reproductive performance.