Cerebellar Mutism Syndrome and Dentato-Thalamo-Cortical Tract Disruption in Diffusion Tractography Following Surgery for Medulloblastoma.

Background Cerebellar mutism syndrome (CMS), a complication following medulloblastoma surgery, has been linked to dentato-thalamo-cortical tract (DTCT) injury; the association of the degree of DTCT injury with severity of CMS-related symptoms has not been investigated. Purpose To investigate the association between severity of CMS-related symptoms and degree and patterns of DTCT injury with use of diffusion tensor imaging (DTI), and if laterality of injury influences neurologic symptoms. Materials and Methods This retrospective case-control study used prospectively collected clinical and DTI data on patients with medulloblastoma enrolled in a clinical trial (between July 2016 and February 2020) and healthy controls (between April and November 2017), matched with the age range of the participants with medulloblastoma. CMS was divided into types 1 (CMS1) and 2 (CMS2). Multivariable logistic regression was used to investigate the relationship between CMS likelihood and DTCT injury. Results Overall, 82 participants with medulloblastoma (mean age, 11.0 years ± 5.2 [SD]; 53 male) and 35 healthy controls (mean age, 18.0 years ± 3.06; 18 female) were included. In participants with medulloblastoma, DTCT was absent bilaterally (AB), absent on the right side (AR), absent on the left side (AL), or present bilaterally (PB), while it was PB in all healthy controls. Odds of having CMS were associated with higher degree of DTCT damage (AB, odds ratio = 272.7 [95% CI: 269.68, 275.75; P < .001]; AR, odds ratio = 14.40 [95% CI: 2.84, 101.48; P < .001]; and AL, odds ratio = 8.55 [95% CI: 1.15, 74.14; P < .001). Left (coefficient = -0.07, χ2 = 12.4, P < .001) and right (coefficient = -0.15, χ2 = 33.82, P < .001) DTCT volumes were negatively associated with the odds of CMS. More participants with medulloblastoma with AB showed CMS1; unilateral DTCT absence prevailed in CMS2. Lower DTCT volumes correlated with more severe ataxia. Unilateral DTCT injury caused ipsilateral dysmetria; AB caused symmetric dysmetria. PB indicated better neurologic outcome. Conclusion The severity of CMS-associated mutism, ataxia, and dysmetria was associated with DTCT damage severity. DTCT damage patterns differed between CMS1 and CMS2. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Dorigatti Soldatelli and Ertl-Wagner in this issue.

pH-Triggered Transformable Peptide Nanocarriers Extend Drug Retention for Breast Cancer Combination Therapy.

Increasing the penetration and accumulation of antitumor drugs at the tumor site are crucial in chemotherapy. Smaller drug-loaded nanoparticles (NPs) typically exhibit increased tumor penetration and more effective permeation through the nuclear membrane, whereas larger drug-loaded NPs show extended retention at the tumor site. In addition, cancer stem cells (CSCs) have unlimited proliferative potential and are crucial for the onset, progression, and metastasis of cancer. Therefore, a drug-loaded amphiphilic peptide, DDP- and ATRA-loaded Pep1 (DA/Pep1), is designed that self-assembles into spherical NPs upon the encapsulation of cis-diamminedichloroplatinum (DDP) and all-trans retinoic acid (ATRA). In an acidic environment, DA/Pep1 transforms into aggregates containing sheet-like structures, which significantly increases drug accumulation at the tumor site, thereby increasing antitumor effects and inhibiting metastasis. Moreover, although DDP treatment can increase the number of CSCs present, ATRA can induce the differentiation of CSCs in breast cancer to increase the therapeutic effect of DDP. In conclusion, this peptide nanodelivery system that transforms in response to the acidic tumor microenvironment is an extremely promising nanoplatform that suggests a new idea for the combined treatment of tumors.

Targeted drug-loaded peptides induce tumor cell apoptosis and immunomodulation to increase antitumor efficacy.

Immunotherapy is an emerging approach for the treatment of solid tumors. Although chemotherapy is generally considered immunosuppressive, specific chemotherapeutic agents can induce tumor immunity. In this study, we developed a targeted, acid-sensitive peptide nanoparticle (DT/Pep1) to deliver doxorubicin (DOX) and triptolide (TPL) to breast cancer cells via the enhanced permeability and retention (EPR) effect and the breast cancer-targeting effect of peptide D8. Compared with administration of the free drugs, treatment with the DT/Pep1 system increased the accumulation of DOX and TPL at the tumor site and achieved deeper penetration into the tumor tissue. In an acidic environment, DT/Pep1 transformed from spherical nanoparticles to aggregates with a high aspect ratio, which successfully extended the retention of the drugs in the tumor cells and bolstered the anticancer effect. In both in vivo and in vitro experiments, DT/Pep1 effectively blocked the cell cycle and induced apoptosis. Importantly, the DT/Pep1 system efficiently suppressed tumor development in mice bearing 4T1 tumors while simultaneously promoting immune system activation. Thus, the results of this study provide a system for breast cancer therapy and offer a novel and promising platform for peptide nanocarrier-based drug delivery.

Aflibercept for long-term treatment of diabetic macular edema and proliferative diabetic retinopathy: a meta-analysis.

Purpose: This meta-analysis compared the long-term (12 months or 24 months) efficacy and safety of intravitreal aflibercept injection (IAI) for diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). Methods: We selected 16 randomized controlled trials (RCTs) performed after 2015 that had a minimum of 12 months and up to 24 months of treatment and conducted a meta-analysis with Review Manager version 5.3. Visual acuity (VA), central subfield thickness (CST) and adverse events were the outcomes selected for evaluation from the eligible studies. Results: Based on 16 RCTs, we evaluated a total of 7125 patients. For PDR and severe DME with poor baseline vision, after a minimum of 12 months and up to 24 months of treatment, the aflibercept treatment group obtained better VA improvement than the focal/grid laser photocoagulation treatment group (MD=13.30; 95%CI: 13.01~13.58; P<0.001) or other treatments (ranibizumab, focal/grid laser photocoagulation, PRP, et al.) group (MD=1.10; 95%CI: 1.05~1.16; P<0.001). In addition, the aflibercept treatment group got higher CST reduction than the focal/grid laser photocoagulation treatment (MD=-33.76; 95%CI: -45.53 ~ -21.99; P<0.001) or other treatments (ranibizumab, focal/grid laser photocoagulation, et al.) group (MD=-33.76; 95%CI: -45.53 ~ -21.99; P<0.001). There was no significant difference in the overall incidence of ocular and non-ocular adverse events in each treatment group. Conclusions: This meta-analysis showed that the advantages of IAI are obvious in the management of DME and PDR with poor baseline vision for long-term observation (a minimum of 12 months and up to 24 months) with both VA improvement and CST reduction. Applied IAI separately trended to be more effective than panretinal photocoagulation separately in VA improvement for PDR. More parameters should be required to assess functional and anatomic outcomes.

Recent progress in nanocarrier-based drug delivery systems for antitumour metastasis.

Tumour metastasis is one of the major factors leading to poor prognosis as well as lower survival among cancer patients. A number of studies investigating the inhibition of tumour metastasis have been conducted. It is difficult to achieve satisfactory results with surgery alone for distant metastatic tumours, and chemotherapy can boost the healing rate and prognosis of patients. However, the poor therapeutic efficacy of chemotherapy drugs due to their low solubility, lack of tumour targeting, instability in vivo, high toxicity and multidrug resistance hinder their application. Immunotherapy is beneficial to the treatment of metastatic cancers, but it also has disadvantages such as adverse reactions and acquired resistance. Fortunately, delivery of chemotherapeutic drugs with nanocarriers can reduce systemic reactions caused by chemotherapeutic agents and inhibit metastasis. This review discusses the underlying mechanisms of metastasis, therapeutic approaches for antitumour metastasis, the advantages of nanodrug delivery systems and their application in reducing metastasis.

Identification, quantitation and organoleptic contributions of furan compounds in brandy.

Furan compounds actively contribute to the characteristics of brandy. Herein, we have attempted to identify and quantify the furan compounds present in brandy using three different extraction methods combined with comprehensive two-dimensional gas chromatography and time-of-flight mass spectrometry. Threshold determination and omission experiments were carried out to verify their organoleptic contribution. Liquid-liquid extraction using dichloromethane was found to be the optimal extraction method. A total of 21 furan compounds were identified, in which 5 were detected in brandy for the first time. Our quantitative results showed a positive correlation between the furan compound content and the aging time. Among them, ethyl 5-oxotetrahydro-2-furancarboxylate exhibited a very high odor activity value (1.64 < OAV < 179.53) and smoky aroma. Omission tests showed that the three furan compounds with an OAV > 1 made a significant difference to brandy. These findings bring a new perspective to the sensory and chemical characteristics of brandy.

Working memory and school readiness in preschool children with sickle cell disease compared to demographically matched controls.

Children diagnosed with sickle cell disease (SCD) are at risk of the development of neurobehavioural problems early in life. Specific impairments in executive function skills, including working memory, have been documented in school-aged children with SCD. These executive skills are known to strongly contribute to early academic skills and preparedness for entering kindergarten. This study examined working memory and school readiness in preschool children with SCD compared to a healthy control group matched for race, sex and parent education. A total of 84 patients diagnosed with SCD (61.9% haemoglobin [Hb]SS/HbSß0 -thalassaemia) and 168 controls completed testing. The mean (SD) ages of patients and controls at testing were 4.53 (0.38) and 4.44 (0.65) years respectively. The SCD group performed worse than controls on measures of executive function, working memory and school readiness (p < 0.01; Cohen's D range: 0.32-0.39). Measures of working memory were associated with school readiness after accounting for early adaptive development. Multiple linear regression models among patients diagnosed with SCD revealed that college education of the primary caregiver was positively associated with school readiness (p < 0.001) after controlling for sex, genotype, age and early adaptive development. These results highlight the need to implement school readiness interventions in young children diagnosed with SCD emphasising executive function skills.

Analysis of the aqueous humor lipid profile in patients with polypoidal choroidal vasculopathy.

This study aimed to investigate the lipid profiles of aqueous humor from polypoidal choroidal vasculopathy (PCV) patients and identify potential biomarkers to increase the understanding of PCV pathomechanism. An ultra-high performance liquid chromatography-tandem mass spectrometry based untargeted lipidomic analysis was performed to acquire lipid profiles of aqueous humor of PCV patients and control subjects. Differentially expressed lipids were identified by univariate and multivariate analyses. A receiver operator characteristic curve (ROC) analysis was conducted to confirm the potential of identified lipids as biomarkers. Sixteen PCV patients and twenty-eight control subjects were enrolled in this study. In total, we identified 33 lipid classes and 639 lipid species in aqueous humor using the LipidSearch software. Of them, 50 differential lipids were obtained by combining univariate and multivariate statistical analyses (VIP>1 and P < 0.05), and 19 potential lipid biomarkers were identified by ROC analysis. In addition, significant alterations were found in several metabolic pathways, including glycerophospholipid, glycerolipid, and glycosylphosphatidylinositol-anchor biosynthesis. This study is the first to systematically characterize the alterations in lipid profiles in aqueous humor of PCV patients and screen for the potential lipid biomarkers for PCV diagnosis and treatment intervention. The results of this study are likely to broaden our understanding of the pathogenesis of PCV and contribute to improvements in the diagnosis and treatment of the disease.

Decomposition and decoupling analysis of carbon emissions from agricultural economic growth in China's Yangtze River economic belt.

In this study, carbon emissions from agricultural energy consumption (CEAEC) are fully analyzed using data from the Yangtze River Economic Belt (YEB) between 2000 and 2017. First, generalized LMDI is adopted to decompose the drivers of CEAEC into five components. Then, the decoupling indicator and the decoupling effort indicator are constructed to quantify the decoupling degrees and examine the government's emission reduction efforts, respectively. The results show that (1) CEAEC in the YEB has shown a phased increase, reaching a peak at 1732.25104t in 2012. Except for some decreases found in Shanghai, Chongqing, and Guizhou, it is shown that all provinces' CEAEC have risen to varying degrees. In contrast, the intensity of CEAEC in the YEB has been declining since 2005. (2) The economic output effect acts as the major contributor to the growth of CEAEC, followed by the population effect. In contrast, both the energy intensity effect and the energy structure effect are the primary reasons for reductions in CEAEC. The spatial difference in CEAEC in the YEB increased significantly from 2000 to 2017. (3) There was an alternating change from decoupling to coupling and then to negative decoupling from 2000 to 2017. Based on the conclusions mentioned above, it is proposed that the formulation of low-carbon agricultural development strategies should consider the structural adjustment of agricultural energy consumption and the advancements of agricultural technology.

Enzyme-Induced Transformable Peptide Nanocarriers with Enhanced Drug Permeability and Retention to Improve Tumor Nanotherapy Efficacy.

Temporal persistence is as important for nanocarriers as spatial accuracy. However, because of the insufficient aggreagtion and short retention time of chemotherapy drugs in tumors, their clinical application is greatly limited. A drug delivery approach dependent on the sensitivity to an enzyme present in the microenvironment of the tumor is designed to exhibit different sizes in different sites, achieving enhanced drug permeability and retention to improve tumor nanotherapy efficacy. In this work, we report a small-molecule peptide drug delivery system containing both tumor-targeting groups and enzyme response sites. This system enables the targeted delivery of peptide nanocarriers to tumor cells and a unique response to alkaline phosphatase (ALP) in the tumor microenvironment to activate morphological transformation and drug release. The amphiphilic peptide AYR self-aggregated into a spherical nanoparticle structure after encapsulating the lipid-soluble model drug doxorubicin (DOX) and rapidly converted to nanofibers via the induction of ALP. This morphological transformation toward a high aspect ratio allowed rapid, as well as effective drug release to tumor location while enhancing specific toxicity to tumor cells. Interestingly, this "transformer"-like drug delivery strategy can enhance local drug accumulation and effectively inhibit drug efflux. In vitro along with in vivo experiments further proved that the permeability and retention of antitumor drugs in tumor cells and tissues were significantly enhanced to reduce toxic side effects, and the therapeutic effect was remarkably improved compared with that of nondeformable drug-loaded peptide nanocarriers. The developed AYR nanoparticles with the ability to undergo morphological transformation in situ can improve local drug aggregation and retention time at the tumor site. Our findings provide a new and simple method for nanocarrier morphology transformation in novel cancer treatments.

Prevalence and Molecular Characteristics of Avian-Origin mcr-1-Harboring Escherichia coli in Shandong Province, China.

The objective of this study was to evaluate the prevalence and characteristics of avian-origin mcr-1-harbouring Escherichia coli in Shandong Province, China. During 2017-2018, a total of 668 non-duplicate E. coli isolates were separately collected from 8eight large intensive poultry farms in Shandong Province. Antimicrobial susceptibility testing for 10 antimicrobial agents commonly used in farms was performed on all E. coli isolates by the agar dilution method; the mobile colistin resistance gene (mcr-1) gene was screened by PCR, and mcr-1 positive isolates were PCR-screened for antimicrobial resistance genes and typed by multi-locus sequence typing (MLST). Among the 668 E. coli, 102 (15.3%) harbored the mcr-1 gene; high antimicrobial resistance rates were observed for ampicillin (100/102, 98.0%), followed by amoxicillin (99/102, 97.1%) and florfenicol (97/102, 95.1%), and a low level of resistance was found for amoxicillin/clavulanic acid (24/102, 23.5%). Five ESBL genes were detected, and all isolates carried bla TEM (102/102, 100%), followed by bla CTX-M (90/102, 88.2%). Four PMQR genes were detected; aac(6)-Ib-cr (40/102, 39.2%) was the most commonly isolated PMQR gene, followed by qnrA (10/102, 9.8%). Thirty-eight different kinds of STs were identified, and the dominant ST was ST93 (19/102, 18.6%), followed by ST48 (9/102, 8.8%). In summary, E. coli from poultry in Shandong could be a reservoir for the mcr-1 gene, which could pose serious risks to human public health.

[Identification and expression analysis of a full-length cDNA encoding Brassica napus small nuclear ribonucleoprotein BnSmD1].

By using substractive hybridization (SSH) and rapid amplification of cDNA ends-polymerase chain reaction (RACE-PCR), a full-length cDNA encoding Brassica napus small nuclear ribonucleoprotein, named BnSmD1, was obtained. It had 484 base pairs in length containing an open reading frame (ORF) of 354 bp and encoding a predicted protein of 118 amino acids with a molecular weight of 13 kDa. The BnSmD1 protein shares two highly conserved Sm folds (Sm-1 and Sm-2) and a C-terminal RG dipeptide repeat. Northern blot analysis revealed that BnSmD1 was expressed in all tested organs in B. napus, but its transcript level in early floral buds was much higher than that in leaf and stem tissues. No obvious expression difference was observed in leaf and stem tissues between the apetalous line Apet33-10 petalled near-isogenic line Pet33-10. Compared with wild type, the expression of BnSmD1 in the early floral buds of apetalous mutant Apet33-10 was significantly reduced. Taken together, our results suggest that BnSmD1 may play an important role in early floral petal development in B. napus.