Integrating Pre-test Probability and Point-of-Care Ultrasound (POCUS) in the Emergency Department (ED) Diagnosis of Small Bowel Obstruction (SBO).

Introduction A computed tomography (CT) scan and point-of-care ultrasound (POCUS) are commonly employed for diagnosing small bowel obstructions (SBOs). Prior studies demonstrated that POCUS has 90-95% sensitivity and specificity compared with CT scanning, which is the gold standard. Unlike other imaging modalities (in which the ordering and performing clinician are not the same), POCUS-performing/interpreting sonologists must recognize the risk of confirmation bias in the POCUS application. Per Bayesian analysis, the likelihood of a diagnosis being true following a diagnostic test is based on the ordering clinician's pre-test probability and the test characteristics (sensitivity and specificity, from which positive and negative likelihood ratios can be calculated). Consequently, establishing pre-test probability is important in informing downstream diagnostic or therapeutic interventions, as pre-test probability influences post-test odds. Little research has been done on the role of POCUS sonologist's pre-test probability and actual POCUS results regarding SBO. This study assessed the role of POCUS, integrating pre-test probability and POCUS results to determine post-test odds. Methods One hundred six patients were recruited on a convenience basis and underwent POCUS and CT between April 2017 and December 2022. All sonographers were credentialed in POCUS. POCUS sonologists' pre-test probabilities and POCUS and CT results were captured, which were compared. Sensitivity, specificity, LR+, and LR- were calculated, and correlations were made between pre-test probability and POCUS and CT results.  Results POCUS exhibited a sensitivity of 92% and specificity of 90%, with a corresponding positive likelihood ratio (LR+) of 9.3 and a negative likelihood ratio (LR-) of 0.09 for diagnosing SBO. Among patients with a high pre-test probability of SBO, a negative ultrasound yielded post-test odds of 0.4%, whereas a positive POCUS yielded post-test odds of 39.6%. Among patients with a low pre-test probability, a negative POCUS resulted in post-test odds of 0%, while a positive POCUS led to post-test odds of 2.1%, yielding a number needed to scan (NNS) of ~50 to identify a patient with an SBO on CT. Conclusion This study confirmed POCUS's sensitivity and specificity of ~90-95% and a corresponding LR+ of 9.2 and LR- of 0.9. Pre-test probability substantially affected post-test odds. Patients with a high pre-test probability and a positive POCUS had post-test odds of 39.6 and should have a confirmatory CT, while those with a negative POCUS have very low post-test odds and very likely will not benefit from CT. Patients with low pre-test probability and a positive POCUS have post-test odds of 2.1%, similar to the Wells Score and HEART score; such patients may not benefit from a CT, though clinicians should use their judgment/discretion. Patients with a low pre-test probability and a negative POCUS have post-test odds of 0% and should not have a CT. Among low pre-test probability patients, the NNS was ~50 to identify patients with an SBO on CT.

Untargeted urine metabolomics and machine learning provide potential metabolic signatures in children with autism spectrum disorder.

Background: Complementary to traditional biostatistics, the integration of untargeted urine metabolomic profiling with Machine Learning (ML) has the potential to unveil metabolic profiles crucial for understanding diseases. However, the application of this approach in autism remains underexplored. Our objective was to delve into the metabolic profiles of autism utilizing a comprehensive untargeted metabolomics platform coupled with ML. Methods: Untargeted metabolomics quantification (UHPLC/Q-TOF-MS) was performed for urine analysis. Feature selection was conducted using Lasso regression, and logistic regression, support vector machine, random forest, and extreme gradient boosting were utilized for significance stratification. Pathway enrichment analysis was performed to identify metabolic pathways associated with autism. Results: A total of 52 autistic children and 40 typically developing children were enrolled. Lasso regression identified ninety-two urinary metabolites that significantly differed between the two groups. Distinct metabolites, such as prostaglandin E2, phosphonic acid, lysine, threonine, and phenylalanine, were revealed to be associated with autism through the application of four different ML methods (p<0.05). The alterations observed in the phosphatidylinositol and inositol phosphate metabolism pathways were linked to the pathophysiology of autism (p<0.05). Conclusion: Significant urinary metabolites, including prostaglandin E2, phosphonic acid, lysine, threonine, and phenylalanine, exhibit associations with autism. Additionally, the involvement of the phosphatidylinositol and inositol phosphate pathways suggests their potential role in the pathophysiology of autism.

Paeonol Derivative, 6'-Methyl Paeonol, Attenuates Aß-Induced Pathophysiology in Cortical Neurons and in an Alzheimer's Disease Mice Model.

Herbs themselves and various herbal medicines are great resources for discovering therapeutic drugs for various diseases, including Alzheimer's disease (AD), one of the common neurodegenerative diseases. Utilizing mouse primary cortical neurons and DiBAC4(3), a voltage-sensitive indicator, we have set up a drug screening system and identified an herbal extraction compound, paeonol, obtained from Paeonia lactiflora; this compound is able to ameliorate the abnormal depolarization induced by Aß42 oligomers. Our aim was to further find effective paeonol derivatives since paeonol has been previously studied. 6'-Methyl paeonol, one of the six paeonol derivatives surveyed, is able to inhibit the abnormal depolarization induced by Aß oligomers. Furthermore, 6'-methyl paeonol is able to alleviate the NMDA- and AMPA-induced depolarization. When a molecular mechanism was investigated, 6'-methyl paeonol was found to reverse the Aß-induced increase in ERK phosphorylation. At the animal level, mice injected with 6'-methyl paeonol showed little change in their basic physical parameters compared to the control mice. 6'-Methyl paeonol was able to ameliorate the impairment of memory and learning behavior in J20 mice, an AD mouse model, as measured by the Morris water maze. Thus, paeonol derivatives could provide a structural foundation for developing and designing an effective compound with promising clinical benefits.

Plasma Amino Acid Profile in Children with Autism Spectrum Disorder in Southern China: Analysis of 110 Cases.

To retrospectively explore the characteristics of plasma amino acids (PAAs) in children with autism spectrum disorder and their clinical association via case-control study. A total of 110 autistic and 55 healthy children were recruited from 2014 to 2018. The clinical phenotypes included severity of autism, cognition, adaptability, and regression. Compared with the control group, autistic children had significantly elevated glutamate, γ-Amino-n-butyric acid, glutamine, sarcosine, δ-aminolevulinic acid, glycine and citrulline. In contrast, their plasma level of ethanolamine, phenylalanine, tryptophan, homocysteine, pyroglutamic acid, hydroxyproline, ornithine, histidine, lysine, and glutathione were significantly lower. Elevated neuroactive amino acids (glutamate) and decreased essential amino acids were mostly distinct characteristics of PAAs of autistic children. Increased level of tryptophan might be associated with severity of autism.

Gestational Diabetes Mellitus Remodels the Fetal Brain Fatty Acid Profile Through Placenta-Brain Lipid Axis in C57BL/6J Mice.

BACKGROUND: Polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), are critical for proper fetal brain growth and development. Gestational diabetes mellitus (GDM) could affect maternal-fetal fatty acid metabolism. OBJECTIVE: This study aimed to explore the effect of GDM and high-fat (HF) diet on the DHA transport signaling pathway in the placenta-brain axis and fatty acid concentrations in the fetal brain. METHODS: Insulin receptor antagonist (S961) and HF diet were used to establish an animal model of GDM. Eighty female C57BL/6J mice were randomly divided into control (CON), GDM, HF, and HF+GDM groups. The fatty acid profiles of the maternal liver and fetal brain were analyzed by gas chromatography. In addition, we analyzed the protein amounts of maternal liver fatty acid desaturase (FADS1/3), elongase (ELOVL2/5) and the regulatory factor sterol-regulatory element-binding protein (SREBP)-1c, and the DHA transport signaling pathway (Wnt3/ß-catenin/MFSD2a) of the placenta and fetal brain using western blotting. RESULTS: GDM promoted the decrease of maternal liver ELOVL2, ELOVL5, and SREBP-1c. Accordingly, we observed a significant decrease in the amount of maternal liver arachidonic acid (AA), DHA, and total n-3 PUFA and n-6 PUFA induced by GDM. GDM also significantly decreased the amount of DHA and n-3 PUFA in the fetal brain. GDM downregulated the Wnt3/ß-catenin/MFSD2a signaling pathway, which transfers n-3 PUFA in the placenta and fetal brain. The HF diet increased n-6 PUFA amounts in the maternal liver, correspondingly increasing linoleic acid, gamma-linolenic acid, AA, and total n-6 PUFA in the fetal brain, but decreased DHA amount in the fetal brain. However, HF diet only tended to decrease placental ß-catenin and MFSD2a amounts (P = 0.074 and P = 0.098, respectively). CONCLUSIONS: Maternal GDM could affect the fatty acid profile of the fetal brain both by downregulating the Wnt3/ß-catenin/MFSD2a pathway of the placental-fetal barrier and by affecting maternal fatty acid metabolism.

A 5+1 assemble-to-activate mechanism of the Lon proteolytic machine.

Many AAA+ (ATPases associated with diverse cellular activities) proteins function as protein or DNA remodelers by threading the substrate through the central pore of their hexameric assemblies. In this ATP-dependent translocating state, the substrate is gripped by the pore loops of the ATPase domains arranged in a universal right-handed spiral staircase organization. However, the process by which a AAA+ protein is activated to adopt this substrate-pore-loop arrangement remains unknown. We show here, using cryo-electron microscopy (cryo-EM), that the activation process of the Lon AAA+ protease may involve a pentameric assembly and a substrate-dependent incorporation of the sixth protomer to form the substrate-pore-loop contacts seen in the translocating state. Based on the structural results, we design truncated monomeric mutants that inhibit Lon activity by binding to the native pentamer and demonstrated that expressing these monomeric mutants in Escherichia coli cells containing functional Lon elicits specific phenotypes associated with lon deficiency, including the inhibition of persister cell formation. These findings uncover a substrate-dependent assembly process for the activation of a AAA+ protein and demonstrate a targeted approach to selectively inhibit its function within cells.

Retargeting video with an end-to-end framework.

Video holds significance in computer graphics applications. Because of the heterogeneous of digital devices, retargeting videos becomes an essential function to enhance user viewing experience in such applications. In the research of video retargeting, preserving the relevant visual content in videos, avoiding flicking, and processing time are the vital challenges. Extending image retargeting techniques to the video domain is challenging due to the high running time. Prior work of video retargeting mainly utilizes time-consuming preprocessing to analyze frames. Plus, being tolerant of different video content, avoiding important objects from shrinking, and the ability to play with arbitrary ratios are the limitations that need to be resolved in these systems requiring investigation. In this paper, we present an end-to-end RETVI method to retarget videos to arbitrary aspect ratios. We eliminate the computational bottleneck in the conventional approaches by designing RETVI with two modules, content feature analyzer (CFA) and adaptive deforming estimator (ADE). The extensive experiments and evaluations show that our system outperforms previous work in quality and running time.

Effects of dietary PUFA patterns and FADS genotype on breast milk PUFAs in Chinese lactating mothers.

BACKGROUND: Breastfeeding affects the growth and development of infants, and polyunsaturated fatty acids (PUFAs) play a crucial role in this process. To explore the factors influencing the PUFA concentration in breast milk, we conducted research on two aspects: dietary fatty acid patterns and single nucleotide polymorphisms (SNPs) in maternal fatty acid desaturase genes. METHODS: Three hundred seventy Chinese Han lactating mothers were recruited. A dietary semi-quantitative food frequency questionnaire (FFQ) was used to investigate the dietary intake of lactating mothers from 22 to 25 days postpartum for 1 year. Meanwhile, breast milk samples were collected from the participants and tested for the concentrations of 8 PUFAs and 10 SNP genotypes. We sought to determine the effect of dietary PUFA patterns and SNPs on breast milk PUFAs. We used SPSS 24.0 statistical software for data analysis. Statistical tests were all bilateral tests, with P < 0.05 as statistically significant. RESULTS: Under the same dietary background, PUFA contents in breast milk expressed by most major allele homozygote mothers tended to be higher than that expressed by their counterparts who carried minor allele genes. Moreover, under the same gene background, PUFA contents in breast milk expressed by the mother's intake of essential PUFA pattern tended to be higher than that expressed by their counterparts who took the other two kinds of dietary. CONCLUSIONS: Our study suggests that different genotypes and dietary PUFA patterns affect PUFA levels in breast milk. We recommend that lactating mothers consume enough essential fatty acids to ensure that their infants ingest sufficient PUFAs.

Coumarin-chalcone hybrid LM-021 and indole derivative NC009-1 targeting inflammation and oxidative stress to protect BE(2)-M17 cells against α-synuclein toxicity.

Parkinson's disease (PD) is featured mainly by the loss of dopaminergic neurons and the presence of α-synuclein-containing aggregates in the substantia nigra of brain. The α-synuclein fibrils and aggregates lead to increased oxidative stress and neural toxicity in PD. Chronic inflammation mediated by microglia is one of the hallmarks of PD pathophysiology. In this report, we showed that coumarin-chalcone hybrid LM-021 and indole derivative NC009-1 reduced the expression of major histocompatibility complex-II, NLR family pyrin domain containing (NLRP) 3, caspase-1, inducible nitric oxide synthase, interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in α-synuclein-activated mouse BV-2 microglia. Release of pro-inflammatory mediators including nitric oxide, IL-1ß, IL-6 and TNF-α was also mitigated. In BE(2)-M17 cells expressing A53T α-synuclein aggregates, LM-021 and NC009-1 reduced α-synuclein aggregation, neuroinflammation, oxidative stress and apoptosis, and promoted neurite outgrowth. These protective effects were mediated by downregulating NLRP1, IL-1ß and IL-6, and their downstream pathways including nuclear factor (NF)-κB inhibitor alpha (IκBα)/NF-κB P65 subunit (P65), c-Jun N-terminal kinase (JNK)/proto-oncogene c-Jun (JUN), mitogen-activated protein kinase 14 (P38)/signal transducer and activator of transcription (STAT) 1, and Janus kinase 2 (JAK2)/STAT3. The study results indicate LM-021 and NC009-1 as potential new drug candidates for PD.

Phosphofructokinase Platelet Overexpression Accelerated Colorectal Cancer Cell Growth and Motility.

Background: Glycolysis is a glucose metabolism pathway that generates the high-energy compound adenosine triphosphate, which supports cancer cell growth. Phosphofructokinase platelet (PFKP) plays a crucial role in glycolysis regulation and is involved in human cancer progression. However, the biological function of PFKP remains unclear in colorectal cancer (CRC). Methods: We analyzed the expression levels of PFKF in colon cancer cells and clinical samples using real-time PCR and western blot techniques. To determine the clinical significance of PFKP expression in colorectal cancer (CRC), we analyzed public databases. In addition, we conducted in vitro assays to investigate the effects of PFKP on cell growth, cell cycle, and motility. Results: An analysis by the Cancer Genome Atlas database revealed that PFKP was significantly overexpressed in CRC. We examined the levels of PFKP mRNA and protein, revealing that PFKP expression was significantly increased in CRC. The results of the univariate Cox regression analysis showed that high PFKP expression was linked to worse disease-specific survival (DSS) and overall survival (OS) [DSS: crude hazard ratio (CHR) = 1.84, 95% confidence interval (CI): 1.01-3.36, p = 0.047; OS: CHR=1.91, 95% CI: 1.06-3.43, p = 0.031]. Multivariate Cox regression analysis revealed that high PFKP expression was an independent prognostic biomarker for the DSS and OS of patients with CRC (DSS: adjusted HR = 2.07, 95% CI: 1.13-3.79, p = 0.018; AHR = 2.34, 95% CI: 1.29-4.25, p = 0.005). PFKP knockdown reduced the proliferation, colony formation, and invasion of CRC cells. In addition, the knockdown induced cell cycle arrest at the G0/G1 phase by impairing cell cycle-related protein expression. Conclusion: Overexpression of PFKP contributes to the growth and invasion of CRC by regulating cell cycle progression. PFKP expression can serve as a valuable molecular biomarker for cancer prognosis and a potential therapeutic target for treating CRC.

Meaningless Use: Assessing Compliance With a Clinically Meaningless Emergency Department Documentation Requirement.

Introduction A New York State initiative requests that Emergency Department (ED) providers document in the electronic health record (EHR) each admitted patient's employment status and, if applicable, their mode of commute. This initiative diverts them from their primary duties and increases the likelihood they will either disregard the request or input incorrect information to complete the data fields as fast as possible. This study intends to understand how well providers adhere to this regulation, which, while important for society as a whole, has little clinical relevance, especially in the ED, where the focus is to identify and treat emergent conditions. We hypothesized that clinician-collected employment data would contain many more "N/A" responses than registration-collected employment data (the "gold standard").  Methods We took a randomly selected convenience sample of 100 patients admitted from the ED and compared each patient's provider-entered response to the employment data field to the registration-recorded response. The EHR operates such that the "Employment" field must be completed in order to complete the admission electronically. Data fields collected were: last name, first name, date of birth, medical record number, date and time of arrival, date and time of admission, attending physician, resident physician (if there was one), mid-level provider (if there was one), provider-entered employment status, registration-entered employment status, admitting service (eg, Medicine, Surgery, OB/Gyn), and disposition level (eg, ICU). We assessed the percent of employment data that was concordant between the provider's entry and the registration clerk's entry. We also assessed for the potential confounding variable of how busy the ED was at time of admission, as providers may not take ask about employment or enter such data during particularly busy times. Finally, we interviewed providers to elicit reasons they did not enter accurate data. Statistical significance was set a priori at p <0.05. Results One hundred six patients were screened; six were excluded because one of the authors (MR) was their attending physician. For 92 of the remaining 100 patients, providers recorded employment as "N/A," and for eight patients they recorded "retired." For seven of these eight patients, provider entry matched registration entry (87.5% concordance). To adjust for whether how busy the ED was may have impacted the accuracy of data entry, admissions were categorized according to what time of day the patient was admitted. There was no statistically significant correlation between how busy the ED was and accuracy of data entry. The majority of providers stated they responded "NA" because the employment information was unrelated to the ED visit.  Conclusion In New York, for each patient admitted from the ED, the ED provider is requested to enter the patient's job information and, if they commute to work, the method they use. However, this takes providers' attention away from what they should be doing most: diagnosing and treating patients. This study highlights the unintended consequence of requesting data fields that are not clinically relevant and, from the patient and provider perspective, are not good investments of time and energy and distract from the clinical visit. Persons interpreting such clinically irrelevant data should do so with caution, as the results are unlikely to reflect the truth of what the questions intend to determine.

Eradicating Helicobacter pylori via 13C-urea breath screening to prevent gastric cancer in indigenous communities: a population-based study and development of a family index-case method.

OBJECTIVE: Screening and eradication of Helicobacter pylori help reduce disparities in the incidence of gastric cancer. We aimed to evaluate its acceptability and feasibility in the indigenous communities and develop a family index-case method to roll out this programme. DESIGN: We enrolled residents aged 20-60 years from Taiwanese indigenous communities to receive a course of test, treat, retest and re-treat initial treatment failures with the 13C-urea breath tests and four-drug antibiotic treatments. We also invited the family members of a participant (constituting an index case) to join the programme and evaluated whether the infection rate would be higher in the positive index cases. RESULTS: Between 24 September 2018 and 31 December 2021, 15 057 participants (8852 indigenous and 6205 non-indigenous) were enrolled, with a participation rate of 80.0% (15 057 of 18 821 invitees). The positivity rate was 44.1% (95% CI 43.3% to 44.9%). In the proof-of-concept study with 72 indigenous families (258 participants), family members of a positive index case had 1.98 times (95% CI 1.03 to 3.80) higher prevalence of H. pylori than those of a negative index case. The results were replicated in the mass screening setting (1.95 times, 95% CI 1.61 to 2.36) when 1115 indigenous and 555 non-indigenous families were included (4157 participants). Of the 6643 testing positive, 5493 (82.6%) received treatment. According to intention-to-treat and per-protocol analyses, the eradication rates were 91.7% (89.1% to 94.3%) and 92.1% (89.2% to 95.0%), respectively, after one to two courses of treatment. The rate of adverse effects leading to treatment discontinuation was low at 1.2% (0.9% to 1.5%). CONCLUSION: A high participation rate, a high eradication rate of H. pylori and an efficient rollout method indicate that a primary prevention strategy is acceptable and feasible in indigenous communities. TRIAL REGISTRATION NUMBER: NCT03900910.

Development and Validation of Prognostic Nomograms Based on Lymph Node Ratio for Young Patients with Gastric Cancer: A SEER-Based Study.

PURPOSE: To investigate the role of lymph node ratio (LNR) in young patients with gastric cancer (GC) and develop nomograms to predict the survival of young GC patients. METHODS: This retrospective study enrolled stage I-III GC patients before the age of 40 between 2010 and 2016 from the Surveillance, Epidemiology, and End Results (SEER) database. Cox proportional hazards models were used to determine the prognosticators and create the nomograms incorporating LNR to predict overall survival (OS) and cancer-specific survival (CSS). The discriminating superiority of the nomograms was examined using calibration curves, C-index, receiver operating characteristic (ROC) curves, decision curve analysis (DCA), and integrated discrimination improvement (IDI) by comparing with the TNM staging. The performance of the nomograms for risk stratification was analyzed by the Kaplan-Meier method. RESULTS: Based on the significant prognosticators identified in multivariate survival analysis, the nomograms were established and showed LNR as the third strongest predictor. The C-index of the nomograms for OS and CSS were higher than those of the TNM staging (OS: 0.773 vs 0.665; CSS: 0.769 vs 0.666). The ROC curves for the nomograms to predict survival exhibited superior sensitivity and specificity when compared with the TNM staging. The calibration plots, DCA curves, and IDI values of the nomograms also demonstrated adequate fit and ideal net benefit in prediction and clinical utility. The Kaplan-Meier analysis observed remarkable differences in patients divided into different risk subgroups (P < .001). CONCLUSIONS: These results found the clinical outperformance of the LNR-based nomograms for predicting survival in young stage I-III GC patients. Our nomograms may improve accuracy of survival risk prediction and facilitate individualized care of young stage I-III GC patients.

HKDC1 upregulation promotes glycolysis and disease progression, and confers chemoresistance onto gastric cancer.

There is increasing evidence that hexokinase is involved in cell proliferation and migration. However, the function of the hexokinase domain containing protein-1 (HKDC1) in gastric cancer (GC) remains unclear. Immunohistochemistry analysis and big data mining were used to evaluate the correlation between HKDC1 expression and clinical features in GC. In addition, the biological function and molecular mechanism of HKDC1 in GC were studied by in vitro and in vivo assays. Our study indicated that HKDC1 expression was upregulated in GC tissues compared with adjacent nontumor tissues. High expression of HKDC1 was associated with worse prognosis. Functional experiments demonstrated that HKDC1 upregulation promoted glycolysis, cell proliferation, and tumorigenesis. In addition, HKDC1 could enhance GC invasion and metastasis by inducing epithelial-mesenchymal transition (EMT). Abrogation of HKDC1 could effectively attenuate its oncogenic and metastatic function. Moreover, HKDC1 promoted GC proliferation and migration in vivo. HKDC1 overexpression conferred chemoresistance to cisplatin, oxaliplatin, and 5-fluorouracil (5-Fu) onto GC cells. Furthermore, nuclear factor kappa-B (NF-κB) inhibitor PS-341 could attenuate tumorigenesis, metastasis, and drug resistance ability induced by HKDC1 overexpression in GC cells. Our results highlight a critical role of HKDC1 in promoting glycolysis, tumorigenesis, and EMT of GC cells via activating the NF-κB pathway. In addition, HKDC1-mediated drug resistance was associated with DNA damage repair, which further activated NF-κB signaling. HKDC1 upregulation may be used as a potential indicator for choosing an effective chemotherapy regimen for GC patients undergoing chemotherapy.

Olefin-linked cationic covalent organic frameworks for efficient extraction of ReO4-/99TcO4.

Efficient extraction of radioactive 99TcO4- from strong acid/base solutions by porous adsorbents is extremely desirable but remains a great challenge. To overcome the challenge, here we report the first example of an olefin-linked cationic covalent organic framework (COF) named BDBI-TMT with excellent acid, base and radiation stability is synthesized by integrating robust imidazolium salt-based linkers with triazine building blocks. BDBI-TMT shows an ultra-fast adsorption kinetics (equilibrium is reached within 1 min) and an excellent ReO4- (a non-radioactive surrogate of 99TcO4-) capture capacity of 726 mg g-1, which can be attributed to the abundance of precisely tailored imidazolium salt-based units on the highly accessible pore walls of the ordered pore channels. Furthermore, the formation of the highly conjugated bulky alkyl skeleton enhances the hydrophobicity of BDBI-TMT, which significantly improves not only the affinity toward ReO4-/99TcO4- but also the chemical stability, allowing selective and reversible extraction of ReO4-/99TcO4- even under extreme conditions. This work demonstrates the great potential of olefin-linked cationic COFs for ReO4-/99TcO4- extraction, providing a new avenue to construct high-performance porous adsorbents for radionuclide remediation.

Plant growth-promoting properties of the phosphate-solubilizing red yeast Rhodosporidium paludigenum.

Phosphorus (P) is one of the essential elements that are necessary for plant development and growth. However, the availability of soluble forms of P for plants in the soils is limited, because a large proportion of it is bound to soil constituents. Thus, the concentration of P available to plants at any time is very low and, moreover, its availability depends on the soil pH. As a solution, phosphate-solubilizing microorganisms (PSMs) are employed that render inorganic P available to plants in soluble form. Thus far, research into PSMs has been insufficient, and only few such organisms have been considered for exploitation as microbial fertilizer strains. The characteristics of plant growth promotion with the plant-PSMs coculture system remain to be elucidated. In the current study, we report on the isolate Rhodosporidium paludigenum JYC100 that exhibits good performance for solubilizing calcium phosphate. We found that it can be regulated by the amount of soluble phosphate. Furthermore, R. paludigenum JYC100 promotes plant growth under specific conditions (P deficiency, but with insoluble phosphate) in different media and soil pots. In contrast, the yeast Aureobasidium pullulans JYC104 exhibited weak phosphate-solubilizing capacities and no plant growth-promoting ability. Compared to control plants, the biomass, shoot height, and cellular inorganic P content of plants increased in plants cocultivated with R. paludigenum JYC100. In addition, histochemical GUS and qRT-PCR assays of phosphate starvation-induced (PSI) genes showed that the transcript levels of these PSI genes are decreased in the plants cocultured with R. paludigenum JYC100. These findings reflect the unique ability of R. paludigenum JYC100 to convert insoluble P compounds to plant-available P, thereby leading to growth promotion. Our study results highlight the use of yeasts as potential substitutes for inorganic phosphate fertilizers to meet the P demands of plants, which may eventually improve yields in sustainable agricultures.

Investigating the interaction between neuropsychiatry features and daily activities on social function in patients with Parkinson's disease with mild cognitive impairment.

BACKGROUND: Social functioning is crucial for daily living and is an essential indicator of dementia in patients with Parkinson's disease. The pattern of social functioning in patients with Parkinson's disease without dementia (i.e. those who are cognitively intact or have mild cognitive impairment (PD-MCI)) and its determinants are unclear. AIMS: In exploring the heterogeneity of social functioning among patients with Parkinson's disease-associated dementia, we determined the optimal cut-off score of the Parkinson's Disease Social Functioning Scale (PDSFS) for patients with PD-MCI, and the variables influencing patients' social functioning. METHOD: A total of 302 participants underwent the Mini-Mental State Examination (MMSE) and PDSFS; 120 patients with Parkinson's disease completed the measurements (MMSE, Activities of Daily Living Scale and Neuropsychiatric Inventory). Group comparisons, receiver operating characteristic curves, Spearman correlation and multiple and hierarchical regression analyses were conducted. RESULTS: The PD-MCI group scored the lowest on the PDSFS (F = 10.10, P < 0.001). The PDSFS cut-off score was 53 (area under the curve 0.700, sensitivity 0.800, specificity 0.534). The MMSE (ß = 0.293, P = 0.002), Activities of Daily Living Scale (ß = 0.189, P = 0.028) and Neuropsychiatric Inventory (ß = -0.216, P = 0.005) scores predicted the PDSFS score. Further, there was an interaction effect between the Activities of Daily Living Scale and Neuropsychiatric Inventory scores on the PDSFS score (ß = 0.305, P < 0.001). CONCLUSIONS: We determined a PDSFS cut-off score for detecting PD-MCI and found that patients with PD-MCI have social dysfunction. Future research should focus on the effects of neuropsychiatry symptoms and activities of daily living on social functioning, and tailor the intervention programme for patients with Parkinson's disease.

Breast Cancer with Increased Drug Resistance, Invasion Ability, and Cancer Stem Cell Properties through Metabolism Reprogramming.

Breast cancer is a heterogeneous disease, and the survival rate of patients with breast cancer strongly depends on their stage and clinicopathological features. Chemoradiation therapy is commonly employed to improve the survivability of patients with advanced breast cancer. However, the treatment process is often accompanied by the development of drug resistance, which eventually leads to treatment failure. Metabolism reprogramming has been recognized as a mechanism of breast cancer resistance. In this study, we established a doxorubicin-resistant MCF-7 (MCF-7-D500) cell line through a series of long-term doxorubicin in vitro treatments. Our data revealed that MCF-7-D500 cells exhibited increased multiple-drug resistance, cancer stemness, and invasiveness compared with parental cells. We analyzed the metabolic profiles of MCF-7 and MCF-7-D500 cells through liquid chromatography−mass spectrometry. We observed significant changes in 25 metabolites, of which, 21 exhibited increased levels (>1.5-fold change and p < 0.05) and 4 exhibited decreased levels (<0.75-fold change and p < 0.05) in MCF-7 cells with doxorubicin resistance. These results suggest the involvement of metabolism reprogramming in the development of drug resistance in breast cancer, especially the activation of glycolysis, the tricarboxylic acid (TCA) cycle, and the hexamine biosynthesis pathway (HBP). Furthermore, most of the enzymes involved in glycolysis, the HBP, and the TCA cycle were upregulated in MCF-7-D500 cells and contributed to the poor prognosis of patients with breast cancer. Our findings provide new insights into the regulation of drug resistance in breast cancer, and these drug resistance-related metabolic pathways can serve as targets for the treatment of chemoresistance in breast cancer.

Mass screening and eradication of Helicobacter pylori as the policy recommendations for gastric cancer prevention.

Gastric cancer is an inflammation-related cancer triggered by Helicobacter pylori infection. Understanding of the natural disease course has prompted the hypothesis that gastric cancer can be prevented by administering a short-course antibiotic treatment to eradicate the H. pylori infection and interrupt this carcinogenic cascade. Results from randomized controlled trials and cohort studies have repeatedly confirmed this concept, which has moved attention from individual management of H. pylori infection to population-wide implementation of screening programs. Such a paradigm shift follows a three-tier architecture. First, healthcare policy-makers determine the most feasible and applicable eligibility, invitation, testing, referral, treatment, and evaluation methods for an organized screening program to maximize the population benefits and cost-effectiveness. Second, provision of knowledge and effective feedback to frontline general practitioners, including choice of diagnostic tests, selection of eradication regimens, and the indication of endoscopic examination, ensures the quality of care and increases the likelihood of desired treatment responses. Third, initiatives to raise population awareness are designed regarding the impact of H. pylori infection and risky lifestyle habits on the stomach health. These programs, with increased accessibility and geographic coverage in progress, will accelerate the decline in morbidity, mortality, and associated costs of this preventable malignancy.