Machine Learning-Driven Prediction of Brain Age for Alzheimer's Risk: APOE4 Genotype and Gender Effects.

Background: Alzheimer's disease (AD) is a leading cause of dementia, and it is significantly influenced by the apolipoprotein E4 (APOE4) gene and gender. This study aimed to use machine learning (ML) algorithms to predict brain age and assess AD risk by considering the effects of the APOE4 genotype and gender. Methods: We collected brain volumetric MRI data and medical records from 1100 cognitively unimpaired individuals and 602 patients with AD. We applied three ML regression models-XGBoost, random forest (RF), and linear regression (LR)-to predict brain age. Additionally, we introduced two novel metrics, brain age difference (BAD) and integrated difference (ID), to evaluate the models' performances and analyze the influences of the APOE4 genotype and gender on brain aging. Results: Patients with AD displayed significantly older brain ages compared to their chronological ages, with BADs ranging from 6.5 to 10 years. The RF model outperformed both XGBoost and LR in terms of accuracy, delivering higher ID values and more precise predictions. Comparing the APOE4 carriers with noncarriers, the models showed enhanced ID values and consistent brain age predictions, improving the overall performance. Gender-specific analyses indicated slight enhancements, with the models performing equally well for both genders. Conclusions: This study demonstrates that robust ML models for brain age prediction can play a crucial role in the early detection of AD risk through MRI brain structural imaging. The significant impact of the APOE4 genotype on brain aging and AD risk is also emphasized. These findings highlight the potential of ML models in assessing AD risk and suggest that utilizing AI for AD identification could enable earlier preventative interventions.

Diagnosis-Related Groups payment reform and hospital cost control.

BACKGROUND: This study explores the influence of Diagnosis-Related Groups (DRG) payment reform on hospital cost control and offers pertinent cost management strategies for public hospitals. It situates the research by elucidating the significance of the DRG payment method and comparing its advantages and drawbacks with the traditional 'pay per project' model. OBJECTIVE: The primary aim is to assess the impact of DRG payment reform on hospital cost control and propose effective cost management strategies for public hospitals. The objective is to provide insights into DRG payment implications and attempt practical recommendations for its implementation in the public healthcare sector. METHODS: Employing a comprehensive approach, the study analyzes DRG payment, delineates advantages and drawbacks, and proposes cost management strategies. Methods include staff training, an information management platform, disease analysis, and optimized cost accounting. The study highlights the potential for improved medical diagnosis and treatment through industry-finance integration. RESULTS: Findings reveal advantages and limitations of DRG payment, emphasizing strategies for optimizing hospital operations. Enhanced medical diagnosis and treatment procedures through industry-finance integration contribute to overall cost control effectiveness. CONCLUSION: The study serves as a practical guide for implementing DRG payment reforms, offering valuable insights for policymakers and healthcare professionals in navigating the complexities of cost control in public healthcare.

[Chemical profiling of Xiaochaihu Granules and characterization of absorbed components in rat plasma after oral administration].

The chemical components of Xiaochaihu Granules and absorbed components in rats after oral administration were identified by using ultra performance liquid chromatography-quadrupole orbitrap mass spectrometry(UPLC-Q-Exactive-Orbitrap-MS)and UPLC-triple quadrupole mass spectrometry(UPLC-MS/MS). Separation was performed on a CORTECS UPLC C~+_(18)(2.1 mm×100 mm, 1.6 µm)column with gradient elution using acetonitrile-0.1% formic acid aqueous solution as the mobile phase. Data on the chemical components were collected in positive and negative ion modes and identified based on the retention time, precise molecular weight, fragment ion information in comparison with the reference substance, and literature report. The rat fever model was established by subcutaneous injection of dry yeast. Subsequently, the normal and model rats received oral administration of Xiaochaihu Granules. Blood samples were taken from the orbital vein at different time points after administration, and the plasma was isolated for scanning and identification of absorbed components using the multi reaction monitoring mode(MRM).A total of 112 chemical components were identified in Xiaochaihu Granules, including 63 flavonoids, 31 saponins, 6 organic acids, 4 phenylpropanoids, 3 amino acids and 5 other compounds. Additionally, 18 prototypical components were identified in rat plasma. This study lays the foundation for further study of the therapeutic material and quality control of Xiaochaihu Granules.

Synergistic effects of Pleistocene geological and climatic events on complex phylogeographic history of widespread sympatric species of Megaloptera in East Asia.

Unraveling the phylogeographic histories of species remains a key endeavor for comprehending the evolutionary processes contributing to the rich biodiversity and high endemism found in East Asia. In this study, we explored the phylogeographic patterns and demographic histories of three endemic fishfly and dobsonfly species ( Neochauliodes formosanus, Protohermes costalis, and Neoneuromus orientalis) belonging to the holometabolan order Megaloptera. These species, which share a broad and largely overlapping distribution, were analyzed using comprehensive mitogenomic data. Our findings revealed a consistent influence of vicariance on the population isolation of Neoc. formosanus and P. costalis between Hainan, Taiwan, and the East Asian mainland during the early Pleistocene, potentially hindering subsequent colonization of the later diverged Neon. orientalis to these islands. Additionally, we unveiled the dual function of the major mountain ranges in East Asia, serving both as barriers and conduits, in shaping the population structure of all three species. Notably, we demonstrated that these co-distributed species originated from Southwest, Southern, and eastern Central China, respectively, then subsequently migrated along multi-directional routes, leading to their sympatric distribution on the East Asian mainland. Furthermore, our results highlighted the significance of Pleistocene land bridges along the eastern coast of East Asia in facilitating the dispersal of mountain-dwelling insects with low dispersal ability. Overall, this study provides novel insight into the synergistic impact of Pleistocene geological and climatic events in shaping the diversity and distribution of aquatic insects in East Asia.

[Prospective,multi-center,and large-scale hospital centralized monitoring of clinical safety of Reduning Injection in 100249 children cases].

This study utilized a prospective, large-sample, multi-center, and registered key specialty approach of hospitals to monitor the application of Reduning Injection. A total of 100 249 adolescent patients aged 14 years and below who received Reduning Injection were monitored, resulting in 83 cases of adverse events, with 76 of them being classified as adverse drug reaction(ADR). The calculated incidence rate of ADR for Reduning Injection was 0.076%, indicating a very rare ADR. The main symptoms of ADR were pruritus, diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsion, and chills. All ADR cases were reported for the first time, including three new ADR cases and 73 known ADR cases. The categories of ADR was general ADR. All ADR was mild in severity. There were more males than females in ADR patients. One patient had a history of ADR, and the drug causing ADR was buprofen. The largest number of ADR cases occurred when the dosage of Reduning injection was 5-10 mL. The dropping speed was 30 drops or less per min, and the solvent type was 5% glucose injection. The most common manifestation of ADR patients was pruritus, followed by diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsions, and chills. 72 patients(94.74% of ADR patients) discontinued the drug, and three patients(3.95% of ADR patients) were given oxygen inhalation. 47 cases(61.84% of ADR patients) were treated with medication, of which dexamethasone was the most used(24 cases, 46.15% of ADR patients). 76 ADR patients were cured or improved. ADRs are more likely to occur when diagnosed with acute bronchitis by western medicine and cough by traditional Chinese medicine(TCM), TCM syndrome type is wind heat syndrome, and the combination medicine is ambroxol hydrochloride and bromhexine hydrochloride injection, ascorbic acid/vitamin C injection. This result provides an evidence-based safety basis for active pharmacovigilance of Reduning Injection in adolescents aged 14 years and below.

Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

BACKGROUND: Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. FINDINGS: Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. INTERPRETATION: Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. FUNDING: National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

mTOR inhibition enhances synaptic and mitochondrial function in Alzheimer's disease in an APOE genotype-dependent manner.

Apolipoprotein ε4 (APOE4) carriers develop brain metabolic dysfunctions decades before the onset of Alzheimer's disease (AD). A goal of the study is to identify if rapamycin, an inhibitor for the mammalian target of rapamycin (mTOR) inhibitor, would enhance synaptic and mitochondrial function in asymptomatic mice with human APOE4 gene (E4FAD) before they showed metabolic deficits. A second goal is to determine whether there may be genetic-dependent responses to rapamycin when compared to mice with human APOE3 alleles (E3FAD), a neutral AD genetic risk factor. We fed asymptomatic E4FAD and E3FAD mice with control or rapamycin diets for 16 weeks from starting from 3 months of age. Neuronal mitochondrial oxidative metabolism and excitatory neurotransmission rates were measured using in vivo 1H-[13C] proton-observed carbon-edited magnetic resonance spectroscopy, and isolated mitochondrial bioenergetic measurements using Seahorse. We found that rapamycin enhanced neuronal mitochondrial function, glutamate-glutamine cycling, and TCA cycle rates in the asymptomatic E4FAD mice. In contrast, rapamycin enhances glycolysis, non-neuronal activities, and inhibitory neurotransmission of the E3FAD mice. These findings indicate that rapamycin might be able to mitigate the risk for AD by enhancing brain metabolic functions for cognitively intact APOE4 carriers, and the responses to rapamycin are varied by APOE genotypes. Consideration of precision medicine may be needed for future rapamycin therapeutics.

[Mechanism of Notoginseng Radix et Rhizoma in regulating PI3K/Akt/mTORC1-mitochondrial energy metabolism to treat chronic renal failure in rats with blood stasis syndrome].

This study observed the effects of Notoginseng Radix et Rhizoma on the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin complex 1(mTORC1) signaling pathway and mitochondrial energy metabolism in the rat model of adriamycin-induced renal fibrosis with blood stasis syndrome to explore the mechanism of Notoginseng Radix et Rhizoma in protecting the kidney. Thirty male rats with adriamycin-induced renal fibrosis were randomized into model, low-, medium-, and high-dose Notoginseng Radix et Rhizoma, and positive control groups(n=6). Six clean SD male rats were selected into the normal group. The normal group and model group were administrated with normal saline, and other groups with corresponding drugs. After 8 weeks of treatment, the renal function, renal pathology, adenosine triphosphate(ATP) levels, Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase activities, and the protein levels of ATP5B, mTORC1, 70 kDa ribosomal protein S6 kinase(P70S6K), P85, Akt, p-Akt, and SH2-containing inositol phosphatase(SHIP2) in the renal tissue were determined. Compared with the normal group, the model group showed elevated levels of blood urea nitrogen(BUN) and serum creatinine(SCr)(P<0.01). Compared with the model group, Notoginseng Radix et Rhizoma and the positive control lowered the levels of BUN and SCr, which were significant in the medium-and high-dose Noto-ginseng Radix et Rhizoma groups and the positive control group(P<0.05). Compared with the model group, Notoginseng Radix et Rhizoma and the positive control alleviated the pathological changes in the renal tissue, such as vacuolar and fibroid changes, glomerulus atrophy, cystic expansion of renal tubules, and massive infiltration of inflammatory cells. Compared with the normal group, the model group showed decreased mitochondrial ATP content and Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase activities in the renal tissue(P<0.05), and medium-and high-dose Notoginseng Radix et Rhizoma and positive control mitigated such decreases(P<0.05). Compared with the model group, medium-and high-dose Notoginseng Radix et Rhizoma and the positive control up-regulated the protein levels of ATP5B and SHIP2 and down-regulated the protein levels of mTORC1, P70S6K, P85, Akt, and p-Akt(P<0.05 or P<0.01 or P<0.001). Notoginseng Radix et Rhizoma may exert an anti-fibrosis effect by inhibiting the activation of the PI3K/Akt/mTORC1 pathway to restore mitochondrial energy metabolism, thus protecting the kidney.

Evidence-based screening, clinical care and health education recommendations for Alaska Native peoples with prediabetes living in southcentral Alaska: findings from the Alaska EARTH follow-up study.

Pre-diabetes (pre-DM) is a strong predictor of diabetes (DM) over time. This study investigated how much of the recent increase in pre-DM identified among Alaska Native (AN) peoples living in urban southcentral Alaska may be due to changes in diagnostic methods. We used clinical and demographic data collected at baseline between 2004 and 2006 and at follow-up collected between 2015 and 2017 from the urban southcentral Alaska Education and Research Towards Health (EARTH) cohort. We used descriptive statistics and logistic regression to explore differences in demographic and clinical variables among the identified pre-DM groups. Of 388 participants in the follow-up study, 243 had A1c levels indicating pre-DM with only 20 demonstrating pre-DM also by fasting blood glucose (FBG). Current smoking was the sole predictor for pre-DM by A1c alone while abdominal obesity and elevated FBG-predicted pre-DM by A1c+FBG. No participants had an elevated FBG without an A1c elevation. A substantial portion of the rise in pre-DM found among urban southcentral AN peoples in the EARTH follow-up study was due to the addition of A1c testing. Pre-DM by A1c alone should be used to motivate behavioural changes that address modifiable risk factors, including smoking cessation, physical activity and weight management.

Living well with diabetes in Alaska.

Many people with diabetes mellitus experience minimal or no complications. Our objective was to determine the proportion of Alaska Native people who experienced four major complications or mortality and to identify factors that may be associated with these outcomes. We used records in a diabetes registry and clinical and demographic variables in our analyses. We used logistic regression and Cox Proportional Hazards models to evaluate associations of these parameters with death and complications that occurred prior to 2013. The study included 591 Alaska Native people with non-type 1 diabetes mellitus, diagnosed between 1986 and 1992. Over 60% of people in this study remained free of four major diabetes-related complications for the remainder of life or throughout the approximately 20-year study period. Lower BMI, higher age at diagnosis of diabetes, and use of at least one diabetes medication were associated with death and a composite of four complications. A majority of Alaska Native people with DM had none of four major complications over a 20-year period. Lower BMI and use of diabetes medications were associated with higher hazard for some deleterious outcomes. This suggests that goals in care of elders should be carefully individualised. In addition, we discuss several programme factors that we believe contributed to favourable outcomes.

Pedigree Analysis of Nonclassical Cholesteryl Ester Storage Disease with Dominant Inheritance in a LIPA I378T Heterozygous Carrier.

BACKGROUND: Cholesterol ester storage disorder (CESD; OMIM: 278,000) was formerly assumed to be an autosomal recessive allelic genetic condition connected to diminished lysosomal acid lipase (LAL) activity due to LIPA gene abnormalities. CESD is characterized by abnormal liver function and lipid metabolism, and in severe cases, liver failure can occur leading to death. In this study, one Chinese nonclassical CESD pedigree with dominant inheritance was phenotyped and analyzed for the corresponding gene alterations. METHODS: Seven males and eight females from nonclassical CESD pedigree were recruited. Clinical features and LAL activities were documented. Whole genome Next-generation sequencing (NGS) was used to screen candidate genes and mutations, Sanger sequencing confirmed predicted mutations, and qPCR detected LIPA mRNA expression. RESULTS: Eight individuals of the pedigree were speculatively thought to have CESD. LAL activity was discovered to be lowered in four living members of the pedigree, but undetectable in the other four deceased members who died of probable hepatic failure. Three of the four living relatives had abnormal lipid metabolism and all four had liver dysfunctions. By liver biopsy, the proband exhibited diffuse vesicular fatty changes in noticeably enlarged hepatocytes and Kupffer cell hyperplasia. Surprisingly, only a newly discovered heterozygous mutation, c.1133T>C (p. Ile378Thr) on LIPA, was found by gene sequencing in the proband. All living family members who carried the p.I378T variant displayed reduced LAL activity. CONCLUSIONS: Phenotypic analyses indicate that this may be an autosomal dominant nonclassical CESD pedigree with a LIPA gene mutation.

A Review of the Extent of Pain Catastrophizing in Patients Who Have Undergone Total Knee Replacement.

OBJECTIVES: This study aimed to analyze the current status and influencing factors of pain catastrophizing in patients undergoing total knee replacement (TKR) and to provide a basis and reference for the clinical improvement of pain catastrophizing in these patients. DESIGN: This study was designed in accordance with PRISMA guidelines. DATA SOURCES: PubMed, the Web of Science, the Elton B. Stephens Company, the Cochrane Library, Embase, Chinese National Knowledge Infrastructure, the WanFang, Weipu and Chinese Biomedical Literature Databases. REVIEW/ANALYSIS METHODS: A scoping review was performed using PubMed, the Web of Science, the Elton B. Stephens Company, the Cochrane Library, Embase, Chinese National Knowledge Infrastructure, the WanFang, Weipu, and Chinese Biomedical Literature Databases, and after literature screening and data extraction, the results were summarized. RESULTS: A total of 23 articles were included in the study. Pain catastrophizing is mostly assessed using the Pain Catastrophizing Scale and the Coping Strategies Questionnaire. The level of pain catastrophizing is an independent predictor of pain in patients undergoing TKR and is influenced by demographic, psychological, co-morbid, and prognostic factors. Pain catastrophizing interventions mainly consist of surgery, physiotherapy, medication, and psychological therapy. CONCLUSIONS: Pain catastrophizing involves multiple factors, and it is necessary to explore the predictors affecting pain catastrophizing, improve the systematic evaluation of pain catastrophizing and adopt the appropriate intervention methods.

[A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020]. / 2019­2020å¹´160ä¾‹å„¿ç«¥è‚ºç‚Žé“¾çƒèŒè„‘è†œç‚Žä¸´åºŠæµè¡Œç— å­¦å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To investigate the clinical characteristics and prognosis of pneumococcal meningitis (PM), and drug sensitivity of Streptococcus pneumoniae (SP) isolates in Chinese children. METHODS: A retrospective analysis was conducted on clinical information, laboratory data, and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country. RESULTS: Among the 160 children with PM, there were 103 males and 57 females. The age ranged from 15 days to 15 years, with 109 cases (68.1%) aged 3 months to under 3 years. SP strains were isolated from 95 cases (59.4%) in cerebrospinal fluid cultures and from 57 cases (35.6%) in blood cultures. The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87) and 27% (21/78), respectively. Fifty-five cases (34.4%) had one or more risk factors for purulent meningitis, 113 cases (70.6%) had one or more extra-cranial infectious foci, and 18 cases (11.3%) had underlying diseases. The most common clinical symptoms were fever (147 cases, 91.9%), followed by lethargy (98 cases, 61.3%) and vomiting (61 cases, 38.1%). Sixty-nine cases (43.1%) experienced intracranial complications during hospitalization, with subdural effusion and/or empyema being the most common complication [43 cases (26.9%)], followed by hydrocephalus in 24 cases (15.0%), brain abscess in 23 cases (14.4%), and cerebral hemorrhage in 8 cases (5.0%). Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old, with rates of 91% (39/43) and 83% (20/24), respectively. SP strains exhibited complete sensitivity to vancomycin (100%, 75/75), linezolid (100%, 56/56), and meropenem (100%, 6/6). High sensitivity rates were also observed for levofloxacin (81%, 22/27), moxifloxacin (82%, 14/17), rifampicin (96%, 25/26), and chloramphenicol (91%, 21/23). However, low sensitivity rates were found for penicillin (16%, 11/68) and clindamycin (6%, 1/17), and SP strains were completely resistant to erythromycin (100%, 31/31). The rates of discharge with cure and improvement were 22.5% (36/160) and 66.2% (106/160), respectively, while 18 cases (11.3%) had adverse outcomes. CONCLUSIONS: Pediatric PM is more common in children aged 3 months to under 3 years. Intracranial complications are more frequently observed in children under 1 year old. Fever is the most common clinical manifestation of PM, and subdural effusion/emphysema and hydrocephalus are the most frequent complications. Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates. Adverse outcomes can be noted in more than 10% of PM cases. SP strains are high sensitivity to vancomycin, linezolid, meropenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.

Metabolomics study reveals increased deoxycholic acid contributes to deoxynivalenol-mediated intestinal barrier injury.

AIMS: Deoxynivalenol (DON), namely vomitoxin, is one of the most prevalent fungal toxins in cereal crops worldwide. However, the underlying toxic mechanisms of DON remain largely unknown. MAIN METHODS: DON exposure-caused changes in the murine plasma metabolome and gut microbiome were investigated by an LC-MS/MS-based nontargeted metabolomics approach and sequencing of 16S rRNA in fecal samples, respectively. Cellular models were then used to validate the findings from the metabolomics study. KEY FINDINGS: DON exposure increased intestinal barrier permeability evidenced by its-mediated decrease in colonic Claudin 5 and E-cadherin, as well as increases in colonic Ifn-γ, Cxcl9, Cxcl10, and Cxcr3. Furthermore, DON exposure resulted in a significant increase in murine plasma levels of deoxycholic acid (DCA). Also, DON exposure led to gut microbiota dysbiosis, which was associated with DON exposure-caused increase in plasma DCA. In addition, we found not only DON but also DCA dose-dependently caused a significant increase in the levels of IFN-γ, CXCL9, CXCL10, and/or CXCR3, as well as a significant decrease in the expression levels of Claudin 5 and/or E-cadherin in the human colonic epithelial cells (NCM460). SIGNIFICANCE: DON-mediated increase in DCA contributes to DON-caused intestinal injury. DCA may be a potential therapeutic target for DON enterotoxicity.

Prebiotic inulin enhances gut microbial metabolism and anti-inflammation in apolipoprotein E4 mice with sex-specific implications.

Gut dysbiosis has been identified as a crucial factor of Alzheimer's disease (AD) development for apolipoprotein E4 (APOE4) carriers. Inulin has shown the potential to mitigate dysbiosis. However, it remains unclear whether the dietary response varies depending on sex. In the study, we fed 4-month-old APOE4 mice with inulin for 16 weeks and performed shotgun metagenomic sequencing to determine changes in microbiome diversity, taxonomy, and functional gene pathways. We also formed the same experiments with APOE3 mice to identify whether there are APOE-genotype dependent responses to inulin. We found that APOE4 female mice fed with inulin had restored alpha diversity, significantly reduced Escherichia coli and inflammation-associated pathway responses. However, compared with APOE4 male mice, they had less metabolic responses, including the levels of short-chain fatty acids-producing bacteria and the associated kinases, especially those related to acetate and Erysipelotrichaceae. These diet- and sex- effects were less pronounced in the APOE3 mice, indicating that different APOE variants also play a significant role. The findings provide insights into the higher susceptibility of APOE4 females to AD, potentially due to inefficient energy production, and imply the importance of considering precision nutrition for mitigating dysbiosis and AD risk in the future.

Gut microbiome association with brain imaging markers, APOE genotype, calcium and vegetable intakes, and obesity in healthy aging adults.

Introduction: Advanced age is a significant factor in changes to brain physiology and cognitive functions. Recent research has highlighted the critical role of the gut microbiome in modulating brain functions during aging, which can be influenced by various factors such as apolipoprotein E (APOE) genetic variance, body mass index (BMI), diabetes, and dietary intake. However, the associations between the gut microbiome and these factors, as well as brain structural, vascular, and metabolic imaging markers, have not been well explored. Methods: We recruited 30 community dwelling older adults between age 55-85 in Kentucky. We collected the medical history from the electronic health record as well as the Dietary Screener Questionnaire. We performed APOE genotyping with an oral swab, gut microbiome analysis using metagenomics sequencing, and brain structural, vascular, and metabolic imaging using MRI. Results: Individuals with APOE e2 and APOE e4 genotypes had distinct microbiota composition, and higher level of pro-inflammatory microbiota were associated higher BMI and diabetes. In contrast, calcium- and vegetable-rich diets were associated with microbiota that produced short chain fatty acids leading to an anti-inflammatory state. We also found that important gut microbial butyrate producers were correlated with the volume of the thalamus and corpus callosum, which are regions of the brain responsible for relaying and processing information. Additionally, putative proinflammatory species were negatively correlated with GABA production, an inhibitory neurotransmitter. Furthermore, we observed that the relative abundance of bacteria from the family Eggerthellaceae, equol producers, was correlated with white matter integrity in tracts connecting the brain regions related to language, memory, and learning. Discussion: These findings highlight the importance of gut microbiome association with brain health in aging population and could have important implications aimed at optimizing healthy brain aging through precision prebiotic, probiotic or dietary interventions.

Self-Supervised Learning Application on COVID-19 Chest X-ray Image Classification Using Masked AutoEncoder.

The COVID-19 pandemic has underscored the urgent need for rapid and accurate diagnosis facilitated by artificial intelligence (AI), particularly in computer-aided diagnosis using medical imaging. However, this context presents two notable challenges: high diagnostic accuracy demand and limited availability of medical data for training AI models. To address these issues, we proposed the implementation of a Masked AutoEncoder (MAE), an innovative self-supervised learning approach, for classifying 2D Chest X-ray images. Our approach involved performing imaging reconstruction using a Vision Transformer (ViT) model as the feature encoder, paired with a custom-defined decoder. Additionally, we fine-tuned the pretrained ViT encoder using a labeled medical dataset, serving as the backbone. To evaluate our approach, we conducted a comparative analysis of three distinct training methods: training from scratch, transfer learning, and MAE-based training, all employing COVID-19 chest X-ray images. The results demonstrate that MAE-based training produces superior performance, achieving an accuracy of 0.985 and an AUC of 0.9957. We explored the mask ratio influence on MAE and found ratio = 0.4 shows the best performance. Furthermore, we illustrate that MAE exhibits remarkable efficiency when applied to labeled data, delivering comparable performance to utilizing only 30% of the original training dataset. Overall, our findings highlight the significant performance enhancement achieved by using MAE, particularly when working with limited datasets. This approach holds profound implications for future disease diagnosis, especially in scenarios where imaging information is scarce.

The Mediating Role of Emotion Management, Self-Efficacy and Emotional Intelligence in Clinical Nurses Related to Negative Psychology and Burnout.

Objective: To explore the influence of negative psychology and burnout in clinical nurses, and to analyse the mediating role between self-efficacy and emotional intelligence in emotion management. Methods: From January 2022 to December 2022, 12,704 clinical nurses from 32 general hospitals in Hunan Province were selected as research participants by convenience sampling. Negative psychology, emotion management, self-efficacy, emotional intelligence and burnout in clinical nurses were measured, and structural equation models were constructed to explore their impact on burnout in clinical nurses. Results: Clinical nurses' negative psychology had a positive effect on burnout (ß=0.60, 95% CI: 0.63-0.66), emotional intelligence (ß=-0.08, 95% CI: -0.10, -0.06) and the self-efficacy of emotion management (ß=-0.60, 95% CI: -0.05, -0.03) on burnout. Moreover, emotional intelligence and emotion management self-efficacy played a mediating role between negative psychology and burnout in nurses. Conclusion: Clinical nurses' negative psychology had a positive impact on burnout, and emotional intelligence and the self-efficacy of emotion management could alleviate the influence of negative psychology on burnout among nurses. Nurses' emotional intelligence and emotion management self-efficacy can be improved through practical training to help them cope with emotionally loaded situations and reduce stress responses.

Application of antimicrobial peptides in plant protection: making use of the overlooked merits.

Pathogen infection is one of the major causes of yield loss in the crop field. The rapid increase of antimicrobial resistance in plant pathogens has urged researchers to develop both new pesticides and management strategies for plant protection. The antimicrobial peptides (AMPs) showed potential on eliminating plant pathogenic fungi and bacteria. Here, we first summarize several overlooked advantages and merits of AMPs, which includes the steep dose-response relations, fast killing ability, broad synergism, slow resistance selection. We then discuss the possible application of AMPs for plant protection with above merits, and highlight how AMPs can be incorporated into a more efficient integrated management system that both increases the crop yield and reduce resistance evolution of pathogens.

Associations between serum trace elements and the risk of nasopharyngeal carcinoma: a multi-center case-control study in Guangdong Province, southern China.

Background: Associations between trace elements and nasopharyngeal carcinoma (NPC) have been speculated but not thoroughly examined. Methods: This study registered a total of 225 newly diagnosed patients with NPC and 225 healthy controls matched by sex and age from three municipal hospitals in Guangdong Province, southern China between 2011 and 2015. Information was collected by questionnaire on the demographic characteristics and other possibly confounding lifestyle factors. Eight trace elements and the level of Epstein-Barr virus (EBV) antibody were measured in casual (spot) serum specimens by inductively coupled plasma-mass spectrometry (ICP-MS) and enzyme-linked immunosorbent assay (ELISA), respectively. Restricted cubic splines and conditional logistic regression were applied to assess the relationship between trace elements and NPC risk through single-and multiple-elements models. Results: Serum levels of chromium (Cr), cobalt (Co), nickel (Ni), arsenic (As), strontium (Sr) and molybdenum (Mo) were not associated with NPC risk. Manganese (Mn) and cadmium (Cd) were positively associated with NPC risk in both single-and multiple-element models, with ORs of the highest tertile compared with the reference categories 3.90 (95% CI, 1.27 to 7.34) for Mn and 2.30 (95% CI, 1.26 to 3.38) for Cd. Restricted cubic splines showed that there was a linear increasing trend between Mn and NPC risk, while for Cd there was a J-type correlation. Conclusion: Serum levels of Cd and Mn was positively related with NPC risk. Prospective researches on the associations of the two trace elements with NPC ought to be taken into account within the future.