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ABSTRACT Purpose This pilot study explored the use of fast volumetric four‐dimensional magnetic resonance imaging (4D‐MRI) for motion characterization in the abdomen, ultimately aiming for the translation to future MR‐guided radiotherapy (MRgRT) applications. Methods Nine healthy subjects and four patients underwent shallow free‐breathing abdominal scans on a 1.5 T MR simulator using a fast volumetric 4D‐MRI sequence with a temporal resolution up to three frames per second. The reference left/right liver and gross target volume (GTV) were segmented on the first frame, and the following consecutive dynamic images were nonlinearly registered to the reference to create the dynamic binary masks. Respiratory probabilistic volumes (rPPVj,i%), which correspond to the probability of being occupied by a volume of interest (VOI), were generated by summating the dynamic binary masks. Subject‐specific rPPV144,0% and rPPV144,5% of the GTV were quantitatively compared to the 4D computed tomography (CT)‐determined internal target volume (ITV) using the dice similarity coefficient (DSC), volumetric difference, and Hausdorff distance (HD). Results The results showed slightly smaller rPPV144,0% and rPPV144,5% but larger DSC and small HD compared to the 4D‐CT‐determined ITV, which preliminarily demonstrates the feasibility and capability of characterizing abdominal respiratory motion using the volumetric 4D‐MRI‐derived rPPV approach. Conclusion The potential usefulness of fast volumetric 4D‐MRI for personalized motion management in future MRgRT is proposed.

Abstract Objective We aimed to determine the planning target volume margins applicable to magnetic resonance‐guided stereotactic body radiation therapy (MRgSBRT) of localized prostate cancer on a 1.5 T MR‐Linac. Methods A total of 10 patients with low‐ to intermediate‐risk prostate cancer were retrospectively enrolled. All patients received five‐fraction MRgSBRT treatments, and underwent daily endorectal ballooning and bladder control. Five patients were implanted with the hydrogel rectal spacer. Three MR scans at each fraction were acquired to evaluate the intrafractional prostate motion. The required planning target volume margin was determined using the van Herk margin recipe based on direct MR‐MR prostate registration. The set‐up margin for localization using bony anatomy was also estimated. Results The mean and standard deviation of translational displacement in left‐right (LR), superior‐inferior (SI), and anterior‐posterior (AP) directions were –0.3 ± 0.7, 2.0 ± 1.5, and 1.4 ± 1.1 mm, respectively. Planning target volume margins over the MRgSBRT fraction duration were 2.8 (LR), 5.3 (SI), and 3.9 mm (AP). Set‐up margins were estimated to 2.6 (LR), 3.3 (SI), and 3.3 mm (AP). Prostate motion increased considerably with treatment duration. Adapt‐to‐position had smaller intrafractional motions than adapt‐to‐shape. The rectal spacer insignificantly (p > 0.1) reduced the prostate motion in SI and AP. Conclusion Online workflow efficiency enhancement and intrafractional motion monitoring are vital for planning target volume margin reduction and precision enhancement in MRgSBRT.

Pathological cardiac hypertrophy serves as a significant foundation for cardiac dysfunction and heart failure. Recently, growing evidence has revealed that microRNAs (miRNAs) play multiple roles in biological processes and participate in cardiovascular diseases. In the present research, we investigate the impact of miRNA-34c-5p on cardiac hypertrophy and the mechanism involved. The expression of miR-34c-5p was proved to be elevated in heart tissues from isoprenaline (ISO)-infused mice. ISO also promoted miR-34c-5p level in primary cultures of neonatal rat cardiomyocytes (NRCMs). Transfection with miR-34c-5p mimic enhanced cell surface area and expression levels of foetal-type genes atrial natriuretic factor (Anf) and β-myosin heavy chain (β-Mhc) in NRCMs. In contrast, treatment with miR-34c-5p inhibitor attenuated ISO-induced hypertrophic responses. Enforced expression of miR-34c-5p by tail intravenous injection of its agomir led to cardiac dysfunction and hypertrophy in mice, whereas inhibiting miR-34c-5p by specific antagomir could protect the animals against ISO-triggered hypertrophic abnormalities. Mechanistically, miR-34c-5p suppressed autophagic flux in cardiomyocytes, which contributed to the development of hypertrophy. Furthermore, the autophagy-related gene 4B (ATG4B) was identified as a direct target of miR-34c-5p, and miR-34c-5p was certified to interact with 3′ untranslated region of Atg4b mRNA by dual-luciferase reporter assay. miR-34c-5p reduced the expression of ATG4B, thereby resulting in decreased autophagy activity and induction of hypertrophy. Inhibition of miR-34c-5p abolished the detrimental effects of ISO by restoring ATG4B and increasing autophagy. In conclusion, our findings illuminate that miR-34c-5p participates in ISO-induced cardiac hypertrophy, at least partly through suppressing ATG4B and autophagy. It suggests that regulation of miR-34c-5p may offer a new way for handling hypertrophy-related cardiac dysfunction.

Obesity is increasingly prevalent globally, searching for therapeutic agents acting on adipose tissue is of great importance. Equisetin (EQST), a meroterpenoid isolated from a marine sponge-derived fungus, has been reported to display antibacterial and antiviral activities. Here, we revealed that EQST displayed anti-obesity effects acting on adipose tissue through inhibiting adipogenesis in vitro and attenuating HFD-induced obesity in mice, doing so without affecting food intake, blood pressure or heart rate. We demonstrated that EQST inhibited the enzyme activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a therapeutic target of obesity in adipose tissue. Anti-obesity properties of EQST were all offset by applying excessive 11β-HSD1's substrates and 11β-HSD1 inhibition through knockdown in vitro or 11β-HSD1 knockout in vivo. In the 11β-HSD1 bypass model constructed by adding excess 11β-HSD1 products, EQST's anti-obesity effects disappeared. Furthermore, EQST directly bond to 11β-HSD1 protein and presented remarkable better intensity on 11β-HSD1 inhibition and better efficacy on anti-obesity than known 11β-HSD1 inhibitor. Therefore, EQST can be developed into anti-obesity candidate compound, and this study may provide more clues for developing higher effective 11β-HSD1 inhibitors.

Abstract Radiomics has increasingly been investigated as a potential biomarker in quantitative imaging to facilitate personalized diagnosis and treatment of head and neck cancer (HNC), a group of malignancies associated with high heterogeneity. However, the feature reliability of radiomics is a major obstacle to its broad validity and generality in application to the highly heterogeneous head and neck (HN) tissues. In particular, feature repeatability of radiomics in magnetic resonance imaging (MRI) acquisition, which is considered a crucial confounding factor of radiomics feature reliability, is still sparsely investigated. This study prospectively investigated the acquisition repeatability of 93 MRI radiomics features in ten HN tissues of 15 healthy volunteers, aiming for potential magnetic resonance-guided radiotherapy (MRgRT) treatment of HNC. Each subject underwent four MRI acquisitions with MRgRT treatment position and immobilization using two pulse sequences of 3D T1-weighed turbo spin-echo and 3D T2-weighed turbo spin-echo on a 1.5 T MRI simulator. The repeatability of radiomics feature acquisition was evaluated in terms of the intraclass correlation coefficient (ICC), whereas within-subject acquisition variability was evaluated in terms of the coefficient of variation (CV). The results showed that MRI radiomics features exhibited heterogeneous acquisition variability and uncertainty dependent on feature types, tissues, and pulse sequences. Only a small fraction of features showed excellent acquisition repeatability (ICC > 0.9) and low within-subject variability. Multiple MRI scans improved the accuracy and confidence of the identification of reliable features concerning MRI acquisition compared to simple test-retest repeated scans. This study contributes to the literature on the reliability of radiomics features with respect to MRI acquisition and the selection of reliable radiomics features for use in modeling in future HNC MRgRT applications.

Abstract Objective Even though extensive studies have surveyed long non-coding RNA (lncRNA)-related networks in hypoxic-ischemic brain damage (HIBD), the concrete function of lncRNA H19 (H19) in HIBD is still in ambiguity. Therein, this work intends to decipher H19-related network of microRNA (miR)-140-5p and signal transducer and activator of transcription 3 (STAT3) in HIBD. Methods Brain microvascular endothelial cells (BMECs) from BALB/c mice were isolated and induced by oxygen glucose deprivation (OGD). OGD-induced BMECs were transfected with depleted or restored H19, miR-140-5p or STAT3, and cell apoptosis, migration and angiogenesis were examined. H19, miR-140-5p and STAT3 expression and their internal connections were tested. Results H19 and STAT3 were overexpressed while miR-140-5p was down-regulated in OGD-induced BMECs. H19 or STAT3 knockdown, or miR-140-5p restoration repressed apoptosis and improved migration and angiogenesis of OGD-induced BMECs. MiR-140-5p restoration negated the impacts of up-regulated H19 on OGD-induced BMECs. H19 bound to miR-140-5p to modulate STAT3 expression. Conclusion The work illustrates that depleting H19 or STAT3 or restoring miR-140-5p attenuates HIBD and supplies a novel perspective for HIBD management.

ObjectivesThe shoulder-hand syndrome (SHS) severely impedes the function recovery process of patients after stroke. It is incapable to identify the factors at high risk for its occurrence, and there is no effective treatment. This study intends to apply the random forest (RF) algorithm in ensemble learning to establish a predictive model for the occurrence of SHS after stroke, aiming to identify high-risk SHS in the first-stroke onset population and discuss possible therapeutic methods.MethodsWe retrospectively studied all the first-onset stroke patients with one-side hemiplegia, then 36 patients that met the criteria were included. The patients’ data concerning a wide spectrum of demographic, clinical, and laboratory data were analyzed. RF algorithms were built to predict the SHS occurrence, and the model’s reliability was measured with a confusion matrix and the area under the receiver operating curves (ROC).ResultsA binary classification model was trained based on 25 handpicked features. The area under the ROC curve of the prediction model was 0.8 and the out-of-bag accuracy rate was 72.73%. The confusion matrix indicated a sensitivity of 0.8 and a specificity of 0.5, respectively. And the feature importance scored the weights (top 3 from large to small) in the classification were D-dimer, C-reactive protein, and hemoglobin.ConclusionA reliable predictive model can be established based on post-stroke patients’ demographic, clinical, and laboratory data. Combining the results of RF and traditional statistical methods, our model found that D-dimer, CRP, and hemoglobin affected the occurrence of the SHS after stroke in a relatively small sample of data with tightly controlled inclusion criteria.

Ischemic stroke has been a prominent focus of scientific investigation owing to its high prevalence, complex pathogenesis, and difficulties in treatment. Mitochondria play an important role in cellular energy homeostasis and are involved in neuronal death following ischemic stroke. Hence, maintaining mitochondrial function is critical for neuronal survival and neurological improvement in ischemic stroke, and mitochondria are key therapeutic targets in cerebral stroke research. With the benefits of high efficacy, low cost, and high safety, traditional Chinese medicine (TCM) has great advantages in preventing and treating ischemic stroke. Accumulating studies have explored the effect of TCM in preventing and treating ischemic stroke from the perspective of regulating mitochondrial structure and function. In this review, we discuss the molecular mechanisms by which mitochondria are involved in ischemic stroke. Furthermore, we summarized the current advances in TCM in preventing and treating ischemic stroke by modulating mitochondria. We aimed to provide a new perspective and enlightenment for TCM in the prevention and treatment of ischemic stroke by modulating mitochondria.

BackgroundSocial deficits are among the most important functional impairments in attention-deficit/hyperactivity disorder (ADHD). However, the relationship between social impairment and ADHD core symptoms as well as the underlying cerebral blood flow (CBF) characteristics remain unclear.MethodsA total of 62 ADHD subjects with social deficits (ADHD + SD), 100 ADHD subjects without social deficits (ADHD-SD) and 81 age-matched typically developing controls (TDC) were enrolled. We first examined the correlation between the Social Responsiveness Scale (SRS-1) and ADHD core symptoms (inattention, hyperactivity, and impulsion) and then explored categorical and dimensional ADHD-related regional CBF by arterial spin labeling (ASL). For the categorical analysis, a voxel-based comparison of CBF maps between the ADHD + SD, ADHD-SD, and TDC groups was performed. For the dimensional analysis, the whole-brain voxel-wise correlation between CBF and ADHD symptoms (inattention, hyperactivity/impulsivity, and total scores) was evaluated in three groups. Finally, correlations between the SRS-1 and ADHD-related regional CBF were investigated. We applied Gaussian random field (GRF) for the correction of multiple comparisons in imaging results (voxel-level P < 0.01, and cluster-level P < 0.05).ResultsThe clinical characteristics analysis showed that social deficits positively correlated with ADHD core symptoms, especially in social communication and autistic mannerisms domains. In the categorical analysis, we found that CBF in the left middle/inferior temporal gyrus in ADHD groups was higher than TDCs and was negatively correlated with the social motivation scores. Moreover, in dimensional analysis, we found that CBF in the left middle frontal gyrus was negatively correlated with the inattention scores, SRS total scores and autistic mannerisms scores in ADHD + SD subjects.ConclusionThe present study shows that inattention, hyperactivity, and impulsivity may be responsible for the occurrence of social deficits in ADHD, with autistic traits being another significant contributing factor. Additionally, CBF in the left middle/inferior temporal gyrus and the left middle frontal gyrus might represent the corresponding physiological mechanisms underlying social deficits in ADHD.

Automated ICD coding via machine learning that focuses on some specific diseases has been a hot topic. As one of the leading causes of death, coronary heart diseases (CHD) have seldom been specifically studied by related research, probably due to lack of data concretely targeting at the diseases. Based on Fuwai-CHD and MIMIC–III–CHD, which are a private dataset from Fuwai Hospital and the CHD-related subset of a public dataset named MIMIC-III respectively, this study aimed at automated CHD coding by a deep learning method, which mainly consists of three modules. The first is a BERT variant module responsible for encoding clinical text. In the module, we fine-tuned BERT variants with masked language model on clinical text, and proposed a truncation method to tackle the problem that BERT variants generally cannot handle sequences containing more than 512 tokens. The second is a word2vec module for encoding code titles and the third is a label-attention module for integrating the embeddings of clinical text and code titles. In short, we named the method BW_att. We compared BW_att against some widely studied baselines, and found that BW_att performed best in most of the coding missions. Specifically, BW_att reached a Macro-F1 of 96.2% and a Macro-AUC of 98.9% for the top-100 most frequent codes in Fuwai-CHD, which covered 89.2% of the total code occurrences. When predicting the top-50 most frequent codes in MIMIC–III–CHD, BW_att reached a Macro-F1 of 40.5% and a Macro-AUC of 66.1%. Moreover, BW_att was capable of locating informative tokens from clinical text for predicting the target codes. In summary, BW_att can not only suggest CHD codes accurately, but also possess robust interpretability, hence has great potential in facilitating CHD coding in practice.

ObjectiveFurther studies are needed to improve the understanding of the pathological process underlying cognitive impairments. The purpose of this study is to investigate the global and topographic changes of white matter integrity and cortical structure related to cognitive impairments in a community-based population.MethodsA cross-sectional analysis was performed based on 995 subjects (aged 56.8 ± 9.1 years, 34.8% males) from the Shunyi study, a community-dwelling cohort. Cognitive status was accessed by a series of neurocognitive tests including Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), category Verbal Fluency Test (VFT), Digit Span Test (DST), and Trail Making Tests A and B (TMT-A and TMT-B). Structural and diffusional MRI data were acquired. White matter integrity was assessed using fractional anisotropy (FA), mean diffusivity (MD), and peak width of skeletonized mean diffusivity (PSMD). Cortical surface area, thickness, and volume were measured using Freesurfer. Probabilistic tractography was further conducted to track the white matter fibers connecting to the cortical regions related to cognition. General linear models were used to investigate the association between brain structure and cognition.ResultsGlobal mean FA and MD were significantly associated with performances in VFT (FA, β 0.119, p

IntroductionThe increased prevalence of non-alcoholic fatty liver disease (NAFLD) and sarcopenia among the elderly are facing a significant challenge to the world’s health systems. Our study aims to identify the coexpressed genes in NAFLD and sarcopenia patients.MethodsWe downloaded the transcriptome data of NAFLD tissue from patients, as well as muscle tissues from sarcopenia patients, from the GEO database in order to investigate the shared transcriptional regulation mechanisms between these two diseases. Then, focusing on the genes that were frequently expressed in these diseases, together with GSVA and WGCNA, we utilized a range of analysis methods to identify the main co-expressed genes in both diseases by taking intersections. We investigated these changes after learning that they mostly affected lipid metabolism and oxidative stress injury pathways.ResultsBy analyzing these genes and their interactions with transcription factors and proteins, we were able to identify 8 genes that share common patterns. From these 8 genes, we were possible to forecast potential future medicines. Our research raises the possibility of NAFLD and sarcopenia transcriptome regulatory pathways in aging populations.DiscussionIn conclusion, a complete transcription pattern mapping was carried out in order to identify the core genes, underlying biological mechanisms, and possible therapeutic targets that regulate aging in NAFLD and sarcopenia patients. It provides novel insights and proof in favor of decreasing the increased prevalence of sarcopenia in the elderly caused by NAFLD.

Staphylococcus aureus is an opportunistic pathogen that shows a unique ability to quickly respond to a variety of antibiotics. The Crp/Fnr family transcriptional regulator ArcR controls expression of arginine deiminase pathway genes arcABDC, which enable the utilization of arginine as an energy source for cell growth under anaerobic conditions. However, ArcR shares low overall similarity with other Crp/Fnr family proteins, suggesting that they differ in the response to environmental stress. In this study, MIC and survival assays were performed to determine the role of ArcR in antibiotic resistance and tolerance. The results showed that deletion of arcR reduced tolerance of S.aureus to fluoroquinolone antibiotics, mainly through a defect in the response to oxidative stress. In ΔarcR mutant, the expression of the major catalase gene katA was downregulated, and katA overexpression restored bacterial resistance to oxidative stress and antibiotics. We showed that ArcR directly regulated katA transcription by binding to the promoter region of katA. Therefore, our results revealed the contribution of ArcR in bacterial tolerance to oxidative stress and subsequently to fluoroquinolones antibiotics. This study added our understanding on the role of Crp/Fnr family in bacterial susceptibility to antibiotics.

A recent, unprecedented outbreak of human mpox virus infection has led to cases in non-African nations, and the number of confirmed or suspected cases outside of Africa has exceeded 1,000 within 5 weeks. Mpox may pose a double threat to public health in the context of the ongoing COVID-19 pandemic. It is difficult to distinguish mpox virus infection from other diseases in the early stages, and patients are contagious from the onset of nonspecific symptoms; therefore, it is crucial to develop rapid and specific diagnostic methods. The diagnosis of mpox relies on real-time polymerase chain reaction, a time-consuming method that requires a highly sophisticated thermal cycler, which makes it unsuitable for widespread use in underdeveloped areas, where the outbreak is still severe. In this study, we developed a recombinase-aided amplification (RAA) assay that can detect mpox virus within 5–10 minutes. The conserved regions of the A27L gene and F3L gene were selected as targets, as they amplify well from different mpox virus clades with no cross-reaction from other pathogens. The sensitivity of this RAA assay is 10 copies/reaction for the A27L gene and 102 copies/reaction for the F3L gene. When applied to simulated clinical samples, both targets showed 100% specificity, and the detection limits were consistent with the sensitivity results. Moreover, through clinical blinded sample detection, RAA exhibits the same detection power as RT-PCR. In summary, the RAA mpox assay described here exhibits rapid detection, high sensitivity and specificity, and low operational difficulty, making it suitable for mpox virus detection in less developed countries and regions.

Objective. We aim to evaluate the impact of diabetes management shared care clinic (DMSCC) on glycated hemoglobin A1c (HbA1c) compliance and self-management abilities in patients with type 2 diabetes mellitus (T2DM). Methods. This study was a prospective cohort study of patients with T2DM participating in the DMSCC. At baseline and after management, the HbA1c levels were measured, the HbA1c compliance rate were calculated, and the Summary of Diabetes Self-Care Activities-6 (SDSCA-6), Diabetes Empowerment Scale-DAWN Short Form (DES-DSF), and Problem Areas in Diabetes Scale—Five-item Short Form (PAID-5) were completed. These pre- and post-management data were compared. Results. A total of 124 eligible patients were enrolled. After the diabetes management of DMSCC, the average HbA1c decreased and the HbA1c compliance rate increased significantly (P

The transition period is the stage of the high incidence of metabolic and infectious diseases in dairy cows. Improving transition dairy cows’ health is crucial for the industry. This study aimed to determine the effects of dietary supplementation medium-chain fatty acids (MCFAs) on immune function, metabolic status, performance of transition dairy cows. Twenty multiparous Holstein cows randomly assigned to two treatments at 35 d before calving. 1) CON (fed the basal 2) MCFA treatment (basal diet was supplemented at an additional 20 g MCFAs mixture every day) until 70 d after calving. The results showed that the serum amyloid A myeloperoxidase concentrations in the blood of cows in MCFA treatment significantly decreased during the early lactation (from 1 d to 28 d after calving) 0.03, 0.04, respectively) compared with the CON, while the tumor necrosis factor concentration was significantly decreased at 56 d after calving (P = 0.02). In addition, the concentration of insulin in the pre-calving (from 21 d before calving to calving) blood of cows in MCFA treatment was significantly decreased (P = 0.04), and concentration of triglyceride also showed a downward trend at 28 d after calving 0.07). Meanwhile, MCFAs supplementation significantly decreased the concentrations of lithocholic acid, hyodeoxycholic acid, and hyocholic acid in the blood at 1 d calving (P = 0.02, < 0.01, < 0.01, respectively), and the level of hyocholic acid taurocholic acid concentrations (P < 0.01, = 0.01, respectively) decreased dramatically at 14 d after calving. However, compared with the CON, the pre-calving dry matter intake and the early lactation milk yield in MCFA treatment were significantly decreased (P = 0.05, 0.02, respectively). In conclusion, MCFAs supplementation transition diet could improve the immune function and metabolic status of dairy cows, and the health of transition cows might be beneficial from the endocrine status.

This study is a first report on the identification of multidrug-resistant (MDR) Acinetobacter bereziniae among non-baumannii acinetobacters that had previously escaped automated laboratory detection, and characterize their clinical courses of infection at two tertiary-care hospitals in Shenzhen city, China (2015–2017). Herein, definitive identification by PCR was performed with universal and species-specific primers targeting 16S rDNA and rpoB genes, respectively, followed by Sanger sequencing and blast analysis. Antimicrobial susceptibility of A. bereziniae isolates was assessed accordingly. Three of the five identified A. bereziniae isolates exhibited carbapenem-resistance and were subjected to a multiplex PCR assay to detect drug-resistance genes. Sequences of the rpoB amplicon were aligned with curated sequences from global databases for phylogenetic analysis on evolutionary relations. Five clinical isolates of A. bereziniae were thereby re-identified, whose infections were primarily nosocomial. Automated identification and susceptibility testing systems (Phoenix-100 and VITEK 2) proved insufficient for discriminating A. bereziniae from other acinetobacters such as Acinetobacter baumannii and Acinetobacter guillouiae. Among these isolates, three exhibited carbapenem-resistant phenotypes indistinguishable from that of carbapenem-resistant A. baumannii. The carbapenem-resistant A. bereziniae isolates were subsequently confirmed to carry a blaNDM-1 (New Delhi metallo-β-lactamase-1) gene downstream of ISAba125. Phylogenetic analysis revealed that A. bereziniae isolates evolved slowly but independently in local habitats. A. bereziniae isolates are difficult to distinguish by traditional automated detection systems. PCR-based identification via amplification and sequencing of selected house-keeping genes provides sufficient resolution for discriminating the isolates.

Lake littoral zones with abundant submerged vegetation are considered to harbor diverse biotic communities and additionally serve as spawning grounds for important fishery resources. In recent decades, due to various human activities submerged vegetation in lakes have declined dramatically resulting in the function loss of spawning grounds. In order to enhance the recruitment of lacustrine fish (mainly Carassius auratus and Cyprinus carpio) and the proliferation of fishery resources, we explored a method of constructing artificial spawning ground based on artificial spawning substrate in lake. The results of present study indicate that the artificial substrates with complex and dense three-dimensional structure which have enough space to enable material exchange and oxygen circulation could be efficient to enhance fish recruitment. The water temperature of spawning peaks of artificial substrates were within the range of 20 ~ 25°C, and the water temperature provides a basis for the deployment period of artificial spawning grounds. The spawning substrate in the upper layer of water column was more attractive for fish to spawn. The above results provide guidance for the deployment of artificial spawning grounds from both temporal and spatial scales. Observations on the behavior of aggregations found that spawning activities mainly occurred at night and in the early morning. The abundance of larger individuals (>20 cm), as potential spawning groups, increased during this period. The above findings are informative to the construction and management of artificial spawning ground in lakes.

ObjectiveTo identify trends in the prevalence of mild cognitive impairment (MCI) and dementia, and to determine risk factors associated with the early detection of dementia among U.S. middle-aged and older adults.MethodsWe used 10-year nationally representative longitudinal data from the Health and Retirement Study (HRS) (2006–2016). Adults aged 55 years or older were included to examine the trend. To identify the associated factors, adults aged 55 years or older in 2006 who developed MCI or dementia in subsequent waves until the 2016 wave were included. Early and late detection of dementia were identified using the Langa-Weir classification of cognitive function. Multivariate logistic regression models were used to identify factors associated with the early detection of dementia.ResultsThe sample size for the analysis of the prevalence of MCI and dementia ranged from 14,935 to 16,115 in the six survey years, and 3,729 individuals were identified to determine associated factors of the early detection of dementia. Among them, participants aged 65 years or older accounted for 77.9%, and male participants accounted for 37.2%. The 10-year prevalence of MCI and dementia was 14.5 and 6.6%, respectively. We also found decreasing prevalence trends in MCI (from 14.9 to 13.6%) and dementia (from 7.4 to 6.0%) overall in the past decade. Using logistic regression controlling for the year, non-Hispanic black (MCI: OR = 2.83, P < 0.001; dementia: OR = 2.53, P < 0.001) and Hispanic (MCI: OR = 2.52, P < 0.001; dementia: OR = 2.62, P < 0.001) had a higher prevalence of both MCI and dementia than non-Hispanic white participants. In addition, men had a lower prevalence of MCI (OR = 0.94, P = 0.035) and dementia (OR = 0.84, P < 0.001) compared to women. Associated factors of the early detection of dementia include age, gender, race, educational attainment, stroke, arthritis diseases, heart problems, and pensions.ConclusionThis study found a decreasing trend in the prevalence of MCI and dementia in the past decade and associated racial/ethnic and gender disparities among U.S. middle-aged and older adults. Healthcare policies and strategies may be needed to address health disparities in the prevalence and take the associated factors of the early detection of dementia into account in clinical settings.

Diarrhea with physical weakness is a highly prevalent symptom in patients with inflammatory bowel disease. Based on the dextran sodium sulfate (DSS) -induced mouse ulcerative colitis model, the present study was undertaken to investigate the effect and the possible mechanism of Hericium caput-medusae (Bull.: Fr.) Pers. fermentation concentrate polysaccharide (HFP) on diarrhea in mice. HFP alleviated DSS-induced symptoms in ulcerative colitis mice, including elevated body weight, increased colonic length as well as mucus layer thickness, and relief of diarrhea. Daily assays revealed that HFP regulated the expression and activity of intestinal ion transport proteins as well as alleviated inflammation. HFP could also reduce the rate of intestinal transit and improved the expression of the tight junction. In summary, HFP had a palliative effect on diarrhea in DSS-induced preliminary stage of ulcerative colitis, which basically make HFP a promising drug for the relief of ulcerative colitis diarrhea.

ABSTRACT: Egg production levels in late laying hens are negatively correlated with increasing age. Decreased liver and ovarian function in aging laying hens is accompanied by decreased antioxidant capacity, reproductive hormone levels, and follicular development, resulting in decreased synthesis of yolk precursors. The golden needle mushroom (Flammulina velutipes) has been reported to exhibit anti-inflammatory, antioxidant, and hypolipidemic properties. We aimed to reveal the therapeutic effects of F. velutipes stem (FVS) on liver–blood–ovary axis and investigate the underlying mechanisms. A total of 360 sixty-seven-wk-old laying hens were randomized into 4 treatment groups: 1) basal maize–soybean meal diet (CON); 2) basal maize + 20 g/kg FVS (2% FVS); 3) basal maize + 40 g/kg FVS (4% FVS); and 4) basal maize + 60 g/kg FVS (6% FVS). FVS groups demonstrated significantly increased egg production and ovarian development compared with the CON group. The addition of FVS increased the levels of antioxidant enzymes (GSH-Px, T-SOD, and T-AOC) in the liver, serum, and ovaries and decreased malondialdehyde levels by regulating the expression of proteins related to the Keap1-Nrf2/ARE signaling pathway. Additionally, FVS significantly decreased ovarian apoptosis by regulating Bax, Bcl-2, and caspase3 mRNA and protein expression levels. FVS significantly increased the expression levels of estradiol, progesterone, luteinizing hormone, and follicle stimulating hormone and their respective receptors. With increased levels of estradiol transported to the liver through the bloodstream, targeted binding to estrogen receptor (ER)-α and ER-β led to significant increases in ApoVLDL II, ApoB, and VTG II mRNA expression associated with yolk precursor synthesis. FVS decreased the levels of triglyceride and total cholesterol and significantly increased the expression of lipid metabolism, and transport-related mRNAs (FAS, PPAR-a/γ, and MTTP) in the liver. Therefore, the dietary supplementation of FVS can maintain the productive performance of aging laying hens by alleviating the degree of oxidative stress and regulating the transport of functional substances along the liver–blood–ovary axis, thereby improving the synthesis of yolk precursors.

High-definition fluorescent micro-optical sectioning tomography is employed to resolve fine structures of multiple vessel types in the intact liver.

Abstract Background Rapid and accurate detection of drug resistance in Mycobacterium tuberculosis is critical for effective control of tuberculosis (TB). Herein, we established a novel, low cost strategy having high accuracy and speed for the detection of M. tuberculosis drug resistance, using gene splicing by overlap extension PCR (SOE PCR). Methods The SOE PCR assay and Sanger sequencing are designed and constructed to detect mutations of rpoB, embB, katG, and inhA promoter, which have been considered as the major contributors to rifampicin (RFP), isoniazid (INH), and ethambutol (EMB) resistance in M. tuberculosis. One hundred and eight M. tuberculosis isolates came from mycobacterial cultures of TB cases at Chongqing Public Health Medical Center in China from December 2018 to April 2019, of which 56 isolates were tested with the GeneXpert MTB/RIF assay. Performance evaluation of the SOE PCR technique was compared with traditional mycobacterial culture and drug susceptibility testing (DST) or GeneXpert MTB/RIF among these isolates. Kappa identity test was used to analyze the consistency of the different diagnostic methods. Results We found that the mutations of S531L, S315T and M306V were most prevalent for RFP, INH and EMB resistance, respectively, in the 108 M. tuberculosis isolates. Compared with phenotypic DST, the sensitivity and specificity of the SOE PCR assay for resistance detection were 100.00% and 88.00% for RFP, 94.64% and 94.23% for INH, and 68.97% and 79.75% for EMB, respectively. Compared with the GeneXpert MTB/RIF, the SOE PCR method was completely consistent with results of the GeneXpert MTB/RIF, with a concordance of 100% for resistance to RFP. Conclusions In present study, a novel SOE PCR diagnostic method was successfully developed for the accurate detection of M. tuberculosis drug resistance. Our results using this method have a high consistency with that of traditional phenotypic DST or GeneXpert MTB/RIF, and SOE PCR testing in clinical isolates can also be conducted rapidly and simultaneously for detection of drug resistance to RFP, EMB, and INH. Graphical Abstract

Marine oil spills accidents has caused a large amount of crude oil to leak into the marine environment and threaten marine ecological environment. Hyperspectral remote sensing images (HRSI) technology can quickly and accurately identify oil film of different thickness on marine surface. In order to overcome the traditional spectrum analysis method and space extraction method of long time sampling, calculation, analysis and other shortcomings. On account of the advantages of the spectral and spatial information in the field of HRSI classification, a spectral-spatial features extraction (SSFE) method based convolutional neural networks (CNNs) was proposed to analyse oil spills. In this way, one and two dimensional models based on convolutional neural networks (1D-CNN,2D-CNN) have been introduced as the spectral and spatial features extractor. When extracting spatial features, double-two convolution layers are connected to increasing nonlinearity and reduce the number of parameters. Furthermore, in order to address overfitting and imbalance samples, L2 regularization, class_weight and drouput is added to classes data modeling. More importantly, principal component analysis (PCA) is applied to data dimension reduction, 1D-CNN and 2D-CNN is combined into a unified model further extract the joint spatial-spectral features. To evaluate the effectiveness of the proposed approach, three hyperspectral datasets were utilized, including: University of Pavia dataset, oil spill area 1, oil spill area 2. Experimental results reveal that the proposed method have a very satisfactory performance and better distinguish oil spills.

Triangular planar ring resonant cavities are widely used in cavity ring-down spectroscopes (CRDS) because of the unique optical path advantage. Hermite-Gaussian theory is the classical method used to describe the beam in the resonant cavity. Since this theory can express the transverse electromagnetic mode (TEM) in the meridian plane and sagittal surface separately in an astigmatic triangular cavity, it has a unique advantage in the analysis of triangular cavities. However, among the many analyses of triangular ring-down cavities, existing theories of Hermite-Gaussian modes have not been able to reasonably explain the many phenomena observed in alignment and ring-down experiments. In this paper, the mechanisms of the effects of first-order Hermite-Gaussian mode on mounting alignment in CRDS instruments are investigated in depth. The frequency separation characteristics of the lower-order mode in the triangular cavity are verified in the mounting alignment stage. The separation characteristics of first-order mode can guide the misalignment of the two orthogonal planes separately. The resonant frequency separation property of the Hermite-Gaussian mode in a triangular ring-down cavity can also be applied to more complex odd-numbered cavity mirror resonant systems.

The fermentation process and composition of volatile compounds play a crucial role in the production of Huaniu apple cider. This study aimed to optimize the fermentation conditions of Huaniu apple cider and quantify its volatile compounds using headspace solid-phase microextraction-gas chromatography–mass spectrometry (HS-SPME-GC/MS). The optimal fermentation parameters were determined using response surface methodology (RSM). The optimal fermentation temperature was 25.48 °C, initial soluble solids were 18.90 degrees Brix, inoculation amount was 8.23%, and initial pH was 3.93. The fermentation rate was determined to be 3.0, and the predicted value from the verification test was 3.014. This finding demonstrated the excellent predictability of a RSM-optimized fermentation test for Huaniu apple cider, indicating the reliability of the process conditions. Moreover, the analysis of volatile compounds in the optimized Huaniu cider identified 72 different ingredients, including 41 esters, 16 alcohols, 6 acids, and 9 other substances. Notably, the esters exhibited high levels of ethyl acetate, ethyl octanoate, and ethyl capricate. Similarly, the alcohols demonstrated higher levels of 3-methyl-1-butanol, phenethylethanol, and 2-methyl-1-propanol, while the acids displayed increased concentrations of acetic acid, caproic acid, and caprylic acid. This study provides the essential technical parameters required for the preparation of Huaniu apple cider while also serving as a valuable reference for investigating its distinct flavor profile.

Recently, considerable efforts have been devoted to the estimation of soil properties using optical payloads mounted on drones or satellites. Nevertheless, many studies focus on diverse pretreatments and modeling techniques, while there continues to be a conspicuous absence of research examining the impact of parameters related to optical remote sensing payloads on predictive performance. The main aim of this study is to evaluate how the spectral resolution and signal-to-noise ratio (SNR) of spectrometers affect the precision of predictions for soil organic matter (SOM) content. For this purpose, the initial soil spectral library was partitioned into to two simulated soil spectral libraries, each of which were individually adjusted with respect to the spectral resolutions and SNR levels. To verify the consistency and generality of our results, we employed four multiple regression models to develop multivariate calibration models. Subsequently, in order to determine the minimum spectral resolution and SNR level without significantly affecting the prediction accuracy, we conducted ANOVA tests on the RMSE and R2 obtained from the independent validation dataset. Our results revealed that (i) the factors significantly affecting SOM prediction performance, in descending order of magnitude, were the SNR levels > spectral resolutions > estimation models, (ii) no substantial difference existed in predictive performance when the spectral resolution fell within 100 nm, and (iii) when the SNR levels exceeded 15%, altering them did not notably affect the SOM predictive performance. This study is expected to provide valuable insights for the design of future optical remote sensing payloads aimed at monitoring large-scale SOM dynamics.

Pulse signals refer to electromagnetic waveforms with short duration and high peak energy in the time domain. Spatial electromagnetic pulse interference signals can be caused by various factors such as lightning, arc discharge, solar disturbances, and electromagnetic disturbances in space. Pulse disturbance signals appear as instantaneous, high-energy vertical-line pulse trains (VLPTs) on the spectrogram. This paper uses computer vision techniques and unsupervised clustering algorithms to process and analyze VLPT on very-low-frequency (VLF) waveform spectrograms collected by the China Seismo-Electromagnetic Satellite (CSES) electric field detector. First, the waveform data are transformed into time–frequency spectrograms with a duration of 8 s using the short-time Fourier transform. Then, the spectrograms are subjected to grayscale transformation, vertical line feature extraction, and binarization preprocessing. In the third step, the preprocessed data are dimensionally reduced and fed into an unsupervised K-means++ clustering model to achieve automatic recognition and labeling of VLPTs. By recognizing and studying VLPT, not only can interference be recognized, but the temporal and spatial locations of these interferences can also be determined. This lays the foundation for identifying VLPT sources and gaining deeper insights into the generation, propagation, and characteristics of electromagnetic radiation.

Ionospheric disturbances are mainly caused by solar and Earth surface activity. The electromagnetic data collected by the CSES (China Seismo-Electromagnetic Satellite, popularly known as the Zhangheng-1 satellite) can capture many space disturbances. Different spatial disturbances can exhibit distinctive shapes on spectrograms. Constant-frequency electromagnetic disturbances (CFEDs) such as artificially transmitted VLF radio waves, power line harmonics, and satellite platform disturbances can appear as horizontal lines on spectrograms. Therefore, we used computer vision and machine learning techniques to extract the frequency of global CFEDs and analyze their strong spatial signal characteristics. First, we obtained time-frequency spectrograms from CSES VLF electric-field waveform data using Fourier transform. Next, we employed an unsupervised clustering algorithm to automatically recognize CFED horizontal lines on spectrograms, merging horizontal lines from different spectrograms, to obtain the CFED horizontal-line frequency range. In the third stage, we verified the presence of CFEDs in power spectrograms, thus extracting their true frequency values. Finally, for strong CFED signals, we generated eight revisited periods, resulting in 10,230 power spectrograms for analyzing each CFED’s spatial characteristics using a combined periodic sequence and spatial region that included frequency offsets, frequency fluctuations, and signal non-observation areas. These findings contribute to enhancing the quality of CSES observational data and provides a theoretical basis for constructing global CFED spatial background fields and earthquake monitoring and early prediction systems.

Tritium waste deposition in air-unsaturated groundwater zones poses great challenges to optimal water allocation. This paper reviews the research progress of air-unsaturated-groundwater interaction. Traditional interaction studies typically model the fate and migration of pollutants in different regions. This can lead to biased results and simulation errors. The development of air-unsaturated-ground integrated modeling will be a breakthrough and a hotspot in tritium management. In this paper, the fate and migration of tritium leakage is further studied using the existing extended Environment Multimedia Modeling System (EEMMS). Moreover, to better understand its distribution in three zones, using tritium as a typical pollutant, it is necessary to consider its characteristics in different zones, especially its migration from unsaturated zones to groundwater and air zones. The result shows that the tritiated water vapor transfer in unsaturated groundwater areas decreases and part of the tritiated water vapor transfers to atmospheric areas as tritiated gas vapor. Compared with the analytical test accuracy (5 pCi mL−1), the accuracy of the tritium modeling using the finite element method can reach the minimum concentration limit of 0 pCi mL−1. The study of its distribution in air-unsaturated-groundwater zones can provide reference for other similar tritium management or NAPLs distribution across multimedia area.

Objective: To elucidate the bidirectional correlation of sarcopenia with coronary heart disease (CHD), as well as to investigate the mediating role of cardiometabolic factors and inflammatory biomarkers, a bidirectional two-sample, two-step Mendelian randomization (MR) study was conducted. Methods: Summary statistics were obtained from genome-wide association studies (GWAS). In our bidirectional two-sample MR, genetic variants associated with sarcopenia-related traits and CHD were instrumented for the estimation of bidirectional correlations. Besides, genetic variants associated with thirteen cardiometabolic factors and six inflammatory biomarkers were selected for further mediation analyses. To confirm the consistency of the results, several sensitivity analyses were carried out. Results: Genetically predicted higher appendicular lean mass (OR = 0.835, 95% CI: 0.790–0.882), left hand grip strength (OR = 0.703, 95% CI: 0.569–0.869), right hand grip strength (OR = 0.685, 95% CI: 0.555–0.844), and walking pace (OR = 0.321, 95% CI: 0.191–0.539) reduced CHD risk, while genetic predisposition to CHD did not affect any of the sarcopenia-related traits. Seven mediators were identified for the effects of appendicular lean mass on CHD, including waist-to-hip ratio, hip circumference, systolic blood pressure, low-density lipoprotein cholesterol, total cholesterol, triglycerides, and fasting insulin. The mediation proportion ranged from 10.23% for triglycerides to 35.08% for hip circumference. Hip circumference was found to mediate the relationships between both left (mediation proportion: 24.61%) and right-hand grip strength (24.14%) and CHD, and the link between walking pace and CHD was partially mediated by waist-to-hip ratio (31.15%) and body mass index (26.66%). Conclusion: Our results showed that higher appendicular lean mass, hand grip strength, and walking pace reduced CHD risk, but the causal relationship was not bidirectional. Several mediators were found to mediate the causal pathways between sarcopenia-related traits and CHD, and intervention of these factors may be helpful in terms of CHD prevention in sarcopenia patients.

Abstract Whether the definition of hypertension according to 2017 AHA/ACC guidelines and blood pressure (BP) changes was related to the increased risk of chronic kidney disease (CKD) remained debated. This prospective cohort study aimed to investigate the association of BP and long‐term BP change with CKD risk with different glucose metabolism according to the new hypertension guidelines. This study examined 12 951 participants and 11 183 participants derived from the older people cohort study, respectively. Participants were divided into three groups based on blood glucose and the risks were assessmented by the logistic regression model. During a 10 years of follow‐up period, 2727 individuals developed CKD (21.1%). Compared with those with BP

Abstract Background Normal-weight maintenance hemodialysis (MHD) patients with abdominal obesity exhibited a more proatherogenic profile than overweight and obesity patients with abdominal obesity, highlighting the importance of early identification of metabolically unhealthy nonobese (MUNO) in this population. Visceral fat accumulation plays a crucial role in the development of MUNO. Lipid accumulation product (LAP), visceral adiposity index (VAI) have been proved as reliable visceral obesity markers. The Chinese visceral adiposity index (CVAI) and a body shape index (ABSI) are newly discovered indexes of visceral obesity and have been reported to be associated with multiple metabolic disorders. There are limited studies investigating the associations between different visceral obesity indices and risk of MUNO, especially in hemodialysis patients. Moreover, no general agreement has been reached to date regarding which of these obesity indices performs best in identifying MUNO. We aimed to investigate the prevalence of MUNO in MHD patients and compare the associations between different adiposity indices (CVAI, ABSI,VAI, LAP, body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHtR)) with MUNO risk in this population. Methods We conducted a multi-center cross-sectional study in Guizhou Province, Southwest China. 1302 nonobese adult MHD patients were included in our study. MUNO was defined as being nonobese and having the presence of > = 2 components of metabolic syndrome (MetS). Nonobese was defined as BMI less than 25 kg/m2. VAI, LAP, CVAI, ABSI, BMI, WC and WHtR were calculated. Logistic regression analyses and receiver operator curve (ROC) analyses were performed. Results 65.6% participants were metabolically unhealthy. The ROC curve analysis demonstrated that of the seven obesity indices tested, the VAI (AUC 0.84 for women and 0.79 for men) followed by LAP (AUC 0.78 for women and 0.72 for men) had the highest diagnostic accuracy for MUNO phenotype while ABSI exhibited the lowest AUC value for identifying MUNO phenotype Conclusions Metabolically unhealthy is highly prevalent in nonobese MHD patients. VAI and LAP outperformed CVAI in discriminating MUNO in MHD patients. Though ABSI could be a weak predictor of MUNO, it is not better than WHtR, WC and BMI.

New SARS-CoV-2 mutants have been continuously indentified with enhanced transmission ever since its outbreak in early 2020. As an RNA virus, SARS-CoV-2 has a high mutation rate due to the low fidelity of RNA polymerase. To study the single nucleotide polymorphisms (SNPs) dynamics of SARS-CoV-2, 158 SNPs with high confidence were identified by deep meta-transcriptomic sequencing, and the most common SNP type was C > T. Analyses of intra-host population diversity revealed that intra-host quasispecies’ composition varies with time during the early onset of symptoms, which implicates viral evolution during infection. Network analysis of co-occurring SNPs revealed the most abundant non-synonymous SNP 22,638 in the S glycoprotein RBD region and 28,144 in the ORF8 region. Furthermore, SARS-CoV-2 variations differ in an individual’s respiratory tissue (nose, throat, BALF, or sputum), suggesting independent compartmentalization of SARS-CoV-2 populations in patients. The positive selection analysis of the SARS-CoV-2 genome uncovered the positive selected amino acid G251V on ORF3a. Alternative allele frequency spectrum (AAFS) of all variants revealed that ORF8 could bear alternate alleles with high frequency. Overall, the results show the quasispecies’ profile of SARS-CoV-2 in the respiratory tract in the first two months after the outbreak.

Abstract Background The incidence of hand foot and mouth disease (HFMD) has increased in recent years, making it a very common childhood illness worldwide. The relationship between different enterovirus genotypes and disease severity is not clearly understood. Given that enteroviruses are transmitted through the gastrointestinal tract, we hypothesized that variation in intestinal microorganisms of the host might play a role in the prognosis of HFMD. Methods We carried out a meta-transcriptomic-wide association study of fecal samples obtained from a cohort of children (254 patients, 227 tested positive for enterovirus, including 16 patients co-infectied with 2 kinds of enterovirus) with mild and severe HFMD and healthy controls. Results We found there was no significant difference in the amount of each virus type between the mild and severe cases. Genes of enterovirus 71 (EV71) and coxsackievirus A (CV-A) from the severe and mild cases did not show significant clustering. Clostridium sp. L2-50 and Bacteroides stercoris ATCC 43183 were enriched in the guts of children with severe HFMD and KEGG enrichment was found between mild and severe cases. Conclusions Intestinal microorganisms appear to interact with enterovirus to determine the progression of HFMD. Genes of Bacteroides and Clostridium may be used as predictive markers for a more efficient prognosis and intervention. The enrichment of intestinal bacteria genes with functions may facilitate the development of severe symptoms for HFMD patients.

Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is a disease with an incomplete pathological mechanism, long treatment time, and uncertain factors affecting the therapeutic effect. This study explored prognostic factors for DEACMP patients treated with hyperbaric oxygen therapy (HBOT) in 15 hospitals in China. The findings might provide a theoretical basis for further improving the prognosis of DEACMP patients.In this study, data from 330 patients with DEACMP who were admitted to HBOT centers of 15 hospitals in Hunan Province (China) from June 2015 to June 2020 were retrospectively analyzed, and their medical records related to disease prognosis were collected and followed up by telephone. Univariate and multivariate analyses were used to identify independent risk factors for the prognosis of DEACMP patients after HBOT. Univariate analysis revealed 11 possible prognostic factors. Consistent with univariate analysis, multivariate analysis found that underlying diseases (Odds radio(OR) = 2.886, P = 0.048), hypermyotonia (OR = 5.2558, P = 0.008), and HBOT pressure no less Than 2.3 atm absolute (ATA) ((OR = 7.812, P = 0.004) were identified as independent prognostic factors among 20 variables for poor prognosis of DEACMP patients treated with HBOT in the study. This multicenter retrospective analysis revealed that the adverse prognostic markers for DEACMP patients treated with HBOT might be underlying diseases, hypermyotonia, and an HBOT pressure of 2.3 ATA or higher.

Static facultative heap composting of animal manure is widely used in China, but there is almost no systematic research on the phytotoxicity of the produced compost. Here, we evaluated the phytotoxic variation in compost produced by facultative heap composting of four types of animal manure (chicken manure, pig manure, sheep manure, and cattle manure) using different plant seeds (cucumber, radish, Chinese cabbage, and oilseed rape) to determine germination index (GI). The key factors that affected GI values were identified, including the dynamics of the phytotoxicity and microbial community during heap composting. Sensitivity to toxicity differed depending on the type of plant seed used. Phytotoxicity during facultative heap composting, evaluated by the GI, was in the order: chicken manure (0–6.6 %)

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare neurological disease of unknown etiology, and most patients with PERM are positive for anti-glycine receptor (GlyR) antibody. In this case study, we report a clinical case of a varicella-zoster virus-infected patient who developed anti-GlyR antibody-positive PERM. He initially suffered from herpes zoster and gradually developed symptoms of impaired brainstem functions including hoarse voice and dysphagia, accompanied by paroxysmal sympathetic hyperactivity. The patient also suffered from severe spasms, which were easily triggered by external stimuli. Glycine receptor antibodies were then found to be positive in serum and cerebrospinal fluid, and the diagnosis of PERM was confirmed. Methylprednisolone and gamma globulin treatments were given, and spasms were improved after treatment. Unfortunately, the patient's family insisted on automatic discharge and the patient passed away several days later.

Abstract Axonal projection conveys neural information. The divergent and diverse projections of individual neurons imply the complexity of information flow. It is necessary to investigate the relationship between the projection and functional information at the single neuron level for understanding the rules of neural circuit assembly, but a gap remains due to a lack of methods to map the function to whole‐brain projection. Here an approach is developed to bridge two‐photon calcium imaging in vivo with high‐resolution whole‐brain imaging based on sparse labeling with the genetically encoded calcium indicator GCaMP6. Reliable whole‐brain projections are captured by the high‐definition fluorescent micro‐optical sectioning tomography (HD‐fMOST). A cross‐modality cell matching is performed and the functional annotation of whole‐brain projection at the single‐neuron level (FAWPS) is obtained. Applying it to the layer 2/3 (L2/3) neurons in mouse visual cortex, the relationship is investigated between functional preferences and axonal projection features. The functional preference of projection motifs and the correlation between axonal length in MOs and neuronal orientation selectivity, suggest that projection motif‐defined neurons form a functionally specific information flow, and the projection strength in specific targets relates to the information clarity. This pipeline provides a new way to understand the principle of neuronal information transmission.

This trial aimed to evaluate the effectiveness and safety of SGL 121(ginsenoside F2-enhanced mixture) in ameliorating human liver dysfunction. A total of 120 participants (46 ≤ alanine aminotransferase (ALT) ≤ 135 IU/L) were randomly distributed into two groups, the SGL 121 and placebo (crystalline cellulose) groups, which received 500 mg and 0 mg SGL 121 per day, respectively. After 12 weeks of intervention, gamma-glutamyl transferase (GGT) levels in the SGL 121 group were significantly decreased compared to the placebo group (p = 0.022). Similarly, ALT levels showed a tendency to decrease (p = 0.080). Regarding fatigue, the subscale scores (interference in daily living activities) and the total multidimensional fatigue scale (MFS) scores were lower in the SGL 121 group than in the placebo group (p = 0.009 and p = 0.046, respectively). No significant differences in adverse events were apparent between the two groups. The results of this study suggest that SGL 121 exerted beneficial effects on liver dysfunction by improving liver enzyme levels and fatigue.

Background: Dexmedetomidine (Dex), as a new and highly selective α2 adrenergic receptor agonist, has been widely used in mechanically ventilated patients. In the present study, we used meta-analysis to study the effect of Dex on the prognosis of mechanically ventilated patients with sepsis. Methods: We searched PubMed, Cochrane clinical trial, EMBASE, Web of Science, and Chinese biomedical literature database to analyze relevant literature published from January 2000 to January 2021. We conducted the quality evaluation and data extraction for studies that met the inclusion criteria. RevMan 5.3 software was used to perform a meta-analysis of the 28-day mortality, hospital mortality, the length of ICU stay, and other adverse indicators. Results: Ten randomized controlled trials (RCTs) that met the inclusion criteria were finally included, including 9 RCTs in English and one in Chinese, with a total of 892 patients. Our meta-analysis results found that in mechanically ventilated patients with sepsis, Dex could significantly reduce the length of ICU stay (P=0.02), but did not reduce the patients' 28-day mortality (P=0.06), hospital mortality (P=0.17) and ventilator-free days (P=0.33). Furthermore, our meta-analysis results also found that Dex had no significant effect on the respiratory rate (P=0.53), heart rate (P=0.02), mean arterial pressure (P=0.63), the level of creatinine (P=0.82) and continuous renal replacement therapy (P=0.39) in mechanically ventilated patients with sepsis. Conclusion: In mechanically ventilated patients with sepsis, Dex can reduce the length of ICU stay, but which cannot reduce the 28-day mortality, hospital mortality, and ventilator-free days.

ABSTRACT Pneumonia caused by multidrug-resistant (MDR) Klebsiella pneumoniae of sequence types ST11 and ST383 have highlighted the necessity for new therapies against these prevalent pathogens. Bacteriophages (phages) may be used as alternatives or complements to antibiotics for treating MDR bacteria because they show potential efficacy in mouse models and even individual clinical cases, and they also cause fewer side effects, such as microbiota-imbalance-induced diseases. In the present study, we screened two phages, pKp11 and pKp383, that targeted ST11 and ST383 MDR K. pneumoniae isolates collected from patients with pneumonia, and they exhibited a broad host range, high lytic activity, and high environmental adaptability. Both phages pKp11 and pKp383 provided an effective treatment for the early stage of pneumonia in a murine infection model without promoting obvious side effects, and cocktails consisting of the two phages were more effective for reducing bacterial loads, inflammation, and pathogenic injuries. Our findings support the application of phages as new medications for refractory ST11 and ST383 K. pneumoniae infections and emphasize the potential of enhancing phage therapy modalities through phage screening. These data provided important resources for assessing and optimizing phage therapies for MDR ST11 and ST383 infection treatment. However, substantial amounts of further work are needed before phage therapy can be translated to human therapeutics. IMPORTANCE K. pneumoniae is recognized as the most common pathogen of hospital- and community-acquired pneumonia across the world. The strains of ST11 and ST383 are frequently reported in patients with pneumonia. However, the efficacy of antibiotics toward K. pneumoniae is decreasing dramatically. As a new approach to combat MDR bacteria, phages have exhibited positive clinical effects and efficacy as synergetic or alternative strategies to antibiotics. Thus, we screened two phages that targeted ST11 and ST383 MDR K. pneumoniae, and they exhibited a broad host range, high lytic activity, and high environmental adaptability. Both phages provided an effective treatment for the early stage of pneumonia in mice, and cocktails consisting of the two phages were more effective in reducing bacterial loads, inflammation, and pathogenic injuries. Although these data suggest that phages are effective alternatives or complements to antibiotics, more research is needed before they can be translated into therapeutics for humans.

ABSTRACT Monkeypox virus (MPXV) is a human pathogenic virus that belongs to the genus Orthopoxvirus. In 2022, MPXV caused an unprecedented number of infections in many countries. As it is difficult to distinguish MPXV from other pathogens by its symptoms in the early stage of infection, a rapid and reliable assay for MPXV detection is needed. In this study, we developed a loop-mediated isothermal amplification (LAMP) assay for the specific detection of MPXV and evaluated its application in simulated clinical samples. The A27L-1 and F3L-1 primer sets were identified as the optimal primers, and 63°C was the most appropriate reaction temperature for sequence amplification. The detection limits of the LAMP assay using primer sets A27L-1 and F3L-1 were both 20 copies/reaction mixture, which were >100-fold higher in terms of sensitivity, compared with conventional PCR. The LAMP assay findings were negative for all 21 non-MPXV pathogens, confirming the high specificity of our assay. All three types of simulated clinical samples were clearly identified by our LAMP assay, and the detection limits were consistent with the sensitivity results, indicating efficient clinical sample identification. Our rapid and reliable MPXV LAMP assay could be useful for MPXV detection and on-site diagnosis, especially in primary hospitals and rural areas. IMPORTANCE MPXV outbreaks rapidly grew in the first half of 2022, and this virus has been recognized as an increasing public health threat, particularly in the context of the COVID-19 pandemic. Thus, developing reliable and fast detection methods for MPXV is necessary.

Introduction: Cognitive impairment is prevalent in patients undergoing hemodialysis (HD), which is related to the nutritional and inflammatory status of this population. Malnutrition-inflammation score (MIS) has been identified as a useful tool to evaluate nutrition and inflammation status. The aim of this study is to investigate the association between MIS and cognitive impairment in HD patients. Methods: This was a multicenter observational cohort study with 1591 patients undergoing HD. Nutritional and inflammatory status was evaluated with MIS, anthropometric measurements, and body composition assessments. Cognitive function was evaluated with the Mini Mental State Examination (MMSE). The associations between MIS and cognitive impairment were analyzed by multivariable logistic regression models. Results: Among 1591 HD patients, the mean MIS was 6.0±2.6. Patients with higher MIS had significantly lower MMSE scores. 311 patients had cognitive impairment. After adjusting clinical confounders, higher MIS was independently associated with increased rate of cognitive impairment both as a categorized variable (OR, 1.358; 95%CI, 1.010-1.825; P=0.045) and as a continuous variable (OR, 1.113; 95%CI, 1.053-1.178; P

Osteoporosis is a disease that impacts the elderly. Low estrogen is related to changes in DNA methylation and consequent alterations in gene expression, leading to a new direction in research related to the pathophysiology of osteoporosis. We constructed an Ovariectomized (OVX) mouse model in our study, and the mouse models had osteoporosis based on the phenotype and methylation levels in the mouse’s bone. Furthermore, the methylation level of the OVX mice was significantly changed compared to that of SHAM mice. Therefore, we performed genome-level analysis on the mouse model using transcriptome and Whole Genome Bisulfite Sequencing (WGBS) by combining the data of two omics and discovered that the changes in gene expression level caused by osteoporosis primarily focused on the decrease of bone and muscle development and the activation of the immune system. According to intersection analysis of methylation and transcriptome data, the differentially expressed genes and pathways are consistent with the differentially expressed methylation locations and regions. Further, the differentially expressed methylation sites were mainly concentrated in promoters, exons, and other critical functional regions of essential differentially expressed genes. This is also the primary cause of gene differential expression variations, indicating that estrogen deficiency might regulate gene expression by altering methylation modification, leading to osteoporosis. We demonstrated the clinical value of methylation modification research, and these findings would improve the current understanding of underlying molecular mechanisms of osteoporosis incidence and development and provide new ideas for early detection and treatment of osteoporosis.

Inverted light-sheet microscopy (ILSM) is widely employed for fast large-volume imaging of biological tissue. However, the scattering especially in an uncleared sample, and the divergent propagation of the illumination beam lead to a trade-off between axial resolution and imaging depth. Herein, we propose naturally modulated ILSM (NM-ILSM) as a technique to improve axial resolution while simultaneously maintaining the wide field-of-view (FOV), and enhancing imaging contrast via background suppression. Theoretical derivations, simulations, and experimental imaging demonstrate 15% axial resolution increases, and fivefold greater image contrast compared with conventional ILSM. Therefore, NM-ILSM allows convenient imaging quality improvement for uncleared tissue and could extend the biological application scope of ILSM.

Acute kidney injury (AKI) is a complex and common set of multifactorial clinical syndromes, and associated with increased in-hospital mortality. There is increasing evidence that Hyperhomocysteinemia (HHcy) is highly associated with the development of a variety of kidney diseases, including AKI. However, the pathogenesis of HHcy in AKI remains unclear. In this study, we investigated the effect and mechanism of HHcy on cisplatin-induced AKI in mice and NRK-52E cells cultured with HHcy. We confirmed that mice with HHcy had higher serum levels of creatinine and more severe renal tubule injury after cisplatin injection. We found that HHcy aggravated renal mitochondrial damage, mainly manifested as decreased ATP β, significantly increased cytoplasmic Cyt C expression and the ADP/ATP ratio, and a significantly decreased mitochondrial DNA (mtDNA) copy number. In addition, we found that HHcy accelerated cisplatin-induced renal DNA damage; culturing NRK-52E cells with homocysteine (Hcy) could significantly increase apoptosis and mitochondrial damage. Interestingly, we found that Mdivi-1 reduced Hcy-induced mitochondrial damage, thereby reducing the level of apoptosis. In conclusion, these results suggest that HHcy might aggravate the development of AKI by increasing mitochondrial damage and that reducing Hcy levels or inhibiting mitochondrial damage may be a potential therapeutic strategy to delay the development of AKI.

Visualizing the relationships and interactions among different biological components in the whole brain is crucial to our understanding of brain structures and functions. However, an automatic multicolor whole-brain imaging technique is still lacking. Here, we developed a multicolor wide-field large-volume tomography (multicolor WVT) to simultaneously acquire fluorescent signals in blue, green, and red channels in the whole brain. To facilitate the segmentation of brain regions and anatomical annotation, we used 4′, 6-diamidino-2-phenylindole (DAPI) to provide cytoarchitecture through real-time counterstaining. We optimized the imaging planes and modes of three channels to overcome the axial chromatic aberration of the illumination path and avoid the crosstalk from DAPI to the green channel without the modification of system configuration. We also developed an automatic contour recognition algorithm based on DAPI-staining cytoarchitecture to shorten data acquisition time and reduce data redundancy. To demonstrate the potential of our system in deciphering the relationship of the multiple components of neural circuits, we acquired and quantified the brain-wide distributions of cholinergic neurons and input of ventral Caudoputamen (CP) with the anatomical annotation in the same brain. We further identified the cholinergic type of upstream neurons projecting to CP through the triple-color collocated analysis and quantified its proportions in the two brain-wide distributions. Both accounted for 0.22%, implying CP might be modulated by non-cholinergic neurons. Our method provides a new research tool for studying the different biological components in the same organ and potentially facilitates the understanding of the processing mechanism of neural circuits and other biological activities.

A 90-day feeding trial was conducted to evaluate the effects of cottonseed protein concentrate (CPC) replacing dietary fishmeal on growth performance, feed utilization and protein metabolism of large yellow croaker (initial body weight: 191.60 ± 1.36 g). Seven iso-nitrogenous and iso-lipidic experimental diets were formulated by replacing 0%, 15%, 30%, 45%, 60%, 75% and 100% of dietary fishmeal with CPC. The experimental diets were named as CPC0, CPC15, CPC30, CPC45, CPC60, CPC75 and CPC100, respectively. Results showed that when CPC replacement level was less than 60%, there were no significant differences in survival, weight gain rate, feed intake, feed conversion ratio, protein efficiency ratio, hepatosomatic index, visceral somatic index and condition factor of large yellow croaker compared with those in the CPC0 group (P > 0.05). The dorsal muscle proximate compositions and amino acid profiles were not significantly affected by dietary CPC replacement levels (P > 0.05). Compared with those in the control group, digestive and absorptive enzymes activities in the intestine and liver in the CPC75 and CPC100 groups decreased significantly (P < 0.05). The perimeter ratio, muscularis thickness and villus height in the intestine decreased linearly with increasing replacement levels of dietary fishmeal by CPC (P < 0.05). Compared with those in the CPC0 group, the mRNA levels of mammalian target of rapamycin, ribosomal protein S6, eukaryotic translation initiation factor 4E in the muscle were down-regulated with increasing dietary CPC levels, and while the expressions of eukaryotic translation initiation factor 4E-binding protein, general amino acid control nonderepressible 2 and eukaryotic translation initiation factor 2 α were up-regulated. Take the growth performance, feed utilization and protein metabolism into account, 60% of dietary fishmeal could be replaced by CPC in large yellow croaker.