Study Partner Report of Apathy in Older Adults is Associated with AD Biomarkers: Findings from the Harvard Aging Brain Study.

OBJECTIVES: We examined relationships between apathy (self and study-partner-reported) and markers of Alzheimer's disease (AD) in older adults. DESIGN: The study utilized a well-characterized sample of participants from the Harvard Aging Brain Study (HABS), a longitudinal cohort study. Participants were cognitively unimpaired without clinically significant neuropsychiatric symptoms at HABS baseline. The dependent variables, apathy evaluation scale-self (AES-S) and informant (AES-I), were administered cross-sectionally between years 6-9 and compared to the independent variables, amyloid and tau PET neuroimaging, from the same year. SETTING: Community-dwelling participants assessed at research visits in an academic medical center. PARTICIPANTS: Participants (n = 170) completed assessments within 1.5 years of their neuroimaging visit. At the time of apathy assessment, N = 156 were cognitively unimpaired and 14 had progressed to mild cognitive impairment (n = 8) or dementia (n = 6). MEASUREMENTS: We utilized linear regression models to assess cross-sectional associations of AES-S and AES-I with AD PET imaging measures (beta-amyloid (Pittsburgh Compound B) and tau (Flortaucipir)), covarying for age, sex, education, and the time between PET scan-apathy assessment. RESULTS: AES-I was significantly associated with beta-amyloid and temporal lobe tau, and the associations were retained after further adjusting for depressive symptoms. The associations between AES-S and AD biomarkers were not significant. In an exploratory subgroup analysis of cognitively unimpaired individuals with elevated Aß, we observed an association between AES-I and inferior temporal tau. CONCLUSIONS: Study-partner-reported, but not self-reported, apathy in older adults is associated with AD pathology, and we observed this relationship starting from the preclinical stage. Our findings highlight the importance of collateral information in capturing AD-related apathy.

Serological investigation and isolation of Salmonella abortus equi in horses in Xinjiang.

BACKGROUND: Salmonella enterica subspecies enterica serovar abortus equi (S. abortus equi) is one of the main pathogens that causes abortion in pregnant horses and donkeys, which was highly infectious and greatly restricts the healthy development of the horse industry. OBJECTIVES: In order to investigate the prevalence and biological characteristics of S. abortus equi in different regions and breeds of horses in Xinjiang. METHODS: This study conducted ELISA detection of S. abortus equi antibodies on serum samples of 971 horses collected from three large-scale horse farms and five free-range horse farms in Yili Prefecture and Bayingol Mongolian Autonomous Prefecture of Xinjiang from 2020 to 2023. On this basis, bacterial isolation, culture, identification, and drug sensitivity tests were conducted on 42 samples of aborted foal tissues and 23 mare vaginal swabs. RESULTS: The results showed that the positive rate of S. abortus equi antibody was as high as 20.91% in 971 horse serum samples. Among them, the positive rate in the Ili region (29.09%) was significantly higher than that in the Bayingole region (11.24%), and the positive rate in mares (22.45%) was higher than that in stallions (14.05%). In terms of horse breeds, the positive rates of self-propagating thoroughbred horses, half-bred horses, Ili horses and Yanqi horses were 43.22%, 28.81%, 14.72% and 11.24% respectively. In addition, S. abortus equi was more susceptible to juvenile and elderly horses, with positive rates of 70.00%and 41.86%, respectively, both of which were significantly higher than young (10.97%) and adult (19.79%) horses. Further, 9 strains of S. abortus equi were obtained through bacterial isolation, culture and identification, which were resistant to five antibiotics (Clarithromycin, Clindamycin, penicillin, Sulfamethoxazole and Rifampicin), and sensitive to 13 antimicrobial agents (Amoxicillin, Ciprofloxacin and Gentamicin, et al.). CONCLUSION: There was a high infection rate of S. abortus equi in Ili Prefecture and self-propagating thoroughbred horses, and juvenile or old mares were more susceptible, which will provide scientific basis for the prevention of S. abortus equi infection in different regions and breeds of horses in Xinjiang.

Shaoyao decoction improves damp-heat colitis by activating the AHR/IL-22/STAT3 pathway through tryptophan metabolism driven by gut microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: The efficacy of Shaoyao Decoction (SYD), a traditional Chinese medicine prescription, in treating damp-heat colitis is established, but its underlying mechanism remains to be elucidated. AIM OF THE STUDY: Our study aims to investigate the effect and mechanism of action of SYD in treating damp-heat colitis. MATERIALS AND METHODS: A mouse model of damp-heat colitis was induced and treated with SYD via gavage for seven days. The therapeutic efficacy of SYD was assessed through clinical indicators and histopathological examinations. The inflammatory factors and oxidative stress parameters were detected by ELISA and biochemical kits. We also analyzed alterations in the gut microbiome via 16 S rRNA gene sequencing and quantified serum indole derivatives using targeted tryptophan metabolomics. Western blotting and immunofluorescence were used to detect the expressions of AHR, CYP1A1, STAT3 and tight junction (TJ) proteins. The ELISA kit was utilized to detect the content of antibacterial peptides (Reg3ß and Reg3γ) in colon. The immunohistochemistry was employed to detect the expressions of proliferating cell nuclear antigen (PCNA) protein. RESULTS: SYD effectively alleviated symptoms in mice with damp-heat colitis, including body weight loss, shortened colon, elevated DAI, enlarged spleen, and damage to the intestinal mucosa. SYD notably reduced IL-6, TNF-α, IL-1ß and MDA levels in colon tissues, while increasing IL-10 and T-AOC levels. Furthermore, SYD mitigated gut microbiota disturbance, restored microbial tryptophan metabolite production (such as IA, IAA, and IAld), notably increased the protein levels of AHR, CYP1A1 and p-STAT3 in colon tissue, and elevated the IL-22 level. Moreover, the expression levels of Reg3ß, Reg3γ, occludin, ZO-1 and PCNA were increased in SYD group. CONCLUSION: Our study showed that SYD ameliorates damp-heat colitis by restructuring gut microbiota structure, enhancing the metabolism of tryptophan associated with gut microbiota to activate the AHR/IL-22/STAT3 pathway, thereby recovering damaged intestinal mucosa. This research offers novel insights into the therapeutic mechanisms of SYD on damp-heat colitis.

Screening of polysaccharides from the differently processed products of Angelica sinensis with the best liver protection effect on chicken and the intervention mechanism study based on tandem mass tag proteomics and multiple reaction monitoring approach.

The incidence of colibacillosis in poultry is on the rise, significantly affecting the chicken industry. Ceftiofur sodium (CS) is frequently employed to treat this disease, resulting in lipopolysaccharide (LPS) buildup. Processing plays a vital role in traditional Chinese veterinary medicine. The potential intervention in liver injury by polysaccharides from the differently processed products of Angelica sinensis (PDPPAS) induced by combined CS and LPS remains unclear. This study aims to investigate the protective effect of PDPPAS on chicken liver injury caused by CS combined with LPS buildup and further identify the polysaccharides with the highest hepatoprotective activity in chickens. Furthermore, the study elucidates polysaccharides' intervention mechanism using tandem mass tag (TMT) proteomics and multiple reaction monitoring (MRM) methods. A total of 190 1-day-old layer chickens were randomly assigned into 12 groups, of which 14 chickens were in the control group and 16 in other groups, for a 10-day trial. The screening results showed that charred A. sinensis polysaccharide (CASP) had the most effective and the best hepatoprotective effect at 48 h. TMT proteomics and MRM validation results demonstrated that the intervention mechanism of the CASP high-dose (CASPH) intervention group was closely related to the protein expressions of FCER2, TBXAS1, CD34, AGXT, GCAT, COX7A2L, and CYP2AC1. Conclusively, the intervention mechanism of CASPH had multitarget, multicenter regulatory features.

Mechanisms predictive of Tibetan Medicine Sophora moorcroftiana alkaloids for treatment of lung cancer based on the network pharmacology and molecular docking.

BACKGROUND: Leguminous Sophora moorcroftiana (SM) is a genuine medicinal material in Tibet. Many research results have reveal the Sophora moorcroftiana alkaloids (SMA), as the main active substance, have a wide range of effects, such as antibacterial, antitumor and antiparasitic effects. However, there are few reports on the inhibition of lung cancer (LC) and its inhibitory mechanism, and the pharmacological mechanism of SMA is still unclear, Therefore, exploring its mechanism of action is of great significance. METHODS: The SMA active components were obtained from the literature database. Whereas the corresponding targets were screened from the PubChem and PharmMapper database, UniProt database were conducted the correction and transformation of UniProt ID on the obtained targets. The GeneCards and OMIM databases identified targets associated with LC. Venny tools obtained the intersection targets of SMA and LC. R language and Cytoscape software constructed the visual of SMA - intersection targets - LC disease network. The intersection targets protein-protein interaction (PPI) network were built by the STRING database. The functions and pathways of the common targets of SMA and LC were enriched by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, molecular docking And A549 cells vitro experiment were performed to further validate our finding. RESULTS: We obtained six kinds of alkaloids in SM, 635 potential targets for these compounds, and 1,303 genes related to LC. SMA and LC intersection targets was 33, including ALB, CCND1, ESR1, NOTCH1 and AR. GO enrichment indicated that biological process of SMA was mainly involved in the positive regulation of transcription and nitric oxide biosynthetic process, and DNA-templated, etc. Biological functions were mainly involved in transcription factor binding and enzyme binding, etc. Cell components were mainly involved in protein complexes, extracellular exosome, cytoplasm and nuclear chromatin, etc., Which may be associated with its anti-LC effects. KEGG enrichment analysis showed that main pathways involved in the anti-LC effects of SMA, including pathway in cancer, non small-cell lung cancer, p53, PI3K-Akt and FOXO signaling pathways. Molecular docking analyses revealed that the six active compounds had a good binding activity with the main therapeutic targets 2W96, 2CCH and 1O96. Experiments in vitro proved that SMA inhibited the proliferation of LC A549 cells. CONCLUSIONS: Results of the present study, we have successfully revealed the SMA compounds had a multi-target and multi-channel regulatory mechanism in treatment LC, These findings provided a solid theoretical reference of SMA in the clinical treatment of LC.

Flow-through electrochemically assisted reverse-osmosis: A new process towards low-chemical desalination.

Two-pass reverse osmosis (RO) process is prevailing in seawater desalination, but each process must consume considerable amounts of chemicals to secure product water quality. Caustic soda is used to raise the pH of the first-pass RO permeate (also the second-pass RO feed) to ensure adequate removal of boron in the subsequent second-pass RO, while antiscalants and disinfectants such as hypochlorite are added in the feed seawater for scaling and biofouling control of the first-pass RO membranes. Here, we report for the first time a flow-through electrochemically assisted reverse osmosis (FT-EARO) module system used in the first-pass RO, aiming to dramatically reduce or even eliminate chemical usage for the current RO desalination. This novel system integrated an electroconductive permeate carrier as cathode and an electroconductive feed spacer as anode on each side of the first-pass RO membrane. Upon applying an extremely low-energy (< 0.005 kWh/m3) electrical field, the FT-EARO module could (1) produce a permeate with pH >10 with no alkali dosage, ensuring sufficient boron removal in the second-pass RO, and (2) generate protons and low-concentration free chlorine near the membrane surface, potentially discouraging membrane scaling and biofouling while maintaining satisfactory desalination performance. The current study further elucidated the high scalability of this novel electrified high-pressure RO module design. The low-chemical manner of FT-EARO presents an attractive practical option towards green and sustainable seawater desalination.

The characteristics of brain network in patient with post-stroke depression under cognitive task condition.

Objectives: Post-stroke depression (PSD) may be associated with the altered brain network property. This study aimed at exploring the brain network characteristics of PSD under the classic cognitive task, i.e., the oddball task, in order to promote our understanding of the pathogenesis and the diagnosis of PSD. Methods: Nineteen stroke survivors with PSD and 18 stroke survivors with no PSD (non-PSD) were recruited. The functional near-infrared spectroscopy (fNIRS) covering the dorsolateral prefrontal cortex was recorded during the oddball task state and the resting state. The brain network characteristics were extracted using the graph theory and compared between the PSD and the non-PSD subjects. In addition, the classification performance between the PSD and non-PSD subjects was evaluated using features in the resting and the task state, respectively. Results: Compared with the resting state, more brain network characteristics in the task state showed significant differences between the PSD and non-PSD groups, resulting in better classification performance. In the task state, the assortativity, clustering coefficient, characteristic path length, and local efficiency of the PSD subjects was larger compared with the non-PSD subjects while the global efficiency of the PSD subjects was smaller than that of the non-PSD subjects. Conclusion: The altered brain network properties associated with PSD in the cognitive task state were more distinct compared with the resting state, and the ability of the brain network to resist attack and transmit information was reduced in PSD patients in the task state. Significance: This study demonstrated the feasibility and superiority of investigating brain network properties in the task state for the exploration of the pathogenesis and new diagnosis methods for PSD.

Pulsatilla decoction improves DSS-induced colitis via modulation of fecal-bacteria-related short-chain fatty acids and intestinal barrier integrity.

ETHNOPHARMACOLOGICAL RELEVANCE: Pulsatilla decoction (PD), is an herbal formula commonly used for the treatment of ulcerative colitis (UC) in clinical practice, but the mechanism of PD alters the colitis remains elusive. AIM OF THE STUDY: To evaluate the intervention effect of PD on Dextran Sodium Sulfate (DSS)-induced UC based on gut microbiota and intestinal short-chain fatty acid (SCFAs) metabolism, and to investigate the mechanism of action of PD in treating UC. MATERIALS AND METHODS: A 3% (wt/vol) DSS-induced ulcerative colitis model in C57BL/6 male mice was used to evaluate the effect of oral PD in treating UC. The changes in gut microbiota in mice were analyzed by 16SrDNA gene sequencing, and the content of SCFAs in the intestinal contents of mice was determined by gas chromatography-mass spectrometry (GC-MS). Enzyme-linked immunosorbent assay (ELISA) was applied to analyze the expression of inflammatory cytokines in serum and colonic tissues, and western blotting (WB) was applied to analyze the expression of tight junction proteins in colonic tissues. RESULTS: PD can alleviate the symptoms of UC mice, Pulsatilla Decoction high dose treatment group (PDHT) shows the best effect. Compared with the DSS group, the PDHT had significantly lower body mass, disease activity index (DAI) score, colonic macroscopic damage index (CMDI) score, and pathological damage score, at the phylum level, the relative abundance of Bacteroidetes increased while that of Firmicutes and Proteobacteria decreased, at the Genus level, the abundance of Bacteroides and Lachnospiraceae.NK4A136.group increased while that of Clostridium. sensu.stricto。, Escherichia. shigella and Turicibacter decreased. Compared with the DSS group, acetate, propionate, and total SCFAs in the PDHT with significantly higher levels. The concentrations of interleukin-1ß (L-1ß), tumor necrosis factor-alpha (TNF-α), and interleukin-17 (IL-17) decreased whereby the concentration of interleukin-10 (IL-10) increased in the PDHT group. The expression levels of Occludin, zonula occludens-1 (ZO-1), Claudin1, Claudin5, G protein-coupled receptor43 (GPR43) protein, and the relative expression of ZO-1 and Occludin mRNA were significantly increased PDHT group. CONCLUSIONS: PD has a good therapeutic effect on UC mice. The pharmacological mechanism is probably maintaining the homeostasis and diversity of gut microbiota, increasing the content of SCFAs, and repairing the colonic mucosal barrier.

Regulation of Yujin Powder alcoholic extracts on ILC3s-TD IgA-colonic mucosal flora axis of DSS-induced ulcerative colitis.

The intestinal flora maintained by the immune system plays an important role in healthy colon. However, the role of ILC3s-TD IgA-colonic mucosal flora axis in ulcerative colitis (UC) and whether it could become an innovative pathway for the treatment of UC is unknown. Yujin Powder is a classic prescription for treatment of dampness-heat type intestine disease in traditional Chinese medicine and has therapeutic effects on UC. Hence, the present study aimed to investigate the regulatory mechanism of Yujin Powder alcoholic extracts (YJP-A) on UC via ILC3s-TD IgA-colonic mucosal flora axis. The UC mouse model was induced by drinking 3.5% dextran sodium sulfate (DSS), meanwhile, YJP-A was given orally for prevention. During the experiment, the clinical symptoms of mice were recorded. Then the intestinal injury and inflammatory response of mice about UC were detected after the experiment. In addition, the relevant indicators of ILC3s-TD IgA-colonic mucosal flora axis were detected. The results showed that YJP-A had good therapy effects on DSS-induced mice UC: improved the symptoms, increased body weight and the length of colon, decreased the disease activity index score, ameliorated the intestinal injury, and reduced the inflammation etc. Also, YJP-A significantly increased the ILC3s proportion and the expression level of MHC II; significantly decreased the proportion of Tfh cells and B cells and the expression levels of Bcl6, IL-4, Aicda in mesenteric lymph nodes of colon in UC mice and IgA in colon. In addition, by 16S rDNA sequencing, YJP-A could restore TD IgA targets colonic mucus flora in UC mice by decreasing the relative abundance of Mucispirillum, Lachnospiraceae and increasing the relative abundance of Allprevotella, Alistipes, and Ruminococcaceae etc. In conclusion, our results demonstrated that the ILC3s-TD IgA-colonic mucosal flora axis was disordered in UC mice. YJP-A could significantly promote the proliferation of ILC3s to inhibit Tfh responses and B cells class switching through MHC II, further to limit TD IgA responses toward colonic mucosal flora. Our findings suggested that this axis may be a novel and promising strategy to prevent UC.

Decoding Multi-Class EEG Signals of Hand Movement Using Multivariate Empirical Mode Decomposition and Convolutional Neural Network.

Brain-computer interface (BCI) is a technology that connects the human brain and external devices. Many studies have shown the possibility of using it to restore motor control in stroke patients. One specific challenge of such BCI is that the classification accuracy is not high enough for multi-class movements. In this study, by using Multivariate Empirical Mode Decomposition (MEMD) and Convolutional Neural Network (CNN), a novel algorithm (MECN) was proposed to decode EEG signals for four kinds of hand movements. Firstly, the MEMD was used to decompose the movement-related electroencephalogram (EEG) signals to obtain the multivariate intrinsic empirical functions (MIMFs). Then, the optimal MIMFs fusion was performed based on sequential forward selection algorithm. Finally, the selected MIMFs were input to the CNN model for discriminating four kinds of hand movements. The average classification accuracy of thirteen subjects over the six-fold cross-validation reached 81.14% for 2s-data before the movement onset and 81.08% for 2s-data after the movement onset. The MECN method achieved statistically significant improvement on the state-of-the-art methods. The results showed that the algorithm proposed in this study can effectively decode four kinds of hand movements based on EEG signals.

Thermally assisted efficient electrochemical lithium extraction from simulated seawater.

Extracting lithium electrochemically from seawater has the potential to resolve any future lithium shortage. However, electrochemical extraction only functions efficiently in high lithium concentration solutions. Herein, we discovered that lithium extraction is temperature and concentration dependent. Lithium extraction capacity (i.e., the mass of lithium extracted from the source solutions) and speed (i.e., the lithium extraction rate) in electrochemical extraction can be increased significantly in heated source solutions, especially at low lithium concentrations (e.g., < 3 mM) and high Na+/Li+ molar ratios (e.g., >1000). Comprehensive material characterization and mechanistic analyses revealed that the improved lithium extraction originates from boosted kinetics rather than thermodynamic equilibrium shifts. A higher temperature (i.e., 60 oC) mitigates the activation polarization of lithium intercalation, decreases charge transfer resistances, and improves lithium diffusion. Based on these understandings, we demonstrated that a thermally assisted electrochemical lithium extraction process could achieve rapid (36.8 mg g-1 day-1) and selective (51.79% purity) lithium extraction from simulated seawater with an ultrahigh Na+/Li+ molar ratio of 20,000. The integrated thermally regenerative electrochemical cycle can harvest thermal energy in heated source solutions, enabling a low electrical energy consumption (11.3-16.0 Wh mol-1 lithium). Furthermore, the coupled thermal-driven membrane process in the system can also produce freshwater (13.2 kg m-2 h-1) as a byproduct. Given abundant low-grade thermal energy availability, the thermally assisted electrochemical lithium extraction process has excellent potential to realize mining lithium from seawater.

Task-State Cortical Motor Network Characteristics by Functional Near-Infrared Spectroscopy in Subacute Stroke Show Hemispheric Dominance.

Background: There was a reorganization of the brain network after stroke. Some studies have compared the characteristics of activation or functional connectivity (FC) of cortical and subcortical regions between the dominant and non-dominant hemisphere stroke. Objectives: To analyze hemispheric dominance differences in task-state motor network properties in subacute stroke by functional near-infrared spectroscopy (fNIRS). Materials and Methods: Patients with first ischemic stroke in the basal ganglia within 1-3 months after onset and age- and sex-matched right-handed healthy subjects (HS) were enrolled. fNIRS with 29 channels was used to detect the oxyhemoglobin concentration changes when performing the hand grasping task. Activation patterns of motor cortex and two macroscale and two mesoscale brain network indicators based on graph theory were compared between dominant and non-dominant hemisphere stroke. Results: We enrolled 17 subjects in each of left hemisphere stroke (LHS), right hemisphere stroke (RHS), and HS groups. Both patient groups showed bilateral activation. The average weighted clustering coefficient and global efficiency of patients were lower than those of healthy people, and the inter-density was higher than that of the HS group, but the significance was different between LHS and RHS groups. The intra-density changes in the RHS group were opposite to those in the LHS group. The correlation between mesoscale indicators and motor function differed between dominant and non-dominant hemisphere stroke. Conclusion: The changes in macroscale cortical network indicators were similar between the two patient groups, while those of the mesoscale indicators were different. The mesoscale brain network characteristics were affected by the severity of dysfunction to varying degrees in the LHS and RHS patients.

[Integrated strategy for mechanism of Baitouweng Decoction in treating dampness-heat diarrhea based on urine metabolomics coupled with network pharmacology].

Baitouweng Decoction is a famous Chinese medicinal decoction that has been used to treat diarrhea over thousands of years. In this study, we investigated the effect and mechanism of Baitouweng Decoction in the treatment of diarrhea. Wistar rats were randomly assigned into 4 groups: control group, dampness-heat diarrhea model group(modeling by complex factors including high-sugar and high-fat diet, improper diet, hot and humid environment, drinking and intraperitoneal injection of Escherichia coli), Baitouweng Decoction(3.6 g·kg~(-1)) group, and self-healing group. A urine metabolomics approach was developed with ultra liquid chromatography-quadrupole-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS) for metabolic profiling. The differential metabolites were screened out by the multivariate comparison between groups. Diarrhea-related protein targets and the active compounds of Baitouweng Decoction were used to predict the protein targets of Baitouweng Decoction. Cytoscape 3.2.1 was employed to establish a active component-target protein interaction network. Three protein-protein interaction(PPI) networks of component target proteins, diarrhea-related proteins, and differential metabolite-related proteins were established and then merged by BisoGenet. ClueGO was used to perform the gene enrichment based on the genetic similarity. The results showed that Baitouweng Decoction effectively treated dampness-heat diarrhea in vivo. N-acetylserotonin, L-gamma-glutamylcysteine, glutathione, retinoate, melatonin, indole-3-acetaldehyde, L-cystine, biotin, and L-tryptophan were screened as differential metabolites in dampness-heat diarrhea model group. Tryptophan metabolism, glutathione metabolism, biotin metabolism, retinol metabolism, and cysteine and methionine metabolism were involved in the therapeutic effect of Baitouweng Decoction in vivo. A total of 167 targets were identified as major candidates for diarrhea progression. The gene-set enrichment revealed that the targets were involved in reactive oxygen species production, inflammation, and apoptosis. Baitouweng Decoction can restrain inflammation, production of reactive oxygen, and block apoptosis, thereby contributing to the treatment of dampness-heat diarrhea.

Sheng Mai San ameliorated heat stress-induced liver injury via regulating energy metabolism and AMPK/Drp1-dependent autophagy process.

BACKGROUND: Liver damage is one of the most common complications in humans and animals after heat stress (HS). Sheng Mai San (SMS), a traditional Chinese medicine prescription that originated in the Jin Dynasty, exert a therapeutic effect on HS. However, how SMS prevents liver injury after heat exposure remains unknown. PURPOSE: This study aimed to investigate the pharmacological effect and molecular mechanisms of SMS on HS-induced liver injury. STUDY DESIGN: A comprehensive strategy via incorporating pharmacodynamics, targeted metabolomics, and molecular biology technology was adopted to investigate energy metabolism changes and the therapeutic mechanisms of SMS in HS-induced rat liver injury. METHODS: First, Sprague-Dawley rats were subjected to HS (38 °C/ 75% RH/ 2 h/ day) for 7 consecutive days to establish the HS model, and SMS was given orally for treatment 2 h before heat exposure. Thereafter, liver function and pathological changes in liver tissue were evaluated. Finally, the underlying mechanisms of SMS were determined using targeted energy metabolomics to comprehensively analyze the metabolic pathways and were further verified through Western-blot and qRT-PCR assays. RESULTS: Our results showed that SMS alleviated HS-induced liver dysfunction by reducing the alanine aminotransferase (ALT), aspartate aminotransferase (AST), and AST/ALT ratios in serum and improving hepatic pathological damage. Meanwhile, SMS suppressed inflammatory response, oxidative injury, and overexpression of heat shock proteins in liver tissue after heat exposure. With the help of targeted energy metabolomics, we found that SMS could effectively regulate glycolysis and tricarboxylic acid (TCA) cycle to relieve energy metabolism disorder. Furthermore, we confirmed that SMS can facilitate the phosphorylation of AMP-activated protein kinase (AMPK) to maintain mitochondrial homeostasis through a dynamin protein 1 (Drp1)-dependent mitophagy process. CONCLUSION: On the basis of energy metabolomics, the present study for the first time systematically illustrated the protective effect of SMS on HS-induced liver injury, and preliminarily confirmed that an AMPK-mediated Drp1-dependent mitophagy and mitochondria rebuilding process plays an important role in SMS intervention on HS-induced rat liver. Together, our study lends further support to the use of SMS in treating HS condition.

A Personalized Spring Network Representation of Emphysematous Lungs From CT Images.

Emphysema is a progressive disease characterized by irreversible tissue destruction and airspace enlargement, which manifest as low attenuation area (LAA) on CT images. Previous studies have shown that inflammation, protease imbalance, extracellular matrix remodeling and mechanical forces collectively influence the progression of emphysema. Elastic spring network models incorporating force-based mechanical failure have been applied to investigate the pathogenesis and progression of emphysema. However, these models were general without considering the patient-specific information on lung structure available in CT images. The aim of this work was to develop a novel approach that provides an optimal spring network representation of emphysematous lungs based on the apparent density in CT images, allowing the construction of personalized networks. The proposed method takes into account the size and curvature of LAA clusters on the CT images that correspond to a pre-stressed condition of the lung as opposed to a naïve method that excludes the effects of pre-stress. The main findings of this study are that networks constructed by the new method 1) better preserve LAA cluster sizes and their distribution than the naïve method; and 2) predict different course of emphysema progression compared to the naïve method. We conclude that our new method has the potential to predict patient-specific emphysema progression which needs verification using clinical data.

A new method providing complementary explanation of the blood-enriching function and mechanism of unprocessed Angelica sinensis and its four kinds of processed products based on tissue-integrated metabolomics and confirmatory analysis.

Angelica sinensis (AS) is a common Traditional Chinese Medicine used for tonifying blood in China. Unprocessed AS and its four kinds of processed products (ASs) are used to treat blood deficiency syndrome in the country. The different blood-tonifying mechanisms of ASs remain unclear. In this work, a novel method integrating metabolomics and hematological and biochemical parameters was established to provide a complementary explanation of blood supplementation mechanism of ASs. Our results revealed that different ASs exhibited various blood supplementation effect, and that AS parched with alcohol demonstrated the best blood supplementation effect. Eight metabolites from liver tissue and 12 metabolites from spleen tissue were considered to be potential biomarkers. These biomarkers were involved in four metabolic pathways. Correlation analysis results showed that l-aspartic acid and l-alanine (spleen tissue), linoleic acid, and l-cystathionine (liver tissue) exhibited a high positive or negative correlation with the aforesaid biochemical indicators. The blood-supplementation effect mechanism of ASs were related to four metabolic pathways. l-Aspartic acid and l-alanine (spleen tissue), linoleic acid, and l-cystathionine (liver tissue) were the four key metabolites associated with the blood supplementation effect of ASs. This study gives a complementary explanation of the blood supplementation effect and mechanism of action of ASs.

Effect of BCI-Controlled Pedaling Training System With Multiple Modalities of Feedback on Motor and Cognitive Function Rehabilitation of Early Subacute Stroke Patients.

Brain-computer interfaces (BCIs) are currently integrated into traditional rehabilitation interventions after stroke. Although BCIs bring many benefits to the rehabilitation process, their effects are limited since many patients cannot concentrate during training. Despite this outcome post-stroke motor-attention dual-task training using BCIs has remained mostly unexplored. This study was a randomized placebo-controlled blinded-endpoint clinical trial to investigate the effects of a BCI-controlled pedaling training system (BCI-PT) on the motor and cognitive function of stroke patients during rehabilitation. A total of 30 early subacute ischemic stroke patients with hemiplegia and cognitive impairment were randomly assigned to the BCI-PT or traditional pedaling training. We used single-channel Fp1 to collect electroencephalography data and analyze the attention index. The BCI-PT system timely provided visual, auditory, and somatosensory feedback to enhance the patient's participation to pedaling based on the real-time attention index. After 24 training sessions, the attention index of the experimental group was significantly higher than that of the control group. The lower limbs motor function (FMA-L) increased by an average of 4.5 points in the BCI-PT group and 2.1 points in the control group (P = 0.022) after treatments. The difference was still significant after adjusting for the baseline indicators ( ß = 2.41 , 95%CI: 0.48-4.34, P = 0.024). We found that BCI-PT significantly improved the patient's lower limb motor function by increasing the patient's participation. (clinicaltrials.gov: NCT04612426).

Baitouweng Tang ameliorates DSS-induced ulcerative colitis through the regulation of the gut microbiota and bile acids via pathways involving FXR and TGR5.

In China, Baitouweng Tang (BTWT) is a commonly prescribed remedy for the treatment of ulcerative colitis (UC). Herein, the present study aims to assess the anti-colitis activity of BTWT and its underlying mechanisms in UC BALB/c mice. Induction of UC in BALB/c mice was carried out by adding 3.5% DSS in the drinking water of underlined mice. After UC induction, the mice were administrated with BTWT for 7 days. Clinical symptoms were assessed, followed by analyzing the bile acids (BAs) in serum, liver, colon, bile, and feces of UC mice through UPLC-MS/MS. The modified 16S rDNA high-throughput sequencing was carried out to examine the gut microbiota of feces. BTWT significantly improved the clinical symptoms such as and histological injury and colon shortening in UC induced mice. Furthermore, BTWT remarkably ameliorated colonic inflammatory response. After BTWT treatment, the increased concentrations of UDCA, HDCA, αMCA, ßMCA, CA, and GLCA in UC were decreased, and the levels of some BAs, especially CA, αMCA, and ßMCA were normalized. Moreover, the relative species abundance and gut microbiota diversity in the BTWT-exposed groups were found to be considerably elevated than those in the DSS-treated group. BTWT increased the relative abundance of Firmicutes, Proteobacteria, Actinobacteria, Tenericutes, and TM7, which were statistically lower in the fecal microbiota of UC mice. The relative abundance of Bacteroidetes was found to be elevated in the DSS group and normalized after BTWT treatment. BTWT increased the expression of FXR and TGR5 in the liver. BTWT administration improved DSS-induced mice signs by increasing the TGR5 and FXR expression levels. This result was achieved by the regulation of the BAs and gut microbiota.

One-Dimensional van der Waals Heterostructures as Efficient Metal-Free Oxygen Electrocatalysts.

Two-dimensional covalent organic frameworks (2D-COFs) may serve as an emerging family of catalysts with well-defined atomic structures. However, the severe stacking of 2D nanosheets and large intrinsic bandgaps significantly impair their catalytic performance. Here, we report coaxial one-dimensional van der Waals heterostructures (1D vdWHs) comprised of a carbon nanotube (CNT) core and a thickness tunable thienothiophene-pyrene COF shell using a solution-based in situ wrapping method. Density functional theory calculations and operando and ex situ spectroscopic analysis indicate that carbon-sulfur regions in thienothiophene groups in the COF serve as an active catalytic site for oxygen reduction and evolution reactions. The coaxial structure enables n-doping from the CNT core to the COF shell, which is controllable by varying COF shell thickness. The charge transfer from CNTs lowers COF's bandgap and work function, which reduces the charge transfer barrier between the active catalytic sites and adsorbed oxygen intermediates, resulting in dramatically enhanced catalytic activity. The 1D vdWHs were applied as a bifunctional oxygen electrocatalyst in rechargeable zinc-air batteries, delivering a high specific capacity of 696 mAh gZn-1 under a high current density of 40 mA cm-2 and excellent cycling stability. The 1D vdWHs based on the coaxial structure of 2D COF wrapped around CNT cores may be further used as versatile building units to create multidimensional vdWHs for exploring fundamental physics and chemistry as well as practical applications in electrochemistry, electronics, photonics, and beyond.

Thermo-osmosis-Coupled Thermally Regenerative Electrochemical Cycle for Efficient Lithium Extraction.

Lithium (Li) production based on the soda evaporation process is time-consuming and unsustainable. The emerging electrochemical Li extraction is time-efficient but requires high-concentration Li sources and significant electrical energy input. Here, we demonstrate a fast, energy-saving, and environment-friendly Li production process by coupling a thermally regenerative electrochemical cycle (TREC) using lithium manganese oxide (LMO) and nickel hexacyanoferrate (NiHCF) electrodes with poly(vinylidene fluoride) membrane-based thermo-osmosis (denoted as TO-TREC). The characterization of LMO and NiHCF electrodes confirmed that the relatively high temperature of TO-TREC has negligible adverse effects on the ion intercalation in LMO and NiHCF electrodes. The LMO/NiHCF pair has a positive temperature coefficient of 0.843 mV K-1. In the TO-TREC process, Li ions are selectively extracted from a Li-containing brine warmed by low-grade heat and then released into a room-temperature recovery solution such as LiCl with a production rate of 50-60 mmol Li+ m-2 h-1. Li source solutions are concentrated by thermo-osmosis simultaneously, making it possible to utilize previously unusable Li-containing sources, such as concentrated brines from desalination plants and industrial effluents. Besides, the TREC harvests thermal energy from the heated brine, saving >20% of electrical energy compared to conventional electrochemical methods. The new process shows the potential to meet the growing global Li demands for many applications.