Predicting the efficiency of arsenic immobilization in soils by biochar using machine learning.

Arsenic (As) pollution in soils is a pervasive environmental issue. Biochar immobilization offers a promising solution for addressing soil As contamination. The efficiency of biochar in immobilizing As in soils primarily hinges on the characteristics of both the soil and the biochar. However, the influence of a specific property on As immobilization varies among different studies, and the development and application of arsenic passivation materials based on biochar often rely on empirical knowledge. To enhance immobilization efficiency and reduce labor and time costs, a machine learning (ML) model was employed to predict As immobilization efficiency before biochar application. In this study, we collected a dataset comprising 182 data points on As immobilization efficiency from 17 publications to construct three ML models. The results demonstrated that the random forest (RF) model outperformed gradient boost regression tree and support vector regression models in predictive performance. Relative importance analysis and partial dependence plots based on the RF model were conducted to identify the most crucial factors influencing As immobilization. These findings highlighted the significant roles of biochar application time and biochar pH in As immobilization efficiency in soils. Furthermore, the study revealed that Fe-modified biochar exhibited a substantial improvement in As immobilization. These insights can facilitate targeted biochar property design and optimization of biochar application conditions to enhance As immobilization efficiency.

Raddeanin A Protects the BRB Through Inhibiting Inflammation and Apoptosis in the Retina of Alzheimer's Disease.

Neuroinflammation and endothelial cell apoptosis are prominent features of blood-brain barrier (BBB) disruption, which have been described in Alzheimer's disease (AD) and can predict cognitive decline. Recent reports revealed vascular ß-amyloid (Aß) deposits, Muller cell degeneration and microglial dysfunction in the retina of AD patients. However, there has been no in-depth research on the roles of inflammation, retinal endothelial cell apoptosis, and blood-retinal barrier (BRB) damage in AD retinopathy. We found that Raddeanin A (RDA) could improve pathological and cognitive deficits in a mouse model of Alzheimer's disease by targeting ß-amyloidosis, However, the effects of RDA on AD retinal function require further study. To clarify whether RDA inhibits inflammation and apoptosis and thus improves BRB function in AD-related retinopathy. In vitro we used Aß-treated HRECs and MIO-M1 cells, and in vivo we used 3×Tg-AD mice to investigate the effect of RDA on BRB in AD-related retinopathy. We found that RDA could improve BRB function in AD-related retinopathy by inhibiting NLRP3-mediated inflammation and suppressing Wnt/ß-catenin pathway-mediated apoptosis, which is expected to improve the pathological changes in AD-related retinopathy and the quality of life of AD patients.

Daphmacrimines A-K, Daphniphyllum alkaloids from Daphniphyllum macropodum Miq.

Daphmacrimines A-K (1-11) were isolated from the leaves and stems of Daphniphyllum macropodum Miq. Their structures and stereochemistries were determined by extensive techniques, including HRESIMS, NMR, ECD, IR, and single-crystal X-ray crystallography. Daphmacrimines A-D (1-4) are unprecedented Daphniphyllum alkaloids with a 2-oxazolidinone ring. Daphmacrimine I (9) contains a nitrile group, which is relatively rare in naturally occurring alkaloids. The abilities of daphmacrimines A-D and daphmacrimines G-K to enhance lysosomal biogenesis were evaluated through LysoTracker Red staining. Daphmacrimine K (11) can induce lysosomal biogenesis and promote autophagic flux.

Stereoselective Cyclopropanation of Multisubstituted Enesulfinamides: Asymmetric Construction of α-Tertiary Cyclopropylamine Derivatives Containing ß-Quaternary Stereocenters.

Enesulfinamides with α,ß,ß-trisubstitution undergo a Simmons-Smith reaction to yield multisubstituted cyclopropylamine derivatives with high stereocontrol. The resulting α-tertiary cyclopropylamine derivatives, which feature ß-quaternary stereocenters bearing two electronically and sterically similar substituents (e.g., methyl and ethyl), are seldom achieved by using conventional methods. By adjusting the stereochemistry of the carbon-carbon double bond and/or sulfinyl group within the enesulfinamides, it is feasible to selectively produce four stereoisomers of the cyclopropylamines, each with different absolute configurations at the α- and ß-carbons.

Penthorum chinense Pursh inhibits ferroptosis in cellular and Caenorhabditis elegans models of Alzheimer's disease.

BACKGROUND: Ferroptosis, a unique type of cell death triggered by iron-dependent lipid peroxidation, plays a critical role in the pathogenesis of Alzheimer's disease (AD), a debilitating condition marked by memory loss and cognitive impairment due to the accumulation of beta-amyloid (Aß) and hyperphosphorylated Tau protein. Increasing evidence suggests that inhibitors of ferroptosis could be groundbreaking in the treatment of AD. METHOD: In this study, we established in vitro ferroptosis using erastin-, RSL-3-, hemin-, and iFSP1-induced PC-12 cells. Using MTT along with Hoechst/PI staining, we assessed cell viability and death. To determine various aspects of ferroptosis, we employed fluorescence probes, including DCFDA, JC-1, C11 BODIPY, Mito-Tracker, and PGSK, to measure ROS production, mitochondrial membrane potential, lipid peroxidation, mitochondrial morphology, and intracellular iron levels. Additionally, Western blotting, biolayer interferometry technology, and shRNA were utilized to investigate the underlying molecular mechanisms. Furthermore, p-CAX APP Swe/Ind- and pRK5-EGFP-Tau P301L overexpressing PC-12 cells, along with Caenorhabditis elegans (C. elegans) strains CL4176, CL2331, and BR5270, were employed to examine ferroptosis in AD models. RESULTS: Here, we conducted a screening of our natural medicine libraries and identified the ethanol extract of Penthorum chinense Pursh (PEE), particularly its ethyl acetate fraction (PEF), displayed inhibitory effects on ferroptosis in cells. Specifically, PEF inhibited the generation of ROS, lipid peroxidation, and intracellular iron levels. Furthermore, PEF demonstrated protective effects against H2O2-induced cell death, ROS production, and mitochondrial damage. Mechanistic investigations unveiled PEF's modulation of intracellular iron accumulation, GPX4 expression and activity, and FSP1 expression. In p-CAX APP Swe/Ind and pRK5-EGFP-Tau P301L overexpressing PC-12 cells, PEF significantly reduced cell death, as well as ROS and lipid peroxidase production. Moreover, PEF ameliorated paralysis and slowing rate in Aß and Tau transgenic C. elegans models, while inhibiting ferroptosis, as evidenced by decreased DHE intensity, lipid peroxidation levels, iron accumulation, and expression of SOD-3 and gst-4. CONCLUSION: Our findings highlight the suppressive effects of PEF on ferroptosis in AD cellular and C. elegans models. This study helps us better understand how ferroptosis affects AD and emphasizes the potential of PCP as a candidate for AD intervention.

Rhegmatogenous retinal detachment in highly myopic eyes with implantable collamer lens.

AIM: To investigate the clinical characteristics, treatment methods and outcomes of rhegmatogenous retinal detachment (RRD) in highly myopic eyes with implantable collamer lens (ICL). METHODS: High myopia patients who received treatment for nontraumatic RRD after ICL implantation surgery at the Retinal Department of Zhongshan Ophthalmic Center from Jan 2018 to Dec 2022 were reviewed. Comprehensive ophthalmologic examinations including visual acuity measurement and digital fundus photography were performed in each patient. RESULTS: A total of nine RRD eyes from nine patients who received V4c-ICL implantation were included. The mean time from ICL implantation surgery to the diagnosis of RRD was 32.44±22.56mo (range, 1-60mo). At the initial visit for RRD, giant retinal tear (GRT), horseshoe tear, simple round hole, and horseshoe tear combined with round hole were detected in 3, 3, 2, and 1 eye(s), respectively, with macula-off in eyes. Eight patients received surgical treatment, and one patient was treated by retinal laser photocoagulation alone. The ICL was preserved in 7 eyes. At the last follow-up, the mean best corrected visual acuity (BCVA) improved significantly from 1.76±1.06 logMAR at presentation to 0.81±1.01 logMAR (P=0.035), and no case of recurrent retinal detachment was found. CONCLUSION: The morphological presentation of retinal breaks is diverse in this study. The ICL can be preserved in most cases during the course of retinal detachment repair surgery in our data, companied with acceptable visual and anatomical outcomes.

Novel 18-norspirostane steroidal saponins: Extending lifespan and mitigating neurodegeneration through promotion of mitophagy and mitochondrial biogenesis in Caenorhabditis elegans.

Pharmacological strategies to delay aging and combat age-related diseases are increasingly promising. This study explores the anti-aging and therapeutic effects of two novel 18-norspirostane steroidal saponins from Trillium tschonoskii Maxim, namely deoxytrillenoside CA (DTCA) and epitrillenoside CA (ETCA), using Caenorhabditis elegans (C. elegans). Both DTCA and ETCA significantly extended the lifespan of wild-type N2 worms and improved various age-related phenotypes, including muscle health, motility, pumping rate, and lipofuscin accumulation. Furthermore, these compounds exhibited notable alleviation of pathology associated with Parkinson's disease (PD) and Huntington's disease (HD), such as the reduction of α-synuclein and poly40 aggregates, improvement in motor deficits, and mitigation of neuronal damage. Meanwhile, DTCA and ETCA improved the lifespan and healthspan of PD- and HD-like C. elegans models. Additionally, DTCA and ETCA enhanced the resilience of C. elegans against heat and oxidative stress challenges. Mechanistic studies elucidated that DTCA and ETCA induced mitophagy and promoted mitochondrial biogenesis in C. elegans, while genetic mutations or RNAi knockdown affecting mitophagy and mitochondrial biogenesis effectively eliminated their capacity to extend lifespan and reduce pathological protein aggregates. Together, these compelling findings highlight the potential of DTCA and ETCA as promising therapeutic interventions for delaying aging and preventing age-related diseases.

Carpesii fructus extract exhibits neuroprotective effects in cellular and Caenorhabditis elegans models of Parkinson's disease.

OBJECTIVE: Parkinson's disease (PD) is a debilitating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Despite extensive research, no definitive cure or effective disease-modifying treatment for PD exists to date. Therefore, the identification of novel therapeutic agents with neuroprotective properties is of utmost importance. Here, we aimed to investigate the potential neuroprotective effects of Carpesii fructus extract (CFE) in both cellular and Caenorhabditis elegans (C. elegans) models of PD. METHODS: The neuroprotective effect of CFE in H2O2- or 6-OHDA-induced PC-12 cells and α-synuclein-overexpressing PC-12 cells were investigated by determining the cell viability, mitochondrial damage, reactive oxygen species (ROS) production, apoptosis, and α-synuclein expression. In NL5901, BZ555, and N2 worms, the expression of α-synuclein, motive ability, the viability of dopaminergic neurons, lifespan, and aging-related phenotypes were investigated. The signaling pathway was detected by Western blotting and validated by employing small inhibitors and RNAi bacteria. RESULTS: In cellular models of PD, CFE significantly attenuated H2O2- or 6-OHDA-induced toxicity, as evidenced by increased cell viability and reduced apoptosis rate. In addition, CFE treatment suppressed ROS generation and restored mitochondrial membrane potential, highlighting its potential as a mitochondrial protective agent. Furthermore, CFE reduced the expression of α-synuclein in wide type (WT)-, A53T-, A30P-, or E46K-α-synuclein-overexpressing PC-12 cells. Our further findings reveal that CFE administration reduced α-synuclein expression and improved its induced locomotor deficits in NL5901 worms, protected dopaminergic neurons against 6-OHDA-induced degeneration in BZ555 worms, extended lifespan, delayed aging-related phenotypes, and enhanced the ability of stress resistance in N2 worms. Mechanistic studies suggest that the neuroprotective effects of CFE may involve the modulation of the MAPK signaling pathway, including ERK, JNK, and p38, whereas the interference of these pathways attenuated the neuroprotective effect of CFE in vitro and in vivo. CONCLUSION: Overall, our study highlights the potential therapeutic value of CFE as a neuroprotective agent in the context of PD. Furthermore, elucidation of the active compounds of CFE will provide valuable insights for the development of novel therapeutic strategies for PD.

Artificial intelligence in physical rehabilitation: A systematic review.

BACKGROUND: Physical disabilities become more common with advancing age. Rehabilitation restores function, maintaining independence for longer. However, the poor availability and accessibility of rehabilitation limits its clinical impact. Artificial Intelligence (AI) guided interventions have improved many domains of healthcare, but whether rehabilitation can benefit from AI remains unclear. METHODS: We conducted a systematic review of AI-supported physical rehabilitation technology tested in the clinical setting to understand: 1) availability of AI-supported physical rehabilitation technology; 2) its clinical effect; 3) and the barriers and facilitators to implementation. We searched in MEDLINE, EMBASE, CINAHL, Science Citation Index (Web of Science), CIRRIE (now NARIC), and OpenGrey. RESULTS: We identified 9054 articles and included 28 projects. AI solutions spanned five categories: App-based systems, robotic devices that replace function, robotic devices that restore function, gaming systems and wearables. We identified five randomised controlled trials (RCTs), which evaluated outcomes relating to physical function, activity, pain, and health-related quality of life. The clinical effects were inconsistent. Implementation barriers included technology literacy, reliability, and user fatigue. Enablers included greater access to rehabilitation programmes, remote monitoring of progress, reduction in manpower requirements and lower cost. CONCLUSION: Application of AI in physical rehabilitation is a growing field, but clinical effects have yet to be studied rigorously. Developers must strive to conduct robust clinical evaluations in the real-world setting and appraise post implementation experiences.

Living with COPD: understanding patient experiences through the lens of photovoice.

BACKGROUND: Conventional quantitative or qualitative methodologies may not encompass the wide array of experiences of individuals living with Chronic Obstructive Pulmonary Disease (COPD). We used a novel approach - photovoice-to understand the impact of COPD on activities of daily living (ADLs) in a multicultural Asian country. METHODS: We recruited a purposive sample of eight patients from the outpatient clinics of the National University Health System, Singapore, between December 2020 and August 2021. We adopted a photovoice approach for data collection; participants were invited to take photos of how ADLs were impacted by COPD and attend a follow-up interview. An Interpretative Phenomenological Analysis method was used to analyze the data. Data saturation was reached by the seventh patient. RESULTS: COPD and the resulting breathlessness had a profound and diverse impact on our participants' lives. Living with COPD required substantial changes to how everyday tasks are performed, and participants learnt new strategies to deal with such tasks. A mixture of active and passive coping styles was evident. Feelings of frustration, anxiety and a sense of isolation were also reported. Contextual factors impacting ADLs included challenging climatic conditions and the local popularity of traditional or alternative medicine. CONCLUSION: The photovoice technique improved our understanding of the lived experiences of COPD patients and can benefit those who struggle to articulate their views by offering a different way to communicate beyond conventional interviewing.

The Protective Effects of Reineckia carnea Ether Fraction against Alzheimer's Disease Pathology: An Exploration in Caenorhabditis elegans Models.

Alzheimer's disease (AD) presents a significant challenge to global healthcare systems, with current treatments offering only modest relief and often bringing unwanted side effects, necessitating the exploration of more effective and safer drugs. In this study, we employed the Caenorhabditis elegans (C. elegans) model, specifically the AD-like CL4176 strain expressing the human Aß(1-42) protein, to investigate the potential of Reineckia carnea extract and its fractions. Our results showed that the Reineckia carnea ether fraction (REF) notably diminished the paralysis rates of CL4176 worms. Additionally, REF also attenuated the neurotoxicity effects prompted by Tau proteins in the BR5270 worms. Moreover, REF was observed to counteract the accumulation of Aß and pTau proteins and their induced oxidative stress in C. elegans AD-like models. Mechanistic studies revealed that REF's benefits were associated with the induction of autophagy in worms; however, these protective effects were nullified when autophagy-related genes were suppressed using RNAi bacteria. Together, these findings highlight Reineckia carnea ether fraction as a promising candidate for AD treatment, warranting further investigation into its autophagy-inducing components and their molecular mechanisms.

Lychee seed polyphenol ameliorates DR via inhibiting inflammasome/apoptosis and angiogenesis in hRECs and db/db mice.

Blood retinal barrier (BRB) damage is an important pathogenesis of diabetic retinopathy, and alleviating BRB damage has become a key target for DR treatment. We previously found that Lycopene seed polyphenols (LSP) maintained BRB integrity by inhibiting NLRP3 inflammasome-mediated inflammation. However, it is still unknown whether LSP inhibits retinal neovascularization with abnormal capillaries and its mechanism of action. Here, we employed db/db mice and hRECs to find that LSP increases the level of glycolipid metabolism, maintains the morphology of retinal endothelial cells and inhibits acellular capillary neogenesis. Mechanistic studies revealed that LSP inhibits the NLRP3 inflammasome, reduces cell apoptosis in retinal tissue, increases tight junction protein (TJ) expression, and reduces vascular endothelial growth factor (VEGF) and Ve-Cadherin in vivo and in vitro. Collectively, this study finds that LSP inhibits inflammation and angiogenesis to improve BRB function to ameliorate DR.

Protective effects of Radix Stellariae extract against Alzheimer's disease via autophagy activation in Caenorhabditis elegans and cellular models.

Enhancing the clearance of proteins associated with Alzheimer's disease (AD) emerges as a promising approach for AD therapeutics. This study explores the potential of Radix Stellariae, a traditional Chinese medicine, in treating AD. Utilizing transgenic C. elegans models of AD, we demonstrated that a 75% ethanol extract of Radix Stellariae (RSE) (at 50 µg/mL) effectively diminishes Aß and Tau protein expression, and alleviates their induced impairments including paralysis, behavioral dysfunction, neurotoxicity, and ROS accumulation. Additionally, RSE enhances the stress resistance of C. elegans. Further investigations revealed that RSE promotes autophagy, a critical cellular process for protein degradation, in these models. We found that inhibiting autophagy-related genes negated the neuroprotective effects of RSE, suggesting a central role for autophagy in the actions of RSE. In PC-12 cells, we observed that RSE not only inhibited Aß fibril formation but also promoted the degradation of AD-related proteins and reduced their cytotoxicity. Mechanistically, RSE was found to induce autophagy via modulating PI3K/AKT/mTOR and AMPK/mTOR signaling pathways. Importantly, inhibiting autophagy counteracted the beneficial effects of RSE on the clearance of AD-associated proteins. Moreover, we identified Dichotomine B, a ß-carboline alkaloid, as a key active constituent of RSE in mitigating AD pathology in C. elegans at concentrations ranging from 50 to 1000 µM. Collectively, our study presents novel discoveries that RSE alleviates AD pathology and toxicity primarily by inducing autophagy, both in vivo and in vitro. These findings open up new avenues for exploring the therapeutic potential of RSE and its active component, Dichotomine B, in treating neurodegenerative diseases like AD.

Stereoselective Construction of Acyclic ß,ß-Disubstituted Enesulfinamides via Conjugate Addition of Organocuprates to α-Substituted α,ß-Unsaturated N-Sulfinyl Ketimines.

In the presence of boron trifluoride, conjugate addition of organocuprates to α-substituted α,ß-unsaturated N-tert-butanesulfinyl ketimines provides facile access to acyclic ß,ß-disubstituted enesulfinamides with high ratios of geometric isomers. Diverse and challenging to synthesize, multisubstituted aza-enolates bearing two electronically and sterically similar ß-substituents, which are important precursors for asymmetric construction of the less accessible acyclic quaternary or tetrasubstituted stereocenters at the α-position of ketimines, can be efficiently prepared in good yields with high stereocontrol.

Ameliorative effect of Luffa cylindrica fruits on Caenorhabditis elegans and cellular models of Alzheimer's disease-related pathology via autophagy induction.

BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder without an effective cure. Natural products, while showing promise as potential therapeutics for AD, remain underexplored. AIMS: This study was conducted with the goal of identifying potential anti-AD candidates from natural sources using Caenorhabditis elegans (C. elegans) AD-like models and exploring their mechanisms of action. MATERIALS & METHODS: Our laboratory's in-house herbal extract library was utilized to screen for potential anti-AD candidates using the C. elegans AD-like model CL4176. The neuroprotective effects of the candidates were evaluated in multiple C. elegans AD-like models, specifically targeting Aß- and Tau-induced pathology. In vitro validation was conducted using PC-12 cells. To investigate the role of autophagy in mediating the anti-AD effects of the candidates, RNAi bacteria and autophagy inhibitors were employed. RESULTS: The ethanol extract of air-dried fruits of Luffa cylindrica (LCE), a medicine-food homology species, was found to inhibit Aß- and Tau-induced pathology (paralysis, ROS production, neurotoxicity, and Aß and pTau deposition) in C. elegans AD-like models. LCE was non-toxic and enhanced C. elegans' health. It was shown that LCE activates autophagy and its anti-AD efficacy is weakened with the RNAi knockdown of autophagy-related genes. Additionally, LCE induced mTOR-mediated autophagy, reduced the expression of AD-associated proteins, and decreased cell death in PC-12 cells, which was reversed by autophagy inhibitors (bafilomycin A1 and 3-methyladenine). DISCUSSION: LCE, identified from our natural product library, emerged as a valuable autophagy enhancer that effectively protects against neurodegeneration in multiple AD-like models. RNAi knockdown of autophagy-related genes and cotreatment with autophagy inhibitors weakened its anti-AD efficacy, implying a critical role of autophagy in mediating the neuroprotective effects of LCE. CONCLUSION: Our findings highlight the potential of LCE as a functional food or drug for targeting AD pathology and promoting human health.

Folium Hibisci Mutabilis extract, a potent autophagy enhancer, exhibits neuroprotective properties in multiple models of neurodegenerative diseases.

BACKGROUND: Protein aggregates are considered key pathological features in neurodegenerative diseases (NDs). The induction of autophagy can effectively promote the clearance of ND-related misfolded proteins. OBJECTIVE: In this study, we aimed to screen natural autophagy enhancers from traditional Chinese medicines (TCMs) presenting potent neuroprotective potential in multiple ND models. METHODS: The autophagy enhancers were broadly screened in our established herbal extract library using the transgenic Caenorhabditis elegans (C. elegans) DA2123 strain. The neuroprotective effects of the identified autophagy enhancers were evaluated in multiple C. elegans ND models by measuring Aß-, Tau-, α-synuclein-, and polyQ40-induced pathologies. In addition, PC-12 cells and 3 × Tg-AD mice were employed to further validate the neuroprotective ability of the identified autophagy enhancers, both in vitro and in vivo. Furthermore, RNAi bacteria and autophagy inhibitors were used to evaluate whether the observed effects of the identified autophagy enhancers were mediated by the autophagy-activated pathway. RESULTS: The ethanol extract of Folium Hibisci Mutabilis (FHME) was found to significantly increase GFP::LGG-1-positive puncta in the DA2123 worms. FHME treatment markedly inhibited Aß, α-synuclein, and polyQ40, as well as prolonging the lifespan and improving the behaviors of C. elegans, while siRNA targeting four key autophagy genes partly abrogated the protective roles of FHME in C. elegans. Additionally, FHME decreased the expression of AD-related proteins and restored cell viability in PC-12 cells, which were canceled by cotreatment with 3-methyladenine (3-MA) or bafilomycin A1 (Baf). Moreover, FHME ameliorated AD-like cognitive impairment and pathology, as well as activating autophagy in 3 × Tg-AD mice. CONCLUSION: FHME was successfully screened from our natural product library as a potent autophagy enhancer that exhibits a neuroprotective effect in multiple ND models across species through the induction of autophagy. These findings offer a new and reliable strategy for screening autophagy inducers, as well as providing evidence that FHME may serve as a possible therapeutic agent for NDs.

Effect of mini-dose dexmedetomidine supplemented intravenous analgesia on sleep structure in older patients after major noncardiac surgery: A randomized trial.

STUDY OBJECTIVES: In previous studies, low-dose dexmedetomidine supplemented opioid analgesia improved sleep architecture but increased sedation level. Herein we tested the hypothesis that mini-dose dexmedetomidine supplemented analgesia improves sleep structure without increasing sedation. METHODS: In this randomized trial, 118 older patients (≥65 years) following major noncardiac surgery were randomized to receive patient-controlled intravenous analgesia supplemented with either placebo or dexmedetomidine (median 0.02 µg kg-1 h-1) for up to 3 days. Polysomnogram was monitored from 9:00 p.m. on the day of surgery until 6:00 a.m. on the first day after surgery. Our primary outcome was the percentage of non-rapid eye movement stage 2 (N2) sleep. Secondary outcomes included other sleep structure parameters during the night of surgery and the sedation score during the first five postoperative days. RESULTS: All 118 patients completed the study; of these, 85 were included in sleep structure analysis. Dexmedetomidine supplemented analgesia increased the percentage of N2 sleep (median difference, 10%; 95% CI, 1%-20%; P = 0.03). It also prolonged total sleep time (median difference, 78 min; 95% CI, 21 to 143; P = 0.01), increased sleep efficiency (median difference, 14%; 95% CI, 4%-26%; P = 0.01), decreased percentage of N1 sleep (median difference, -10%; 95% CI, -20% to -1%; P = 0.04), and lowered sleep fragmentation index (median difference, -1.6 times⋅h-1; 95% CI, -3.7 to 0.1; P = 0.04). Sedation score within 5 days did not differ between the two groups. CONCLUSIONS: Supplementing intravenous analgesia with mini-dose dexmedetomidine improved sleep structure without increasing sedation in older patients recovering from major surgery. CLINICAL TRIALS: www. CLINICALTRIALS: gov (NCT03117790), registered 2 April 2017.

Chlorogenic acid delays the progression of Parkinson's disease via autophagy induction in Caenorhabditis elegans.

OBJECTIVES: Parkinson's disease (PD) is the second most common neurodegenerative disease. Chlorogenic acid (CGA) is a polyphenolic substance derived from various medicinal plants. Although CGA is reported to have potential anti-PD effect, the beneficial effect and the underlying mechanism remain unclear. In this study, we aimed to further investigate the protective effect and clarify the mechanism of action of CGA in Caenorhabditis elegans (C. elegans) models of PD. METHODS: Measurements of a-synuclein aggregation, movement disorders, and lipid, ROS and malondialdehyde (MDA) contents were observed in NL5901 nematodes. Determinations of dopamine (DA) neuron degeneration, food perception, and ROS content were performed in 6-OHDA-exposed BZ555 nematodes. The autophagy activation of CGA was monitored using DA2123 and BC12921 nematodes. Meanwhile, RNAi technology was employed to knockdown the autophagy-related genes and investigate whether the anti-PD effect of CGA was associated with autophagy induction in C. elegans. RESULTS: CGA significantly reduced α-synuclein aggregation, improved motor disorders, restored lipid content, and decreased ROS and MDA contents in NL5901 nematodes. Meanwhile, CGA inhibited DA neuron-degeneration and improved food-sensing behavior in 6-OHDA-exposed BZ555 nematodes. In addition, CGA increased the number of GFP::LGG-1 foci in DA2123 nematodes and degraded p62 protein in BC12921 nematodes. Meanwhile, CGA up-regulated the expression of autophagy-related genes in NL5901 nematodes. Moreover, the anti-PD effect of CGA was closely related to autophagy induction via increasing the expression of autophagy-related genes, including unc-51, bec-1, vps-34, and lgg-1. CONCLUSIONS: The present study indicates that CGA exerts neuroprotective effect in C. elegans via autophagy induction.

Relationship Between Expression of microRNA and Chemotherapy Resistance in Cervical Carcinoma.

Cervical cancer (CC), although being a potentially avoidable disease, is the second most often diagnose gynecological cancer, with at minimum 530,000 new instant reported each year, and optimism for CC remains poor. Nearly half of individuals with locally advanced cervical cancer have a poor pathological response to standard therapy. As a result, research into the molecular pathogenesis of cervical cancer and associated therapeutic targets is a must. MicroRNAs (miRNAs) are possible biomarkers in cervical cancer; elevations or reductions in many distinct miRNAs discovered in individuals with this illness indicate that miRNA could contain a function to play in the illness's pathogenesis. Nevertheless, little is known about their significance in detecting individuals who do not respond to traditional therapy. As a consequence, the intention of this study is to look at the relationship among the synthesis of miRNAs (miR 217 and miR-140-3p), which can be utilized as molecular biomarkers to predict pathological responses in cervical cancer patients after radiation and chemotherapy. Various analytical techniques were used to analyze the data, including quantitative real-time PCR (qRT-PCR), growth and apoptosis analysis, western blot analysis, luciferase reporter gene analysis, immunohistochemistry, and statistical analysis. The results show that such miRNAs participate a crucial responsibility in CC cell proliferation inhibition. They might be a new therapeutic target for microRNA-mediated cell proliferation inhibition in cervical cancer.