Thermal utilization techniques and strategies for secondary aluminum dross: A review.

Secondary aluminum ash (SAD) disposal is challenging, particularly in developing countries, and presents severe eco-environmental risks. This paper presents the treatment techniques, mechanisms, and effects of SAD at the current technical-economic level based on aluminum ash's resource utilization and environmental properties. Five recovery techniques were summarized based on aluminum's recoverability in SAD. Four traditional utilization methods were outlined as per the utilization of alumina in SAD. Three new utilization methods of SAD were summarized based on the removability (or convertibility) of aluminum nitride in SAD. The R-U-R (recoverability, utilizability, and removability) theory of SAD was formed based on several studies that helped identify the fingerprint of SAD. Furthermore, the utilization strategies of SAD, which supported the recycling of aluminum ash, were proposed. To form a perfect fingerprint database and develop various relevant techniques, future research must focus on an extensive examination of the characteristics of aluminum ash. This research will be advantageous for addressing the resource and environmental challenges of aluminum ash.

Onion cryptochrome 1 (AcCRY1) regulates photomorphogenesis and photoperiod flowering in Arabidopsis and exploration of its functional mechanisms under blue light.

Cryptochromes (CRYs), as blue-light photoreceptors, play a crucial role in regulating flowering time and hypocotyl and cotyledon development. Their physiological functions have been extensively studied in various plant species. However, research on onions remains limited. In this study, we identified AcCRY1 and conducted preliminary investigations into its function. Our results demonstrate that AcCRY1 possesses a conserved domain typical of cryptochromes with high homology to those found in monocots. Furthermore, we examined the expression level of AcCRY1 in onion. The green tissues is significantly higher compared to non-green tissues, and it exhibits a significant response to blue-light induction. AcCRY1 demonstrates cytoplasmic localization under blue-light conditions, while it localizes in the nucleus during darkness, indicating a strong dependence on blue-light for its subcellular distribution. In comparison to cry1, overexpression of AcCRY1 leads to a significant shorten in seedling hypocotyl length, notable expansion of cotyledons, and acceleration of flowering time. The yeast two-hybrid experiment demonstrated the in vitro interaction between AcCRY1, AcCOP1, and AcSPA1. Additionally, BIFC analysis confirmed their interaction in Onion epidermis. Notably, under blue-light conditions, a significantly enhanced binding activity was observed compared to dark conditions. These findings establish a functional foundation for the regulatory role of AcCRY1 in important physiological processes of onion and provide initial insights into the underlying molecular mechanisms.

[Periplaneta americana extract Câ ¡-3 induces senescence of leukemia K562 cells via SIRT1/mTOR signaling pathway].

This study aims to investigate the role of slient mating-type information regulation 2 homolog 1(SIRT1)/tuberous sclerosis complex 2(TSC2)/mammalian target of rapamycin(mTOR) signaling pathways in the Periplaneta americana extract CⅡ-3-induced senescence of human leukemia K562 cells. K562 cells were cultured in vitro and treated with 0(control), 5, 10, 20, 40, 80, and 160 µg·mL~(-1) of P. americana extract CⅡ-3. Cell counting kit-8(CCK-8) and flow cytometry were employed to examine the proliferation and cell cycle of the K562 cells. Senescence-associated ß-galactosidase stain kit(SA-ß-gal) was used to detect the positive rate of senescent cells. Mitochondrial membrane potential was detected by flow cytometry. The relative mRNA level of telomerase reverse transcriptase(TERT) was determined by fluorescence quantitative PCR. The mRNA and protein levels of SIRT1, TSC2, and mTOR were determined by fluorescence quantitative PCR and Western blot, respectively. The results showed that CⅡ-3 significantly inhibited the proliferation of K562 cells and the treatment with 80 µg·mL~(-1) CⅡ-3 for 72 h had the highest inhibition rate. Therefore, 80 µg·mL~(-1) CⅡ-3 treatment for 72 h was selected as the standard for subsequent experiments. Compared with the control group, CⅡ-3 increased the proportion of cells arrested in G_0/G_1 phase, decreased the proportion of cells in S phase, increased the positive rate of SA-ß-Gal staining, elevated the mitochondrial membrane potential and down-regulated the mRNA expression of TERT. Furthermore, the mRNA expression of SIRT1 and TSC2 was down-regulated, while the mRNA expression of mTOR was up-regulated. The protein expression of SIRT1 and p-TSC2 was down-regulated, while the protein expression of p-mTOR was up-regulated. The results indicated that P. americana extract CⅡ-3 induced the senescence of K562 cells via the SIRT1/mTOR signaling pathway.

Exploration and example interpretation of real-world herbal prescription classification based on similarity matching algorithm / 中国中药杂志

In observational studies, herbal prescriptions are usually studied in the form of "similar prescriptions". At present, the classification of prescriptions is mainly based on clinical experience judgment, but there are some problems in manual judgment, such as lack of unified criteria, labor consumption, and difficulty in verification. In the construction of a database of integrated traditional Chinese and western medicine for the treatment of coronavirus disease 2019(COVID-19), our research group tried to classify real-world herbal prescriptions using a similarity matching algorithm. The main steps include 78 target prescriptions are determined in advance; four levels of importance labeling shall be carried out for the drugs of each target prescription; the combination, format conversion, and standardization of drug names of the prescriptions to be identified in the herbal medicine database; calculate the similarity between the prescriptions to be identified and each target prescription one by one; prescription discrimination is performed based on the preset criteria; remove the name of the prescriptions with "large prescriptions cover the small". Through the similarity matching algorithm, 87.49% of the real prescriptions in the herbal medicine database of this study can be identified, which preliminarily proves that this method can complete the classification of herbal prescriptions. However, this method does not consider the influence of herbal dosage on the results, and there is no recognized standard for the weight of drug importance and criteria, so there are some limitations, which need to be further explored and improved in future research.

Oncocyte Membrane-Camouflaged Multi-Stimuli-Responsive Nanohybrids for Synergistic Amplification of Tumor Oxidative Stresses and Photothermal Enhanced Cancer Therapy.

The combination of various therapeutic modalities has received considerable attention for improving antitumor performance. Herein, an innovative nanohybrid, namely CaO2@FePt-DOX@PDA@CM (CFDPM), was developed for synergistic chemotherapy/chemodynamic therapy/Ca2+ overloading-mediated amplification of tumor oxidative stress and photothermal enhanced cancer therapy. Camouflage of the 4T1 cell membrane enabled CFDPM to escape the immune surveillance and accumulate in the tumor tissue. Ca2+, released from CaO2, could lead to mitochondrial dysfunction and facilitate the production of reactive oxygen species to amplify intracellular oxidative stress. Meanwhile, the increase of H2O2 concentration could enhance the efficiency of the chemodynamic therapy (CDT). Moreover, the hypoxic condition could be alleviated remarkably, which is attributed to the sufficient O2 supply by CaO2, resulting in the suppression of drug resistance and promotion of the chemotherapeutic effect. The nanohybrids involving Ca2+ overloading/CDT/chemotherapy could synergistically amplify the tumor oxidative stresses and remarkably aggravate the death of cancer cells. Significantly, the excellent photothermal conversion performance of CFDPM could further promote the tumoricidal effect. The in vitro and in vivo studies revealed that CFDPM could effectively advance the therapeutic efficiency via the cooperation of various therapeutic modalities to optimize their individual virtue, which would open a valuable avenue for effective cancer treatment.

Mindfulness-Based Stress Reduction, Cognitive Behavioral Therapy, and Acupuncture in Chronic Low Back Pain: Protocol for Two Linked Randomized Controlled Trials.

BACKGROUND: Nonpharmacologic mind-body therapies have demonstrated efficacy in low back pain. However, the mechanisms underlying these therapies remain to be fully elucidated. OBJECTIVE: In response to these knowledge gaps, the Stanford Center for Low Back Pain-a collaborative, National Institutes of Health P01-funded, multidisciplinary research center-was established to investigate the common and distinct biobehavioral mechanisms of three mind-body therapies for chronic low back pain: cognitive behavioral therapy (CBT) that is used to treat pain, mindfulness-based stress reduction (MBSR), and electroacupuncture. Here, we describe the design and implementation of the center structure and the associated randomized controlled trials for characterizing the mechanisms of chronic low back pain treatments. METHODS: The multidisciplinary center is running two randomized controlled trials that share common resources for recruitment, enrollment, study execution, and data acquisition. We expect to recruit over 300 chronic low back pain participants across two projects and across different treatment arms within each project. The first project will examine pain-CBT compared with MBSR and a wait-list control group. The second project will examine real versus sham electroacupuncture. We will use behavioral, psychophysical, physical measure, and neuroimaging techniques to characterize the central pain modulatory and emotion regulatory systems in chronic low back pain at baseline and longitudinally. We will characterize how these interventions impact these systems, characterize the longitudinal treatment effects, and identify predictors of treatment efficacy. RESULTS: Participant recruitment began on March 17, 2015, and will end in March 2023. Recruitment was halted in March 2020 due to COVID-19 and resumed in December 2021. CONCLUSIONS: This center uses a comprehensive approach to study chronic low back pain. Findings are expected to significantly advance our understanding in (1) the baseline and longitudinal mechanisms of chronic low back pain, (2) the common and distinctive mechanisms of three mind-body therapies, and (3) predictors of treatment response, thereby informing future delivery of nonpharmacologic chronic low back pain treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT02503475; https://clinicaltrials.gov/ct2/show/NCT02503475. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/37823.

Quantitative Analysis and Differential Evaluation of Radix Bupleuri Cultivated in Different Regions Based on HPLC-MS and GC-MS Combined with Multivariate Statistical Analysis.

The quality of Radix Bupleuri is greatly affected by its growing environment. In this study, Radix Bupleuri samples that were harvested from seven different regions across northwest China were examined by high-performance liquid chromatography (HPLC) and gas chromatography (GC) coupled with mass spectrometry (MS) to reveal significant differences in quality contributed by the cultivation region. An HPLC-MS method was firstly established and used in the multiple reaction monitoring mode for the quantitative analysis of five saikosaponins in Radix Bupleuri so as to evaluate the difference in the absolute content of saikosaponins attributable to the cultivation region. The effect on the components of Radix Bupleuri was further investigated based on the profiles of the representative saponins and volatile compounds, which were extracted from the Radix Bupleuri samples and analyzed by HPLC-MS and GC-MS. Multivariate statistical analysis was employed to differentiate the Radix Bupleuri samples cultivated in different regions and to discover the differential compositions. The developed quantitative method was validated to be accurate, stable, sensitive, and repeatable for the determination of five saikosaponins. Further statistical tests revealed that the collected Radix Bupleuri samples were distinctly different from each other in terms of both saponins and volatile compounds, based on the provinces where they were grown. In addition, twenty-eight saponins and fifty-eight volatile compounds were identified as the differentially accumulated compositions that contributed to the discrimination of the Radix Bupleuri samples. The Radix Bupleuri samples grown in Shouyang county showed the highest content of saikosaponins. All of the results indicated that the cultivation region significantly affected the accumulation and diversity of the main chemical components of Radix Bupleuri. The findings of this research provide insights into the effect of the cultivation region on the quality of Radix Bupleuri and the differentiation of Radix Bupleuri cultivated in different regions based on the use of HPLC-MS and GC-MS combined with multivariate statistical analysis.

Thalamic nuclei atrophy at high and heterogenous rates during cognitively unimpaired human aging.

The thalamus is a central integration structure in the brain, receiving and distributing information among the cerebral cortex, subcortical structures, and the peripheral nervous system. Prior studies clearly show that the thalamus atrophies in cognitively unimpaired aging. However, the thalamus is comprised of multiple nuclei involved in a wide range of functions, and the age-related atrophy of individual thalamic nuclei remains unknown. Using a recently developed automated method of identifying thalamic nuclei (3T or 7T MRI with white-matter-nulled MPRAGE contrast and THOMAS segmentation) and a cross-sectional design, we evaluated the age-related atrophy rate for 10 thalamic nuclei (AV, CM, VA, VLA, VLP, VPL, pulvinar, LGN, MGN, MD) and an epithalamic nucleus (habenula). We also used T1-weighted images with the FreeSurfer SAMSEG segmentation method to identify and measure age-related atrophy for 11 extra-thalamic structures (cerebral cortex, cerebral white matter, cerebellar cortex, cerebellar white matter, amygdala, hippocampus, caudate, putamen, nucleus accumbens, pallidum, and lateral ventricle). In 198 cognitively unimpaired participants with ages spanning 20-88 years, we found that the whole thalamus atrophied at a rate of 0.45% per year, and that thalamic nuclei had widely varying age-related atrophy rates, ranging from 0.06% to 1.18% per year. A functional grouping analysis revealed that the thalamic nuclei involved in cognitive (AV, MD; 0.53% atrophy per year), visual (LGN, pulvinar; 0.62% atrophy per year), and auditory/vestibular (MGN; 0.64% atrophy per year) functions atrophied at significantly higher rates than those involved in motor (VA, VLA, VLP, and CM; 0.37% atrophy per year) and somatosensory (VPL; 0.32% atrophy per year) functions. A proximity-to-CSF analysis showed that the group of thalamic nuclei situated immediately adjacent to CSF atrophied at a significantly greater atrophy rate (0.59% atrophy per year) than that of the group of nuclei located farther from CSF (0.36% atrophy per year), supporting a growing hypothesis that CSF-mediated factors contribute to neurodegeneration. We did not find any significant hemispheric differences in these rates of change for thalamic nuclei. Only the CM thalamic nucleus showed a sex-specific difference in atrophy rates, atrophying at a greater rate in male versus female participants. Roughly half of the thalamic nuclei showed greater atrophy than all extra-thalamic structures examined (0% to 0.54% per year). These results show the value of white-matter-nulled MPRAGE imaging and THOMAS segmentation for measuring distinct thalamic nuclei and for characterizing the high and heterogeneous atrophy rates of the thalamus and its nuclei across the adult lifespan. Collectively, these methods and results advance our understanding of the role of thalamic substructures in neurocognitive and disease-related changes that occur with aging.

Mechanism Assay of Honeysuckle for Heat-Clearing Based on Metabolites and Metabolomics.

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as cyclooxygenase (Cox)-1/2 inhibitor, have emerged as potent antipyretics and analgesics. However, few herbs with Cox-1/2 inhibitory activity are commonly used for heat-clearing in China. Although these are known to have antipyretic activity, there is a lack of molecular data supporting their activity. Using the traditional Chinese medicine herb honeysuckle (Hon) as an example, we explored key antipyretic active compounds and their mechanisms of action by assessing their metabolites and metabolomics. Mitogen-activated protein kinase (MAPK) 3 and protein kinase B (AKT) 1 were suggested as key targets regulated primarily by chlorogenic acid (CA) and swertiamarin (SWE). CA and SWE synergistically inhibited the production of interleukin (IL)-1 and IL-6, alleviated generation of prostaglandin E2, and played an antipyretic role equivalent to honeysuckle extract at the same dose contents within 3 h. Collectively, these findings indicated that lipopolysaccharide-induced fever can be countered by CA with SWE synergistically, allowing the substitution of a crude extract of complex composition with active compounds. Our findings demonstrated that, unlike the traditional NSAIDs, the Hon extract showed a remote and indirect mechanism for alleviating fever that depended on the phosphatidylinositol-3-kinase-AKT and MAPK pathways by regulating the principal mediator of inflammation.

Effects of emollient therapy with sunflower seed oil on neonatal growth and morbidity in Uttar Pradesh, India: a cluster-randomized, open-label, controlled trial.

BACKGROUND: Newborn oil massage is a widespread practice. Vigorous massage with potentially harmful products and forced removal of vernix may disrupt skin barrier integrity. Hospitalized, very-preterm infants treated with sunflower seed oil (SSO) have demonstrated improved growth but community-based data on growth and health outcomes are lacking. OBJECTIVES: We aimed to test whether SSO therapy enhances neonatal growth and reduces morbidity at the population level. METHODS: We conducted an open-label, controlled trial in rural Uttar Pradesh, India, randomly allocating 276 village clusters equally to comparison (usual care) and intervention comprised of promotion of improved massage practices exclusively with SSO, using intention-to-treat and per-protocol mixed-effects regression analysis. RESULTS: We enrolled 13,478 and 13,109 newborn infants in demographically similar intervention and comparison arms, respectively. Adherence to exclusive SSO increased from 22.6% of intervention infants enrolled in the first study quartile to 37.2% in the last quartile. Intervention infants gained significantly more weight, by 0.94 g · kg-1 · d-1 (95% CI: 0.07, 1.82 g · kg-1 · d-1, P = 0.03), than comparison infants by intention-to-treat analysis. Restricted cubic spline regression revealed the largest benefits in weight gain (2-4 g · kg-1 · d-1) occurred in infants weighing <2000 g at birth. Weight gain in intervention infants was higher by 1.31 g · kg-1 · d-1 (95% CI: 0.17, 2.46 g · kg-1 · d-1; P = 0.02) by per-protocol analysis. Morbidities were similar by intention-to-treat analysis but in per-protocol analysis rates of hospitalization and of any illness were reduced by 36% (OR: 0.64; 95% CI: 0.44, 0.94; P = 0.02) and 44% (OR: 0.56; 95% CI: 0.40, 0.77; P < 0.001), respectively, in treated infants. CONCLUSIONS: SSO therapy improved neonatal growth, and reduced morbidities when applied exclusively, across the facility-community continuum of care at the population level. Further research is needed to improve demand for recommended therapy inside hospital as well as in community settings, and to confirm these results in other settings.This trial was registered at www.isrctn.com as ISRCTN38965585 and http://ctri.nic.in as CTRI/2014/12/005282.

Activating BK channels ameliorates vascular smooth muscle calcification through Akt signaling.

Vascular calcification (VC) is characterized by pathological depositions of calcium and phosphate in the arteries and veins via an active cell-regulated process, in which vascular smooth muscle cells (VSMCs) transform into osteoblast/chondrocyte-like cells as in bone formation. VC is associated with significant morbidity and mortality in chronic kidney disease (CKD) and cardiovascular disease, but the underlying mechanisms remain unclear. In this study we investigated the role of large-conductance calcium-activated potassium (BK) channels in 3 experimental VC models. VC was induced in vascular smooth muscle cells (VSMCs) by ß-glycerophosphate (ß-GP), or in rats by subtotal nephrectomy, or in mice by high-dosage vitamin D3. We showed that the expression of BK channels in the artery of CKD rats with VC and in ß-GP-treated VSMCs was significantly decreased, which was functionally confirmed by patch-clamp recording. In ß-GP-treated VSMCs, BK channel opener NS1619 (20 µM) significantly alleviated VC by decreasing calcium content and alkaline phosphatase activity. Furthermore, NS1619 decreased mRNA expression of ostoegenic genes OCN and OPN, as well as Runx2 (a key transcription factor involved in preosteoblast to osteoblast differentiation), and increased the expression of α-SMA protein, whereas BK channel inhibitor paxilline (10 µM) caused the opposite effects. In primary cultured VSMCs from BK-/- mice, BK deficiency aggravated calcification as did BK channel inhibitor in normal VSMCs. Moreover, calcification was more severe in thoracic aorta rings of BK-/- mice than in those of wild-type littermates. Administration of BK channel activator BMS191011 (10 mg· kg-1 ·d-1) in high-dosage vitamin D3-treated mice significantly ameliorated calcification. Finally, co-treatment with Akt inhibitor MK2206 (1 µM) or FoxO1 inhibitor AS1842856 (3 µM) in calcified VSMCs abrogated the effects of BK channel opener NS1619. Taken together, activation of BK channels ameliorates VC via Akt/FoxO1 signaling pathways. Strategies to activate BK channels and/or enhance BK channel expression may offer therapeutic avenues to control VC.

Effect of sunflower seed oil emollient therapy on newborn infant survival in Uttar Pradesh, India: A community-based, cluster randomized, open-label controlled trial.

BACKGROUND: Hospitalized preterm infants with compromised skin barrier function treated topically with sunflower seed oil (SSO) have shown reductions in sepsis and neonatal mortality rate (NMR). Mustard oil and products commonly used in high-mortality settings may possibly harm skin barrier integrity and enhance risk of infection and mortality in newborn infants. We hypothesized that SSO therapy may reduce NMR in such settings. METHODS AND FINDINGS: This was a population-based, cluster randomized, controlled trial in 276 clusters in rural Uttar Pradesh, India. All newborn infants identified through population-based surveillance in the study clusters within 7 days of delivery were enrolled from November 2014 to October 2016. Exclusive, 3 times daily, gentle applications of 10 ml of SSO to newborn infants by families throughout the neonatal period were recommended in intervention clusters (n = 138 clusters); infants in comparison clusters (n = 138 clusters) received usual care, such as massage practice typically with mustard oil. Primary analysis was by intention-to-treat with NMR and post-24-hour NMR as the primary outcomes. Secondary analysis included per-protocol analysis and subgroup analyses for NMR. Regression analysis was adjusted for caste, first-visit weight, delivery attendant, gravidity, maternal age, maternal education, sex of the infant, and multiple births. We enrolled 13,478 (52.2% male, mean weight: 2,575.0 grams ± standard deviation [SD] 521.0) and 13,109 (52.0% male, mean weight: 2,607.0 grams ± SD 509.0) newborn infants in the intervention and comparison clusters, respectively. We found no overall difference in NMR in the intervention versus the comparison clusters [adjusted odds ratio (aOR) 0.96, 95% confidence interval (CI) 0.84 to 1.11, p = 0.61]. Acceptance of SSO in the intervention arm was high at 89.3%, but adherence to exclusive applications of SSO was 30.4%. Per-protocol analysis showed a significant 58% (95% CI 42% to 69%, p < 0.01) reduction in mortality among infants in the intervention group who were treated exclusively with SSO as intended versus infants in the comparison group who received exclusive applications of mustard oil. A significant 52% (95% CI 12% to 74%, p = 0.02) reduction in NMR was observed in the subgroup of infants weighing ≤1,500 g (n = 589); there were no statistically significant differences in other prespecified subgroup comparisons by low birth weight (LBW), birthplace, and wealth. No severe adverse events (SAEs) were attributable to the intervention. The study was limited by inability to mask allocation to study workers or participants and by measurement of emollient use based on caregiver responses and not actual observation. CONCLUSIONS: In this trial, we observed that promotion of SSO therapy universally for all newborn infants was not effective in reducing NMR. However, this result may not necessarily establish equivalence between SSO and mustard oil massage in light of our secondary findings. Mortality reduction in the subgroup of infants ≤1,500 g was consistent with previous hospital-based efficacy studies, potentially extending the applicability of emollient therapy in very low-birth-weight (VLBW) infants along the facility-community continuum. Further research is recommended to develop and evaluate therapeutic regimens and continuum of care delivery strategies for emollient therapy for newborn infants at highest risk of compromised skin barrier function. TRIAL REGISTRATION: ISRCTN Registry ISRCTN38965585 and Clinical Trials Registry-India (CTRI/2014/12/005282) with WHO UTN # U1111-1158-4665.

Zanthoxylum-specific whole genome duplication and recent activity of transposable elements in the highly repetitive paleotetraploid Z. bungeanum genome.

Zanthoxylum bungeanum is an important spice and medicinal plant that is unique for its accumulation of abundant secondary metabolites, which create a characteristic aroma and tingling sensation in the mouth. Owing to the high proportion of repetitive sequences, high heterozygosity, and increased chromosome number of Z. bungeanum, the assembly of its chromosomal pseudomolecules is extremely challenging. Here, we present a genome sequence for Z. bungeanum, with a dramatically expanded size of 4.23 Gb, assembled into 68 chromosomes. This genome is approximately tenfold larger than that of its close relative Citrus sinensis. After the divergence of Zanthoxylum and Citrus, the lineage-specific whole-genome duplication event η-WGD approximately 26.8 million years ago (MYA) and the recent transposable element (TE) burst ~6.41 MYA account for the substantial genome expansion in Z. bungeanum. The independent Zanthoxylum-specific WGD event was followed by numerous fusion/fission events that shaped the genomic architecture. Integrative genomic and transcriptomic analyses suggested that prominent species-specific gene family expansions and changes in gene expression have shaped the biosynthesis of sanshools, terpenoids, and anthocyanins, which contribute to the special flavor and appearance of Z. bungeanum. In summary, the reference genome provides a valuable model for studying the impact of WGDs with recent TE activity on gene gain and loss and genome reconstruction and provides resources to accelerate Zanthoxylum improvement.

A Pilot Study of Silymarin as Supplementation to Reduce Toxicities in Metastatic Colorectal Cancer Patients Treated With First-Line FOLFIRI Plus Bevacizumab.

Irinotecan, a topoisomerase inhibitor, is a common cytotoxic agent prescribed for metastatic colorectal cancer (mCRC) patients. Diarrhea is the most common adverse event (AE). The underlying mechanism of irinotecan-induced diarrhea is intestinal mucosal damage caused by SN-38 (active metabolite of irinotecan) hydrolyzed from SN-38G (inactive metabolite) by bacterial -glucuronidase (G). According to an animal study, silymarin reduces the activity of bacterial G without impairing antitumor efficacy. We conducted a prospective open-label pilot study to evaluate the effect of silymarin as supplementation in reducing toxicities of mCRC patients undergoing irinotecan-based chemotherapy. We enrolled and randomized 70 mCRC patients receiving first-line FOLFIRI (5-fluorouracil/leucovorin/irinotecan) plus bevacizumab. In each treatment cycle, the study group was administered silymarin capsules (150 mg) three times daily for 7 days. The study group experienced less AEs in diarrhea (5.7% vs. 14.6%, p=0.002) and nausea (27.0% vs. 40.2%, p=0.005) in comparison with the control group, but no significant differences in hepatic toxicities were observed. In conclusion, simultaneous administration of silymarin is a potential effective supplementation for reducing toxicities in mCRC patients undergoing first-line FOLFIRI plus bevacizumab, especially in diarrhea and nausea.

Chemical Constituent of ß-Glucuronidase Inhibitors from the Root of Neolitsea acuminatissima.

Neolitsea acuminatissima (Lauraceae) is an endemic plant in Taiwan. One new carboline alkaloid, demethoxydaibucarboline A (1), two new eudesmanolide-type sesquiterpenes, methyl-neolitacumone A (2), neolitacumone E (3), and twelve known compounds (4-15) were isolated from the root of Neolitsea acuminatissima. Their structures were elucidated by spectroscopic analysis. Glucuronidation represents a major metabolism process of detoxification for carcinogens in the liver. However, intestinal bacterial ß-Glucuronidase (ßG) has been considered pivotal to colorectal carcinogenesis. To develop specific bacterial-ßG inhibitors with no effect on human ßG, methanolic extract of roots of N. acuminatissima was selected to evaluate their anti-ßG activity. Among the isolates, demethoxydaibucarboline A (1) and quercetin (8) showed a strong bacterial ßG inhibitory effect with an inhibition ratio of about 80%. Methylneolitacumone A (2) and epicatechin (10) exhibited a moderate or weak inhibitory effect and the enzyme activity was less than 45% and 74%, respectively. These four compounds specifically inhibit bacterial ßG but not human ßG. Thus, they are expected to be used for the purpose of reducing chemotherapy-induced diarrhea (CID). The results suggest that the constituents of N. acuminatissima have the potential to be used as CID relief candidates. However, further investigation is required to determine their mechanisms of action.

Antidiabetic Effect of Artemether in Db/Db Mice Involves Regulation of AMPK and PI3K/Akt Pathways.

The traditional Chinese medicine has long been used in the treatment of diabetes, one major disease threatening the public health. It has been reported that artemether exerts antidiabetic effects on type 2 diabetes in db/db mice, however the underlying mechanisms remain unknown. In the present study, we show that artemether regulates expression of related enzymes participating in the glucose and lipid metabolism in the liver of db/db mice, which could at least partly explain the improved glucose and lipid metabolism in artemether-treated mice. Additionally, artemether also regulates expression of glycogen synthesis related enzymes in the skeletal muscle of db/db mice, supporting its promotive role in glycogen synthesis. Mechanistically, artemether activates AMPK pathway as well as PI3K/Akt pathway in the liver and skeletal muscle of db/db mice, suggesting that these two signaling pathways are both involved in the antidiabetic effects of artemether on type 2 diabetes in db/db mice. In conclusion, our study connects the antidiabetic effects of artemether to the regulation of metabolic enzymes and signaling pathways, and also provides molecular basis for the potential application of artemether in treating type 2 diabetes.

Effects of Selenium-Enriched Yeast on Performance, Egg Quality, Antioxidant Balance, and Egg Selenium Content in Laying Ducks.

This study investigated the effects of dietary selenium-enriched yeast (Se yeast) supplementation on the laying performance, egg quality, plasma antioxidant balance, and egg selenium (Se) content in laying Longyan ducks. A total of 480 32-week-old ducks were randomly divided into four dietary treatments, each consisting of six replicates of 20 ducks. The dietary treatments were a control basal diet and basal diets with supplementation of 0.05, 0.15, and 0.25 mg Se/kg via Se yeast. The analyzed Se contents of the four diets were 0.15, 0.21, 0.36, and 0.43 mg Se/kg, respectively. Dietary Se yeast supplementation had no apparent effects on laying performance and egg quality (p > 0.05), but it improved the antioxidant balance of ducks, as inferred by greater glutathione peroxidase and catalase activities, and decreased the malondialdehyde content in plasma of ducks (p < 0.05). It was suggested that the Se content in the basal diet containing 0.15 mg/kg of Se requirement is adequate for productive performance, but not for the antioxidant balance of laying ducks. Besides that, the Se contents in the yolk, albumen, and whole egg increased linearly as the Se supplementation levels increased. With more feeding days, the Se contents in the yolk and whole egg from non-Se-yeast-supplemented ducks increased linearly (p < 0.05), while those from Se-yeast-supplemented ducks showed a quadratic relationship (p < 0.05). In conclusion, the Se content of the basal diet at 0.15 mg/kg was adequate for laying performance and egg quality traits in laying ducks. Dietary Se yeast supplementation is beneficial to improve the antioxidant balance of laying ducks and increase the Se deposition in eggs for producing Se-enriched eggs. Based on the quadratic model or the quadratic broken-line model analyses, supplemental 0.19 mg Se/kg via Se yeast, with a total equivalent of 0.34 mg Se/kg in the diet, could provide the optimum antioxidant balance in laying ducks. Dietary supplementation of 0.25 mg Se/kg via Se yeast, with a total equivalent of 0.40 mg Se/kg in the diet, could lead to achieving the desired Se content in the whole egg.

Effect of Electroacupuncture vs Sham Treatment on Change in Pain Severity Among Adults With Chronic Low Back Pain: A Randomized Clinical Trial.

Importance: Chronic low back pain has high societal and personal impact but remains challenging to treat. Electroacupuncture has demonstrated superior analgesia compared with placebo in animal studies but has not been extensively studied in human chronic pain conditions. Objective: To evaluate the treatment effect of real electroacupuncture vs placebo in pain and disability among adults with chronic low back pain and to explore psychophysical, affective, and demographic factors associated with response to electroacupuncture vs placebo in treating chronic low back pain. Design, Setting, and Participants: This double-blind randomized clinical trial was conducted between August 2, 2016, and December 18, 2018, at a single center in Stanford, California. Primary outcomes were collected at approximately 2 weeks before and after intervention. Participants included English-speaking adults with at least 6 months of chronic low back pain, pain intensity of at least 4 on a scale of 0 to 10, and no radiculopathy. Data analyses for this intent-to-treat study were conducted from June 2019 to June 2020. Interventions: Twelve sessions of real or placebo (sham) electroacupuncture administered twice a week over 6 weeks. Main Outcomes and Measures: The main outcome was change in pain severity from baseline to 2 weeks after completion of treatment, measured by the National Institutes of Health PROMIS pain intensity scale. A secondary outcome was change in the Roland Morris Disability Questionnaire (RMDQ). Baseline factors potentially associated with these outcomes included psychophysical testing (ie, thermal temporal summation, conditioned pain modulation, pressure pain threshold), participant's self-report (ie, widespread pain, coping strategies, expectations, self-efficacy, and pain catastrophizing), and demographic characteristics (eg, age, sex, and race). Results: A total of 121 adults were recruited to the study, among whom 59 participants (mean [SD] age, 46.8 [11.9] years; 36 [61.0%] women) were randomized to real electroacupuncture and 62 participants (mean [SD] age, 45.6 [12.8] years; 33 [53.2%] women) were randomized to sham electroacupuncture. At baseline, the mean (SD) PROMIS T-score was 50.49 (3.36) in the real electroacupuncture group and 51.71 (4.70) in the sham acupuncture group, and the mean (SD) RMDQ score was 10.16 (4.76) in the real electroacupuncture group and 10.03 (5.45) in the sham acupuncture group. After adjusting for baseline pain scores, there was no statistically significant difference between groups in change in T-scores 2 weeks after completion of treatment (real electroacupuncture: -4.33; 95% CI, -6.36 to -2.30; sham acupuncture: -2.90; 95% CI, -4.85 to -0.95; difference: -2.09; 95% CI, -4.27 to 0.09; P = .06). After adjusting for baseline RMDQ, there was a significantly greater reduction in RMDQ in the real electroacupuncture group (-2.77; 95% CI, -4.11 to -1.43) compared with the sham electroacupuncture group (-0.67; 95% CI, -1.88 to 0.55; difference: -2.11; 95% CI, -3.75 to -0.47; P = .01). Within the real electroacupuncture group, effective coping at baseline was associated with greater RMDQ reduction (r = -0.32; 95% CI, -0.54 to -0.05; P = .02), and White race was associated with worse outcomes in PROMIS score (ß = 3.791; 95% CI, 0.616 to 6.965; P = .02) and RMDQ (ß = 2.878; 95% CI, 0.506 to 5.250; P = .02). Conclusions and Relevance: This randomized clinical trial found no statistically significant difference in change in PROMIS pain score in real electroacupuncture vs sham electroacupuncture. There was a statistically significant treatment effect for the secondary outcome of RMDQ compared with sham electroacupuncture. Effective coping skills and non-White race were associated with response to electroacupuncture. Trial Registration: ClinicalTrials.gov Identifier: NCT02890810.

Association between microRNA 25 expression in serum and lung cancer: A protocol for systematic review and meta-analysis.

BACKGROUND: This study aims to identify the association between microRNA 25 (mRNA 25) expression in serum and lung cancer (LC). METHODS: This planned study will cover all eligible case-controlled studies that report association between mRNA 25 expression in serum and LC. It will include published studies from inception to the present in Cochrane Library, PUBMED, EMBASE, Web of Science, Allied and Complementary Medicine Database, VIP database, and China National Knowledge Infrastructure regardless language and geographical location. We will also search other sources, such as conference abstracts and reference lists of related known studies and experts in the domain consulted to avoid missing potential studies. Two contributors will independently examine and select studies, collect all necessary data, and judge study quality for all included studies. We will perform statistical analysis using RevMan V.5.3 software and Stata V.12.0 software. RESULTS: This study will summarize current evidence to present first systematic review of research on the association between mRNA 25 expression in serum and LC. CONCLUSION: This study will present comprehensive evidence to determine whether mRNA 25 expression in serum is associated with LC, and will provide helpful evidence for the future studies. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040056.

The role of endogenous thiamine produced via THIC in root nodule symbiosis in Lotus japonicus.

Thiamine is a pivotal primary metabolite which is indispensable to all organisms. Although its biosynthetic pathway has been well documented, the mechanism by which thiamine influences the legume-rhizobium symbiosis remains uncertain. Here, we used overexpressing transgenic plants, mutants and grafting experiments to investigate the roles played by thiamine in Lotus japonicus nodulation. ljthic mutants displayed lethal phenotypes and the defect could be overcome by supplementation of thiamine or by overexpression of LjTHIC. Reciprocal grafting between L. japonicus wild-type Gifu B-129 and ljthic showed that the photosynthetic products of the aerial part made a major contribution to overcoming the nodulation defect in ljthic. Overexpression of LjTHIC in Lotus japonicus (OE-LjTHIC) decreased shoot growth and increased the activity of the enzymes 2-oxoglutarate dehydrogenase and pyruvate dehydrogenase. OE-LjTHIC plants exhibited an increase in the number of infection threads and also developed more nodules, which were of smaller size but unchanged nitrogenase activity compared to the wildtype. Taken together, our results suggest that endogenous thiamine produced via LjTHIC acts as an essential nutrient provided by the host plant for rhizobial infection and nodule growth in the Lotus japonicus - rhizobium interaction.