Dietary vitamin A intakes of chinese children with adequate liver stores as assessed by the retinol isotope dilution technique.

BACKGROUND: We attempted to estimate dietary vitamin A requirements based on dietary vitamin A intake in well-nourished Chinese children with adequate liver vitamin A reserves. METHODS: A cross-sectional study was conducted in a kindergarten and an elementary school in Shiyan city, Hubei province of China from December 2009 to July 2010. After screening, 60 children (22 aged 4 ~ 6 y and 38 aged 7 ~ 9 y) were randomly subjected to a 3-d or 18-d deuterated-retinol-dilution (DRD) procedure to evaluate the vitamin A reserves in the body and liver. Dietary intakes of vitamin A were estimated from two (one in winter and one in summer) consecutive 3-day weighed food records and dietary recalls. RESULTS: The dietary vitamin A intakes were significantly correlated with vitamin A stores in the body and liver, but not with the serum level of retinol. The dietary vitamin A intakes were 476.9 ± 196.7 µg retinol equivalent (RE) (or 377.7 ± 166.2 µg retinol activity equivalent (RAE)) / day for 4 ~ 6 y children and 529.1 ± 87.2 µg RE/d (or 464.0 ± 81.1 µg RAE/d) for 7 ~ 9 y children with adequate liver vitamin A reserves. The estimated liver stores of vitamin A derived from both time points (3-d and 18-d) were similar. CONCLUSION: Adequate dietary vitamin A intakes among the well-nourished Chinese children were estimated to be 477 µg RE/d (95%CI 385 ~ 570) or 378 µg RAE/d (95%CI 304 ~ 441) for 4 ~ 6 y children and 529 µg RE/d (95%CI 500 ~ 560) or 464 µg RAE/d (95%CI 437 ~ 491) for 7 ~ 9 y children. Although it needs to be verified in a larger population of different regions in China, our results provide important data to establish the dietary requirement of vitamin A specifically for Chinese children.

Unveiling Latent Structure of Venture Capital Syndication Networks.

Venture capital (VC) is a form of private equity financing provided by VC institutions to startups with high growth potential due to innovative technology or novel business models but also high risks. To against uncertainties and benefit from mutual complementarity and sharing resources and information, making joint-investments with other VC institutions on the same startup are pervasive, which forms an ever-growing complex syndication network. Attaining objective classifications of VC institutions and revealing the latent structure of joint-investment behaviors between them can deepen our understanding of the VC industry and boost the healthy development of the market and economy. In this work, we devise an iterative Loubar method based on the Lorenz curve to make objective classification of VC institutions automatically, which does not require setting arbitrary thresholds and the number of categories. We further reveal distinct investment behaviors across categories, where the top-ranked group enters more industries and investment stages with a better performance. Through network embedding of joint investment relations, we unveil the existence of possible territories of top-ranked VC institutions, and the hidden structure of relations between VC institutions.

Sulbactam improves binding property and uptake capacity of glutamate transporter-1 and decreases glutamate concentration in the CA1 region of hippocampus of global brain ischemic rats.

Glutamate transporter-1 (GLT-1) removes most glutamate in the synaptic cleft. Sulbactam confers neuronal protection against ischemic insults in the hippocampal CA1 region accompanied by the upregulation of GLT-1 expression in rats. The present study further investigates the effect of sulbactam on the binding property and uptake capacity of GLT-1 for glutamate, and the change in extracellular glutamate concentration in the hippocampal CA1 region of rats with global brain ischemia. The binding property and uptake capacity of GLT-1 were measured using a radioligand binding and uptake assay, respectively, with L-3H-glutamate. The extracellular glutamate concentration was detected using microdialysis and high-performance liquid chromatography-mass spectrometry. Neuropathological evaluation was performed based on thionin staining. It was shown that sulbactam pre-treatment changed GLT-1 binding property, including increased Bmax and decreased Kd values, increased GLT-1 uptake capacity for glutamate, and inhibited the elevation of extracellular glutamate concentration in rats with global cerebral ischemia. These effects of sulbactam were accompanied by its neuronal protection on the hippocampal CA1 neurons against delayed neuronal death resulted from ischemic insult. Furthermore, administration of GLT-1 antisense oligodeoxynucleotides, which inhibited the expression of GLT-1, blocked the aforementioned sulbactam-related effects, which suggested that GLT-1 upregulation mediated the above effect although other mechanisms independent of the upregulation of GLT-1 expression could not be excluded. It could be concluded that sulbactam improves the binding property and uptake capacity of GLT-1 for glutamate and then reduces the glutamate concentration and excitotoxicity during global cerebral ischemia, which contributes to the neuroprotection of sulbactam against brain ischemia.

Prevalence of mental health problems in frontline healthcare workers after the first outbreak of COVID-19 in China: a cross-sectional study.

BACKGROUND: More than 210,000 medical workers have fought against the outbreak of Coronavirus Disease 2019 (COVID-19) in Hubei in China since December 2019. However, the prevalence of mental health problems in frontline medical staff after fighting COVID-19 is still unknown. METHODS: Medical workers in Wuhan and other cities in Hubei Province were invited to participate a cross-sectional and convenience sampling online survey, which assessed the prevalence of anxiety, insomnia, depression, and post-traumatic stress disorder (PTSD). RESULTS: A total of 1,091 responses (33% male and 67% female) were valid for statistical analysis. The prevalence was anxiety 53%, insomnia 79%, depression 56%, and PTSD 11%. Healthcare workers in Wuhan were more likely to face risks of anxiety (56% vs. 52%, P = 0.03) and PTSD (15% vs. 9%, P = 0.03) than those in other cities of Hubei. In terms of educational attainment, those with doctoral and masters' (D/M) degrees may experience more anxiety (median of 7.0, [interquartile range (IQR) 2.0-8.5] vs. median 5.0 [IQR 5.0-8.0], P = 0.02) and PTSD (median 26.0 [IQR 19.5-33.0] vs. median 23.0 [IQR 19.0-31.0], P = 0.04) than those with lower educational degrees. CONCLUSIONS: The mental problems were an important issue for the healthcare workers after COVID-19. Thus, an early intervention on such mental problems is necessary for healthcare workers.

Identification and characteristics of insulin-like growth factor system in the brain, liver, and gonad during development of a seasonal breeding teleost, Pampus argenteus.

Reproductive activity is closely related to the development and function of the brain and liver in teleosts, particularly in seasonal breeding teleosts. This study measured the involvement of the insulin-like growth factor (IGF) system in controlling the reproduction of the silver pomfret Pampus argenteus, a seasonal breeding tropical to temperate commercial fish. We cloned and characterized the cDNAs of igfs (igf2 and igf3) and igfrs (igf1ra, igf1rb, and igf2r) and examined their transcript levels in relation to seasonal reproduction. Phylogenetic analyses revealed that two types of IGFs (IGF-1 and IGF-2) and three types of IGFRs (IGF1RA, IGF1RB, and IGF2R) of the silver pomfret were clustered with those of teleosts; however, IGF-3 was a transmembrane protein different with the IGF-3 of other teleosts. The expression of IGF-3 was gonad-specific in the silver pomfret. The transcript levels of igf1 in the female brain were the highest, and the levels of igfrs in both sexes' brains increased during gametogenesis. Meanwhile, igfs and igfrs maintained high transcript levels in both sexes' liver and gonad during vitellogenesis and spermatogonia proliferation. We concluded that the development and activities of brain, liver, and gonad were related to the IGF system (IGFs and IGFRs). And the IGFs were mainly expressed in the liver. Nevertheless, gonadal development, especially vitellogenesis and spermatogonia proliferation, were related with IGFs in this species.

Immune response of silver pomfret (Pampus argenteus) to Amyloodinium ocellatum infection.

Amyloodinium ocellatum (AO) infection in silver pomfret (Pampus argenteus) causes extensive mortality. Insufficient information exists on the molecular immune response of silver pomfret to AO infestation, so herein we simulated the process of silver pomfret being infected by AO. Translucent trophosomes were observed on the gills of AO-infected fish. Transcriptome profiling was performed to investigate the effects of AO infection on the gill, kidney complex and spleen. Overall, 404,412,298 clean reads were obtained, assembling into 96,341 unigenes, which were annotated against public databases. In total, 2730 differentially expressed genes were detected, and few energy- and immune-related genes were further assessed using RT-qPCR. Moreover, activities of three immune-related (SOD, AKP and ACP) and three energy-related (PKM, LDH and GCK) enzymes were determined. AO infection activated the immune system and increased interleukin-1 beta and immunoglobulin M heavy chain levels. Besides, the PPAR signalling pathway was highly enriched, which played a role in improving immunity and maintaining homeostasis. AO infection also caused dyspnoea, leading to extensive lactic acid accumulation, potentially contributing towards a strong immune response in the host. Our data improved our understanding regarding the immune response mechanisms through which fish coped with parasitic infections and may help prevent high fish mortality in aquaculture.

Massage Therapy in Nursing as Nonpharmacological Intervention to Control Agitation and Stress in Patients With Dementia.

CONTEXT: Agitation, aggression, stress, and anxiety are common in patients with dementia. Another essential feature of dementia is a significant decline in a patient's cognitive ability, and communicating among patients through language becomes virtually ineffective. Scientists have examined techniques to maintain communication with patients with dementia at a basic level, such as through gentle touch in the form of massage. OBJECTIVE: The literature review intended to examine the role of massage therapy, either alone or in conjunction with other nonpharmacological interventions such as aromatherapy or calming music, in attenuating aggression and related behavioral disorders in patients with dementia. DESIGN: The research team performed a literature review, searched the PubMed database, using different keyword combinations, including massage, message AND aromatherapy, dementia, agitation, stress, and anxiety. SETTING: The study was performed in China-Japan Union Hospital of Jilin University (Changchun, China). RESULTS: The employment of massage therapy, either alone or in combination with aromatherapy or calming music, can significantly decrease agitation, aggression, stress, and anxiety in patients with dementia. Moreover, massage therapy can also be beneficial for nursing personnel involved in taking care of patients with dementia. The combination of massage with aromatherapy seems to impart the most significant results in patients with dementia. CONCLUSION: Massage therapy may be a useful nonpharmacological intervention in nursing profession to control agitation and stress in patients with dementia.

Risk factors and therapies in vascular diseases: An umbrella review of updated systematic reviews and meta-analyses.

Aberrant blood vessel functioning and systemic circulation are key causes for vascular disorders; cardiovascular, cerebrovascular, renal artery stenosis, and peripheral artery diseases. Epidemiological and basic science evidence supported genetic reasons, compounded by obesity, hypercholesterolemia, hypertension, diabetes, and smoking as risk factors. This is an umbrella review of risk factors and therapies in vascular disorders, exploring systematic reviews and meta-analyses studies in PubMed, Cochrane, Embase, and Central published in January 2000-May 2018. We made qualitative eligibility gradation of the articles based on inclusion criteria, and independently extracted descriptive and methodologic data to compile their outcomes. We considered 95% confidence interval and the between-study heterogeneity, designated by I 2 . Overall, we extracted 217 studies of impressive quality and at low risk of bias, including 124, 30, 23, 32, and 8, respectively, for the search terms "cardiovascular," "renal," "cerebral," and "limb ischemia" each in combination with "risk factors" and "therapeutics." Our search on genome-wide analyses revealed genes associated with HDL-cholesterol, matrix metalloproteases, angiogenesis, notch3, renin-angiotensin, apolipoprotein E, insulin, and cytokine levels as critical participants in the pathogenesis of vascular diseases. Hypertension and endothelial growth factor-linked polymorphisms were found to contribute to vascular damage. The studies reinforced that lifestyle and dietary patterns influenced susceptibility of circulatory system diseases. Additionally, endovascular medicines, surgical vascularization, angioplasty, and renal artery stenting appeared as major therapeutic approaches in vascular patients. Altogether, our review offers up-to-date information on pathophysiology of vascular diseases and provides insight into existing research, clinical management and clinical gaps in the field.

Development of a prognostic score for recommended TACE candidates with hepatocellular carcinoma: A multicentre observational study.

BACKGROUND & AIMS: Previous prognostic scores for transarterial chemoembolization (TACE) were mainly derived from real-world settings, which are beyond guideline recommendations. A robust model for outcome prediction and risk stratification of recommended TACE candidates is lacking. We aimed to develop an easy-to-use tool specifically for these patients. METHODS: Between January 2010 and May 2016, 1,604 treatment-naïve patients with unresectable hepatocellular carcinoma (HCC), Child-Pugh A5-B7 and performance status 0 undergoing TACE were included from 24 tertiary centres. Patients were randomly divided into training (n = 807) and validation (n = 797) cohorts. A prognostic model was developed and subsequently validated. Predictive performance and discrimination were further evaluated and compared with other prognostic models. RESULTS: The final presentation of the model was "linear predictor = largest tumour diameter (cm) + tumour number", which consistently outperformed other currently available models in both training and validation datasets as well as in different subgroups. The thirtieth percentile and the third quartile of the linear predictor, namely 6 and 12, were further selected as cut-off values, leading to the "six-and-twelve" score which could divide patients into 3 strata with the sum of tumour size and number ≤6, >6 but ≤12, and >12 presenting significantly different median survival of 49.1 (95% CI 43.7-59.4) months, 32.0 (95% CI 29.9-37.5) months, and 15.8 (95% CI 14.1-17.7) months, respectively. CONCLUSIONS: The six-and-twelve score may prove an easy-to-use tool to stratify recommended TACE candidates (Barcelona Clinic Liver Cancer stage-A/B) and predict individual survival with favourable performance and discrimination. Moreover, the score could stratify these patients in clinical practice as well as help design clinical trials with comparable criteria involving these patients. Further external validation of the score is required. LAY SUMMARY: There is currently no prognostic model specifically developed for recommended or ideal transarterial chemoembolization (TACE) candidates with hepatocellular carcinoma, despite these patients being frequently identified as the best target population in pivotal randomized controlled trials. The six-and-twelve score provides patient survival prediction, especially in ideal candidates of TACE, outperforming other currently available models in both training and validation sets, as well as different subgroups. With cut-off values of 6 and 12, the score can stratify ideal TACE candidates into 3 strata with significantly different outcomes and may shed light on risk stratification of these patients in clinical practice as well as in clinical trials.

Effects of formaldehyde on detoxification and immune responses in silver pomfret (Pampus argenteus).

Formaldehyde can effectively control ectoparasites in silver pomfret (Pampus argenteus). However, there is limited information on the effects of formaldehyde treatment at a molecular level in fishes. In the present study, transcriptome profiling was conducted to investigate the effects of formaldehyde treatment (80 mg/L, bath for 1 h every day for three consecutive days) on the liver and kidney tissues of silver pomfret. A total of 617959982 clean reads were obtained and assembled into 265760 unigenes with an N50 length of 1507 bp, and the assembled unigenes were all annotated by alignment with public databases. A total of 2204 differentially expressed genes (DEGs) were detected in the liver and kidney tissues, and they included 7 detoxification- related genes and 9 immune-related genes, such as CYP450, GST, MHC I & II, and CCR. In addition, 1440 DEGs were mapped to terms in the GO database, and 1064 DEGs were mapped to the KEGG database. The expression of 4 detoxification-related genes and 6 immune-related genes in three days formaldehyde treatment were analyzed using RT-qPCR, and the antioxidant enzyme levels were also determined. The results indicate differential expression of detoxification- and immune-related genes during the three days formaldehyde treatment. Our data could provide a reference for the treatment of parasites to avoid high mortality and help in understanding the molecular activity in fishes after formaldehyde exposure.

Lanthanum-Based Compounds: Electronic Band-Gap-Dependent Electrocatalytic Materials for Oxygen Reduction Reaction.

The electronic energy level of lanthanum compounds plays an important role in the oxygen reduction reaction (ORR) electrocatalytic process. In this work, three lanthanum compounds, LaOHCO3 , La2 O2 CO3 , and La2 O3 , have been synthesized through an in situ urea hydrolysis method, followed by annealing at different temperatures. Among these lanthanum compounds, the layer-structured La2 O2 CO3 has the smallest band gap and moderate values of the conduction band (CB) and valence band (VB). Electrochemical measurements in 0.1 m KOH solution have shown that, compared with the other catalysts, La2 O2 CO3 exhibits the best electrocatalytic activity with the lowest H2 O2 production and highest durability for ORR, which proves the close correlation between electronic energy level and electrocatalytic ORR activity. During the ORR process over La2 O2 CO3 , some covalent electrons from the VB are first excited to the CB and then transfer to the unoccupied π*2p orbitals of an active oxygen molecule, leading to strengthened oxygen adsorption and promotion of the reduction of oxygen. Moreover, La2 O2 CO3 has an ability to chemically disproportionate hydrogen peroxide (to give HO2- ), and the produced HO2- at the energy level of O2 /HO2- can undergo prompt chemical disproportionation into O2 and OH- . The O2 generated at this stage is adsorbed on the catalyst surface, which can be utilized for further oxygen reduction.

Extended X-ray absorption fine structure and multiple-scattering simulation of nickel dithiolene complexes Ni[S2C2(CF3)2]2(n) (n = -2, -1, 0) and an olefin adduct Ni[S2C2(CF3)2]2(1-hexene).

A series of Ni dithiolene complexes Ni[S2C2(CF3)]2(n) (n = -2, -1, 0) (1, 2, 3) and a 1-hexene adduct Ni[S2C2(CF3)2]2(C6H12) (4) have been examined by Ni K-edge X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine-structure (EXAFS) spectroscopies. Ni XANES for 1-3 reveals clear pre-edge features and approximately +0.7 eV shift in the Ni K-edge position for `one-electron' oxidation. EXAFS simulation shows that the Ni-S bond distances for 1, 2 and 3 (2.11-2.16 Å) are within the typical values for square planar complexes and decrease by ∼ 0.022 Å for each `one-electron' oxidation. The changes in Ni K-edge energy positions and Ni-S distances are consistent with the `non-innocent' character of the dithiolene ligand. The Ni-C interactions at ∼ 3.0 Å are analyzed and the multiple-scattering parameters are also determined, leading to a better simulation for the overall EXAFS spectra. The 1-hexene adduct 4 presents no pre-edge feature, and its Ni K-edge position shifts by -0.8 eV in comparison with its starting dithiolene complex 3. Consistently, EXAFS also showed that the Ni-S distances in 4 elongate by ∼ 0.046 Å in comparison with 3. The evidence confirms that the neutral complex is `reduced' upon addition of olefin, presumably by olefin donating the π-electron density to the LUMO of 3 as suggested by UV/visible spectroscopy in the literature.

Inhibition of cysteine cathepsin B and L activation in astrocytes contributes to neuroprotection against cerebral ischemia via blocking the tBid-mitochondrial apoptotic signaling pathway.

The roles of cathepsins in the ischemic astrocytic injury remain unclear. Here, we test the hypothesis that activation of cathepsin B and L contributes to the ischemic astrocyte injury via the tBid-mitochondrial apoptotic signaling pathways. In the rat models of pMCAO, CA-074Me or Clik148, a selective inhibitor of cathepsin B or cathepsin L, reduced the infarct volume, improved the neurological deficits and increased the MAP2 and GFAP levels. In OGD-induced astrocyte injury, CA-074Me or Clik148 decreased the LDH leakage and increased the GFAP levels. In the ischemic cortex or OGD-induced astrocytes injury, Clik148 or CA-074Me reversed pMCAO or OGD-induced increase in active cathepsin L or cathepsin B at 3 h or 6 h, increase in tBid, reduction in mitochondrial cytochrome-c (Cyt-c) and increase in cytoplastic Cyt-c and active caspase-3 at 12-24 h of the late stage of pMCAO or OGD. CA-074Me or Clik148 also reduced cytosolic and mitochondrial tBid, increased mitochondrial Cyt-c and decreased cytoplastic Cyt-c and active caspase-3 at 6 h of the early stage of Bid activation. CA-074Me or Clik148 blocked the pMCAO-induced release of cathepsin B or L from the lysosomes into the cytoplasm and activation of caspase-3 in ischemic astrocytes at 12 h after ischemia. Concurrent inhibition of cathepsin B and cathepsin L provided better protection on the OGD-induced astrocytic apoptosis than obtained with separate use of each inhibitor. These results suggest that inhibition of the cysteine cathepsin B and cathepsin L activation in ischemic astrocytes contributes to neuroprotection via blocking the tBid-mitochondrial apoptotic signaling pathway.

Impact of the number of lymph node dissections and a novel risk stratification on the prognosis in elderly locally advanced esophageal adenocarcinoma.

Background: Elderly patients with locally advanced esophageal adenocarcinoma (EAC) have a poor prognosis. The purpose of this study was to identify prognostic factors and construct a risk stratification for assessing the prognosis of elderly (≥ 70 years old) EAC patients who receiving neoadjuvant chemoradiotherapy (NCRT) and esophagectomy. Methods: A total of 688 patients with non-metastatic locally advanced EAC who underwent NCRT and esophagectomy were selected from the Surveillance Epidemiology and End Results (SEER) database. Multivariable Cox analysis was used to identify prognostic factors of overall survival (OS). Restricted Cubic Splines (RCS) was used to examine the linear relationship between the number of lymph node dissection (LND) and OS. Result: RCS showed a linear relationship between LND and OS (P = 0.690). As the number of LND increased, the risk of death decreased. Multivariable analysis demonstrated that LND > 23, grade III/IV, and regional node positive were independent prognostic factors. Subgroup analysis indicated that enlarged lymph node dissection (LND > 23) did not improve OS in patients with grade I/II or T1-2 stage, whereas enlarged lymph node dissection significantly improved OS in patients with grade III/IV or T3-4 stage. Furthermore, we constructed a novel risk score based on LND, grade, and regional node status, which stratified patients into low-, medium-, and high-risk groups. Patients in the high-risk group (risk score = 3) had a worse prognosis. Conclusions: Enlarged lymph node dissection (LND > 23) improved OS in patients with grade III/IV or T3-4 stage. Moreover, a novel risk score was constructed, which facilitated risk stratification and postoperative surveillance in elderly EAC patients.

Efficacy and safety of PD-1 inhibitors plus chemotherapy with or without endostatin for stage IV lung squamous cancer: a retrospective study.

Backgroud: The study aimed to analyze the efficacy and safety of PD-1 inhibitors plus chemotherapy with or without endostatin for stage IV lung squamous cell carcinoma (LUSC). Methods: A total of 219 patients with stage IV LUSC were included. 120 received PD-1 inhibitors plus chemotherapy with or without endostatin (IC ± A), of which 39 received endostatin (IC+A) and 81 did not receive endostatin (IC-A). 99 received chemotherapy with or without endostatin (C ± A). Endpoints included overall survival (OS), progression-free survival (PFS), adverse events (AEs), and immune-related adverse events (irAEs). Results: The median PFS in the IC ± A group versus the C ± A group was 8 and 4 months (P < 0.001), and the median OS was 17 and 9 months (P < 0.001). There was no significant difference in any grade AEs between the IC ± A and C ± A groups (P > 0.05). The median PFS in the IC+A group versus the IC-A group was 11 and 7 months (P = 0.024), and the median OS was 34 and 15 months (P = 0.01). There was no significant difference between the IC+A group and the IC-A group for all grade AEs and irAEs (P > 0.05). The subgroup analysis showed that patients with LIPI = 0 had significant OS and PFS benefits in IC+A group, while for patients with LIPI = 1-2, there was no significant difference in OS and PFS benefits between the IC+A group and IC-A group. Conclusions: PD-1 inhibitors plus chemotherapy with endostatin might be first-line treatment for patients with stage IV LUSC.

Soft X-ray absorption spectroscopy and resonant inelastic X-ray scattering spectroscopy below 100 eV: probing first-row transition-metal M-edges in chemical complexes.

X-ray absorption and scattering spectroscopies involving the 3d transition-metal K- and L-edges have a long history in studying inorganic and bioinorganic molecules. However, there have been very few studies using the M-edges, which are below 100 eV. Synchrotron-based X-ray sources can have higher energy resolution at M-edges. M-edge X-ray absorption spectroscopy (XAS) and resonant inelastic X-ray scattering (RIXS) could therefore provide complementary information to K- and L-edge spectroscopies. In this study, M2,3-edge XAS on several Co, Ni and Cu complexes are measured and their spectral information, such as chemical shifts and covalency effects, are analyzed and discussed. In addition, M2,3-edge RIXS on NiO, NiF2 and two other covalent complexes have been performed and different d-d transition patterns have been observed. Although still preliminary, this work on 3d metal complexes demonstrates the potential to use M-edge XAS and RIXS on more complicated 3d metal complexes in the future. The potential for using high-sensitivity and high-resolution superconducting tunnel junction X-ray detectors below 100 eV is also illustrated and discussed.

Autophagy and cathepsin L are involved in the antinociceptive effect of DMBC in a mouse acetic acid-writhing model.

AIM: 2-(3',5'-Dimethoxybenzylidene) cyclopentanone (DMBC) is a novel synthetic compound with antinociceptive activities. The aim of this study was to investigate the roles of the autophagic-lysosomal pathway in the antinociceptive effect of DMBC in a mouse acetic acid-writhing model. METHODS: Mouse acetic acid-writhing test and hotplate test were used to assess the antinociceptive effects of DMBC, 3-MA (autophagy inhibitor) and Clik148 (cathepsin L inhibitor). The drugs were administered peripherally (ip) or centrally (icv). RESULTS: Peripheral administration of 3-MA (7.5-30 mg/kg) or Clik148 (10-80 mg/kg) produced potent antinociceptive effect in acetic acid-writhing test. Central administration of 3-MA or Clik148 (12.5-50 nmol/L) produced comparable antinociceptive effect in acetic acid-writhing test. Peripheral administration of DMBC (25-50 mg/kg) produced potent antinociceptive effects in both acetic acid-writhing and hotplate tests. Furthermore, the antinociceptive effect produced by peripheral administration of DMBC (50 mg/kg) in acetic acid-writhing test was antagonized by low doses of 3-MA (3.75 mg/kg) or Clik148 (20 mg/kg) peripherally administered, but was not affected by 3-MA or Clik148 (25 nmol/L) centrally administered. CONCLUSION: Activation of central autophagy and cathepsin L is involved in nociception in mice, whereas peripheral autophagy and cathepsin L contributes, at least in part, to the antinociceptive effect of DMBC in mice.

Tumor-derived exosomes promote macrophages M2 polarization through miR-1-3p and regulate the progression of liver cancer.

Hepatic carcinoma is one of the most life-threatening malignancies in the world. In the clinic, it is urgent to establish a clear mechanism of hepatic carcinoma development as the basis for intervention and treatment. The purpose of this study was to explore the regulatory effect of tumor-derived exosomes on the progression of hepatocellular carcinoma.qPCR was used to detect the expression of miR-1-3p. CCk-8 and EdU staining were used to detect the proliferation and activity of hepatocellular carcinoma cells under different conditions. Transwell assay was used to detect migration and invasion of hepatocellular carcinoma cells. The morphology and size of exosomes were detected by transmission electron microscope and nanoparticle tracking analysis. Western blot was used to detect the expression of markers of exosomes. Immunofluorescence staining was used to explore the location of exosomes in hepatocellular carcinoma cells.The results showed that the expression of miR-1-3p was significantly reduced in hepatocellular carcinoma cells, and the exosomes transfected with miR-1-3p could enter macrophages and express miR-1-3p in large quantities. Macrophages polarized to M2 type under the action of miR-1-3p. Polarized M2 macrophages further down-regulated the proliferation, migration and invasion of Huh-7 cells.In summary, miR-1-3p can enter macrophages through exosomes and affect their polarization, thus affecting the growth of hepatic carcinoma cells. miR-1-3p may be a potentially effective target for regulating liver cancer progression.

A deep generative framework with embedded vector arithmetic and classifier for sample generation, label transfer, and clustering of single-cell data.

Multiple-source single-cell datasets have accumulated quickly and need computational methods to integrate and decompose into meaningful components. Here, we present inClust (integrated clustering), a flexible deep generative framework that enables embedding auxiliary information, latent space vector arithmetic, and clustering. All functional parts are relatively modular, independent in implementation but interrelated at runtime, resulting in an all-in general framework that could work in supervised, semi-supervised, or unsupervised mode. We show that inClust is superior to most data integration methods in benchmark datasets. Then, we demonstrate the capability of inClust in the tasks of conditional out-of-distribution generation in supervised mode, label transfer in semi-supervised mode, and spatial domain identification in unsupervised mode. In these examples, inClust could accurately express the effect of each covariate, distinguish the query-specific cell types, or segment spatial domains. The results support that inClust is an excellent general framework for multiple-task harmonization and data decomposition.

High throughput isolation of RNA from single-cells within an intact tissue for spatial and temporal sequencing a reality.

Single-cell transcriptomics is essential for understanding biological variability among cells in a heterogenous population. Acquiring high-quality single-cell sequencing data from a tissue sample has multiple challenges including isolation of individual cells as well as amplification of the genetic material. Commercially available techniques require the isolation of individual cells from a tissue through extensive manual manipulation before single cell sequence data can be acquired. However, since cells within a tissue have different dissociation constants, enzymatic and mechanical manipulation do not guarantee the isolation of a homogenous population of cells. To overcome this drawback, in this research we have developed a revolutionary approach that utilizes a fully automated nanopipette technology in combination with magnetic nanoparticles to obtain high quality sequencing reads from individual cells within an intact tissue thereby eliminating the need for manual manipulation and single cell isolation. With the proposed technology, it is possible to sample an individual cell within the tissue multiple times to obtain longitudinal information. Single-cell RNAseq was achieved by aspirating only1-5% of sub-single-cell RNA content from individual cells within fresh frozen tissue samples. As a proof of concept, aspiration was carried out from 22 cells within a breast cancer tissue slice using quartz nanopipettes. The mRNA from the aspirate was then selectively captured using magnetic nanoparticles. The RNAseq data from aspiration of 22 individual cells provided high alignment rates (80%) with 2 control tissue samples. The technology is exceptionally simple, quick and efficient as the entire cell targeting and aspiration process is fully automated.