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Background: Opioid-free anesthesia (OFA) is increasing being explored due to increased awareness of opioid related adverse events and the national opioid crisis. The objective of this study was to examine the feasibility of Dexmedetomidine-Esketamine-Lidocaine OFA technique for patients diagnosed with breast begin mass underwent Lumpectomy, especially paying attention to its impact on postoperative pain, intraoperative hemodynamic parameters, recovery quality, and adverse events. Methods: In this prospective, randomized study, sixty patients who aged from 20 to 60 years, graded with American Society of Anesthesiologists physical status I or II, diagnosed with breast begin mass and scheduled to undergo Lumpectomy were enrolled. These patients were randomized to receive either OFA (OFA group) or opioid-based (OA group) anesthesia. Dexmedetomidine-Esketamine-Lidocaine or Sufentanil-Remifentanil was administered for induction and maintenance in OFA group or OA group, respectively. Postoperative visual analog scale (VAS) pain score at 2 h, 12 h, and 24 h after extubation was recorded. Intraoperative hemodynamic parameters were recorded at the following time points: entering operating room (T0), immediately after induction of anesthesia (T1), immediately after intubation (T2), 1 minute after surgical incision (T3), 5 minutes after surgical incision (T4), and 10 minutes after surgical incision (T5). Number of rescue analgesics used, rescue vasoactive drugs required, awakening time and recovery time of orientation, and incidence of adverse events were recorded as well. Results: The VAS score at 2, 12, and 24 h after extubation and number of rescue hydromorphone required (0 of 30 [0%] versus 0 of 30 [0%]) had no statistically significant difference between the two groups. The mean arterial pressure and heart rate at T1, T2, T3, T4, T5 were significantly lower in OA group than that in OFA group. The number of rescue ephedrine (1 of 30 [3.3%] versus 12 of 30 [40%], P=0.001) and rescue atropine (2 of 30 [6.7%] versus 6 of 30 [20%], P=0.038) were significantly lower in OFA group compared with OA group. Postoperative nausea and vomiting (3 of 30 [10%] versus 16 of 30 [53%], P=0.001) and application of rescue ondansetron (1 of 30 [3.3%] versus 10 of 30 [33%], P=0.003) were both less in the OFA group compared to those in OA group. However, compared with OA group, patients in OFA group had a longer awakening time ([7.27±2.85] min versus [4.47±1.11] min, P=0.000), longer recovery time of orientation ([11.97±3.19] min versus [6.93±1.17] min, P=0.000), higher analgesia-related drug cost ([$23.89±4.20] versus [ $21.31±3.94], P=0.017). Conclusions: The combination of Dexmedetomidine-Esketamine-Lidocaine OFA technique may be an alternative anesthesia for lumpectomy as better hemodynamic stability, lower incidence of postoperative nausea and vomiting, and adequate postoperative analgesia compared with OBA. But the traditional OA technique has shorter awakening time, shorter recovery time of orientation and lower analgesia-related cost.

A novel nanobody-drug conjugate (NDC) was constructed by incorporating an amphipathic peptide, GALA, which improved the cytotoxicity by one to two orders of magnitude. Mechanistic studies demonstrate that tethering to lipids induces GALA to form a helix, which dramatically enhances endocytosis. Our work provides a general strategy not only for improving the anti-cancer efficacy of protein-drug conjugates but also for increasing the efficiency of other types of endocytosis-dependent cell delivery.

Background Neuroinflammation is an important component mechanism in the development of depression. Exosomal transfer of MDD-associated microRNAs (miRNAs) from neurons to microglia might exacerbate neuronal cell inflammatory injury. Results By sequence identification, we found significantly higher miR-9-5p expression levels in serum exosomes from MDD patients than healthy control (HC) subjects. Then, in cultured cell model, we observed that BV2 microglial cells internalized PC12 neuron cell-derived exosomes while successfully transferring miR-9-5p. MiR-9-5p promoted M1 polarization in microglia and led to over releasing of proinflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which exacerbated neurological damage. Furthermore, we identified suppressor of cytokine signaling 2 (SOCS2) as a direct target of miR-9-5p. Overexpression of miR-9-5p suppressed SOCS2 expression and reactivated SOCS2-repressed Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathways. Consistently, we confirmed that adeno-associated virus (AAV)-mediated overexpression of miR-9-5p polarized microglia toward the M1 phenotype and exacerbated depressive symptoms in chronic unpredictable mild stress (CUMS) mouse mode. Conclusion MiR-9-5p was transferred from neurons to microglia in an exosomal way, leading to M1 polarization of microglia and further neuronal injury. The expression and secretion of miR-9-5p might be novel therapeutic targets for MDD. Graphical Abstract

Context. Stellar coronal mass ejections (CMEs) are the primary driver of the exoplanetary space weather and they could affect the habitability of exoplanets. However, detections of possible stellar CME signatures are extremely rare. Aims. This work aims to detect stellar CMEs from time-domain spectra observed through the LAMOST Medium-Resolution Spectroscopic Survey (LAMOST-MRS). Our sample includes 1,379,408 LAMOST-MRS spectra of 226,194 late-type main-sequence stars ($\rm T_{eff} < 6000$ K, $\rm log [g/(cm\ s^{-2})] > 4.0$). Methods. We first identified stellar CME candidates by examining the asymmetries of H$\alpha$ line profiles, and then performed double Gaussian fitting for H$\alpha$ contrast profiles (differences between the CME spectra and reference spectra) of the CME candidates to analyze the temporal variation of the asymmetric components. Results. Three stellar CME candidates were detected on three M dwarfs. The H$\alpha$ and Mg I triplet lines (at 5168.94 {\AA}, 5174.13 {\AA}, 5185.10 {\AA}) of candidate 1 all exhibit a blue-wing enhancement, and the corresponding Doppler shift of this enhancement shows a gradually increasing trend. The H$\alpha$ line also shows an obvious blue-wing enhancement in candidate 2. In candidate 3, the H$\alpha$ line shows an obvious red-wing enhancement, and the corresponding projected maximum velocity exceeds the surface escape velocity of the host star. The lower limit of the CME mass was estimated to be $\sim$$8 \times 10^{17}$ g to $4 \times 10^{18}$ g for these three candidates., Comment: Accepted by A&A

BackgroundAcute kidney injury (AKI) is a morbid complication and the main cause of multiple organ failure and death in severely burned patients. The objective of this study was to explore the epidemiological characteristics, the risk factors, and impact of both early and late AKIs, respectively.MethodsThis retrospective study was performed with prospectively collected data of severely burned patients from the Institute of Burn Research in Southwest Hospital during 2011-2017. AKI was diagnosed according to Kidney Disease Improving Global Outcomes (KDIGO) criteria (2012), and it was divided into early and late AKIs depending on its onset time (within the first 3 days or >3 days post burn). The baseline characteristics, clinical data, and outcomes of the three groups (early AKI, late AKI and non-AKI) were compared using logistic regression analysis. Mortality predictors of patients with AKI were assessed.ResultsA total of 637 patients were included in analysis. The incidence of AKI was 36.9% (early AKI 29.4%, late AKI 10.0%). The mortality of patients with AKI was 32.3% (early AKI 25.7%, late AKI 56.3%), and that of patients without AKI was 2.5%. AKI was independently associated with obviously increased mortality of severely burned patients [early AKI, OR = 12.98 (6.08-27.72); late AKI, OR = 34.02 (15.69-73.75)]. Multiple logistic regression analysis revealed that age, gender, total burn surface area (TBSA), full-thickness burns of TBSA, chronic comorbidities (hypertension or/and diabetes), hypovolemic shock of early burn, and tracheotomy were independent risk factors for both early and late AKIs. However, sepsis was only a risk factor for late AKI. Decompression escharotomy was a protective factor for both AKIs. ConclusionsAKI remains prevalent and is associated with high mortality in severely burned patients. Compared with early AKI, late AKI has a lower occurrence rate, but greater severity and worse prognosis，is a devastating complication. Late AKI is a poor prognosis sign in severe burns.

Nicotinic acid adenosine dinucleotide phosphate (NAADP) is a Ca2+-mobilizing second messenger that regulates a wide range of biological activities. However, the mechanism of its biogenesis remains controversial. CD38 is the only enzyme known to catalyze NAADP synthesis from NADP and nicotinic acid. CD38-mediated catalysis requires an acidic pH, suggesting that NAADP may be produced in acidic endolysosomes, but this hypothesis is untested. In this study, using human cell lines, we specifically directed CD38 to the endolysosomal system and assessed cellular NAADP production. First, we found that nanobodies targeting various epitopes on the C-terminal domain of CD38 could bind to cell surface–localized CD38 and induce its endocytosis. We also found that CD38 internalization occurred via a clathrin-dependent pathway, delivered CD38 to the endolysosome, and elevated intracellular NAADP levels. We also created a CD38 variant for lysosome-specific expression, which not only withstood the degradative environment in the lysosome, but was also much more active than WT CD38 in elevating cellular NAADP levels. Supplementing CD38-expressing cells with nicotinic acid substantially increased cellular NAADP levels. These results demonstrate that endolysosomal CD38 can produce NAADP in human cells. They further suggest that CD38's compartmentalization to the lysosome may allow for its regulation via substrate access, rather than enzyme activation, thereby providing a reliable mechanism for regulating cellular NAADP production.

ROOT UV-B SENSITIVE4 (RUS4) encodes a Domain of Unknown Function647 (DUF647) protein, whose function is poorly understood. We have previously shown the artificial microRNA knockdown Arabidopsis RUS4 plants, referred to as amiR-RUS4, have severely reduced male fertility with a defect in anther dehiscence. Here, we show that amiR-RUS4 plants are also defective in pollen maturation and germination. Promoter-reporter analysis shows that RUS4 is highly expressed in tapetal layer, developing microspores, mature and germinating pollen, strongly suggesting its role in the process of pollen maturation. As the translational RUS4-GFP fusion protein has been localized to the chloroplasts where the first step of jasmonic acid (JA) biosynthesis takes place, leading to the hypothesis that RUS4 may be involved in JA-mediated stamen development. We show that expression of several JA metabolic genes increased markedly in flower buds of the amiR-RUS4 plants compared to that of the wild-type. We further show that transcript abundance of a clade of the JA-responsive MYB transcript factor genes, especially MYB108, reduced significantly in stamens of amiR-RUS4 plants relative to the wild-type; these MYB transcript factors have been shown to be required for JA-mediated stamen and pollen maturation. Our data suggest that RUS4 may play a role in coordinating anther dehiscence and pollen maturation by affecting the expression of JA-related genes.

CXC195 showed strong protective effects in neuronal apoptosis by exerting its antioxidant activity. However, the anti-cancer effects of CXC195 is still with limited acquaintance. Here, we investigated the role of CXC195 in lipopolysaccharide (LPS)-induced human hepatocellular carcinoma (HCC) cells lines (HepG2) and the possible signaling pathways. CXC195 exhibited significant anti-proliferative effect and induced cell cycle arrest in LPS-induced HepG2 cells. In addition, CXC195 suppressed the release of pro-inflammatory mediators in LPS-induced HepG2 cells, including TNF-α, iNOS, IL-1β, IL-6, CC chemokine ligand (CCL)-2, CCL-22 and epidermal growth factor receptor (EGFR). Moreover, CXC195 inhibited the expressions and interactions of TLR4, MyD88 and TAK1, NF-κB translocation to nucleus and its DNA binding activity, phosphorylation of ERK1/2, p38 and JNK. Our results suggested that treatment with CXC195 could attenuate the TLR4-mediated proliferation and inflammatory response in LPS-induced HepG2 cells, thus might be beneficial for the treatment of HCC.

A brief introduction of hybrid automatic repeat request (HARQ) is given first, and then a description of physical uplink shared channel (PUCCH) or physical uplink shared channel (PUSCH) receiving and reporting the HARQ-ACK information in bundling mode or multiplexing mode is made in detail. Based on the principle, a scheme is designed to solve the problem of receiving and reporting the HARQ-ACK information.

Nicotinic acid adenosine dinucleotide phosphate (NAADP) is a Ca(2+)-mobilizing second messenger that regulates a wide range of biological activities. However, the mechanism of its biogenesis remains controversial. CD38 is the only enzyme known to catalyze NAADP synthesis from NADP and nicotinic acid. CD38-mediated catalysis requires an acidic pH, suggesting that NAADP may be produced in acidic endolysosomes, but this hypothesis is untested. In this study, using human cell lines, we specifically directed CD38 to the endolysosomal system and assessed cellular NAADP production. First, we found that nanobodies targeting various epitopes on the C-terminal domain of CD38 could bind to cell surface–localized CD38 and induce its endocytosis. We also found that CD38 internalization occurred via a clathrin-dependent pathway, delivered CD38 to the endolysosome, and elevated intracellular NAADP levels. We also created a CD38 variant for lysosome-specific expression, which not only withstood the degradative environment in the lysosome, but was also much more active than WT CD38 in elevating cellular NAADP levels. Supplementing CD38-expressing cells with nicotinic acid substantially increased cellular NAADP levels. These results demonstrate that endolysosomal CD38 can produce NAADP in human cells. They further suggest that CD38's compartmentalization to the lysosome may allow for its regulation via substrate access, rather than enzyme activation, thereby providing a reliable mechanism for regulating cellular NAADP production.

In order to analyze the mechanism of backfill and surrounding rock of open stope during subsequent backfill mining, take M1 ore body mining in a mine as engineering background, and simulate the mechanism of surrounding rock and backfill by using FLAC3D numerical software. Results show that the backfill can effectively alleviate or transfer the stress concentration state of the room floor and pillar, apparently restrain the displacement of the cavity plate and pillar, and improve the plasticity distribution range in a limited degree.

Image compressed sensing makes sparse signals information to reconstruct the optimal solution of original signals. The minimum total variation and Bregman algorithm transform constrained optimization problem of 1 l -norm into unconstrained optimization problems by increasing punishment item. Sparse images make the iterative process more simple and rapidness. In this paper, by studying several kinds of reconstruction algorithm for image compressed sensing, the convergences and the speeds of these algorithms are analyzed.

Background Hepatitis B virus (HBV) infection is a major risk factor which can lead to development of hepatocellular carcinoma (HCC). In this study, we aimed to explore the effects of toll-like receptor 4 (TLR4) downregulation on the growth and survival of HBV-related HCC cells and to examine the molecular mechanisms been involved. Methods The expression levels of TLR4 were examined in a panel of HCC cell lines (HepG2, SMMC7721, Huh7, HepG2.2.15 and Hep3B). The effects of TLR4 downregulation on the proliferation, apoptosis, and tumorigenicity of HBV-related HepG2.2.15 cells were determined. The effects of TLR4 downregulation on multiple signaling pathways were also measured. Co-immunoprecipitation and immunofluoresence staining assays were performed to investigate the interaction between TLR4 and HBV X protein (HBx). Results The mRNA and protein levels of TLR4 were significantly increased in HepG2.2.15 cells than those in the other cells which have been studied. Downregulation of TLR4 significantly decreased the proliferation and induced G2/M cell cycle arrest and apoptosis in HepG2.2.15 cells. TLR4 depletion inhibited HepG2.2.15 cell colony formation and tumor growth in nude mice. TLR4 silencing decreased the phosphorylation of ERK1/2 but not JNK1/2, p38, or NF-κB. Chemical inhibition of ERK1/2 approximately phenocopied the growth-suppressive effect of TLR4 downregulation on HepG2.2.15 cells. In addition, TLR4 showed a physical interaction with HBx. Conclusions Taken together, TLR4 plays a tumor-promoting role in HBV-related HCC cells, which is associated with regulation of ERK1/2 activation and interaction with HBx. Therefore, TLR4 may be a potential therapeutic target for HBV-related HCC.

The magnetoresistance (MR) of A/B granular mixture is investigated as a function of B content. A and B are both half-metallic materials, but have opposite spin polarization. The correlation of the angles between magnetic moments of neighboring grains is taken into account. Using Monte Carlo simulations, we model the granular mixture as a random resistor network. The variation of magnetoresistance with B content is calculated. The appearance of MR valley may be attributed to two kinds of materials with the opposite sign of spin polarizations. But in a granular mixture, little inverse magnetoresistance could be observed. Calculated results are consistent with the experiment as well. When there is a large difference between resistances of distinct contact barriers, a weak peak will appear in the magnetoresistance curve. Percolation effect is the probable origin of this weak peak.

The transport properties of ultrasonic-treated CrO 2 particles are studied. The experimental results indicate that the ultrasonic treatment not only leads to an increase in the resistivity, but also reduces the saturation magnetization of CrO 2 powders. These modifications are attributed to a change in the surface state of the CrO 2 particles. Furthermore, a modified surface state can yield a decreasing magnetoresistance of CrO 2 granular compacts. XPS analysis provides supports that the surface nature of CrO 2 particles is altered after ultrasonic treatment. The reduced saturation magnetization is related to the existence of a magnetic dead layer, which is estimated to be of a few nanometers thick. This work reveals that our ultrasonic technique is a method to control magnetotransport of granular materials by altering the surface state of the particles.

We present a study on temperature dependence of impedance spectra of the cold-pressed chromium dioxide (CrO 2 )–titanic dioxide (TiO 2 ) composite over the temperature range of 77–300 K, and over the frequency range of 40 Hz–500 kHz. The microstructure of the sample is analyzed using transmission electron microscopy (TEM), SEM and X-ray diffraction (XRD). The impedance spectra exhibit a strong dependence upon temperature. By evaluating the ac electricity behavior of the composite, we find the experimental data are successfully described by a power-law behavior σ ac = A ( T ) ω s , in which the frequency exponent s shows slightly greater than a universal value (0≤ s ≤1), and rises approximately linearly with temperature over a broad range of low temperature.

We study the dependence of resistivity ρ on graphite volume fraction p in Fe 3 O 4 /C magnetic composite. The measured percolation threshold, p c was determined to be 0.212 and 0.231 at 300 and 77 K, respectively. The difference in values of p c can be attributed to the variation in the value of ρ Fe 3 O 4 / ρ c . Experimental results indicate that the conductivity exhibits non-universal critical behavior. The non-universal critical exponent t is 3.88±0.20 (300 K) and 3.18±0.26 (77 K), which may be related to cavities in powder composite. Transport mechanisms were also discussed with temperature dependence of resistance and I–V characteristics. It is considered that decreasing electrical transport at 77 K leads likely to low critical exponent t in contrast to 300 K.

We report a study of enhanced negative magnetoresistence (MR) in Fe3O4/graphite powder composite. In the vicinity of percolation region, the experiment exhibits that the enhanced MR reaches –32% at the temperature of 77 K with an applied field of 6.5 kOe. The high MR value is due to the enhanced spin-dependent scattering on the surface of Fe3O4 particles. Simultaneously, it is also found that the composite exhibits an adjustable MR from negative to positive with the variation of graphite concentration. This switch effect is ascribed to the transition of MR mechanism.

This letter presents an experimental study of the correlation between low field magnetoresistance (MR) and percolation process, and the dependence of conductance on temperature between 77 and 300 K in the CrO 2 –TiO 2 composites. We also discuss the conduction mechanisms of the composites and conclude that the conductance is mainly attributed to higher-order hopping at higher temperature.

Impedance spectroscopy is used to evaluate the contributions of grain and grain boundary resistance to conduction process and magnetoresistance (MR) in CrO 2 –TiO 2 granular composites. It is found that there is a transition from two semicircles to a single semicircle in the Nyquist plot with increasing CrO 2 concentration. The resistivities of grain and grain boundary reveal very similar percolation processes, but their critical behaviors display slight differences in the conductance critical exponent. The fittings to experimental data indicate the critical exponents t gb =2.42±0.15, and t g =1.65±0.23, for grain boundaries and grains, respectively. The ratio γ g = ρ g / ρ gb depends strongly on CrO 2 concentration. In particular, in the conductance percolation region, we find that the ratio γ g exhibits a switch point from γ g γ g >1, which may have a great influence on MR. The maximum of MR at 77 K appears close to percolation threshold x c , and reaches −9.1% at 6 kOe, which is attributed to the cluster microstructure and the ratio γ g of the composite. As a result, the effective grain boundaries play an important role in manipulating MR in the CrO 2 composite.

Granular CrO 2 /polystyrene composites were prepared by evaporating polystyrene solution. The composites consisting of the acicular half-metallic CrO 2 particles encapsulated properly with a thin layer of insulating polymer can exhibit a large enhancement in room temperature magnetoresistance (MR), up to −8.2% at a low field of 6.5 kOe. The microstructures and thermal behaviors of the composite are analyzed by XRD, SEM, TGA and DSC. The temperature dependence of the electrical resistance is studied at the temperature range (77–298 K). We also argue that the influence of polymer on room temperature MR is more significant than that at low temperature, which may be mainly attributed to spin-dependent tunneling between particles.

To investigate the distribution of hepatitis B virus (HBV) genotypes in patients with chronic HBV infection among 11 cities of China.A total of 1214 serum samples from patients with chronic HBV infection were collected in 11 cities of China, including Beijing, Qingyuan, Shenzhen, Shijiazhuang, Hanchuan, Nanjing, Changchun, Liaocheng, Jinan, Ningbo and Wenzhou. Genotypes of the 1214 HBV strains were identified by PCR method with type specific primers. Parts of the results were confirmed by direct sequencing analysis of PCR products.Among the 1214 patients with chronic HBV infection, 0.7% (9/1214)were genotype A, 28.4% (345/1214)genotype B, 58.4% (709/1214) genotype C, and 12.4% (151/1214) genotype B and genotype C mixed infection. No other genotypes were found. Genotype C was predominant in the northern part of China, such as Changchun, Beijing, Shijiazhuang,while genotype B was more commonly seen in south of China. 71.4% (20/28) for patients from Qingyuan and 63.6% (70/110) from Shenzhen were infected with genotype B.HBV genotypes had distinct geographic distribution. Genotype B and C the predominant strains in patients with chronic HBV infection in China. Genotype C was predominantly identified in the northern part of China versus genotype B the south.

To study hepatitis B virus (HBV) genotype and subtype distribution and its clinical significance in HBV-infected patients.We used type/subtype-specific primers and PCR to detect HBV genotype and subtype of 445 HBV-infected patients from Beijing, Changchun, Hanchuan Shenzhen, Qingyuan and Nanjing, including 7 acute hepatitis (AH), 36 asymptomatic HBV carriers (ASC), 352 chronic hepatitis (CH), 28 liver cirrhosis (LC), and 22 hepatocellular carcinoma (HCC) cases. Genotyping results were confirmed by PCR product sequencing.Among 445 HBV-infected patients, the proportions of genotype B, C, and B/C were 32.6% (145/445), 53.7% (239/445), and 13.7% (61/445), respectively. In genotype C, 13 (5.4%) were subtype C1, 135 (56.5%) were subtype C2, and the remaining 91 (38.1%) were neither C1 nor C2. In genotype B, 100 (69.0%) were subtype Ba, 25 (17.2%) subtype Bj, and the other 20 (13.8%) were neither Ba nor Bj. In genotype B/C, 15 (24.6%) were Ba/C2, 8 (13.1%) Bj/C2, 6 (9.8%) Ba/C1, 3 (4.9%) Bj/C1, 11 (18.0%) Ba/neither C1 nor C2, 7 (11.5%) Bj/neither C1 nor C2, and 6 (9.8%) neither Ba nor Bj/neither C1 nor C2, 2 (3.3%) neither Ba nor Bj/C1, 3 (4.9%) neither Ba nor Bj/C2. The HBV genotype and subtype distribution we found exhibited significant differences in the various clinical types of HBV infection tested, and showed that genotype C was predominant among patients with liver cirrhosis (78.6%) and hepatocellular carcinoma (86.4%) while genotype B was predominant in asymptomatic carriers (72.2%). In addition, genotype and subtype distribution showed no significant differences between male and female patients, but genotype and subtype distribution showed significant differences in patients positive or negative with HBeAg.Subtypes Ba and C2 are predominant in patients with hepatitis B from these 6 cities, and genotype C may be associated with the development of liver cirrhosis and hepatocellular carcinoma.

Crystallographic data for Ni0.41Zn0.60Cu0.01Fe2.04−xSbxO4+δ (0.01≤x≤0.12) ferrites are significantly influenced by small additions of antimony. XRD analysis reveals that changes in crystal data for small Sb substitutions differ markedly from those for greater Sb substitutions. The differences are due to the contribution of the Sb ion. Complete crystal data for six solid solution compositions are reported. An X-ray powder diffraction pattern for Ni0.41Zn0.60Cu0.02Sn0.01Fe2.02Sb0.02O4+δ is given.