Search

Objective: To optimise the dosing regimen of meropenem for treating Pseudomonas aeruginosa (PA) infections in critically ill patients with augmented renal clearance (ARC) using pharmacokinetic/pharmacodynamic (PK/PD) principles and Monte Carlo simulation (MCS). Methods: This research involves an MCS based on PK data from patients with ARC and a minimum inhibitory concentration (MIC) distribution of PA. This study simplifies the methods section, focusing on the critical aspects of simulation and target values for effective treatment. Results: The study highlights key findings and emphasises that tailored dosing based on bacterial MIC values is essential for patients with ARC. It also notes that empirical treatment in patients with ARC should consider the MIC distribution, with 2 g every (q) 6 h administered to achieve the PK/PD target, while 3 g q 6 h is effective in inhibiting resistance. Conclusion: Tailored dosing based on bacterial MIC values is crucial for patients with ARC. Prolonged infusion time alone does not enhance efficacy. Empirical treatment in patients with ARC should consider MIC distribution; a dosage of 2 g q 6 h achieves the PK/PD target, while 3 g q 6 h (≥12 g daily) inhibits resistance.

The biological functions of short open reading frame (sORF)‐encoded micropeptides remain largely unknown. Here, we report that LINC00998, a previously annotated lncRNA, was upregulated in multiple cancer types and the sORF on LINC00998 encoded a micropeptide named SMIM30. SMIM30 was localized in the membranes of the endoplasmic reticulum (ER) and mitochondria. Silencing SMIM30 inhibited the proliferation of hepatoma cells in vitro and suppressed the growth of tumor xenografts and N‐nitrosodiethylamine‐induced hepatoma. Overexpression of the 5′UTR‐sORF sequence of LINC00998, encoding wild‐type SMIM30, enhanced tumor cell growth, but this was abolished when a premature stop codon was introduced into the sORF via single‐base deletion. Gain‐ and loss‐of‐function studies revealed that SMIM30 peptide but not LINC00998 reduced cytosolic calcium level, increased CDK4, cyclin E2, phosphorylated‐Rb and E2F1, and promoted the G1/S phase transition and cell proliferation. The effect of SMIM30 silencing was attenuated by a calcium chelator or the agonist of sarco/endoplasmic reticulum calcium ATPase (SERCA) pump. These findings suggest a novel function of micropeptide SMIM30 in promoting G1/S transition and cell proliferation by enhancing SERCA activity and reducing cytosolic calcium level.

Abstract Background Understanding the relationship between human evolution and environmental changes is the key to lifting the veil on human origin. The hypothesis that environmental changes triggered the divergence of humans from apes (ca. 9.3–6.5 million years ago, Ma) has been poorly tested because of limited continuous environmental data from fossil localities. Lufengpithecus (12.5-6.0 Ma) found on the southeastern margin of the Tibetan Plateau (SEMTP) across the ape–human split provides a good chance for testing this hypothesis. Results Here, we reconstructed the habitats of L. keiyuanensis (12.5–11.6 Ma) with comprehensive vegetation, climate, and potential food web data by palaeobotanical evidence, together with other multidisciplinary data and partly tested the environment-driven hypothesis by revealing the living conditions of Lufengpithecus. Conclusion A detailed comparison of hominoids on different continents reveals their behaviour and fate divergence across the ape–human split against the background of global climate change, i.e., the stable living conditions of SEMTP not only provided a so-called ‘refuge’ for arboreal Lufengpithecus but also acted as a ‘double-edged sword’, preventing their further evolution while vegetation shifts in East Africa probably stimulated the emergence of human bipedalism, and the intense climatic changes in Europe possibly prevented those hominoids from surviving that time interval. Our findings provide interesting insight into the environmental impacts on the behavioural evolution of hominoids.

Based on the modified gravity model and social network analysis method, the evolution characteristics and driving mechanism of logistics network spatial structure in the Zhengzhou metropolitan area (ZMA) from 2008 to 2019 are analyzed at a county (district) scale. Research findings reveal that the following: (1) The distribution of logistics links in ZMA counties (districts) has significant spatial heterogeneity, with a spatial pattern of “sparse in the east and dense in the west,” and the counties (districts) logistics links are concentrated in Zhengzhou. (2) The overall level of the logistics network density in ZMA is low, but it is fluctuating and rising. The overall realization is the logistics radiation effect. The logistics network layout’s core area is primarily concentrated in Zhengzhou’s main urban area and surrounding counties (districts), and the spatial scope is expanding and merging into one piece. The contact density of counties (districts) in the core area is high, whereas that between counties (districts) in the edge area is low. (3) With obvious spatial correlation characteristics, the logistics connection intensity of counties (districts) in ZMA plays a positive role in promoting the logistics connection intensity of surrounding areas. (4) The main factors that promote the formation of the local logistics network structure are the upgrading of industrial structure (ln Ind), the level of economic development (ln GDP), and the size of the population (ln Pop). The ln Ind and ln GDP restrain the logistics network structure and internal logistics network structure in the surrounding areas, whereas the ln Pop and government intervention (ln Gov) promote the formation of the external logistics network structure in the surrounding areas.

Introduction: Intracerebral microglia play a vital role in mediating central immune response, neuronal repair and synaptic pruning, but its precise role and mechanism in fast action of antidepressants have remained unknown. In this study, we identified that the microglia contributed to the rapid action of antidepressants ketamine and YL-0919.Methods: The depletion of microglia was achieved with the diet containing the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 in mice. The tail suspension test (TST), forced swimming test (FST) and novelty suppressed feeding test (NSFT) were employed to evaluate the rapid acting antidepressant behavior of ketamine and YL-0919 in the microglia depletion model. The number of microglia in the prefrontal cortex (PFC) was assayed by the immunofluorescence staining. The expressions of synaptic proteins (synapsin-1, PSD-95, GluA1) and brain-derived neurotrophic factor (BDNF) in the PFC were tested by Western blot.Results: The immobility duration in FST and the latency to feed in NSFT were shortened 24 h after an intraperitoneal (i.p.) injection of ketamine (10 mg/kg). The microglial depletion of PLX3397 blocked the rapid antidepressant-like effect of ketamine in mice. In addition, the immobility time in TST and FST as well as latency to feed in NSFT were reduced 24 h after the intragastric (i.g.) administration of YL-0919 (2.5 mg/kg, administered for 5–6 consecutive days), and the rapid antidepressant effect of YL-0919 was also blocked by the microglial depletion using PLX5622. About 92% of microglia in the prefrontal cortex was depleted in PLX5622 diet-fed mice, while both ketamine and YL-0919 promoted proliferation on the remaining microglia. YL-0919 significantly increased the protein expressions of synapsin-1, PSD-95, GluA1 and BDNF in the PFC, all of which could be blocked by PLX5622.Conclusion: These results suggested the microglia underlying the rapid antidepressant-like effect of ketamine and YL-0919, and microglia would likely constitute in the rapid enhancing impact of synaptic plasticity in the prefrontal cortex by YL-0919.

Introduction: Major depression disorder (MDD) is a common and potentially life-threatening mental illness; however, data on its pathogenesis and effective therapeutic measures are lacking. Pathological changes in astrocytes play a pivotal role in MDD. While hypidone hydrochloride (YL-0919), an independently developed antidepressant, has shown rapid action with low side effects, its underlying astrocyte-specific mechanisms remain unclear.Methods: In our study, mice were exposed to chronic restraint stress (CRS) for 14 days or concomitantly administered YL-0919/fluoxetine. Behavioral tests were applied to evaluate the depression model; immunofluorescence and immunohistochemistry staining were used to explore morphological changes in astrocytes; astrocyte-specific RNA sequencing (RNA-Seq) analysis was performed to capture transcriptome wide alterations; and ATP and oxygen consumption rate (OCR) levels of primary astrocytes were measured, followed by YL-0919 incubation to appraise the alteration of energy metabolism and mitochondrial oxidative phosphorylation (OXPHOS).Results: YL-0919 alleviated CRS-induced depressive-like behaviors faster than fluoxetine and attenuated the number and morphologic deficits in the astrocytes of depressed mice. The changes of gene expression profile in astrocytes after CRS were partially reversed by YL-0919. Moreover, YL-0919 improved astrocyte energy metabolism and mitochondrial OXPHOS in astrocytes.Conclusion: Our results provide evidence that YL-0919 exerted a faster-onset antidepressant effect on CRS-mice possibly via astrocyte structural remodeling and mitochondria functional restoration.

Abstract Background Functional MRI (fMRI) parameters analysis has been proven to be a promising tool of predicting therapeutic response to induction chemotherapy (IC) in nasopharyngeal carcinoma (NPC). The study was designed to identify and compare the value of fMRI parameters in predicting early response to IC in patients with NPC. Methods This prospective study enrolled fifty-six consecutively NPC patients treated with IC from January 2021 to May 2021. Conventional diffusion weighted imaging (DWI), diffusion kurtosis imaging (DKI), intravoxel incoherent motion (IVIM) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) protocols were performed before and after IC. Parameters maps (ADC, MD, MK, Dslow, Dfast, PF, Ktrans, Ve and Kep) of the primary tumor were calculated by the Functool post-processing software. The participants were classified as responding group (RG) and non-responding group (NRG) according to Response Evaluation Criteria in Solid Tumors 1.1. The fMRI parameters were compared before and after IC and between RG with NRG. Logistic regression analysis and ROC were performed to further identify and compare the efficacy of the parameters. Results After IC, the mean values of ADC(p

The influence of different Mg concentrations on the mechanical properties and microstructure of an Al–Li alloy was studied. The highest Mg content was up to 1.1 wt.%. To the best of the authors knowledge, alloys with such a high Mg content has not been reported in the literature. The mechanical properties, yield strength and elongation at failure, of all of the alloys were investigated by tensile tests. Characterisation of the precipitates by analysing the dark field images and related diffraction patterns revealed that precipitation of the T1 phase (Al2CuLi) was retarded by high (1.1 wt.%) Mg concentration. We hypothesized that a competition between the precipitation of T1 phase and S' phase in high Mg containing alloy caused sluggish precipitation phenomenon and associated strengthening.

PurposeThe aim of this study was to identify the efficacy of diffusion kurtosis imaging (DKI) in tracking and monitoring the dynamic change of parotid glands (PGs), submandibular glands (SMGs), sublingual glands (SLGs), and acute xerostomia in nasopharyngeal carcinoma (NPC) patients treated with induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT).MethodsThe prospective study recruited 42 participants treated with IC+CCRT. All patients underwent DKI scanning six times: before IC, before RT, in the middle of the RT course, immediately after RT, and 1 and 3 months post-RT. Mean diffusion coefficient (MD) and mean kurtosis (MK) of PG, SMG, SLG, saliva flow rate measured under resting (uSFR) and stimulated condition (sSFR), and xerostomia questionnaire (XQ) scores were recorded.ResultsAt each time point, sSFR was significantly higher than uSFR (p < 0.05 for all). MD of the salivary glands and XQ scores increased over time while MK, uSFR, and sSFR decreased. After IC, the significant differences were detected in MD and MK of bilateral SMG and MK of the left SLG (p < 0.05 for all), but not in MD and MK of PG, uSFR, sSFR, and XQ scores. After RT, sSFR at 1m-RT decreased significantly (p = 0.03) while no significant differences were detected in uSFR and XQ scores. Moderate-strong correlations were detected in ΔMD-PG-R%, ΔMK-PG-R%, ΔMD-PG-L%, ΔMK-PG-L%, ΔMD-SMG-R%, ΔMK-SMG-R%, ΔMD-SMG-L%, ΔMK-SMG-L%, and ΔMD-SLG-R%, with correlation coefficients (p < 0.05 for all) ranging from 0.401 to 0.714. ΔuSFR% was correlated with ΔMD-SMG% (p = 0.01, r = −0.39), ΔMD-SLG% (p < 0.001, r = −0.532), and ΔMK-SMG% (p < 0.001, r = −0.493). ΔsSFR% correlated with ΔMD-PG% (p = 0.001, r = −0.509), ΔMD-SMG% (p = 0.015, r = −0.221), and ΔMK-PG% (p < 0.001, r = 0.524). ΔXQ% was only correlated with ΔMK-PG% (p = 0.004, r = 0.433).ConclusionDKI is a promising tool for tracking and monitoring the acute damage of PG, SMG, and SLG induced by IC+CCRT in NPC patients.

Improving green total factor productivity (GTFP) is an important theme. Whether collaborative agglomeration between logistics industry and manufacturing (LMCA) can effectively promote GTFP is worth further research. Based on the panel data of 284 cities in China from 2005 to 2018, GTFP is calculated by using the Biennial Malmquist-Luenberger productivity index (BMLPI), and this research investigates the impact of LMCA on GTFP by adopting the spatial Durbin model (SDM) and threshold regressive model (TRM). First, LMCA plays a significant role in promoting the improvement of GTFP in the local and surrounding areas through the knowledge spillover effect, scale economy effect, resource allocation effect and symbiotic economic effect, and the spillover effect is greater than the local effect. Second, the positive direct effect of LMCA on GTFP comes mainly from technological progress, and the positive indirect effect of LMCA on GTFP comes mainly from the positive spillover effect of technological progress and technical efficiency improvement. Finally, the Williamson hypothesis exists significantly in the collaborative agglomeration scenario of the logistics industry and manufacturing of China. With the improvement of the level of economic development, the impact of LMCA on GTFP changes from insignificant to promoting. However, when it is further improved, the promoting effect turns into an inhibiting effect, and this change is dominated mainly by the impact of LMCA on technical change.

The influence of Ag on the microstructure evolution of an aged Al–Cu–Li–Mg alloy was studied. The coarse Cu-rich precipitates containing Ag and Mg were found during the whole ageing process of Al–Cu–Li–Mg–Ag alloy. Besides, Ag addition in the Al–Cu–Li–Mg alloy accelerates the hardness value reduction of the overaged alloy. When the alloy was over heat-treated, more coarse Cu-rich phases containing Ag and Mg are presented at the grain boundaries. These discrete coarse precipitates accelerate the hardness reduction of the overaged alloy.

Background: Procambarus clarkii produces high-quality, delicious meat that is high in protein, low in fat, and rich in calcium and phosphorus. It has become an important aquatic resource in China. Our objectives are (i) to analyze the level of genetic diversity of P. clarkii populations; (ii) to explore the genetic differentiation (Gst); and (iii) to propose appropriate strategies for the conservation. Results: In this study, Shannon's index (I) and Nei's gene diversity index (H) for P. clarkii were high (I = 0.3462 and H = 0.2325 on average and I = 0.6264, H = 0.4377 at the species level) based on the SSR markers. The expected heterozygosity value of 17 microsatellite loci in 25 crayfish populations was 0.9317, the observed heterozygosity value was 0.9121, and the observed number of alleles per locus was 2.000; and the effective number of alleles per locus was 1.8075. Among the P. clarkii populations, the inbreeding coefficient within populations (Fis) was 0.2315, overall inbreeding coefficient (Fit) was 0.4438, genetic differentiation coefficient among populations (Fst) was 0.3145 and gene differentiation (Gst) was 0.4785 based on SSR analyses. The cluster analysis results obtained by unweighted pair-group method with arithmetic mean (UPGMA) analysis, principal coordinate analysis (PCoA) and STRUCTURE analysis were similar. A mantel test showed that the isolation-by-distance pattern was not significant. Conclusions: The high Gst among P. clarkii populations is attributed to genetic drift and geographic isolation. The results indicated that more P. clarkii populations should be collected when formulating conservation and aquaculture strategies. How to cite: Liu F, Qu Y-K, Geng C, et al. Analysis of the population structure and genetic diversity of the red swamp crayfish (Procambarus clarkii) in China using SSR markers. Electron J Biotechnol 2020;47. https://doi.org/10.1016/j.ejbt.2020.06.007.

The logistics and manufacturing industries are basic industries that support social development. First, this study classifies the carbon emissions from the logistics industry and pollution emissions from the manufacturing industry as undesirable outputs and evaluates the ecological efficiency of the logistics and manufacturing industries in the Yangtze River Delta from 2006 to 2016 by using the unexpected slacks-based measure (SBM) model. Second, the study analyzes the spatial differences in industrial correlation efficiency by using the exploratory spatial data analysis method. Third, the spatial econometric model is used to analyze the driving factors of the linkage ecological efficiency between logistics industry and manufacturing industry. Finally, the neural network model is used to predict the linkage ecological efficiency. The results show that the ecological efficiency of the manufacturing industry has steadily improved. The ecological efficiency of the logistics industry presents the rising trend in fluctuation. The level of the linkage development between the logistics and manufacturing industries is high. The results of the spatial heterogeneity analysis show that the spatial differentiation of high–high agglomeration and low–low agglomeration is obvious. The spatial agglomeration characteristics are relatively stable, and the spatial diffusion effect is strong. In space, the linkage ecological efficiency shows a trend of development from multiple agglomeration areas to one agglomeration area. The results of driving factor analysis show that foreign direct investment (FDI), government intervention (GI), and human capital (HP) have positive effects on linkage ecological efficiency, while industrial structure (IS), environmental regulation (ER), and energy intensity (EI) have negative effects on linkage ecological efficiency. The results of the linkage development trend analysis show that the linkage ecological efficiency of the two industries will tend to be stable in the future.

The tensile properties and corrosion behaviours of an ageing Al-1.7 Cu-4.0 Li- 0.4 Mg alloys (in at. %) with or without 0.3 Zn addition were investigated by detailed microstructure evolution using TEM and STEM. Herein, the Zn addition to the Al-1.7 Cu-4.0 Li- 0.4 Mg ageing alloy is determined as a convincing approach to optimising the strength-corrosion resistance balance. With Zn addition, the increasing quantity of T1 phase in grain led to the increase of the tensile property of the Al-1.7 Cu-4.0 Li- 0.4 Mg alloy. While the studied alloy with Zn addition possessed preferable corrosion resistance in respect of intergranular corrosion (IGC) depth reducing. Moreover, the emergence of Zn elements in the coarse phases at grain boundary (GB) may decrease the potential differences between the precipitates at GB and free precipitation zone (PFZ), which could increase corrosion resistance. Keywords: Al-1.7 Cu-4.0 Li- 0.4 Mg alloy, Zn addition, Tensile properties, Corrosion behaviours, Microstructure characteristics, Electrochemical features

Psoriasis is characterized by keratinocyte proliferation and immune cell infiltration. M2 isoform of pyruvate kinase (PKM2) was reported to have an important role in cell proliferation, which is a rate-limiting enzyme that regulates the final step of glycolysis. However, how PKM2 regulates cell metabolism and proliferation in psoriatic keratinocytes is still poorly understood. Interestingly, we found that PKM2 was highly expressed in psoriatic epidermis from patients and mouse models. PKM2 overexpression promoted keratinocyte glycolytic metabolism while knockdown inhibited keratinocyte proliferation and glycolysis. Mice lacking PKM2 specifically in keratinocytes, pharmacological inhibition of PKM2 or glycolysis inhibited keratinocyte proliferation and showed obvious remission in an imiquimod-induced psoriatic mouse model. Moreover, the inhibitor of the EGF-receptor blocked EGF-stimulated PKM2 expression and glycolysis in keratinocytes. We identify PKM2 as an upregulated gene in psoriasis. PKM2 is essential in keratinocyte over-proliferation and may represent a therapeutic target for psoriasis.

Summary: The evolution of the Asian monsoon from the Late Oligocene to the Early Miocene is poorly understood. Here, we first reconstruct the precipitation data of central Tibet during 26–16 million years ago (Ma), applying the coexistence approach to sedimentary pollen data, and detect an intensified Asian monsoon with ∼1.35 Ma and ∼0.33 Ma cycles. Paleoclimate modeling is used to show the importance of paleogeographic location in the development of the paleomonsoon. In addition, the results of spectral analysis suggest that the fluctuations in the Asian monsoon during 26–16 Ma can be attributed to the long-period cyclicities in obliquity (∼1.2 Ma). These findings provide climate data that can be used to understand the Asian monsoon evolution during the Late Oligocene to Early Miocene and highlight the effects of paleogeographic patterns and long-period orbital forcings on the tectonic-scale evolution of the Asian monsoon.

Amylosporus sulcatus sp. nov. is described from Nonggang Nature Reserve, southern China, on the basis of morphological and molecular data. The morphological description and illustrations for the new species are provided. The species is characterized by pileate and stipitate basidiocarps. The pileus surface is obviously concentrically and radiately sulcate and tomentum, and the pore surface is snow white. Phylogenetic analyses based on sequences of the internal transcribed spacer and nuclear large subunit ribosomal DNA confirmed it to be a new species.

Abstract Background First identified in the United States in 2016, porcine circovirus type 3 (PCV3) is a newly emerging porcine circovirus exhibiting a wide range of clinical syndromes, which may be associated with the pathogenicity observed in pigs. Results The aim of this study was to identify and characterize the full genome sequence of PCV3 strains circulating in Northeast China. Herein, 105 lung samples isolated from sick pigs in Northeast China during 2018 were analyzed for PCV3. Using PCR, the total PCV3-positive rate was 33.3% (35/105), with rates of 17.8% (8/45), 66.7% (10/15), and 37.8% (17/45) in Heilongjiang, Jilin, and Liaoning province, respectively. Additionally, our findings showed that PCV3-positive samples had a high rate of co-infection with PCV2, PPV6, and PPV7. To study the evolution of the PCV3 in Northeast China, we sequenced the entire genome of 13 strains of PCV3. The results of phylogenetic analyses revealed that PCV3 could be divided into two clades, PCV3a and PCV3b. Interestingly, a G deletion at position 1072 was found in the 1999 nt genome of PCV3-CN2018LN-4 (MH277118). The G deletion terminated replicase protein translation and induced a truncated replicase protein. Conclusion These results contribute to the understanding of PCV3 molecular epidemiology and evolution in Northeast China. A new strain of PCV3 with truncated replicase protein was identified.

Objective To evaluate alterations in phase-shift values in the gray matter of patients with amyotrophic lateral sclerosis (ALS) using susceptibility-weighted imaging (SWI). Methods Twenty patients with definite or probable ALS and 19 age- and sex-matched healthy controls were enrolled. SWI was performed using a 3.0 T magnetic resonance imaging scanner. Phase-shift values were measured in corrected phase images using regions of interest, which were placed on the bilateral precentral gyrus, frontal cortex, caudate nucleus, globus pallidus, and putamen. Results Phase-shift values of the precentral gyrus were significantly lower in ALS patients (−0.176 ± 0.050) than in the control group (−0.119 ± 0.016) on SWI. The average phase-shift values of the frontal cortex, caudate nucleus, globus pallidus, and putamen in ALS patients (−0.089 ± 0.023, −0.065 ± 0.016, −0.336 ± 0.191, and −0.227 ± 0.101, respectively) were not significantly different from those in the healthy controls (−0.885 ± 0.015, −0.079 ± 0.018, −0.329 ± 0.136, and −0.229 ± 0.083, respectively). Conclusions Compared with healthy controls, ALS patients had a lower phase-shift value in the precentral gyrus, which may be related to abnormal iron overload. Thus, SWI is a potential method for identifying ALS patients.

Added risk portended by diabetes in addition to hypertension has been related to an amplification of endothelial dysfunction. β-blockers are widely used for cardiovascular diseases and improve the endothelial function compared with a placebo. However, the effect of β-blockers on the endothelial progenitor cells (EPCs) function in diabetes is still unknown. Five β-blockers (metoprolol, atenolol, propranolol, bisoprolol, and nebivolol) were tested in EPC functional screening. Metoprolol improved EPC function significantly among the five β-blockers and was chosen for the in vivo tests in STZ induced diabetic mice. Reactive hyperemia peripheral arterial tonometry (RH-PAT) measurements were performed using the Endo-PAT2000 device in diabetic patients. Metoprolol, but not other β-blockers, improved EPC function in both tube formation and migration assay. EPC function was significantly decreased in diabetic mice, and metoprolol treatment restored damaged EPC migration capabilities and circulation EPC number. Metoprolol treatment promoted wound healing and stimulated angiogenesis in diabetic mice. Furthermore, metoprolol significantly enhanced eNOS phosphorylation and decreased O2− levels in EPCs of diabetic mice. In clinical trials, the RH-PAT index was significantly higher in metoprolol-treated versus bisoprolol-treated diabetics. Metoprolol could accelerate wound healing in diabetic mice and improve endothelial function in diabetic subjects, which may be mediated in part by improving impaired EPC function.

Background. The aim of this study was to investigate the effects of human umbilical cord mesenchymal stem cell activated by curcumin (hUC-MSCs-CUR) on Parkinson’s disease (PD). hUC-MSCs can differentiate into many types of adult tissue cells including dopaminergic (DA) neurons. CUR could protect DA neurons from apoptosis induced by 6-hydroxydopamine (6-OHDA). Therefore, we used the hUC-MSCs activated by CUR for the treatment of PD in an animal model. Methods. The hUC-MSCs-CUR was transplanted into the MPTP-induced PD mouse models via the tail vein. We found that hUC-MSCs-CUR significantly improved the motor ability, increased the tyrosine hydroxylase (TH), dopamine (DA), and Bcl-2 levels, and reduced nitric oxide synthase, Bax, and cleaved caspase 3 expression in PD mice. The supernatant of hUC-MSCs-CUR (CM-CUR) was used to stimulate the SH-SY5Y cellular model of PD; cell proliferation, differentiation, TH, and neuronal-specific marker microtubular-associated protein 2 (MAP2) expressions were examined. Results. Our data showed that CM-CUR significantly promoted cell proliferation and gradually increased TH and MAP2 expression in SH-SY5Y PD cells. The beneficial effects could be associated with significant increase of rough endoplasmic reticulum in the hUC-MSCs-CUR, which secretes many cytokines and growth factors beneficial for PD treatment. Conclusions. Transplantation of hUC-MSCs-CUR could show promise for improving the motor recovery of PD.

The data presented in this article are related to the research article entitled “Pollen spectrum, a cornerstone for tracing the evolution of the eastern central Asian desert” (JQSR 5260) (Lu et al., 2018) [1] In this paper, we supply a dataset, which provides a descriptive and general summary of pollen characteristic of desert dominant species in the eastern arid central Asia (ACA). The other important component is the illustration on pollen grains traits under light microscopy (LM) and scanning electron microscopy (SEM). Pollen grains of 56 species are extracted from voucher specimens from the PE herbarium at the Institute of Botany. It is worth noting that these species own special distribution patterns in China. The distribution maps are plotted using the Google Maps and the species distribution data at the county level supplied by the Chinese Virtual Herbarium (http://www.cvh.ac.cn/). Keywords: Arid central Asia, Desert vegetation, Pollen morphological traits, Temperate desert

AIM: To explore clinical effect of pranoprofen combined with deproteinized calf blood extract eye drops for moderate to severe dry eye. METHODS: A total of 84 patients(132 eyes)who received treatment at the Zhengzhou Second Hospital were selected from January 2016 to January 2017. According to random number table method they were divided into control group 42 cases(68 eyes)and observation group 42 cases(64 eyes), the control group using polyvinyl alcohol eye drops with pranoprofen, observation group with pranoprofen with deproteinized extract of calf blood eye drops. Subjective and objective scores before and after treatment were recorded. RESULTS: There was no statistically significant difference on the four objective indicators of pretreatment FL, BUT, SⅠt, and vision between the two groups(P>0.05). Dry eye symptom scores of the two groups decreased after treatment, both with significantly different(PPPPCONCLUSION: The clinical effect of praprofen on the treatment of moderate to severe dry eye with the deproteinized calf blood extract is better.

Background/Aims: The study aimed to investigate the protective effect of curcumin against oxidative stress-induced injury of Parkinson’s disease (PD) through the Wnt/β-catenin signaling pathway in rats. Methods: The successfully established PD rat models and normal healthy rats were randomly assigned into the 6-hydroxydopamine (6-OHDA), the curcumin (Cur) and the control groups. Immunohistochemistry was used to detect the positive expression of tyrosine hydroxylase (TH), dopamine transporter (DAT) and glial fibrillary acidic protein (GFAP). Deutocerebrum primary cells were extracted and classified into the control, 6-OHDA, Cur (5, 10, 15 µmol/L), Dickkopf-1 (DKK-1) and Cur + DKK-1 groups. MTT assays, adhesion tests and TUNEL staining were used to assess cell viability, adhesion and apoptosis, respectively. Western blotting and qRT-PCR were used to examine the protein and mRNA expressions of Wnt3a and β-catenin and the c-myc and cyclinD1 mRNA expressions. Results: TH and DAT expressions in the Cur group were elevated and GFAP was reduced compared with the 6-OHDA group. Curcumin enhanced viability, survival and adhesion and attenuated apoptosis of deutocerebrum primary cells by activating the Wnt/β-catenin signaling pathway. Higher Wnt3a and β-catenin mRNA and protein expressions and c-myc and cyclinD1 mRNA expressions, enhanced superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) contents, decreased malondialdehyde (MDA) content and elevated mitochondrial membrane potential (∆ψm) were found in the 10 and 15 µmol/L Cur groups compared with the 6-OHDA group. However, opposite tendencies were found in the Cur + DKK-1 group compared to the 10 µmol/L Cur group. Conclusion: This study suggests that curcumin could protect against oxidative stress-induced injury in PD rats via the Wnt/β-catenin signaling pathway.

Chronic primary pain (CPP) is a group of diseases with long-term pain and functional disorders but without structural or specific tissue pathologies. CPP is becoming a serious health problem in clinical practice due to the unknown cause of intractable pain and high cost of health care yet has not been satisfactorily addressed. During the past decades, a significant role for the descending pain modulation and alterations due to specific diseases of CPP has been emphasized. It has been widely established that central sensitization and alterations in neuroplasticity induced by the enhancement of descending pain facilitation and/or the impairment of descending pain inhibition can explain many chronic pain states including CPP. The descending serotonergic neurons in the raphe nuclei target receptors along the descending pain circuits and exert either pro- or antinociceptive effects in different pain conditions. In this review, we summarize the possible underlying descending pain regulation mechanisms in CPP and the role of serotonin, thus providing evidence for potential application of analgesic medications based on the serotonergic system in CPP patients.

Background/Aims: Human SIRT1 is reported to be involved in tumorgenesis, mainly due to its modulating effect on p53 by deacetylation on lysine382. A large quantity of SIRT1 inhibitors was applied in chemotherapeutic study, but few of them were applied into clinical trials. Methods and Results: In the current study, a novel series of compounds with 1,4-bispiperazinecarbodithioic acid methyl esters scaffold were characterized to have inhibitory potency to SIRT1 by molecular docking and biochemical evaluation. Further cell level study revealed that one of the most potent SIRT1 inhibitors, compound 3a, is cell active. It can upregulate the amount of p53 by accumulating the K382 acetylation of p53, which lead to the stabilization of p53 in human gastric cancer cell line MGC-803 cells. Meanwhile, we also found compound 3a can inactivate SIRT2 in cells, which suggests the compound as a non-selective SIRT inhibitor. Conclusion: All these findings indicate that compound 3a is a potent, reversible and cell active SIRT1 inhibitor and deserves further investigation as an anticancer agent or a biological tool.

In this paper, the microstructure evolution of the 2195 Al-Li alloy under different isothermal annealing schedules and ramp heating-up heat treatments prior to solution heat treatment and the tensile properties of the aging alloy were investigated. The grain structure characteristics of the aging alloy could be influenced by the change of different heat treatment schedules prior to the solution heat treatment. Meanwhile, the mechanical properties of the aging alloy including strength, heterogeneity, and anisotropy were closely related to the grain structure characteristics. There were evident differences in the mechanical properties of aging samples, attributed to the mutual effect of grain structure evolution and texture change. Annealing at a lower temperature (300–350 °C) resulted in the growth of the grain size and the aspect ratio as well as the decrease of the deformation texture components, related to the decline of the strength and the heterogeneity. While grains refined and the deformation texture components increased as the annealing temperature rose (350–400 °C), the strength along the transverse direction decreased, and the heterogeneity increased. Fibrous and overall texture components significantly strengthened in the grain structure of aging samples treated with the low heating-up rate, resulting in a higher strength in the longitudinal direction.

The body-mounted inertial systems for pedestrian navigation do not require any preinstalled facilities and can run autonomously. The advantages over other technologies make it especially attractive for the applications such as first responders, military and consumer markets. The hardware platform integrating the low-cost, low-power and small-size MEMS (micro-electro-mechanical systems) inertial sensors and GPS (global positioning system) receiver is proposed. When the satellite signals are available, the location of the pedestrian is directly obtained from the GPS receiver. The inertial sensors are the complement of the GPS receiver in places where the GPS signals are not available, such as indoors, urban canyons and places under dense foliages. The height tracking is achieved by the barometer. The proposed PDR (pedestrian dead reckoning) algorithm is real-timely implemented in the platform. The simple but effective step detection and step length estimation method are realized to reduce the computation and memory requirements on the microprocessor. A complementary filter is proposed to fuse the data from the accelerometer, gyroscope and digital compass for decreasing the heading error, which is the main error source in positioning. The reliability and accuracy of the proposed system is verified by field pedestrian walking tests in outdoors and indoors. The positioning error is less than 4% of the total traveled distance. The results indicate that the pedestrian dead reckoning system is able to provide satisfactory tracking performance.

Global positioning system (GPS) offers a perfect solution to the 3-dimension(3D) navigation. However, the GPS-only solution can’t provide continuous and accurate position information in the unfavourable environments, such as urban canyons, indoor buildings, dense foliages due to signal blockage, interference, or jamming etc. A pedestrian dead reckoning (PDR) system integrating the self-contained inertial sensors with GPS receiver is proposed to provide a seamless outdoor/indoor 3D pedestrian navigation. The MEM sensor module attached to the user’s waist is composed of a 3-axis accelerometer, a 3-axis gyroscope, a 3-axis digital compass and a barometric pressure sensor, which doesn’t rely on any infrastructure. The positioning algorithm implements a loosely coupled GPS/PDR integration. The sensor data are fused via a complementary filter to reduce the integral drift and magnetic disturbance for accurate heading. The four key components of the PDR algorithm: step detection, stride length estimation, heading and position determination are described in detail and implemented by the microcontroller. The step is detected using the accelerometer signals by the combination of three approaches: sliding window, peak detection and zero-crossing. The step length is estimated using a simple linear relationship with the step frequency. By coupling the step length, azimuth and height, 3D navigation is achieved. The performance of the proposed system is carefully verified through several field outdoor and indoor walking tests. The positioning errors are below 3% of the total traveled distance. The main error source comes from the orientation estimation. The results indicate that the proposed system is effective in accurate tracking.

Because wear is one of the most common reasons for the failure of metals, the development of a low-cost coating with enhanced wear resistance is of great importance. In the present study, Fe–Si–Al coatings with superior and stable wear resistance were prepared by laser cladding Fe–Si–Al industrial waste onto 1045 carbon steel. The microstructure, as well as the wear mechanism of the Fe–Si–Al coatings, was investigated. The Fe–Si–Al coatings consist of a (Al, Fe, Si) solid solution phase in both columnar grain form and equiaxed grain form. The Fe–Si–Al coatings possess enhanced microhardness of 494 ± 15 HV0.3 and low mass loss of 5 × 10−5 mg·(N·m)−1. The wear resistance is ten times higher than that of the 1045 carbon steel matrix. The wear of the Fe–Si–Al coatings is mainly dominated by abrasive wear and adhesive wear. This work provides important insight into the preparation of low-cost, wear-resistant coatings, as well as stable, superior wear resistance.

Fossil blister pearls attached to the shells of an Anodonta mollusk from China, early Early Pleistocene, are reported here for the first time. The pearls were investigated in detail using a variety of methods. Micro-CT scanning of the fossil pearls was carried out to discover the inner structure and the pearl nucleus. Using CTAn software, changes in the gray levels of the biggest pearl, which reflect the changing density of the material, were investigated. The results provide us with some clues on how these pearls were formed. Sand grains, shell debris or material with a similar density could have stimulated the development of these pearls. X-ray diffraction analysis of one fossil pearl and the shell to which it was attached reveals that only aragonite exists in both samples. The internal structures of our fossil shells and pearls were investigated using a Scanning Electron Microscope. These investigations throw some light on pearl development in the past.

The superhalogen properties of polynuclear structures without halogen ligand are theoretically explored here for several [M2(CN)5]−1 (M = Ca, Be) clusters. At CCSD(T) level, these clusters have been confirmed to be superhalogens due to their high vertical electron detachment energies (VDE). The largest one is 9.70 eV for [Ca2(CN)5]−1 which is even higher than those of corresponding traditional structures based on fluorine or chlorine ligands. Therefore the superhalogens stronger than the traditional halogen-based structures could be realized by ligands other than halogen atoms. Compared with CCSD(T), outer valence Green’s function (OVGF) method either overestimates or underestimates the VDEs for different structures while MP2 results are generally consistent in the aspect of relative values. The extra electrons of the highest VDE anions here aggregate on the bridging CN units with non-negligible distribution occurring on other CN units too. These two features lower both the potential and kinetic energies of the extra electron respectively and thus lead to high VDE. Besides superhalogen properties, the structures, relative stabilities and thermodynamic stabilities with respect to the detachment of cyanide ligand were also investigated. The sum of these results identifies the potential of polynuclear structures with pseudohalogen ligand as suitable candidates with enhanced superhalogens properties.

A number of epidemiologic studies examining the relationship between body mass index (BMI) and the future occurrence of Parkinson's disease (PD) reported largely inconsistent findings. We conducted a dose-response meta-analysis of prospective studies to clarify this association.Eligible prospective studies were identified by a search of PubMed and by checking the references of related publications. The generalized least squares trend estimation was employed to compute study-specific relative risks (RR) and 95% confidence intervals (CI) for an increase in BMI of 5 kg/m2, and the random-effects model was used to compute summary RR and 95% CI.A total of 10 prospective studies were included in the final analysis. An increase in BMI of 5 kg/m2 was not associated with PD risk, with a summary RR of 1.00 (95% CI = 0.89-1.12). Results of subgroup analysis found similar results except for a week positive association in studies that adjusted for alcohol consumption (RR = 1.13, 95% CI = 0.99-1.29), and a week inverse association in studies that did not (RR = 0.90, 95% CI = 0.78-1.04). In a separate meta-analysis, no significant association between overweight (25 kg/m2 ≤ BMI ≤29.9 kg/m2), obesity (BMI≥30 kg/m2) or excess weight (BMI≥25 kg/m2) and PD risk was observed.This meta-analysis does not support the notion that higher BMI materially increases PD risk. However, a week positive BMI-PD association that may be masked by confounders still cannot be excluded, and future prospective studies with a good control for potential confounding factors are needed.

Multiple sclerosis (MS) is a complex disease of neurological disability, affecting more than 300 out of every 1 million people in the world. The purpose of the study was to evaluate the therapeutic effects of human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation in MS patients. Twenty-three patients were enrolled in this study, and 13 of them were given hUC-MSC therapy at the same time as anti-inflammatory treatment, whereas the control patients received the anti-inflammatory treatment only. Treatment schedule included 1,000 mg/kg of methylprednisolone intravenously (IV) daily for 3 days and then 500 mg/kg for 2 days, followed by oral prednisone 1 mg/kg/day for 10 days. The dosage of prednisone was then reduced by 5 mg every 2 weeks until reaching a 5-mg/day maintenance dosage. Intravenous infusion of hUC-MSCs was applied three times in a 6-week period for each patient. The overall symptoms of the hUC-MSC-treated patients improved compared to patients in the control group. Both the EDSS scores and relapse occurrence were significantly lower than those of the control patients. Inflammatory cytokines were assessed, and the data demonstrated a shift from Th1 to Th2 immunity in hUC-MSC-treated patients. Our data demonstrated a high potential for hUC-MSC treatment of MS. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation .

Palynomorphs extracted from the mud coffins and plant remains preserved at the archaeological site of Xiaohe Cemetery (Cal. 3980 to 3540 years BP) in Lop Nur Desert of Xinjiang, China were investigated for the reconstruction of the ancient environments at the site. The results demonstrate that the Xiaohe People lived at a well-developed oasis, which was surrounded by extensive desert. The vegetation in the oasis consisted of Populus, Phragmites, Typha and probably of Gramineae, while the desert surrounding the oasis had some common drought-resistant plants dominated by Ephedra, Tamarix, Artemisia and Chenopodiaceae. This present work provides the first data of the environmental background at this site for further archaeological investigation.

In the title compound, C10H7BrN2, the non-H atoms, except the N atom of the acetonitrile group and the C atom bonded to it, lie in the least-squares plane defined by the atoms of the indole ring system (r.m.s deviation = 0.019 Å), with the N and C atom of the cyano group displaced by 2.278 (1) and 1.289 (1) Å, respectively, out of that plane. In the crystal, N—H...N hydrogen bonds link the molecules into a C(7) chain along [100].

In the title compound, C11H10N2O, the O atom and the C atom of the methylene group deviate only slightly [0.029 (3) and 0.055 (3) Å, respectively] from the approximately planar ring system (r.m.s. deviation = 0.013 Å). In the crystal, N—H...O hydrogen bonds link the molecules into zigzag chains running along the b axis.

In the title compound, C10H7ClN2, the carbonitrile group is twisted away from the plane of the indole ring system [Ccy—Cme—Car—Car = −44.7 (8)°; cy = cyanide, me = methylene and ar = aromatic]. In the crystal, N—H...N hydrogen bonds link the molecules into C(7) chains propagating in [010]. Aromatic π–π stacking interactions [minimum centroid–centroid separation = 3.663 (3) Å] are also observed.

In the crystal structure of the title compound, C5H5NO3, all the non-H atoms are approximately coplanar: the carboxy O atoms deviating by 0.013 (2) and −0.075 (2) Å from the isoxazole ring plane. In the crystal, the molecules form inversion dimers linked by pairs of O—H...O hydrogen bonds and the dimers stack via π–π interactions [centroid–centroid distance = 3.234 (2) Å].

In the title compound, C7H5Br4NO2, intramolecular O—H...N hydrogen bonds are observed. In the crystal structure, intermolecular O—H...O hydrogen bonds link the molecules into dimers.

In the title compound, [CoCl2(C13H20N4)]·H2O, the CoII atom lies on a mirror plane and is four-coordinated by two N atoms of the imidazole ligand and two Cl atoms in a distorted tetrahedral arrangement. The water molecule participates in the formation of hydrogen bonds, resulting in a three dimensional network involving the Cl atoms and the NH groups. The terminal C atom of the ethyl group is disordered over two sites of equal occupancy.

In the title compound, [Ni(NO3)(C13H20N4)2]NO3, the NiII ion shows a distorted octahedral geometry formed by four N atoms from two bis(2-ethyl-5-methyl-1H-imidazol-4-yl)methane ligands and two O atoms from a chelating nitrate anion. Three ethyl groups in the complex cation and the O atoms of the uncoordinated nitrate anion are disordered over two sets of positions [occupancy ratios of 0.52 (3):0.48 (3) and 0.63 (3):0.37 (3), respectively]. In the crystal, intermolecular N—H...O hydrogen bonds connect the complex cations into a zigzag chain along [010] and further N—H...O hydrogen bonds between the chains and the uncoordinated nitrate anions lead to layers parallel to (100).

In the title compound, [Cu(C2O4)(C13H20N4)(H2O)]·2H2O, the CuII atom exhibits a distorted square-pyramidal geometry with the two N atoms of the imidazole ligand and the two O atoms of the oxalate ligand forming the basal plane, while the O atom of the coordinated water molecule is in an apical position. The CuII atom is shifted 0.232 (2) Å out of the basal plane toward the water molecule. The asymmetric unit is completed by two solvent water molecules. These water molecules participate in the formation of an intricate three-dimensionnal network of hydrogen bonds involving the coordinated water molecule and the NH groups.

BACKGROUND: Depletion of the circulating actin-binding protein, plasma gelsolin (pGSN) has been described in critically ill surgical patients. We hypothesized that the extent of pGSN reduction might correlate with different outcome of burn patients. The study was performed to evaluate the prognostic implications of pGSN levels on the development of multiple organ dysfunction syndrome (MODS) and fatal outcome in a group of severely burn patients. METHODS AND FINDINGS: 95 patients were included, and they were divided into three groups with different burn area: group I (n = 33), group II (n = 32) and group III (n = 30). According to whether there was development of MODS or not, patients were divided into MODS group (n = 28) and none-MODS group (n = 67); then the patients with MODS were further divided into non-survivor group (n = 17) and survivor group (n = 11). The peripheral blood samples were collected on postburn days (PBD) 1, 3, 7, 14, and 21. The levels of pGSN were determined and T cells were procured from the blood. The contents of cytokines (IL-2, IL-4 and IFN-γ) released by T cells were also measured. The related factors of prognosis were analyzed by using multivariate logistic regression analysis. The results showed that pGSN concentrations, as well as the levels of IL-2 and IFN-γ, decreased markedly on PBD 1-21, whereas, the levels of IL-4 increased markedly in all burn groups as compared with normal controls (P

Photothermal therapy (PTT) of nanomaterials is an emerging novel therapeutic strategy for breast cancer. However, there exists an urgent need for appropriate strategies to enhance the antitumor efficacy of PTT and minimize damage to surrounding normal tissues. Piezo1 might be a promising novel photothermal therapeutic target for breast cancer. This study aims to explore the potential role of Piezo1 activation in the hyperthermia therapy of breast cancer cells and investigate the underlying mechanisms. Results showed that the specific agonist of Piezo1 ion channel (Yoda1) aggravated the cell death of breast cancer cells triggered by heat stress in vitro. Reactive oxygen species (ROS) production was significantly increased following heat stress, and Yoda1 exacerbated the rise in ROS release. GSK2795039, an inhibitor of NADPH oxidase 2 (NOX2), reversed the Yoda1-mediated aggravation of cellular injury and ROS generation after heat stress. The in vivo experiments demonstrate the well photothermal conversion efficiency of TiCN under the 1,064 nm laser irradiation, and Yoda1 increases the sensitivity of breast tumors to PTT in the presence of TiCN. Our study reveals that Piezo1 activation might serve as a photothermal sensitizer for PTT, which may develop as a promising therapeutic strategy for breast cancer. [ABSTRACT FROM AUTHOR]