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Abstract Background Tuberculosis (TB) poses a major public health challenge, particularly in children. A substantial proportion of children with TB disease remain undetected and unconfirmed. Therefore, there is an urgent need for a highly sensitive point-of-care test. This study aims to assess the performance of serological assays based on various antigen targets and antibody properties in distinguishing children (0–18 years) with TB disease (1) from healthy TB-exposed children, (2) children with non-TB lower respiratory tract infections, and (3) from children with TB infection. Methods The study will use biobanked plasma samples collected from three prospective multicentric diagnostic observational studies: the Childhood TB in Switzerland (CITRUS) study, the Pediatric TB Research Network in Spain (pTBred), and the Procalcitonin guidance to reduce antibiotic treatment of lower respiratory tract infections in children and adolescents (ProPAED) study. Included are children diagnosed with TB disease or infection, healthy TB-exposed children, and sick children with non-TB lower respiratory tract infection. Serological multiplex assays will be performed to identify M. tuberculosis antigen-specific antibody features, including isotypes, subclasses, Fc receptor (FcR) binding, and IgG glycosylation. Discussion The findings from this study will help to design serological assays for diagnosing TB disease in children. Importantly, those assays could easily be developed as low-cost point-of-care tests, thereby offering a potential solution for resource-constrained settings. ClinicalTrials.gov Identifier NCT03044509.

Abstract Background Kupffer cells (KCs) originate from yolk-sac progenitors before birth. Throughout adulthood, they self-maintain independently from the input of circulating monocytes (MOs) at a steady state and are replenished within 2 weeks after having been depleted, but the origin of repopulating KCs in adults remains unclear. The current paradigm dictates that repopulating KCs originate from preexisting KCs or monocytes, but there remains a lack of fate-mapping evidence. Methods We first traced the fate of preexisting KCs and that of monocytic cells with tissue-resident macrophage-specific and monocytic cell-specific fate-mapping mouse models, respectively. Secondly, we performed genetic lineage tracing to determine the type of progenitor cells involved in response to KC-depletion in mice. Finally, we traced the fate of hematopoietic stem cells (HSCs) in an HSC-specific fate-mapping mouse model, in the context of chronic liver inflammation induced by repeated carbon tetrachloride treatment. Results By using fate-mapping mouse models, we found no evidence that repopulating KCs originate from preexisting KCs or MOs and found that in response to KC-depletion, HSCs proliferated in the bone marrow, mobilized into the blood, adoptively transferred into the liver and differentiated into KCs. Then, in the chronic liver inflammation context, we confirmed that repopulating KCs originated directly from HSCs. Conclusion Taken together, these findings provided in vivo fate-mapping evidence that repopulating KCs originate directly from HSCs, which presents a completely novel understanding of the cellular origin of repopulating KCs and shedding light on the divergent roles of KCs in liver homeostasis and diseases.

Abstract Background Extensive studies have revealed the function and mechanism of lncRNAs in development and differentiation, but the majority have focused on those lncRNAs adjacent to protein-coding genes. In contrast, lncRNAs located in gene deserts are rarely explored. Here, we utilize multiple differentiation systems to dissect the role of a desert lncRNA, HIDEN (human IMP1-associated "desert" definitive endoderm lncRNA), in definitive endoderm differentiation from human pluripotent stem cells. Results We show that desert lncRNAs are highly expressed with cell-stage-specific patterns and conserved subcellular localization during stem cell differentiation. We then focus on the desert lncRNA HIDEN which is upregulated and plays a vital role during human endoderm differentiation. We find depletion of HIDEN by either shRNA or promoter deletion significantly impairs human endoderm differentiation. HIDEN functionally interacts with RNA-binding protein IMP1 (IGF2BP1), which is also required for endoderm differentiation. Loss of HIDEN or IMP1 results in reduced WNT activity, and WNT agonist rescues endoderm differentiation deficiency caused by the depletion of HIDEN or IMP1. Moreover, HIDEN depletion reduces the interaction between IMP1 protein and FZD5 mRNA and causes the destabilization of FZD5 mRNA, which is a WNT receptor and necessary for definitive endoderm differentiation. Conclusions These data suggest that desert lncRNA HIDEN facilitates the interaction between IMP1 and FZD5 mRNA, stabilizing FZD5 mRNA which activates WNT signaling and promotes human definitive endoderm differentiation.

Background Norepinephrine (NE) is recommended for children and full-term neonates (born at >37 gestational weeks) with septic shock. Meanwhile, data on the effectiveness of NE in preterm neonates are still limited. This study aimed to evaluate the clinical efficacy of NE in preterm neonates with dopamine-resistant shock compared with that in full-term neonates.Methods This was a single-centre, retrospective (January 2010–December 2020) cohort study of neonates with persistent shock despite adequate fluid resuscitation and dopamine or dobutamine administration at ≥10 μg/kg/min. Medical records of neonates treated with NE were retrospectively reviewed to collect respiratory and haemodynamic parameters and results of arterial blood gas (ABG) tests before and 8 hours after NE infusion. The effectiveness of NE was assessed using changes in clinical parameters and multiple regression models for mortality among subgroups of preterm and full-term neonates.Results Ninety-two neonates (76% preterm) who received NE infusion were included in the study. NE infusion was started after a median of 7 hours (IQR 2–19 hours) after shock onset. Among the preterm neonates, the maximum dose of NE infusion was 0.5 (IQR 0.3–1.0) µg/kg/min with a median duration of 45 (IQR 24.0–84.5) hours. Haemodynamic dysfunction was ameliorated with increased blood pressure, decreased heart rate and improved ABG results. Preterm neonates with septic shock tended to have a reduced response to NE; however, preterm neonates with persistent pulmonary hypertension of the newborn tended to have a better response. Thirty-four (37%) neonates died in our cohort. The timing, dose and duration of NE use were not associated with neonatal mortality.Conclusions Although using NE effectively improves clinical parameters in preterm neonates with dopamine-resistant shock, our study is underpowered to identify the association between NE infusion and mortality in preterm neonates with dopamine-resistant shock.

[Introduction] Integrated Gasification Combined Cycle (IGCC) power generation technology is a high-efficiency and low-carbon power generation technology. A waste heat boiler is one of the components of IGCC. This paper aims to study the off-design operating characteristics of waste heat boilers and improve the efficiency of integrated coal gasification combined cycle power generation technology. [Method] The working principle and heat and mass transfer principle of the waste heat boiler were mainly analyzed by MATLAB software to carry out programming calculations to explore the relationship between feed water temperature, feed water pressure, liquid-phase heat transfer coefficient, gas-phase heat transfer coefficient and heat absorption in waste heat boiler. [Result] The results show that when the liquid-phase heat transfer coefficient is in the range of 200～1 000 W/(m2·K) and the gas-phase heat transfer coefficient is in the range of 20～100 W/(m2·K), as if the feed water temperature increases from 30 ℃ to 100 ℃ or the feed water pressure increases, the heat absorption of the waste heat boiler decreases continuously. In case the feed water temperature is in the range of 30～100 ℃, when the liquid phase heat transfer coefficient increases from 200 W/(m2·K) to 1 000 W/(m2·K) or the gas phase heat transfer coefficient increases from 20 W/(m2·K) to 100 W/(m2·K), the heat absorption of the waste heat boiler increases continuously.[Conclusion] Under the condition that liquid-phase heat transfer coefficient and gas-phase heat transfer coefficient remain unchanged, the feed water temperature or pressure increases, and the heat absorption capacity of the waste heat boiler will decrease; While the feed water temperature and pressure remain unchanged, the liquid-phase heat transfer coefficient or gas-phase heat transfer coefficient increases, and the heat absorption capacity of the waste heat boiler will increase.

Growing evidence shows that there is a comorbid mechanism between the central nervous system (CNS) and the peripheral organs. The bilateral transmission of signal molecules in periphery-brain crosstalk plays an important role in the underlying mechanism, which result from complex networks of neurohumoral circuits. Secreted by almost all cells and considered innovative information transport systems, extracellular vesicles (EVs) encapsulate and deliver nucleic acids, proteins, lipids, and various other bioactive regulators. Moreover, EVs can cross the blood-brain barrier (BBB), they are also identified primarily as essential communicators between the periphery and the CNS. In addition to transporting molecules under physiological or pathological conditions, EVs also show novel potential in targeted drug delivery. In this review, we discuss the mechanisms implicated in the transport of EVs in crosstalk between the peripheral and the central immune systems as well as in crosstalk between the peripheral organs and the brain in CNS disorders, especially in neurodegenerative diseases, stroke, and trauma. This work will help in elucidating the contributions of EVs to brain health and disorders, and promote the development of new strategies for minimally invasive treatment.

Pyruvate carboxylase (PC) deficiency (PCD), due to biallelic PC variants, is a rare inherited metabolic disease, which is characterized by seizures, global developmental delay, as well as lactic acidosis, and elevated plasma pyruvate and alanine levels in affected individuals. In the present study, a new induced pluripotent stem cell line (SHCDNi007-A) was generated from the peripheral blood mononuclear cells of a 2-month-old male infant with biallelic PC mutations c.(182 T > C;2581G > A), i.e. p.(Ile61Thr;Val861Met). This cell line is expected to facilitate the in vitro modeling of the disease pathophysiology and the development of future therapeutics for PCD.

Abstract WX-0593 (Iruplinalkib) is a novel, highly selective oral ALK and ROS1 tyrosine kinase inhibitor (TKI). In this study, the safety, antitumor activity, and pharmacokinetics of WX-0593 were evaluated in advanced non-small cell lung cancer (NSCLC) patients with ALK or ROS1 rearrangement. In the dose-escalation phase and dose-expansion phase, patients were treated with WX-0593 until disease progression, unacceptable toxicity, or subject withdrawal. In the dose-escalation phase, the primary endpoints were maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and safety assessed by investigators. In the dose-expansion phase, the primary endpoint was objective response rate (ORR) assessed by investigators. Between September 25, 2017 and October 15, 2018, a total of 153 patients received WX-0593 treatment. Two dose-limiting toxicities (DLTs) including one grade 3 QT interval prolonged and one grade 2 chronic heart failure were reported at the dose of 300 mg in one patient. MTD was not reached. Overall, 140 of the 152 (92%) patients experienced treatment-related adverse events (TRAEs) and 35 of the 152 (23%) patients had TRAEs ≥grade 3. The overall ORR was 59.3% (32 of 54) for the dose-escalation phase and 56.6% (56 of 99) for the dose-expansion phase. For patients who were ALK-rearranged and ALK TKI naive, the ORR were 81.0% (17 of 21) in the dose-escalation phase and 76.3% (29 of 38) in the dose-expansion phase, and for patients who previously received crizotinib as the only ALK TKI, the ORR were 38.1% (8 of 21) and 45.7% (21 of 46) for the two phases, respectively. For patients who were ROS1-rearranged, the ORR were 30.0% (3 of 10) in the dose-escalation phase and 44.4% (4 of 9) in the dose-expansion phase. WX-0593 showed favorable safety and promising antitumor activity in advanced NSCLC patients with ALK or ROS1 rearrangement.

Abstract Background The purpose of the current study was to explore the role and underlying mechanism of FGF-2 in dexamethasone (DEX)-induced apoptosis in MC3T3-E1 cells. Methods GSE21727 was downloaded from the Gene Expression Omnibus (GEO) database to identify the differentially expressed genes (DEGs) by the limma/R package. MC3T3-E1 cells were exposed to DEX at different concentrations (0, 10−8, 10−7, 10−6, 10−5 and 10−4 mol/L), and cell viability, flow cytometry and TUNEL assay were used to detect cell proliferation and apoptosis. An FGF-2-pcDNA3 plasmid (oe-FGF-2) was used to overexpress FGF-2, and western blotting was conducted to detect protein expression. Results We found that FGF-2 was downregulated in the DEX-treated group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that DEGs were associated with PI3K/Akt signaling pathway. DEX downregulated FGF-2 gene and protein expression, inhibited viability and induced MC3T3-E1 cell apoptosis. Overexpression of FGF-2 reversed DEX-induced apoptosis in MC3T3-E1 cells. FGF-2-mediated anti-apoptosis was impaired by inactivating the PI3K/AKT pathway with LY294002. Moreover, overexpression of FGF2 delayed the progression of DEX-induced osteonecrosis of the femoral head (ONFH) animal model by regulation PI3K/Akt signaling pathway. Conclusion In conclusion, FGF-2 is effective at inhibiting DEX-induced MC3T3-E1 cell apoptosis through regulating PI3K/Akt signaling pathway.

Since 1969, an herbal medicine extracted from Quercus salicina Blume/Quercus stenophylla Makino (QS) has been clinically used for the management of urolithiasis in Japan. Historically, the decoction of leaves and shoots of QS trees was popularly utilized as a folk prescription to remove urinary calculi. This study was designed to perform a brief review of the updated progress of QS extract for urinary stones based on previous studies. A comprehensive literature search was conducted in multiple electronic databases, including Web of Science, PubMed, and EMBASE, and relevant data on QS extract were extracted. As a result, the major mechanism of QS extract for urolithiasis is observed to be closely related to the anti-oxidative activities according to recent studies, leading to inhibition of the accumulation of renal calcium and prevention of stone formation and recurrence of stones. As for the effect of discharging stones, loosening the upper urinary tract has also been noticed recently. More extensive studies are still necessary to systemically evaluate the individual dosage, drug safety, and targeted stone types.

Fe-based chemical looping gasification is a clean biomass technology, which has the advantage of reducing CO2 emissions and the potential of self-sustaining operation without supplemental heating. A novel process combining Fe-based chemical looping and biomass pyrolysis was proposed and simulated using Aspen Plus. The biomass was first subjected to pyrolysis to coproduce biochar, bio-oil and pyrolysis gas; the pyrolysis gas was subjected to an Fe looping process to obtain high-purity hydrogen and carbon dioxide. The influences of the pyrolysis reactor operating temperature and fuel reactor operation temperature, and the steam reactor and air reactor on the process performance are researched. The results showed that, under the operating condition of the established process, 23.07 kg/h of bio-oil, 24.18 kg/h of biochar, 3.35 kg/h of hydrogen and a net electricity of 3 kW can be generated from 100 kg/h of rice straw, and the outlet CO2 concentration of the fuel reactor was as high as 80%. Moreover, the whole exergy efficiency and total exergy loss of the proposed process was 58.98% and 221 kW, respectively. Additionally, compared to biomass direct chemical looping hydrogen generation technology, the new process in this paper, using biomass pyrolysis gas as a reactant in the chemical looping hydrogen generation process, can enhance the efficiency of hydrogen generation.

The effective exploitation of renewable energy and the recovery of waste heat are two crucial strategies in achieving carbon neutrality. As an efficient and reliable heat–to–power conversion technology, the organic Rankine cycle (ORC) has been recognized and accepted by academia and industry for use in solar energy, geothermal energy, biomass energy, and waste heat applications. However, there remain unsolved technical challenges related to the design and operation of the components and system. As the exergy destruction and investment cost of heat exchangers exert significant influence on the performance of ORC, investigations on the performance improvement of heat exchangers are of great significance. The aim of this paper was to provide a review on the performance improvement of ORC in relation to heat transfer enhancement, heat exchanger design optimization, and cycle construction based on a novel heat exchanger. The performance of ORC using different types of heat exchangers was discussed and the importance of revealing the influence of heat exchanger structural parameters on ORC performance was assessed. The heat transfer enhancement, novel heat exchanger investigation, and the ORC configuration development based on a novel heat exchanger were emphasized. Finally, developments and current challenges were summarized and future research trends were also identified.

Nanomaterials refer to new materials that are constructed from a unit structure of one to one hundred nanometers according to certain organizational rules. The purpose of this paper is to apply nanomaterials in the study of visual effects of ethnic dress pattern design. This paper first gives a brief overview of ethnic costumes, including the status quo, development, characteristics of ethnic costumes, and also studies the pattern design and visual effects of ethnic costumes, as well as the image shaping of pattern design. Then, the content of nanomaterials is elaborated. Finally, nanomaterials are applied in the design of ethnic costumes, and they are compared with traditional ethnic costumes, and the functionalities of the costumes and the visual effects of pattern design are observed, respectively. The results show that the overall average score of the visual effect test of ethnic dress pattern design using nanomaterials reaches 8.54 points, which verifies its effectiveness.

Bi4Ti3O12 ferroelectric nanomaterials are mainly used in the manufacture of biosensors, biomedical imaging reagents, or other biomedical applications. Due to the different arrangements of Bi4Ti3O12 ferroelectric nanoparticles, complex nanofibers with specific geometries can be obtained. In this paper, Bi4Ti3O12 ferroelectric nanomaterials were used to study the volatilization state of the acrylic paint used in the coating process. This article explains that some Bi4Ti3O12 nanoparticles were difficult to be dispersed in spinning solution, which made the preparation of composite fibers difficult. Therefore, these issues need further research and resolution. This work proposes to selectively reduce the use of graphene oxide by using an environmentally friendly water solvent to prepare water-reduced graphene oxide (rGO) and then inject octadecylamine into the selectively reduced graphene oxide to prepare octadecylamine-grafted reduced graphene oxide (rG-ODA). The experimental results in this paper showed that through seeding and reduction, functional groups such as carboxyl groups and epoxy groups on the surface of graphene oxide disappeared, and graphene oxide was well reduced. The presence of oxygen-containing functional groups increased the distance between the graphitic layers to 0.713 nm. GS-EDA had a characteristic diffraction peak close to 2θ = 24.3°, indicating that GO was effectively reduced after inoculation reduction.

Nowadays, sensor-based air pollution sensing systems are widely deployed for fine-grained pollution monitoring. In-field calibration plays an important role in maintaining sensory data quality. Determining the model structure is challenging using existing methods of variable global fitting models for in-field calibration. This is because the mechanism of interference factors is complex and there is often insufficient prior knowledge on a specific sensor type. Although Artificial-Neuron-Net-based (ANN-based) methods ignore the complex conditions above, they also have problems regarding generalization, interpretability, and calculation cost. In this paper, we propose a clustering-based segmented regression method for particulate matter (PM) sensor in-field calibration. Interference from relative humidity and temperature are taken into consideration in the particulate matter concentration calibration model. Samples for modeling are divided into clusters and each cluster has an individual multiple linear regression equation. The final calibrated result of one sample is calculated from the regression model of the cluster the sample belongs to. The proposed method is evaluated under in-field deployment and performs better than a global multiple regression method both on PM2.5 and PM10 pollutants with, respectively, at least 16% and 9% improvement ratio on RMSE error. In addition, the proposed method is insensitive to reduction of training data and increase in cluster number. Moreover, it may bear lighter calculation cost, less overfitting problems and better interpretability. It can improve the efficiency and performance of post-deployment sensor calibration.

Two-dimensional (2D) transition metal dichalcogenide nanosheets (TMDC NSs) have attracted growing interest due to their unique structure and properties. Although various methods have been developed to prepare TMDC NSs, there is still a great need for a novel strategy combining simplicity, generality, and high efficiency. In this study, we developed a novel polymer-assisted ball milling method for the efficient preparation of TMDC NSs with small sizes. The use of polymers can enhance the interaction of milling balls and TMDC materials, facilitate the exfoliation process, and prevent the exfoliated nanosheets from aggregating. The WSe2 NSs prepared by carboxymethyl cellulose sodium (CMC)-assisted ball milling have small lateral sizes (8~40 nm) with a high yield (~60%). The influence of the experimental conditions (polymer, milling time, and rotation speed) on the size and yield of the nanosheets was studied. Moreover, the present approach is also effective in producing other TMDC NSs, such as MoS2, WS2, and MoSe2. This study demonstrates that polymer-assisted ball milling is a simple, general, and effective method for the preparation of small-sized TMDC NSs.

With the rapid development of the Internet and information technology (in particular, generative adversarial networks and deep learning), network data are exploding. Due to the misuse of technology and inadequate supervision, deep-network-generated face images flood the network, and the forged image is called a deepfake. Those realistic faked images launched a serious challenge to the human eye and the automatic identification system, resulting in many legal, ethical, and social issues. For the needs of network information security, deep-network-generated face image identification based on different color spaces is proposed. Due to the extremely realistic effect of deepfake images, it is difficult to achieve high accuracy with ordinary methods for neural networks, so we used the image processing method here. First, by analyzing the differences in different color space components in the deep learning network model for face sensitivity, a combination of color space components that can effectively improve the discrimination rate of the deep learning network model is given. Second, to further improve the discriminative performance of the model, a channel attention mechanism was added at the shallow level of the model to further focus on the features contributing to the model. The experimental results show that this scheme achieved better accuracy in the same face generation model and in different face generation models than the two compared methods, and its accuracy reached up to 99.10% in the same face generation model. Meanwhile, the accuracy of this model only decreased to 98.71% when coping with a JPEG compression factor of 100, which shows that this model is robust.

Yes-associated protein-1 (YAP1) is an important effector of the Hippo pathway and has crosstalk with other cancer signaling pathways. It induces an immunosuppressive tumor microenvironment by activating pathways in several cellular components. However, the mechanisms by which it drives immune infiltration in pancreatic cancer remain poorly understood. We analyzed the expression of YAP1 as well as its prognostic value and correlations with immune infiltrates in various cancers, with a focus on pancreatic cancer. In particular, using the Oncomine database and Gene Expression Profiling Interactive Analysis (GEPIA) database, we found that YAP1 is differentially expressed between tumor tissues and control tissues in a number of cancers and in particular, is elevated in pancreatic cancer. Using the Kaplan–Meier plotter, GEPIA, and Long-term Outcome and Gene Expression Profiling database of pan-cancers (LOGpc), we further established the prognostic value of YAP1. We found that YAP1 expression was significantly related to outcomes in multiple types of cancer based on data from The Cancer Genome Atlas, particularly in pancreatic cancer. Correlations between YAP1 and immune cell infiltration and immune cell marker expression were examined using Tumor Immune Estimation Resource and GEPIA. High expression levels of YAP1 were significantly associated with a variety of immune markers and immune cell subsets in pancreatic cancer. These results suggest that YAP1 is correlated with patient outcomes and tumor immune cell infiltration in multiple cancer types and is a valuable prognostic biomarker in pancreatic cancer.

Semaphorins, the neuronal guidance cues, were shown to have broad influences on pathophysiological processes such as bone remodeling, immune responses, and angiogenesis. In particular, Class-3 Semaphorins (SEMA3) is considered a vital regulator involved in angiogenesis. Scientific evidence has pointed to the role of angiogenesis in many diseases, and numerous efforts have been made to explore the possibilities of curing those diseases by targeting angiogenesis. Nevertheless, the efficacies are limited owing to the complex mechanisms of angiogenesis. Hence, investigating the mechanisms of SEMA3 in angiogenesis may contribute to novel therapeutics for diseases. Previous reviews mainly focused on the various functions of semaphorins in one particular disease, and the specific angiogenesis mechanism of SEMA3 in diverse diseases has not been well elucidated. Additionally, the role of SEMA3 in angiogenesis remains elusive, as contradicting results have been found in different disease types. Some evidence from recent studies implies that, while most SEMA3 molecules inhibit pathological angiogenesis in different diseases, occasionally SEMA3 may also promote angiogenesis. This review summarizes the specific role of SEMA3 in a variety of angiogenesis-associated diseases, and documents SEMA3 may be a promising therapeutic target for treating angiogenesis-associated diseases.

Objective To investigate the effect of VRK1 expression downregulated by siRNA on BANF1 expression and the proliferation and migration abilities of esophageal squamous cell carcinoma (ESCC) cells. Methods VRK1 siRNA was transfected into EC109 and EC1 cell lines to interfere VRK1 expression. Western blot was used to detect the interference efficiency of VRK1 siRNA and BANF1 expression in esophageal carcinoma cells after siRNA interference. CCK-8 and flow cytometry were performed to detect the effect of VRK1 expression on cell proliferation. Transwell assay was used to observe the changes of cell migration ability. Results After VRK1 siRNA transfection, VRK1 expression were down-regulated for 62.40% and 52.14%, and BANF1 protein expression were down-regulated significantly for 24.51% and 52.87% in EC109 and EC1 cell lines, respectively. The proliferation of EC109 and EC1 cell lines were decreased 12h after transfection, with the highest inhibition rate at 36h(19.41% and 20.10%). The cells percentages in G2 and G1 phases were decreased while that in S phase was increased after down-regulation of VRK1 and BANF1 expression. The number of cell migration was decreased in the experimental group, compared with control group (P < 0.01). Conclusion Down-regulation of VRK1 expression by siRNA could inhibit the proliferation and migration abilities of esophageal squamous carcinoma cells, which may be achieved by down-regulating BANF1 expression.

Abstract Background To investigate whether unilateral pedicle screw fixation is superior than bilateral pedicle screw fixation for lumbar degenerative diseases. Methods Electronic databases including PubMed, Embase, and the Cochrane Library up to August 2018 were searched. All the high-quality randomized controlled trials (RCTs) and prospective clinical controlled studies comparing the unilateral pedicle screw fixation and bilateral pedicle screw fixation for lumbar degenerative diseases were enrolled in this study. Fusion rate was the main outcome. Stata 12.0 was used for the meta-analysis. Results Twelve RCTs including 808 patients (unilateral pedicle screw fixation = 393, bilateral pedicle screw fixation = 415) were included in our meta-analysis. There was a significant difference between unilateral pedicle screw fixation and bilateral pedicle screw fixation in terms of the fusion rate (risk ratio (RR) = 0.96, 95%CI [0.92, 1.00], P = 0.073), visual analog scale (VAS) at final follow-up, Oswestry Disability Index (ODI), Japanese Orthopedic Association scores (JOA), short-form health survey (SF-36), and length of hospital stay. Compared with bilateral pedicle screw fixation, unilateral pedicle screw fixation was associated with a reduction of the total blood loss and operation time (P

It has been well recognized that exposure to chronic stress could increase pain responding and exacerbate pain symptoms, resulting in stress-induced hyperalgesia. However, the mechanisms underlying stress-induced hyperalgesia are not yet fully elucidated. To this end, we observed that restraint as a stressful event exacerbated mechanical and thermal hyperalgesia, accompanied with up-regulation of nitric oxide (NO) (P < 0.001), GTP cyclohydrolase 1 (GCH1) (GCH1 mRNA: P = 0.001; GCH1 protein: P = 0.001), and tetrahydrobiopterin (BH4) concentration (plasma BH4: P < 0.001; spinal BH4: P < 0.001) on Day 7 in restraint stress (RS) rats. Intrathecal injection of Nω-nitro-L-arginine methyl ester (L-NAME), a non-specific NO synthase inhibitor, or N-([3-(aminomethyl)phenyl]methyl) ethanimidamide, a special inhibitor of inducible NO synthase (iNOS), for seven consecutive days attenuated stress-induced hyperalgesia and decreased the production of NO (P < 0.001). Interestingly, 7-nitro indazole, a special inhibitor of neuronal NO synthase, alleviated stress-induced hyperalgesia but did not affect spinal NO synthesis. Furthermore, intrathecal injection of BH4 not only aggravated stress-induced hyperalgesia but also up-regulated the expression of spinal iNOS (iNOS mRNA: P = 0.015; iNOS protein: P < 0.001) and NO production (P < 0.001). These findings suggest that hyperalgesia induced by RS is associated with the modulation of the GCH1–BH4 system and constitutively expressed spinal iNOS. Thus, the GCH1–BH4–iNOS signaling pathway may be a new novel therapeutic target for pain relief in the spinal cord.

Soil erosion in sloping cropland is a major water and soil conservation issue in the Loess Plateau region, one of the main areas with sloping cropland in China. However, the effect of crop root systems, a major factor potentially influencing soil and water conservation in cropland, on farmland erosion, remains unclear. In the present study, soil erosion was investigated using indoor runoff scouring experiments with millet, maize, and soybean cover, with a bare surface as the control (CK), on sloping surfaces. Crop root system characteristics, rill initiation time, and erosion law, as well as their interactions, were investigated. Rill initiation time in slopes with all three crops slope were greater than that in the bare slope, indicating that crops could significantly enhance soil anti-scourability. Soil detachment rate decreased under crop cover when compared with bare land, considering the average soil detachment rate was the highest under CK, followed by under maize and soybean, and the least under millet. Slope gradient and unit discharge rate were positively correlated with soil detachment rate. Root length density, root surface area density, and root volume density were negatively correlated with soil detachment rate. Moreover, roots in the 0–1 mm diameter range dominantly influenced soil erosion.

Objective This study aimed to compare the efficacy and safety of Super-mini percutaneous nephrolithotomy (SMP) and flexible ureteroscopy (F-URS) in the treatment of 20–30 mm renal stones in obese patients. Methods We conducted a retrospective analysis of outcomes of patients who underwent SMP and F-URS to treat 20–30 mm renal stones from August 2017 to September 2018. Patients with BMI >30 kg/m2 were enrolled into this study. Forty-eight patients underwent SMP, while 104 patients underwent F-URS by the same surgeon. The patients’ demographic data, stone characteristics, perioperative parameters and outcomes, complications, stone-free rate (SFR) and overall costs were retrospectively assessed. Results No significant differences were found between the two groups in terms of age, gender, BMI, operation side, stone size, number, locations, stone compositions and CT value. The mean operation time was significantly shorter in the SMP group (p

Abstract Background To observe the efficacy of self-help position therapy (SHPT) after holmium laser lithotripsy via flexible ureteroscopy (FURS). Methods From January 2010 to November 2015, 736 nephrolithiasis patients who had received FURS lithotripsy were analyzed retrospectively. In position group, 220 cases accepted SHPT after lithotripsies, and 428 cases as control, coming from another independent inpatient area in the same center. The stone-free status (SFS) between two groups were compared at the 2nd, 4th and 12th week ends by X-ray examinations. Results The preoperative incidence of hydronephrosis (25.9% vs. 18.0%, p = 0.018) or lower calyceal seeper (33.6% vs. 24.3%, p = 0.012) and the proportion of patients with > 2.0 cm stones (33.6% vs. 24.3%, p = 0.003) were all significantly higher in position group than in control group. There were no substantial difference between two groups in age, BMI, gender and medical histories. In postoperative followup, the incidence of hydronephrosis in position group was significantly lower than in control group (9.5% vs. 15.7%, p = 0.032) after removing double-J stents. In position group, the SFS of the 2nd week end (60.9% vs. 47.2%, p = 0.001), the 4th week end (74.1% vs. 62.8%, p = 0.004) and the 12th week end (86.9% vs. 79.4%, p = 0.021) were all significantly higher than those in control group. Conclusions SHPT after holmium laser lithotripsy via FURS may increase postoperative SFS, accelerate stone fragment clearance, and decrease the incidence of hydronephrosis after removal of double-J stents. The therapy does not require professional assistance and is economical, simple, and effective.

Previous studies have revealed that high-intensity focused ultrasound (HIFU) ablation can trigger an antitumor immune response. The aim of this study was to investigate immune response in tumor-draining lymph nodes (TDLNs) after HIFU treatment. Forty-eight female patients with biopsy-confirmed breast cancer were divided into a control group and an HIFU group. In the control group, 25 patients underwent modified radical mastectomy, but 23 patients in the HIFU group received HIFU ablation of primary cancer, followed by the same operation. Using HE and immunohistochemical staining, the immunologic reactivity pattern and immune cell profile were assessed in paraffin-embedded axillary lymph nodes (ALNs) in all patients. The results showed that ALNs presented more evident immune reactions in the HIFU group than in the control group (100% vs. 64%). Among the ALNs, 78.3% had mixed cellular and humoral immune response, whereas 36% in the control group showed cellular immune response. The numbers of CD3+, CD4+, NK cell, and activated CTLs with Fas ligand+, granzyme+ and perforin+ expression were significantly higher in the ALNs in the HIFU group. It was concluded that HIFU could stimulate potent immune response and significantly increase T cell, activated CTLs and NK cell populations in the TDLNs of breast cancer.

Abstract Background Hereditary diffuse gastric carcinoma (HDGC) accounts for 1–3% of all gastric carcinomas. Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal (GI) tract but they comprise fewer than 1% of all GI malignancies. Small-cell carcinoma (SmCC) is a rare histological type of esophageal carcinoma, accounting for 0.4% to 2.8% of all esophageal tumors. Co-occurrence of SmCC with esophageal tumors caused by squamous carcinoma is also very uncommon. Although multiple primary malignancies are no longer rare in clinical practice, the simultaneous appearance of HDGC, GIST, esophageal small cell and squamous carcinoma in situ is extremely rare and very few cases have been reported. Case presentation We present a case of a 53 year-old woman with synchronous occurrence of four malignancies including HDGC, GIST, esophageal small cell- and local squamous carcinoma in situ. A total gastrectomy with D2 lymph node dissection and postoperative adjuvant chemotherapy with oxaliplatin and paclitaxel liposome were performed. After a 1-year follow-up, this patient was still in good condition with no evidence of recurrence. Conclusion This is the unique case that describes the co-existence of the aforementioned four types of neoplasm. This case demonstrates that a diagnosis of gastric cancer does not preclude the presence of other malignancies and every case should be thoroughly analyzed to avoid missing other problems, which may worsen the prognosis.

Purpose: To obtain a better understanding of the structures around L5 vertebra and provide some anatomical evidence of the feasibility of total en-bloc spondylectomy (TES) on L5 in a posterior-only approach. Methods: 12 simulated TESs on L5 by a posterior-only approach were conducted on human cadavers. The distance between the traction point of L4 nerve root and the dural sac (Da), the anterior-posterior diameter of the vertebral body,(Va), the distance between the start point of L4 nerve root and the traction point of L5 nerve root (Dh) and the height of the vertebral body (Vh) were measured. Paired t-test and liner regression were performed to determine the difference and correlation between Da and Va, and between Dh and Vh. The risk of nerve roots or blood vessels damages, and the obstruction caused by iliac wings were evaluated. Results: Liner correlations were found between Da and Va, and between Dh and Vh. The regression equations were Da = 0.6673Va + 11.28 and Dh = 1.009Vh + 1.003. There are statistical significant differences between Dh and Vh, and between Da and Va in those whose Va

During the course of infection, Mycobacterium tuberculosis (Mtb) is exposed to diverse redox stresses that trigger metabolic and physiological changes. How these stressors are sensed and relayed to the Mtb transcriptional apparatus remains unclear. Here, we provide evidence that WhiB6 differentially regulates the ESX-1 and DosR regulons through its Fe-S cluster. When challenged with NO, WhiB6 continually activates expression of the DosR regulons but regulates ESX-1 expression through initial activation followed by gradual inhibition. Comparative transcriptomic analysis of the holo- and reduced apo-WhiB6 complemented strains confirms these results and also reveals that WhiB6 controls aerobic and anaerobic metabolism, cell division, and virulence. Using the Mycobacterium marinum zebrafish infection model, we find that holo- and apo-WhiB6 modulate levels of mycobacterial infection, granuloma formation, and dissemination. These findings provide fresh insight into the role of WhiB6 in mycobacterial infection, dissemination, and disease development.

The glycosylation of alpha-dystroglycan (α-DG) is crucial in maintaining muscle cell membrane integrity. Dystroglycanopathies are identified by the loss of this glycosylation leading to a breakdown of muscle cell membrane integrity and eventual degeneration. However, a small portion of fibers expressing functionally glycosylated α-DG (F-α-DG) (revertant fibers, RF) have been identified. These fibers are generally small in size, centrally nucleated and linked to regenerating fibers. Examination of different muscles have shown various levels of RFs but it is unclear the extent of which they are present. Here we do a body-wide examination of muscles from the FKRP-P448L mutant mouse for the prevalence of RFs. We have identified great variation in the distribution of RF in different muscles and tissues. Triceps shows a large increase in RFs and together with centrally nucleated fibers whereas the pectoralis shows a reduction in revertant but increase in centrally nucleated fibers from 6 weeks to 6 months of age. We have also identified that the sciatic nerve with near normal levels of F-α-DG in the P448Lneo- mouse with reduced levels in the P448Lneo+ and absent in LARGEmyd. The salivary gland of LARGEmyd mice expresses high levels of F-α-DG. Interestingly the same glands in the P448Lneo-and to a lesser degree in P448Lneo+ also maintain considerable amount of F-α-DG, indicating the non-proliferating epithelial cells have a molecular setting permitting glycosylation.

Background: Voltage-dependent anion channel (VDAC), a channel protein, exists in the outer mitochondrial membrane of somatic cells and is involved in multiple physiological and pathophysiological processes. Up until now, little has been known about VDAC in male germ cells. In the present study, the relationship between VDAC and human sperm motility was explored. Methods: Highly motile human spermatozoa were incubated in vitro with anti-VDAC antibody. Total sperm motility, straight line velocity (VSL), curvilinear velocity (VCL), and average path velocity (VAP) were recorded. Intracellular free calcium concentration ([Ca2+]i), pH value (pHi), and ATP content were determined. Results: Co-incubation with anti-VDAC antibody reduced VSL, VCL, and VAP of spermatozoa. Co-incubation further reduced [Ca2+]i. Anti-VDAC antibody did not significantly alter total sperm motility, pHi and intracellular ATP content. Conclusion: The data suggest that co-incubation with anti-VDAC antibody reduces sperm motility through inhibition of Ca2+ transmembrane flow. In this way, VDAC participates in the modulation of human sperm motility through mediating Ca2+ transmembrane transport and exchange.

Background: Clusterin, a heterodimeric glycoprotein of approximately 80 kDa, exists extensively in human body fluids. The abnormal expression of clusterin is closely related to the occurrence, progression, and prognosis of tumors. Up to now, few studies have focused on clusterin in human testicular cancer. This study describes an extensive exploration of the presence and expression of clusterin in testicular seminoma. Methods: Tumor tissues and normal testis tissues were collected from 13 patients with testicular seminoma and 16 patients undergoing surgical castration for prostate cancer. Real-time polymerase chain reaction (PCR) was performed to detect the expression difference of clusterin mRNA between testicular seminoma and normal testis. Western blot and immunohistochemical analysis were performed to detect the presence and expression difference of clusterin protein between two groups. Results: Real-time PCR showed the expression of clusterin mRNA in testicular seminoma to be significantly lower than in normal testis (only 13% relative quantification). Western blot analysis indicated marked reductions in the expression of clusterin protein in testicular seminoma. Similar results were observed upon immunohistochemical analysis. Conclusion: In testicular seminoma and normal testis, clusterin exists in its heterodimeric secretory isoform. Clusterin expression is significantly lower in testicular seminoma than in normal testis. This is the first comprehensive study of the presence and expression of clusterin in human testicular cancer.

AIM:Esophageal squamous cell carcinoma (ESCC) is one of the most common fatal malignances of the digestive tract. Its prognosis is poor mainly due to the lack of reliable markers for early detection and prognostic prediction. Here we aim to identify the molecules involved in ESCC carcinogenesis and those as potential markers for prognosis and as new molecular therapeutic targets. METHODS:We performed genome-wide gene expression profile analyses of 10 primary ESCCs and their adjacent normal tissues by cDNA microarrays representing 47,000 transcripts and variants. Candidate genes were then validated by semi quantitative reverse transcription-PCR (RT-PCR), tissue microarrays (TMAs) and immunohistochemistry (IHC) staining. RESULTS:Using an arbitrary cutoff line of signal log ratio of ≥1.5 or ≤-1.5, we observed 549 up-regulated genes and 766 down-regulated genes in ESCCs compared with normal esophageal tissues. The functions of 302 differentially expressed genes were associated with cell metabolism, cell adhesion and immune response. Several candidate deregulated genes including four overexpressed (CTTN, DMRT2, MCM10 and SCYA26) and two underexpressed (HMGCS2 and SORBS2) were subsequently verified, which can be served as biomarkers for ESCC. Moreover, overexpression of cortactin (CTTN) was observed in 126/198 (63.6%) of ESCC cases and was significantly associated with lymph node metastasis (P = 0.000), pathologic stage (P = 0.000) and poor survival (P

Pathogenic Yersinia species employ the Ysc-Yop type III secretion system (T3SS) encoded by a highly conserved pYV virulence plasmid to export the virulence effectors into host cells. The Ysc-Yop T3SS is tightly regulated by multiple contributing proteins that function at different levels. However, systematic transcriptional regulation analysis of Ysc-Yop T3SS is lacking and the detailed mechanism under this regulation process is still elusive. Aimed at systematically characterizing transcriptional regulations of all T3SS genes in Y. pseudotuberculosis, we amplified 97 non-coding fragments from the pYV plasmid and analyzed transcriptional responses of the T3SS genes under different growth conditions. Transcriptions of T3SS genes were induced at 37°C and genes encoding T3SS effectors were highly induced by further depletion of Ca2+. The temperature induced gene transcription process is mediated by modules encoded on the chromosome, while the Ca2+ depletion-induced process is controlled by the positive regulatory protein LcrF as well as the negative regulatory protein LcrQ. In this process, LcrQ shares the same targets with LcrF and the effect of LcrQ is dependent on the presence of LcrF. Furthermore, over-expression of LcrF showed the same phenotype as that of the lcrQ mutant strain and intracellular amount balance of LcrQ and LcrF is important in T3SS regulation. When the expression level of LcrF exceeds LcrQ, expression of the Ysc-Yop T3SS genes is activated and vice versa. Together, these data support a model in which LcrQ blocks the activation role of LcrF in regulating the transcription of T3SS genes in Yersinia.

INTRODUCTION: The overall effect of pamidronate on bone mass density (BMD) in the early renal transplant period varies considerably among studies. The effects of pamidronate on graft function have not been determined. MATERIALS AND METHODS: A comprehensive search was conducted in PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL) and Embase independently by two authors. Randomized controlled trials of pamidronate evaluating bone loss in the first year of renal transplantation were included. Methods reported in the "Cochrane Handbook for Systematic Reviews of Interventions 5.0.2" were used to evaluate changes of lumbar spine and femoral neck BMD, and serum creatinine, calcium and intact parathyroid hormone (iPTH) levels. Fixed or random effect models were used as appropriate. RESULTS: Six randomized trials evaluating 281 patients were identified. One hundred forty-four were treated with pamidronate and 137 were control patients. Administration of pamidronate was associated with significant reduction of bone loss in the lumbar spine, compared to the control group (standardized mean difference (SMD) = 24.62 [16.25, 32.99]). There was no difference between the pamidronate treated and control femoral neck BMD (SMD = 3.53 [-1.84, 8.90]). A significant increase in the serum creatinine level of the intervention group was seen, compared to the control group. The serum calcium and iPTH of the pamidronate and control groups were not different after 1 year (serum creatinine: SMD = -3.101 [-5.33, -0.89]; serum calcium: SMD = 2.18 [-0.8, 5.16]; serum iPTH: SMD = 0.06 [-0.19, 0.31]). Heterogeneity was low for serum calcium and iPTH and high for serum creatinine. CONCLUSIONS: This meta-analysis demonstrated the beneficial clinical efficacy of pamidronate on BMD with no association with any alteration in graft function during the first year of renal transplantation. Significant heterogeneity precludes the conclusion of the relationship between serum creatinine and pamidronate.

Direct cloning of PCR fragments by TA cloning or blunt end ligation are two simple methods which would greatly benefit high-throughput (HTP) cloning constructions if the efficiency can be improved. In this study, we have developed a ribosomal binding site (RBS) switching strategy for direct cloning of PCR fragments. RBS is an A/G rich region upstream of the translational start codon and is essential for gene expression. Change from A/G to T/C in the RBS blocks its activity and thereby abolishes gene expression. Based on this property, we introduced an inactive RBS upstream of a selectable marker gene, and designed a fragment insertion site within this inactive RBS. Forward and reverse insertions of specifically tailed fragments will respectively form an active and inactive RBS, thus all background from vector self-ligation and fragment reverse insertions will be eliminated due to the non-expression of the marker gene. The effectiveness of our strategy for TA cloning and blunt end ligation are confirmed. Application of this strategy to gene over-expression, a bacterial two-hybrid system, a bacterial one-hybrid system, and promoter bank construction are also verified. The advantages of this simple procedure, together with its low cost and high efficiency, makes our strategy extremely useful in HTP cloning constructions.

BACKGROUND: Plant infection models provide certain advantages over animal models in the study of pathogenesis. However, current plant models face some limitations, e.g., plant and pathogen cannot co-culture in a contained environment. Development of such a plant model is needed to better illustrate host-pathogen interactions. METHODOLOGY/PRINCIPAL FINDINGS: We describe a novel model plant system for the study of human pathogenic bacterial infection on a large scale. This system was initiated by co-cultivation of axenic duckweed (Lemna minor) plants with pathogenic bacteria in 24-well polystyrene cell culture plate. Pathogenesis of bacteria to duckweed was demonstrated with Pseudomonas aeruginosa and Staphylococcus aureus as two model pathogens. P. aeruginosa PAO1 caused severe detriment to duckweed as judged from inhibition to frond multiplication and chlorophyll formation. Using a GFP-marked PAO1 strain, we demonstrated that bacteria colonized on both fronds and roots and formed biofilms. Virulence of PAO1 to duckweed was attenuated in its quorum sensing (QS) mutants and in recombinant strains overexpressing the QS quenching enzymes. RN4220, a virulent strain of S. aureus, caused severe toxicity to duckweed while an avirulent strain showed little effect. Using this system for antimicrobial chemical selection, green tea polyphenols exhibited inhibitory activity against S. aureus virulence. This system was further confirmed to be effective as a pathogenesis model using a number of pathogenic bacterial species. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that duckweed can be used as a fast, inexpensive and reproducible model plant system for the study of host-pathogen interactions, could serve as an alternative choice for the study of some virulence factors, and could also potentially be used in large-scale screening for the discovery of antimicrobial chemicals.