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Background and AimRuptured hepatocellular carcinoma (rHCC) is classified as T4 according to the TNM staging system with a very poor (does not achieve expected) prognosis, which has always been controversial. This study aimed at assessing the specific impact of different tumor diameters on the posttreatment prognosis of BCLC stage 0/A rHCC patients.MethodsData from 258 patients with BCLC stage 0/A HCC treated in our center from January 2008 to December 2017 were collected, including 143 rHCC patients and 115 patients with non-ruptured HCC (nrHCC). With the help of X-tile software, we determined the cutoff value of the tumor diameter in patients with rHCC. Using 8 cm as the cutoff, we divided rHCC patients into Small-rHCC (n = 96) and Large-rHCC (n = 47) groups, compared the prognoses of the S-rHCC and L-rHCC groups, as well as the prognoses of the two groups with the nrHCC group using the Kaplan–Meier method, and screened the prognostic factors of rHCC patients using the multivariate Cox risk model.ResultsThe OS of the S-rHCC group was significantly higher than that of the L-rHCC group [HR = 2.41 (1.60–3.63)], and the OS of the nrHCC group was comparable to that of the S-rHCC group (P = 0.204). In patients treated with surgery only, OS and RFS were also comparable in the S-rHCC nrHCC group. Meanwhile, multivariate Cox regression analysis revealed that alpha-fetoprotein (AFP), alkaline phosphatase (ALP), and the main method of treatment were also prognostic factors for OS in patients with rHCC.ConclusionsRuptured HCC with a relatively small diameter (≤8 cm) can also achieve the same prognosis as nrHCC patients after aggressive treatment. It is also not recommended to include all patients with rHCC in stage T4.

BackgroundLarge hepatocellular carcinoma (LHCC) is highly malignant and prone to recurrence, leading to a poor long-term prognosis for patients. There is an urgent need for measures to intervene in postoperative recurrence. Preoperative Transcatheter Arterial Embolization (TACE) is an effective treatment. However, there is a lack of reliable preoperative indicators to guide the application of preoperative TACE. We, therefore, investigated whether the preoperative status of circulating tumor cells (CTCs) could be used to guide preoperative TACE for HCC treatment.MethodsThis study recruited 361 HCC patients and compared recurrence-free survival (RFS) and overall survival (OS) in patients treated with TACE prior to surgery and those not treated with TACE. Patients were divided into CTC-positive group and CTC-negative group according to CTC status, and the effect of preoperative TACE on RFS and OS was compared in each subgroup.ResultsIn CTC-positive patients, preoperative TACE reduces early recurrence and improves long-term survival. However, HCC patients did not benefit from preoperative TACE for the overall population and CTC-negative patients.ConclusionsPreoperative CTC testing is a reliable indicator of whether HCC patients received TACE preoperatively. CTC positivity was associated with early tumor recurrence, and preoperative TACE could reduce early recurrence and long-term prognosis in CTC-positive patients.

Organizational citizenship behavior (OCB) can foster organizational competitiveness and survival especially, facing a rapidly changing environment. There are some empirical pieces of research that shed light on the effects of OCB on extrinsic rewards, since OCB, through performance appraisal, affects extrinsic rewards which will influence OCB as well. However, researchers have overlooked the reverse effect of extrinsic rewards (i.e., positive verbal rewards) on OCB. It is necessary to explore the mechanism between positive verbal rewards and OCB. This study integrated psychological ownership and affective commitment to form a structural model based on social exchange theory and cognitive evaluation theory. These results show that positive verbal rewards are positively correlated with psychological ownership, psychological ownership is positively correlated with affective commitment and OCB, and affective commitment is positively correlated with OCB. As refers to the mediating effects, psychological ownership fully mediates the relationship between positive verbal rewards and affective commitment. Furthermore, affective commitment plays a partial mediating role in the effect of psychological ownership on OCB. Accordingly, this psychological mechanism between positive verbal rewards and OCB reveals important theoretical and practical implications.

Background and AimTo investigate the effect of preoperative circulation tumor cells (CTCs) on postoperative recurrence and overall survival prognosis of pancreatic head cancer after pancreaticoduodenectomy (PD).MethodsFrom March 2014 to January 2018, 73 patients with pancreatic head cancer underwent radical resection (R0) in Zhongshan People's Hospital. CTCs in peripheral blood of patients with pancreatic head cancer were detected by “Cyttel” method before PD. Seventy-three patients were divided into positive and negative groups according to the positive criteria. To explore the relationship between the clinical data of CTCs and disease-free survival (DFS) and overall survival (OS). Cox proportional hazards model was used to analyzing the risk factors affecting the postoperative recurrence and the survival prognosis of patients.Results41 patients (56.2%) were in the CTC-positive group. Preoperative CTCs were correlated with tumor vascular invasion, CA199 level and postoperative liver metastasis (P < 0.05). Preoperative CTC-positive, lymph node metastasis, vascular invasion, and nerve invasion were independent risk factors for DFS (P < 0.05). Preoperative CTC-positive, tumor diameter > 2 cm and vascular invasion were independent risk factors for OS of patients (P < 0.05).ConclusionThe detection of CTCs before PD is an important factor affecting the DFS and OS of pancreatic head cancer, which is significant in guiding clinical work.

Abstract A new strategy for designing single‐band and dual‐band balanced bandpass filters (BPFs) based on a circular patch resonator is proposed in this study. By altering the output balanced ports of the balanced BPFs to inhibit or transport the TM31 mode of the circular patch resonator under the differential‐mode (DM) excitation, a single‐band or dual‐band balanced BPF can be realized. As the odd modes could be restrained under the common‐mode (CM) excitation, the balanced BPFs could feature high CM suppression in the DM passbands. Meanwhile, several perturbing tactics are introduced to improve the performance of the balanced BPFs. Specifically, perturbation vias are presented to disturb the electric field distribution to enhance the CM suppression in the DM passbands, and slots are applied on the circular patch resonators to perturb the current distribution to amend the second DM passband of the dual‐band balanced BPF. The proposed single‐band and dual‐band balanced BPFs are fabricated and characterized. Good agreement can be achieved between the simulated and measured results of the fabricated balanced BPFs, which validates the feasibility of the proposed design method.

Reverse conduction loss of GaN high electron mobility transistors (HEMTs) in very high frequency (VHF) converters is non-neglectable due to the absence of body diode. To reduce the reverse conduction time, this paper proposes a linear equivalent model for class $\Phi _{2}$ inverter to derive optimal duty cycles for different working conditions. The proposed model is derived from frequency-domain perspective, which simplifies the derivation process and provides an intuitive physical insight for class $\Phi _{2}$ inverter. Firstly, the power switch is modeled as a current source according to time-domain expressions of inductor current, which simplifies the circuit to a linear network. Based on quantitative analysis of the current source spectrum characteristics, the linear network response to the current excitation is derived, which forms the linear equivalent model. Then, drain voltage of the main switch under different working conditions is obtained. With the zero-crossing point of the drain voltage, numerical solutions of the optimal duty cycles are calculated. Finally, the optimal duty cycles are implemented with a high-resolution duty cycle generation circuit in a 27.12MHz prototype, which achieves not only a peak efficiency of 93.6% at full load, but also higher efficiency over the whole load and input voltage range compared to conventional fixed duty cycle.

Nonideal switching characteristics of voltage source inverter (VSI) will result in distortions in both phase currents and reference voltages of a permanent magnet synchronous machine (PMSM) drive system, which will also consequently introduce ripples into the output speed and shaft torque, and result in a performance deterioration in the state observation control. To solve this issue, a method of directly extracting and compensating the nonlinear voltage disturbance due to VSI nonlinearity employed in PMSM drives is proposed in this paper. Firstly, the distorted voltage due to VSI nonlinearity is directly extracted via a harmonic separation scheme, which can be easily compensated by a proportional integral controller afterwards. Since both 6th harmonic and DC terms of dq-axis distorted voltages due to VSI nonlinearity are well compensated, the proposed method shows sufficiently good performance under both $i_{d}=0$ and maximum torque per ampere controls ( $i_{d} < 0$ ), as verified on two prototype PMSMs being salient pole and non-salient pole, respectively, both developed for a low-speed rotary actuator. In addition, the application of proposed method to state observation controls such as the model-based sensorless control and the deadbeat predictive current control, is finally investigated. Test results manifest that the proposed method can effectively improve the accuracy of observed rotor position/speed, and the ability of current tracking.

Abstract Background Association of arterial stiffness and osteoporosis has been well documented in elderly population. However, it is not clear whether they co-progress from the early stages through common mechanisms. The object of this study was to evaluate possible associations between arterial stiffness and osteoporosis by measuring brachial-ankle pulse wave velocity (baPWV) and the Osteoporosis Self-Assessment Tool for Asia (OSTA) index among a healthy population of Chinese aged 40 years and older. Whether baPWV can be used as a predictor of osteoporosis on OSTA was further assessed. Methods This study was cross-sectional in design. Of 3984 adults aged 40 years and older in the Yunyan district of Guiyang (Guizhou, China) who underwent both OSTA and baPWV measurements within 1 month, 1407 were deemed eligible for inclusion (women, 1088; men, 319). Results The mean baPWV was 1475 ± 302 cm/s (range,766–3459 cm/s). baPWV in 110 individuals with high risk of osteoporosis (OSTA index < − 4) was higher than that of individuals with non-high risk (1733 ± 461 cm/s vs. 1447 ± 304 cm/s, P < 0.001). OSTA index was negatively correlated with baPWV(ρ = − 0.296, P < 0.001) after adjusting for age, sex, body mass index, waist circumference, diastolic blood pressure, and creatinine clearance rate. baPWV was an independent predictor for the presence of high risk of osteoporosis (β = − 0.001, P < 0.001) and was consistent across age and sex subgroups, and the optimal baPWV cutoff value for predicting the presence of high risk of osteoporosis and fracture was 1693 cm/s. The AUC was 0.722 (95% confidence interval [CI], 0.667–0.777; P < 0.001, sensitivity of 52.8% and specificity of 83.6%). Conclusions We conclude that arterial stiffness measured by baPWV is well correlated with the severity of osteoporosis evaluated by OSTA. baPWV index may be a valuable tool for identifying individuals with risk of developing osteoporosis.

The Cucker-Smale (C-S) model describes an interacting particle system in which the connection weights decrease with increasing distance. This model features emergent behaviors by which the velocities of the particles converge to a common value without a central command. However, the consensus value of the original C-S flocking model is restricted to the leader-following consensus or average consensus. Moreover, for the short-range communication-based C-S model, consensus can only be obtained for specific initial configurations. In this paper, the short-range communication-based C-S model is extended to achieve distributed optimization, where the consensus value optimizes the objective function of the group for any bounded initial configuration. Simulation examples are provided to demonstrate the effectiveness of our approach.

The growing need for deep-sea biological research and environmental monitoring has expanded the demand for benthic landers. Compared with remotely operated vehicles (ROVs) and autonomous underwater vehicles (AUVs), benthic landers can reduce overall operation cost and also possess longer endurance. Configuring a suitable descent velocity is important for benthic lander designs, helping them avoid retrieval failure and improve sea trial efficiencies. In this study, an effective scheme for the configuration and optimization of a self-developed benthic lander was outlined. First, the structural characteristics of the benthic lander were analyzed, and then a dynamic model was established. Second, the hydrodynamic coefficients of the benthic lander during its descent process were calculated using computational fluid dynamics (CFD) methods. Third, the MATLAB Simulink simulation environment was used to solve the dynamic model, and then the multi-objective optimization algorithm was introduced for the optimization design. Finally, the model was validated based on sea trial data, which demonstrated that the designed configuration and optimization scheme were correct and efficient. Collectively, this work provides a useful reference for the rational configuration and practical application of benthic landers.

Human microphysiological systems (MPS) have some advantages over animal models to study the mechanisms of disease. Here the authors use a tissue-engineered blood vessel MPS to create a model of early stage atherosclerosis and assess the effect of several drugs.

Abstract Nigella A, also named Sieboldianoside A, has been extracted from many kinds of Traditional Chinese Medicine (TCM), such as Nigella glandulifera, Stauntonia chinensis DC., and the leaves of Acanthopanax sieboldianus. Nigella A exhibited potential analgesic, anti-inflammatory, anti-tumor, and antioxidant activities. However, whether Nigella A could treat ulcerative colitis (UC) is still unknown. As saponins always be regarded as the kinds of ingredients that could regulate immunity and intestinal flora. This research aimed to investigate the therapeutic effect of Nigella A on UC and explore its effect on intestinal flora. We noted that Nigella A and Sulfasalazine (SASP) could significantly improve the signs and symptoms, alleviate colonic pathological injury in DSS-induced mice. The changing of many specific bacterial genus such as Lactobacillus, Porphyromonadaceae, Bacteroides and Escherichia might closely related to the recovery of intestinal inflammatory response. This study initially confirmed the therapeutic effect of Nigella A and SASP on DSS-induced colitis by improving the diversity of intestinal microbial composition. Nigella A has the potential to be developed for the treatment of UC and other disorders related to the imbalance of intestinal flora.

Abstract Background Glucose 6-phosphate dehydrogenase (G6PD) serves key roles in cancer cell metabolic reprogramming, and has been reported to be involved in certain carcinogenesis. Previous results from our laboratory demonstrated that overexpressed G6PD was a potential prognostic biomarker in clear cell renal cell carcinoma (ccRCC), the most common subtype of kidney cancer. G6PD could stimulate ccRCC growth and invasion through facilitating reactive oxygen species (ROS)-phosphorylated signal transducer and activator of transcription 3 (pSTAT3) activation and ROS-MAPK-MMP2 axis pathway, respectively. However, the reasons for ectopic G6PD overexpression and the proliferation repressive effect of G6PD inhibition in ccRCC are still unclear. Methods The impact of ROS accumulation on NF-κB signaling pathway and G6PD expression was determined by real-time RT-PCR and Western blot in ccRCC cells following treatment with ROS stimulator or scavenger. The regulatory function of NF-κB signaling pathway in G6PD transcription was analyzed by real-time RT-PCR, Western blot, luciferase and ChIP assay in ccRCC cells following treatment with NF-κB signaling activator/inhibitor or lentivirus infection. ChIP and Co-IP assay was performed to demonstrate protein-DNA and protein–protein interaction of NF-κB and pSTAT3, respectively. MTS assay, human tissue detection and xenograft model were conducted to characterize the association between NF-κB, pSTAT3, G6PD expression level and proliferation functions. Results ROS-stimulated NF-κB and pSTAT3 signaling over-activation could activate each other, and exhibit cross-talks in G6PD aberrant transcriptional regulation. The underlying mechanism was that NF-κB signaling pathway facilitated G6PD transcription via direct DNA–protein interaction with p65 instead of p50. p65 and pSTAT3 formed a p65/pSTAT3 complex, occupied the pSTAT3-binding site on G6PD promoter, and contributed to ccRCC proliferation following facilitated G6PD overexpression. G6PD, pSTAT3, and p65 were highly expressed and positively correlated with each other in ccRCC tissues, confirming that NF-κB and pSTAT3 synergistically promote G6PD overexpression. Moreover, G6PD inhibitor exhibited tumor-suppressor activities in ccRCC and attenuated the growth of ccRCC cells both in vitro and in vivo. Conclusion ROS-stimulated aberrations of NF-κB and pSTAT3 signaling pathway synergistically drive G6PD transcription through forming a p65/pSTAT3 complex. Moreover, G6PD activity inhibition may be a promising therapeutic strategy for ccRCC treatment.

Benzo(a)pyrene [B(a)P], a ubiquitous environmental pollutant, causes lung inflammatory damage. Pyroptosis，a new inflammation-dependent programmed cell death, happened when pyroptosis-related GSDMD is activated mediated by NLRP3 inflammasome. microRNA-223 (miRNA-223) is involved in inflammatory diseases by regulating NLRP3. However, whether GSDMD regulate NLRP3 inflammasome through miR-223 in B(a)P induced lung inflammatory injury remain unknown. In this study, alveolar epithelial cells (A549) were stimulated with 0, 2, 4, 8 μM B(a)P for 12 h or 24 h. The inflammatory injury and pyroptosis were determined. And the activation of NLRP3 inflammasomes and the level of miRNA-223 were detected. Then, the change of inflammatory injury and activation of NLRP3 inflammasomes in B(a)P-induced A549 cells were detected after inhibiting of GSDMD or miR-223 using siRNA-GSDMD (siGSDMD) or miR-223 inhibitor, respectively. Our results indicated that after B(a)P exposure, TNF-α and IL-6 in the supernatant were increased. Transmission electron microscope (TEM) results showed that A549 cells were obviously swollen and the cell membrane ruptured. Hoechest33342/PI staining showed that pyroptosis occurred. NLRP3, IL-1β, IL-18, GSDMD, GSDMD-N, pro caspase-1 and cleaved caspase-1 were significantly increased. Additionally, after transfecting with siGSDMD in B(a)P-induced A549 cells, the expression level of miR-223 was significantly increased. But IL-6 and TNF-α in the supernatant, the expression of NLRP3, IL-1β, IL-18 and cleaved caspase-1 protein were also decreased. And after inhibiting miR-223 in B(a)P-induced A549 cells, the expression of TNF-α and IL-6 in the supernatant, the protein expression of NLRP3, IL-1β, IL-18 and cleaved caspase-1 were increased. In conclusion, GSDMD may regulate NLRP3 inflammasome through miR-223, which is involved in B(a)P induced inflammatory damage in A549 cells.

Background and AimThe effect of perioperative blood transfusion (PBT) on the prognosis of patients with ruptured hepatocellular carcinoma (rHCC) with different Barcelona Clinic Liver Cancer (BCLC) stages is not clear. We identified the independent predictors of PBT for postoperative rHCC and investigated the effects of PBT on the prognosis of patients with rHCC at different BCLC stages.MethodsA total of 340 patients who underwent curative hepatectomy for rHCC between January 2010 and March 2018 were abstracted from the databases of two centers. A total of 166 patients underwent PBT. The prognosis of patients who received PBT and those who did not was compared before and after propensity score matching (PSM) in different BCLC stages. Univariate and multivariate Cox regression analyses were also used to identify independent predictors of PBT.ResultsWe divided the 340 patients into two groups: early tumor stage (BCLC-A) n = 196 and advanced tumor stage (BCLC-B/C) n = 144. Overall, the median survival time of the PBT group was lower than that of the nonPBT group before and after PSM. However, in the BCLC-BC group, the prognosis of patients with PBT was not statistically different from that of patients without blood transfusion. Univariate Cox analysis showed that PBT was a risk factor affecting the overall survival (OS) and recurrence-free survival (RFS) in BCLC-A, and PBT was not a risk factor for poor OS and RFS in BCLC-B/C.ConclusionPerioperative blood transfusion has a negative impact on the postoperative prognosis of patients with rHCC in the early stage, but has no significant impact on the postoperative prognosis of patients with rHCC in the advanced stage.

Objective: The aim of the study was to develop the early diagnostic criteria for Wilson’s disease (WD) in young children in southern China by using alanine aminotransferase (ALT) elevation as the first manifestation.Methods: A cross-sectional retrospective analysis of the clinical data and genetic test results of children with WD in southern China in the past 4 years and the follow-up of their short-term prognosis were performed in this study.Results: A total of 30 children (5.08 ± 2.06 years old) with elevated ALT as the first manifestation of WD in southern China were enrolled in this study, including 14 females and 16 males. Specifically, in all of the 30 cases (100%), the serum ceruloplasmin (CP) level was decreased, whereas the 24-h urinary copper level was increased. The genetic mutation test of the ATP7B gene was used to confirm the diagnosis. In particular, the two mutation sites, including p.R778L and p.I1148T, had the highest mutation frequencies, approximately 23.0 and 10.7%, respectively. Through follow-up, most of the children had good recovery.Conclusion: Early diagnosis and treatment of WD would substantially increase the survival rate and have a better prognosis. In addition, in 5-year-old children from southern China, early diagnosis could be performed quickly by referring to the following three parameters: elevated ALT, decreased ceruloplasmin level, and increased 24-h urinary copper level. It lays a foundation for further studies with a larger sample size.

Aiming at the problems of intensified deformation and serious stress damage of stope overburden during mining in deep typical geological environment, taking the deep mining face of a mine in the northwest as the research background, the characteristics and influencing factors of overburden collapse in deep geological environment are analyzed, a comprehensive evaluation system affecting overburden instability and deformation is established, and the temporal and spatial evolution law of deep stope roof failure is obtained by using the “three-zone” distribution theory of overburden, analytic hierarchy process, and numerical simulation method. The results show that high ground stress has the most significant impact on the geological environment of deep stope, followed by the properties of surrounding rock, hydrogeological conditions, and unloading disturbance. The damage degree of the plastic zone at the top of the overburden is greater than that at the bottom. With the increase of mining time, the damage range of the roof and floor gradually increases. In the process of coal seam mining, the increasing range and sinking trend of roof stress are larger near the working face, and the farther away from the working face, the increasing range decreases continuously. The research conclusion provides an important reference for coal seam safety mining and surrounding rock control in complex environments such as deep mining, high stress, and strong disturbance.

Rapid integration into the host tissue is critical for long-term patency after small diameter tissue engineering vascular grafts (sdTEVGs) transplantation. Neural recognition may be required for host integration and functionalization of the graft. However, immune rejection and inflammation hinder nerve regeneration of sdTEVGs. Here, a CRISPR/dCas9-nanocarrier was used for targeted programming of regulatory T cells (Treg cells) in situ to promote nerve regeneration of sdTEVGs by preventing excessive inflammation. Treg cells and (C-C chemokine receptor) CCR2+ macrophage recruitment occurred after transplantation. The nanodelivery system upregulated ten eleven translocation (TET2) in Treg cells in vitro. Reprogrammed Treg cells upregulated anti-inflammatory cytokines and decreased the proportion of CCR2+ macrophages. IL-6 concentrations decreased to the levels required for nerve regeneration. Implantation of CRISPR/dCas9 nanodelivery system-modified sdTEVGs in rats resulted in Treg cell editing, control of excessive inflammation, and promoted nerve regeneration. After 3 months, nerve regeneration was similar to that observed in normal blood vessels; good immune homeostasis, consistency of hemodynamics, and matrix regeneration were observed. Neural recognition promotes further integration of the graft into the host, with unobstructed blood vessels without intimal hyperplasia. Our findings provide new insights into vascular implant functionalization by the host.

Taking two typical stopes with variable length of working face inclined length from small to large and from large to small as the research object, the stope overburden structure model under different face length conditions is constructed through laboratory similar material simulation test, and the dynamic evolution laws of overburden instability deformation, unloading expansion, and collapse failure of forward and reverse knife handle stopes are analyzed. The three-dimensional perspective technology of parallel network electrical method is used to study the spatial distribution range and fracture development characteristics of overburden internal failure. The research shows that the overburden fracture of stope with variable length has the “time-pace-scale” evolution effect of short-time sudden change, zoning load transfer, and continuous extension. The evolution of roof fracture has experienced the development process of unloading expansion, tensile fracture instability, shrinkage deformation, and closure stability. The rise and fall of resistivity during mining in stope with variable length is closely related to the mining time step. When mining 40 cm, it is the position where the resistivity value changes suddenly. The rise of resistivity in the vertical direction makes the electric field show the transient response characteristics of dynamic expansion and rapid evolution. The development height of water conducting fracture zone of the reverse knife handle working face with the inclined length changing from large to small is slightly larger, the degree of overburden damage is high, and the fracture development is relatively sufficient.

For the urgent need of gas management in high gas and coal and gas herniated mines, liquid CO2 fracturing is used to increase the permeability and promote the pumping treatment of low permeability coal seams. In this paper, we construct the coal deformation and damage model, gas diffusion and seepage model, and coal seam permeability change model; simulate and solve the plastic zone and gas pressure of coal seam after fracturing with the COMSOL Multiphysics software; and set 4 different hole spacing groups of 2 m, 3 m, 4 m, and 5 m and 3 different hole layout methods of single hole, double hole, and net hole to get the best solution for liquid CO2 fracturing. At the same time, the specific effect of liquid CO2 on coal seam fracturing was verified by field experiments using coal seam No. 2 of the 12316 comprehensive mining working face of Wangjialing Coal Mine as the background of the study. The numerical simulation results show that the stress concentration area around the fracturing hole appears in single-hole fracturing, and the coal seam is prone to fatigue damage in this area, but the damage range is limited, and the reduction of gas pressure after fracturing is small; the fracturing effect of double-hole and net-hole fracturing is better than that of single-hole fracturing due to the existence of sufficient critical air surface. After negative pressure extraction, the coal seam gas pressure is positively correlated with the distance from extraction hole to fracturing hole, and the best extraction effect can be seen from the field experimental results with the netted hole layout at the hole distance of 3 m. The field test results show that the pure amount of gas extraction is improved about 4 times after liquid CO2 fracturing, which proves that liquid CO2 fracturing has a better enhancement effect on gas management in low permeability coal seams.

Aim: To comprehensively profile the landscape of the mRNA N6-methyladenosine (m6A) modification in human colorectal cancer (CRC).Methods: Methylated RNA immunoprecipitation sequencing (MeRIP-seq) was explored to compare the difference in mRNA N6-methyladenosine (m6A) methylation between CRC tissues and adjacent normal control (NC) tissue. RNA-sequencing (RNA-seq) was performed to transcribe differentially expressed mRNAs. Conjoint analysis of MeRIP-seq and RNA-seq data was conducted to predict RNA-binding proteins (RBPs).Results: MeRIP-seq identified 1110 differentially m6A methylated sites (DMMSs) and 980 differentially m6A methylated genes (DMMGs) in CRC, with 50.13% of all modified genes showing unique m6A-modified peaks in CRC. RNA-seq showed 915 upregulated genes and 1463 downregulated genes in CRC. QRT-PCR verified the RNA-seq results by detecting the expression of some mRNAs. Conjoint analysis of MeRIP-seq and RNA-seq identified 400 differentially m6A methylated and expressed genes (DEGs), and pathway analysis detected that DMMGs and DEGs were closely related to cancer. After analyzing these DMMGs and DEGs through the GEPIA database, we found that the expression of B3GNT6, DKC1, SRPK1, and RIMKLB were associated with prognosis, and the expression of B3GNT6 and RIMKLB were associated with clinical stage. 17 RBPs were identified based on the DMMGs and DEGs, among which FXR1, FXR2, FMR1, IGF2BP2, IGF2BP3, and SRSF1 were obviously highly expressed in CRC, and FMR1, IGF2BP2, and IGF2BP3 were closely related to methylation, and might be involved in the development of CRC.Conclusion: This study comprehensively profiled m6A modification of mRNAs in CRC, which revealed possible mechanisms of m6A-mediated gene expression regulation.

Single modality MRI data is not enough to depict and discern the cause of the underlying brain pathology of Alzheimer's disease (AD). Most existing studies do not perform well with multi-group classification. To reveal the structural, functional connectivity and functional topological relationships among different stages of mild cognitive impairment (MCI) and AD, a novel method was proposed in this paper for the analysis of regional importance with an improved deep learning model. Obvious drift of related cognitive regions can be observed in the prefrontal lobe and surrounding the cingulate area in the right hemisphere when comparing AD and healthy controls (HC) based on absolute weights in the classification mode. Alterations of these regions being responsible for cognitive impairment have been previously reported. Different parcellation atlases of the human cerebral cortex were compared, and the fine-grained multimodal parcellation HCPMMP performed the best with 180 cortical areas per hemisphere. In multi-group classification, the highest accuracy achieved was 96.86% with the utilization of structural and functional topological modalities as input to the training model. Weights in the trained model with perfect discriminating ability quantify the importance of each cortical region. This is the first time such a phenomenon is discovered and weights in cortical areas are precisely described in AD and its prodromal stages to the best of our knowledge. Our findings can establish other study models to differentiate the patterns in various diseases with cognitive impairments and help to identify the underlying pathology.

Background. Studies of chronic airway inflammatory diseases have increasingly focused on airway microbiota. However, the microbiota characteristics of asthma and chronic obstructive pulmonary disease (COPD) patients with different airway inflammatory phenotypes remain unclear. Objective. We aimed to reveal the differences of fungal and bacterial microbiota between eosinophilic asthma (EA) and noneosinophilic asthma (NEA) patients and between eosinophilic COPD (EC) and noneosinophilic COPD (NEC) patients. Further, explore whether similarities exist in the airway microbiota of patients with the same phenotype. Methods. Induced sputum samples were collected from 45 asthma subjects and 39 COPD subjects. The airway microbiota of the subjects was profiled by nearly full-length 16S rRNA and internal transcribed space (ITS) sequencing. Results. Subjects with eosinophilic phenotype (EA and EC) showed significant differences in both fungal and bacterial microbiota compared to the corresponding subjects with noneosinophilic phenotype (NEA and NEC). In addition, no differences were observed between the fungal microbiota of subjects with the same phenotype (EA vs. EC, NEA vs. NEC). In bacterial microbiota, the greater relative abundance of Streptococcus thermophilus was observed in EA and EC subjects, while Ochrobactrum was enriched in NEA and NEC subjects. In fungal microbiota, the EA and EC subjects showed higher relative abundances of Aspergillus and Bjerkandera, while the NEA and NEC subjects were enriched in Rhodotorula and Papiliotrema. Conclusions. Different airway inflammatory phenotypes were related to specific fungal and bacterial microbiota in both asthma and COPD, while the same airway inflammatory phenotype revealed a degree of similarity in airway microbiota, particularly in fungal microbiota.

Background/purpose: Oral squamous cell carcinoma (OSCC) is one of the most lethal malignancies which accounts for approximately 90% of all malignant oral tumours. SAMMSON is a lncRNA located on chromosome 3p13–3p14 and is known to act as an oncogene in several malignancies. However, its expression and clinical significance in oral squamous cell carcinoma (OSCC) remain mostly unclear. In this study, we investigated the expression and clinical relevance of lncRNA SAMMSON in human OSCC. Materials and methods: Human OSCC cell lines (Tca8113, SCC9, SCC25, CAL27, HN12, HSU3, FADU) and a human normal oral keratinocyte cell line (HNOK) were used to detect the difference of SAMMSON expression. A total of 90 OSCC patients confirmed by pathological and clinical diagnoses at the Hospital of Stomatology, Department of Periodontology, Shandong University were enrolled. The mRNA expression level was analyzed by reverse transcription PCR (QRT-PCR). Statistical analyses including Student's t-test, chi-square method, Kaplan-Meier method, Univariate and, Multivariate Cox regression analysis were performed to analyse all data. Results: This study showed that the expression of SAMMSON was significantly increased in OSCC tissues and cell lines. High SAMMSON expression was significantly associated with TMN stage, tumour differentiation, lymph node metastasis distant metastasis and neighboring tissue infiltration. Patients with high expression of SAMMSON had poor overall survival and disease-free survival compared to those with low levels. Cox regression analysis showed that SAMMSON could act as an independent prognostic factor in OSCC. Conclusion: Serum SAMMSON expression was associated with tumour SAMMSON expression. ROC curve analysis indicated the high diagnostic sensitivity and specificity of serum SAMMSON expression in OSCC patients as compared to other traditional serum biomarker SCCA, TSGF, and CEA. These results indicated that SAMMSON might play an essential role in OSCC progression and could serve as a novel prognostic and diagnostic biomarker in OSCC.

Abstract Background Long intergenic non-coding RNA 00511 (LINC00511) is highly expressed in diverse cancers and has a correlation with poor clinical outcomes for cancer patients. In view of contradictory data among published data, we aim to evaluate the prognostic role of LINC00511 for cancer patients. Methods In the present study, a meta-analysis of related studies has been performed to investigate the prognostic significance of LINC00511 in cancer patients. Relevant studies published before December 22, 2019 were systematically searched online in PubMed, EMBASE, Web of Science, and the Cochrane Library databases. The relationship between LINC00511 expression and cancer patients’ survival, including overall survival (OS), disease-free survival (DFS)/relapse-free survival (RFS) and progression-free survival (PFS), was evaluated using pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs). The association between LINC00511 expression and clinicopathological features was assessed using odd ratios (ORs) and their corresponding 95% CIs. Results A total of 14 eligible studies with 1883 patients were enrolled in the present meta-analysis. The results demonstrated that elevated expression of LINC00511 was significantly associated with poor OS (HR = 2.62; 95% CI: 2.00–3.45; p

Rational design of multicomponent nanocrystals requires atomic-level understanding of reaction kinetics. Here, the authors apply single-particle liquid-cell electron microscopy imaging coupled with atomistic simulations to understand pathways and rates of bimetallic core-shell nanocubes undergoing oxidative dissolution.

Abstract Background Our study aims to investigate the mechanisms of lncRNA Gm12664–001 improved hepatic lipid accumulation-initiated NAFLD via regulating miR-295-5p and CAV1 in AML12 cells. Methods The animals were divided into normal control (NC) group and high fat diet (HFD) group (20 mice per group) for 8w. The steatotic liver was measured by hematoxylin eosin (HE) staining and kits. We performed systematical analyses on hepatic expression profiles of long noncoding RNAs (lncRNAs) and microRNAs in a high-fat diet (HFD)-induced steatotic animal model. The expression profile of targets was confirmed by bioinformatics analysis, luciferase assay, RT-PCR and western blot in AML12 cells. Results HFD treatment markedly observed hepatic fatty degeneration with primarily fat vacuoles, and increased TG level compared with control. According to microarray data, we found that transfection of Gm12664–001 siRNA (siRNA-118,306) obviously enhanced TG accumulation and repressed CAV1 in AML12 cells. Furthermore, the TG accumulation markedly increased by siRNA-mediated knockdown of CAV1 in AML12 cells. By bioinformatics prediction, AML12 cells were transfected of siRNA-118,306 obviously upregulated miR-295-5p. Transfection of miR-295-5p mimics significantly increased TG accumulation and obviously suppressed the target CAV1. Conclusions The results revealed that lncRNA Gm12664–001 attenuated hepatic lipid accumulation through negatively regulating miR-295-5p and enhancing CAV1 expression in AML12 cells.

Background: The role of Epstein–Barr virus (EBV) in inflammatory bowel disease (IBD) remains to be elucidated. The aim of this study was to investigate the presence of EBV in the blood and intestinal mucosa of patients with IBD and evaluate the association between EBV positivity and IBD. Methods: Patients with IBD, hospitalized between January 2015 and April 2018, were enrolled. The EBV-DNA load in blood samples from each subject was analyzed by quantitative real-time polymerase chain reaction. EBV-encoded small-RNA 1 (EBER-1) was detected by in-situ hybridization in intestinal mucosa tissue sections of patients with IBD. Result: EBV-DNA was detected in 48 out of 568 patients with IBD (8.4%), and EBER-1 positivity was detected in 27 of these patients (56.3%). Refractory IBD and severe mucosal inflammation were more common in patients with detectable levels of EBER-1 than in those without; the number of EBER-1-positive cells positively correlated with mucosal inflammation (P value < 0.05). Age (≥60 years old) and use of azathioprine were risk factors for EBV infection. There was no significant difference in clinical remission rate and surgical rate between the EBER-1 positive group and EBER-1 negative group, antiviral group and the non-antiviral group, among IBD patients who tested positive for EBV-DNA. Conclusion: Elderly patients with IBD, treated with azathioprine, are more susceptible to EBV positivity. Further, EBV mucosal detection correlated with the severity of mucosal damage and refractoriness, but not prognosis.

Valley-switching (VS) and zero-voltage switching (ZVS) improves overall efficiency in critical conduction mode (CRM) boost converters. To achieve VS/ZVS, off-time of the main switch is often extended to match the resonance period by circuit inductor and parasitic capacitors of switching components. In this article, a piecewise equivalent model for parasitic capacitors is proposed to derive analytical solutions of the resonant process, by which the numerical solutions of VS/ZVS time is calculated. To precisely achieve VS/ZVS in a boost converter, corresponding extended off-time based on the numerical solutions is implemented with an extended off-time (EOT) controller. The EOT controller makes the inductor volt-second unbalance in continuous conduction mode (CCM) operation during one switching cycle, leading to the convergence to CRM operation. The analytical and experimental results correct the results derived by conventional equivalent model for parasitic capacitors, which leads to deviated VS/ZVS boundary and wrongly calculated off-time. The proposed model and controller are verified in a non-synchronous CRM boost converter based on GaN high electron mobility transistor (HEMT) and SiC diode. With the derived extended off-time, a peak efficiency of 99.15% is achieved at output power level of 200W.

In motor drives, distortions of phase voltages and currents are often caused by nonlinear effects of inverters such as dead time, turn-on delay, turn-off delay and voltage drop of power devices. To eliminate these distortions, the dead-time compensation voltage is usually investigated. Furthermore, the relationship between the dead-time compensation voltage and phase currents is nonlinear, which is related to not only the parameters mentioned above, but also the snubber and parasitic capacitance of inverters. A nonlinear function is constructed to model the nonlinear relationship in this paper. To identify the nonlinear function, a method based on artificial neural networks is proposed without inverter parameters. According to the criterion that the trajectory of voltage vector in α-β coordinate system is a circle, an adaptive law is constructed to modify the parameters of the nonlinear function. Therefore, the nonlinear dead-time compensation voltage model is obtained accurately, where the distortions of voltages and currents are reduced without any additional hardware. Applying this method to the current predictive control, the bandwidth of a current loop is increased by 500Hz. Effectiveness of the method is verified by experiments.

JHDM1A participates in cancer development via demethylate dimethyl histone H3 lysine 36 (H3K36me2). p300 is an intrinsic acetyltransferase. This study explored the acetyltransferase activity of p300 on JHDM1A and analyzed the JHDM1A acetylation on H3K36me2 demethylation in osteosarcoma. Co-immunoprecipitation (CoIP) and immunoblotting assay found that p300 directly acetylated JHDM1A at K409 residue in osteosarcoma MG-63 and HOS cells. Nucleosomes and mononucleosomes were prepared and found that acetylation of JHDMIA disrupted its association with nucleosomes and thereby impaired its capability to induce H3K36me2 demethylation. Moreover, chromatin immunoprecipitation (ChIP) assay discovered that the input levels of H3K36me2 in the promoter regions of p21 and puma were increased after acetylation of JHDM1A, which raised the p21 and puma mRNA levels in the cells. Finally, the analysis of JHDM1A acetylation on osteosarcoma cell proliferation and invasion, along with tumor growth pointed out that acetylation of JHDMIA inhibited the proliferation and invasion of osteosarcoma HOS cells, as well as suppressed the tumor growth of osteosarcoma. In conclusion, the outcomes of our research verified that p300 could directly acetylate JHDM1A at K409 site, which reduces the demethylation of H3K36me2, enhanced the transcription of p21 and puma, and thereby inhibited the growth and metastasis of osteosarcoma.

Objective: The primary aim of this systematic review was to examine the relationship of polycyclic aromatic hydrocarbon (PAH) exposure with cardiovascular diseases (CVDs) and elaborate the current knowledge and recent advances in the area of PAH and its effects on CVDs and discuss the growing epidemiological evidence linking PAH to CVDs on the health of human populations. In this systematic review, the increased risk of cardiovascular diseases and their relationship with PAHs were discussed in detail.Methods: On 05th April 2021, a systematic literature search was conducted using PubMed/Medline and Web of Science search engines in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The search was limited to articles that were written in English and dealt with human issues. All original peer-review publications were considered for inclusion. Comments, case reports, reviews, duplicated papers, and conference reports were excluded. Data was collected from included papers by two independent reviewers.Results: Conclusively, 20 research articles published between 2005 and 2021 were chosen for the final analysis. The systemic review included 20 studies with a variety of geographical studies. The most common research category among the nominated studies were time-series studies followed by retrospective cohort, cross-sectional, quasi-experimental, panel, and case-control studies. Most of the studies were conducted in the United States, whereas others were showed in various geographical countries around the world, such as Denmark, Germany, Finland, Netherlands, France, China, Norway, Korea, Sweden, Saudi Arabia, and Belgium. Eight studies assessed the association between PAH exposure and CVDs, four articles observed this relationship with blood pressure (BP), two observed association between atherosclerotic CVD and PAH, one congenital heart disease, cardiovascular events, and two with obesity. Furthermore, in some investigations, a favorable association between PAH exposure and hypertension as well as PAH exposure and obesity was found.Conclusion: In conclusion, this systematic review examined the relationship of PAH exposure with CVDs and CVD-related risk factors by searching several digital databases. After a comprehensive literature searches and summarizing findings from 20 articles, the authors concluded that a positive relationship was observed between PAH exposure and CVD risks.

Background: The neurological manifestation of Behcet's disease (BD) is known as Neuro-Behcet's disease (NBD). The lack of a specific diagnostic method for NBD renders the diagnosis and treatment of NBD challenging.Methods and Results: We report a boy aged 11 years and 11 months who underwent right-eye intraocular lens implantation, appendectomy, perianal abscess removal, thalidomide therapy, and infliximab infusions for his Crohn disease. Magnetic resonance venography (MRV) and magnetic resonance imaging (MRI) were performed to address the onset of headache during the course of his treatment, and cerebral venous sinus thrombosis was detected. After the diagnosis of NBD, the patient was treated with anticoagulation therapy (nadroparin calcium), low-dose corticosteroids, and an immunosuppressant (cyclophosphamide), and consequently, he recovered.Conclusion: This case report shows that NBD is prone to misdiagnosis and missed diagnosis and should be diagnosed based on clinical manifestations and results from colonoscopy, pathological examination, and MRI or MRV.

The paper dealt with the thermoelastic responses of biological tissues subjected to an abrupt input of temperature load in the context of generalized thermoelasticity with three phase lag times. A modified thermoelastic model with three phase lag times was proposed to resolve the discrepancy between the three-phase-lag thermoelastic model and existing models in propagation of thermal wave. The Laplace transform and numerical inverse transform methods were applied to acquire the distributions of temperature, displacement and stresses. The effects of rate of thermal conductivity, phase lag times and rate of blood perfusion on thermoelastic behaviors were discussed specifically. The rate of thermal conductivity plays a crucial role in determining the propagation speed of thermal wave in the framework of Three-Phase-Lag (TPL) or Green-Naghdi (G-N) thermoelasticity.

Stem cell transplantation has been applied to treat spinal cord injury (SCI) in clinical trials for many years. However, the clinical efficacies of stem cell transplantation in SCI have been quite diverse. The purpose of our study was to systematically investigate the efficacy of stem cell transplantation in patients with SCI. The PubMed, Web of Science, Ovid-Medline, Cochrane Library, China National Knowledge Infrastructure, VIP, Wanfang, and SinoMed databases were searched until October 27, 2020. Quantitative and qualitative data were analyzed by Review Manager 5.3 and R. Nine studies ( n = 328) were included, and the overall risk of bias was moderate. The ASIA Impairment Scale (AIS) grading improvement rate was analyzed in favor of stem cell transplantation group [odds ratio (OR) = 6.06, 95% confidence interval (CI): 3.16–11.62, P < 0.00001]. Urodynamic indices also showed improvement in bladder function. In subgroup analyses, the results indicated that in patients with complete (AIS A) SCI, with the application of cell numbers between n *(10 7 –10 8 ), two cell types (i.e., bone marrow–derived mesenchymal stem cells and bone marrow mononuclears), and treatment time of more than 6 months, stem cell transplantation was more beneficial for sensorimotor function ( P < 0.05 for all groups). The risk of fever incidence in the stem cell transplantation group was 4.22 (95% CI: 1.7–10.22, P = 0.001), and principal component analysis (PCA) suggested it was more related to transplanted cell numbers. Thus, stem cell transplantation can promote functional recovery in SCI patients. Moreover, the type and quantity of transplanted stem cells and treatment time are important factors affecting the therapeutic effect of stem cell transplantation in SCI. Further studies are needed to evaluate the effects and elucidate the mechanisms of these factors on stem cell therapy in SCI.

The COVID-19 outbreak caused by the Severe Acute Respiratory Syndrome CoronaVirus type 2 (SARS-CoV-2) has spread across the world. However, our understanding of the public responses, in particular in adopting protective behaviors, has been limited. The current study aimed to determine the level of protective behaviors adopted by the residents in China and its association with their cultural attributes. A national cross-sectional online survey was conducted in mainland China from 4th to 13th August 2020. Protective behaviors were assessed as a summed score (ranging from 0 to 40) measured by ten items. The self-report tendency of study participants toward the four cultural attributes (individualism, egalitarianism, fatalism, hierarchy) was rated on a seven-point Likert scale. A total of 17651 respondents returned a valid questionnaire, representing 47.9% of those who accessed the online survey. Most (89.8%) respondents aged between 18 and 45 years in the age range of and 47.7% were male. High levels of protective behaviors (34.04 ± 5.78) were reported. The respondents had high scores in the cultural attributes of hierarchy (Median = 5) and egalitarianism (Median = 5), compared with low scores in individualism (Median = 1) and fatalism (Median = 1). High levels of protective behaviors were associated a higher tendency toward egalitarianism (AOR = 2.90, 95% CI 2.67–3.15) and hierarchy (AOR = 1.66, 95% CI 1.53–1.81) and a low tendency toward fatalism (AOR = 1.79, 95% CI 1.63–1.97) and individualism (AOR = 2.62, 95% CI 2.41–2.85). The cultural attributes explained 17.3% of the variations in the protective behavioral scores. In conclusion, the adoption of protective behaviors is associated a risk culture characterized by high levels of hierarchy and egalitarianism and low levels of individualism and fatalism. Government actions and communication strategies need to adapt to the cultural characteristics of their target audience.

Sepsis and acute lung injury (ALI) are linked to mitochondrial dysfunction; however, the underlying mechanism remains elusive. We previously reported that c-Jun N-terminal protein kinase 2 (JNK2) promotes stress-induced mitophagy by targeting small mitochondrial alternative reading frame (smARF) for ubiquitin-mediated proteasomal degradation, thereby preventing mitochondrial dysfunction and restraining inflammasome activation. Here we report that loss of JNK2 exacerbates lung inflammation and injury during sepsis and ALI in mice. JNK2 is downregulated in mice with endotoxic shock or ALI, concomitantly correlated inversely with disease severity. Small RNA sequencing revealed that miR-221-5p, which contains seed sequence matching to JNK2 mRNA 3’ untranslated region (3’UTR), is upregulated in response to lipopolysaccharide, with dynamically inverse correlation with JNK2 mRNA levels. miR-221-5p targets the 3’UTR of JNK2 mRNA leading to its downregulation. Accordingly, miR-221-5p exacerbates lung inflammation and injury during sepsis in mice by targeting JNK2. Importantly, in patients with pneumonia in medical intensive care unit, JNK2 mRNA levels in alveolar macrophages flow sorted from non-bronchoscopic broncholaveolar lavage (BAL) fluid were inversely correlated strongly and significantly with the percentage of neutrophils, neutrophil and white blood cell counts in BAL fluid. Our data suggest that miR-221-5p targets JNK2 and thereby aggravates lung inflammation and injury during sepsis.

The fractional derivative (FD) and memory-dependent derivative (MDD) are efficient methods to predict the transient thermal responses. In the present paper, for the first time, the FD and MDD are introduced into classical Pennes bio-heat conduction equation with single phase-lag and the corresponding bio-heat transfer models have been formulated with the aids of thermal energy conservation equation. The Laplace transform and numerical inverse transform method are adopted to get access to thermal responses due to temperature shock. Reductions of the present models to classical Pennes and single phase-lag bio-heat transfer models are presented and comparison between different FD and MDD in transient bio-heat transfer is carried out firstly. An approximate formulation of propagation speed of thermal signal in FD models is given according to results firstly. Influences of fractional derivative parameter and tempered parameter in FD, delay time in MDD, phase-lag time and rate of blood perfusion on temperature variation and distribution are carried out numerically. Both fractional derivative and memory-dependent derivative have the ability to predict thermal response between diffusion and wave behavior and CF fractional derivative and MDD with K3 may be suitable methods.

Background: Trichohepatoenteric syndrome (THES) is a rare disease that mainly causes intractable diarrhea. It is classified into THES1 and THES2, which are associated with the tetratricopeptide repeat domain 37 (TTC37) gene and Ski2-like RNA helicase (SKIV2L) gene, respectively. THES is not very prevalent in China or worldwide, but new cases have increasingly been reported.Methods and Results: Here, we report the clinical and genetic information of a 1.5-month-old girl who was admitted to our hospital due to diarrhea and failure to thrive. Whole-exome sequencing (WES) revealed novel compound-heterozygous variants of the SKIV2L gene, c.3602_3609delAGCGCCTG (p.Q1201Rfs*2), and c.1990A > G (p.T664A) as the causative factors, which were confirmed via Sanger sequencing. Upon continuous feeding with an amino-acid formula through a gastric tube and parenteral nutrition, the patient resumed thriving and her stool frequency decreased.Conclusion: We report a girl carrying novel variants of the SKIV2L gene that cause THES2, thereby providing valuable information on the diagnosis of THES2 and expanding the spectrum of disease-causing SKIV2L mutations.

This paper proposes a fully analytical loss model to reduce circling currents and improve the power efficiency of a class Φ2 inverter. Firstly, analytical expression of the switching node voltage is derived by analyzing its harmonic components. Based on the result, the power switch is modeled as a voltage source, where the circuit is simplified to a linear network and analytical expressions of branch currents are solved. Secondly, root mean square (RMS) values of branch currents and component losses are calculated to form the analytical loss model for a Φ2 inverter. The influence of circuit parameters on the circling current and power efficiency are thoroughly analyzed, which derives optimal design constraints to reduce circling currents of a class Φ2 inverter. Furthermore, detailed design guidance and equations are provided to calculate circuit parameters of a class Φ2 inverter, which reduces its circling currents and improves overall power efficiency. Finally, a class Φ2 inverter prototype is built, and experimental results demonstrate a 7% efficiency improvement compared to conventional empirical design methods.

A high-fat diet plays an important role in aggravating cancers. Palmitic acid (PA) is one of the components of saturated fatty acids; it has been reported to promote tumor proliferation in melanomas, but the signal transduction pathway mediated by palmitic acid remains unclear. This study showed that palmitic acid can promote the lung metastasis of melanomas. Moreover, the interaction between palmitic acid and toll-like receptor 4 (TLR4) was predicted by molecular docking. The experimental results proved that palmitic acid could promote the TLR4 and Toll/IL-1 receptor domain-containing adaptor-inducing IFN-β (TRIF) expression. The expression of Pellino1 (Peli1) and the phosphorylation of NF-kappa B (pNF-κB) were downregulated after the suppression of TLR4 and the silencing of Peli1 also inhibited the phosphorylation of NF-κB. Therefore, we concluded that palmitic acid promoted the lung metastasis of melanomas through the TLR4/TRIF-Peli1-pNF-κB pathway.

Addressing the shortcomings of existing low-frequency oscillation research on electrified railways, which has mainly focused on single-type trains and lacks the accurate modeling of traction inverter systems, in this paper we modeled and analyzed low-frequency oscillations in an electrified railway passenger and freight mixed-operation vehicle–grid system. First, an equivalent model of the DC side of the traction inverter was established, with the inverter system being equivalent to the parallel connection of the load resistance and the current source, and the specific mathematical expression was determined and verified by impedance measurement. Secondly, based on the equivalent model of the DC side of the traction inverter, a small signal model of the vehicle–grid system under the mixed operating conditions of CRH5 and HXD2B considering the inverter system was established. The generalized Nyqusit criterion was used to study the low-frequency oscillation characteristics under mixed transportation conditions. The accuracy of the established model and the correctness of the theoretical analysis were verified based on Matlab/Simulink. Finally, using the dominant pole theory to analyze the low-frequency stability conditions, the relationship between the number of mixed trains and the minimum short-circuit ratio was obtained, and the simulation verification was carried out.

This paper presents a triple-mode average current control (TACC) strategy to achieve unity power factor and reduce the current stress for a boost PFC converter. The controller switches among different modes in each half-line cycle, and smooth transition is ensured by mapping of the operation region. By adaptive mode shifting, it reduces the current stress and current distortion caused by non-linear effects. With valley current shaping and comparisons, the TACC controller accordingly incorporates three control laws to adapt different modes. In discontinuous conduction mode (DCM), a variable on-time is calculated while the modulation is equivalent to PWM. In critical conduction mode (CRM), a constant on-time is derived, while the switching cycle is modified to regulate the current average value. For both DCM and CRM, the switching cycle is slightly extended to realize valley switching. Furthermore, with valley current shaping, the proposed controller reuses the CRM calculation to form continuous conduction mode (CCM) control law. To make the control laws compatible, normalized mapping and design rules are provided with respect to mode boundaries. This allows the TACC controller to automatically switch among different modes. Finally, experimental results prove the effectiveness of the controller in reducing the current stress and enlarging the preferable power range.

ABSTRACT HIV-1 remains incurable due to viral reservoirs, which lead to durably latent HIV infection. Identifying novel host factors and deciphering the molecular mechanisms involved in the establishment and maintenance of latency are critical to discover new targets for the development of novel anti-HIV agents. Here, we show that ubiquitin-like with PHD and RING finger domain 1 (UHRF1) modulates HIV-1 5′-long terminal repeat (LTR)-driven transcription of the viral genome as a novel HIV-1 restriction factor. Correspondingly, UHRF1 depletion reversed the latency of HIV-1 proviruses. Mechanistically, UHRF1 competed with positive transcription factor b (p-TEFb) for the binding to the cysteine-rich motifs of HIV-1 Tat via its TTD, PHD, and RING finger domains. Furthermore, UHRF1 mediated K48-linked ubiquitination and proteasomal degradation of Tat in RING-dependent ways, leading to the disruption of Tat/cyclin T1/CDK9 complex and consequential impediment of transcription elongation. In summary, our findings revealed that UHRF1 is an important mediator of HIV-1 latency by controlling Tat-mediated transcriptional activation, providing novel insights on host-pathogen interaction for modulating HIV-1 latency, beneficial for the development of anti-AIDS therapies. IMPORTANCE HIV-1 latency is systematically modulated by host factors and viral proteins. In our work, we identified a critical role of host factor ubiquitin-like with PHD and RING finger domain 1 (UHRF1) in HIV-1 latency via the modulation of the viral protein Tat stability. By disrupting the Tat/cyclin T1/CDK9 complex, UHRF1 promotes the suppression of HIV-1 transcription and maintenance of HIV-1 latency. Our findings provide novel insights in controlling Tat expression via host-pathogen interaction for modulating HIV-1 latency. Based on our results, modulating UHRF1 expression or activity by specific inhibitors is a potential therapeutic strategy for latency reversal in HIV-1 patients.

In order to explore the clinical characteristics of pediatric patients admitted to the pediatric intensive care unit (PICU) who suffered from hematological neoplasms complicated with acute respiratory distress syndrome (ARDS), we retrospectively analyzed 45 ARDS children with hematological neoplasms who were admitted to the PICU of Shanghai Children's Medical Center from January 1, 2014, to December 31, 2020. The 45 children were divided into a survival group and a non-survival group, a pulmonary ARDS group and an exogenous pulmonary ARDS group, and an agranulocytosis group and a non-agranulocytosis group, for statistical analysis. The main clinical manifestations were fever, cough, progressive dyspnea, and hypoxemia; 55.6% (25/45) of the children had multiple organ dysfunction syndrome (MODS). The overall mortality rate was 55.6% (25/45). The vasoactive inotropic score (VIS), pediatric critical illness scoring (PCIS), average fluid volume in the first 3 days and the first 7 days, and the incidence of MODS in the non-survival group were all significantly higher than those in the survival group (P < 0.05). However, total length of mechanical ventilation and length of hospital stay and PICU days in the non-survival group were significantly lower than those in the survival group (P < 0.05). The PCIS (OR = 0.832, P = 0.004) and the average fluid volume in the first 3 days (OR = 1.092, P = 0.025) were independent risk factors for predicting death. Children with exogenous pulmonary ARDS were more likely to have MODS than pulmonary ARDS (P < 0.05). The mean values of VIS, C-reactive protein (CRP), and procalcitonin (PCT) in children with exogenous pulmonary ARDS were also higher (P < 0.05). After multivariate analysis, PCT was independently related to exogenous pulmonary ARDS. The total length of hospital stay, peak inspiratory pressure (PIP), VIS, CRP, and PCT in the agranulocytosis group were significantly higher than those in the non-agranulocytosis group (P < 0.05). Last, CRP and PIP were independently related to agranulocytosis. In conclusion, children with hematological neoplasms complicated with ARDS had a high overall mortality and poor prognosis. Children complicated with MODS, positive fluid balance, and high VIS and PCIS scores were positively correlated with mortality. In particular, PCIS score and average fluid volume in the first 3 days were independent risk factors for predicting death. Children with exogenous pulmonary ARDS and children with agranulocytosis were in a severely infected status and more critically ill.

In this experiment, a Sn35Bi0.3Ag–xIn (x = 0, 0.5, 1.0, 1.5) alloy solder was prepared by electromagnetic induction heating furnace. The effects of In on the thermodynamic properties, wettability, interface microstructure, and soldering performance of Sn35Bi0.3Ag–xIn/Cu solder joints were studied by a synchrotron thermal analyzer (DSC), contact-angle measuring instrument, scanning electron microscope (SEM), energy dispersive spectrometer (EDS), and universal tensile testing machine. The research showed that adding a small amount of In reduced the solid–liquid temperature and improved the wettability of the alloy solder. At the interface of SnBiAg–xIn/Cu joint, it was found that In atoms replaced part of Sn atoms, forming the Cu6 (Sn, In)5 phase and scallop-like Cu3 (Sn, In) phase. When adding 0.5% and 1.0% In elements, it was found that the Bi phase appeared on the solder side of the interface layer, which hindered the growth of the intermetallic compound (IMC) and reduced the thickness of the IMC layer. Among them, the thickness of the IMC layer of the SnBiAg–1.0In/Cu joint was the smallest, and the shear strength was the highest, which was 55.1 MPa. In addition, the fracture morphology of the solder joint was observed, and it was found that the fracture mode was brittle fracture, and the SnBiAg–xIn/Cu solder joint fractured from the IMC and solder side.