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Abstract Background Portal hypertension is a severe complication caused by various chronic liver diseases. The standard methods for detecting portal hypertension (hepatic venous pressure gradient and free portal pressure) are available in only a few hospitals due to their technical difficulty and invasiveness; thus, non-invasive measuring methods are needed. This study aimed to establish and assess a novel model to calculate free portal pressure based on biofluid mechanics. Result Comparison of each dog’s virtual and actual free portal pressure showed that a biofluid mechanics-based model could accurately predict free portal pressure (mean difference: -0.220, 95% CI: − 0.738 to 0.298; upper limit of agreement: 2.24, 95% CI: 1.34 to 3.14; lower limit of agreement: -2.68, 95% CI: − 3.58 to − 1.78; intraclass correlation coefficient: 0.98, 95% CI: 0.96 to 0.99; concordance correlation coefficient: 0.97, 95% CI: 0.93 to 0.99) and had a high AUC (0.984, 95% CI: 0.834 to 1.000), sensitivity (92.3, 95% CI: 64.0 to 99.8), specificity (91.7, 95% CI: 61.5 to 99.8), positive likelihood ratio (11.1, 95% CI: 1.7 to 72.8), and low negative likelihood ratio (0.08, 95% CI: 0.01 to 0.6) for detecting portal hypertension. Conclusions Our study suggests that the biofluid mechanics-based model was able to accurately predict free portal pressure and detect portal hypertension in canines. With further research and validation, this model might be applicable for calculating human portal pressure, detecting portal hypertensive patients, and evaluating disease progression and treatment efficacy.

Abstract Background China is the second highest pulmonary tuberculosis (PTB) burden country worldwide. However, retreatment of PTB has often developed resistance to at least one of the four first-line anti-TB drugs. The cure rate (approximately 50.0–73.3%) and management of retreatment of PTB in China needs to be improved. Qinbudan decoction has been widely used to treat PTB in China since the 1960s. Previously clinical studies have shown that the Qinbudan tablet (QBDT) promoted sputum-culture negative conversion and lesion absorption. However, powerful evidence from a randomized controlled clinical trial is lacking. Therefore, the aim of this study was to compare the efficacy and safety of QBDT as an adjunct therapy for retreatment of PTB. Methods We conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial in China. People diagnosed with PTB were enrolled who received previous anti-TB treatment from April 2011 to March 2013. The treatment group received an anti-TB regimen and QBDT, and the control group was administered an anti-TB regimen plus placebo. Anti-TB treatment options included isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin for 2 months (2HRZES), followed by isoniazid, rifampicin, ethambutol for 6 months (6HRE), daily for 8 months. Primary outcome was sputum-culture conversion using the MGIT 960 liquid medium method. Secondary outcomes included lung lesion absorption and cavity closure. Adverse events and reactions were observed after treatment. A structured questionnaire was used to record demographic information and clinical symptoms of all subjects. Data analysis was performed by SPSS 25.0 software in the full analysis set (FAS) population. Results One hundred eighty-one cases of retreatment PTB were randomly divided into two groups: the placebo group (88 cases) and the QBDT group (93 cases). A total of 166 patients completed the trial and 15 patients lost to follow-up. The culture conversion rate of the QBDT group and placebo group did not show a noticeable improvement by using the covariate sites to correct the rate differences (79.6% vs 69.3%; rate difference = 0.10, 95% confidence interval (CI): - 0.02–0.23; F = 2.48, P = 0.12) after treatment. A significant 16.6% increase in lesion absorption was observed in the QBDT group when compared with the placebo group (67.7% vs 51.1%; rate difference = 0.17, 95% CI: 0.02–0.31; χ 2 = 5.56, P = 0.02). The intervention and placebo group did not differ in terms of cavity closure (25.5% vs 21.1%; rate difference = 0.04, 95% CI: - 0.21–0.12; χ 2 = 0.27, P = 0.60). Two patients who received chemotherapy and combined QBDT reported pruritus/nausea and vomiting. Conclusions No significant improvement in culture conversion was observed for retreatment PTB with traditional Chinese medicine plus standard anti-TB regimen. However, QBDT as an adjunct therapy significantly promoted lesion absorption, thereby reducing lung injury due to Mycobacterium tuberculosis infection. Trial registration This trial is registered at ClinicalTrials.gov, NCT02313610 .

Abstract Background MicroRNA-612 (miR-612) has been proven to suppress EMT, stemness, and tumor metastasis of hepatocellular carcinoma (HCC) via PI3K/AKT2 and Sp1/Nanog signaling. However, its biological roles on HCC progression are far from elucidated. Methods We found direct downstream target of miR-612, hadha by RNA immunoprecipitation and sequencing. To explore its biological characteristic, potential molecular mechanism, and clinical relevance in HCC patients, we performed several in-vitro and in-vivo models, as well as human tissue chip. Results Ectopic expression of miR-612 could partially reverse the level of HADHA, then suppress function of pseudopods, and diminish metastatic and invasive potential of HCC by lipid reprogramming. In detail, miR-612 might reduce invadopodia formation via HADHA-mediated cell membrane cholesterol alteration and accompanied with the inhibition of Wnt/β-catenin regulated EMT occurrence. Our results showed that the maximum oxygen consumption rates (OCR) of HCCLM3miR-612-OE and HCCLM3 hadha-KD cells were decreased nearly by 40% and 60% of their counterparts (p 0.05) or 1/2 (p

A compact high-speed active quenching and recharging circuit (AQRC) is proposed for single-photon avalanche diode (SPAD) detectors fabricated in standard 0.18 μm CMOS technology. A novel sensing and quenching scheme is employed to speed up the process of avalanche detection, enabling a low afterpulsing probability and a high photon-counting rate. The simulation and experimental results indicate that the sensing and quenching time is reduced down to 0.7 ns and the maximum photon-counting rate is close to 200 Mcps (counts per second), meanwhile the afterpulsing probability as low as 0.75% is obtained. Due to the compact configuration, the area occupation of the AQRC is only 306 μm2. Such outstanding advantages suggest that the proposed AQRC is very suitable for the miniaturized and high-speed SPAD-array detectors.

Background: Molecular features underlining the multistage progression of gastric lesions and development of early gastric cancer (GC) are poorly understood, restricting the ability to GC prevention and management. Methods: We portrayed proteomic landscape and explored proteomic signatures associated with progression of gastric lesions and risk of early GC. Tissue proteomic profiling was conducted for a total of 324 subjects. A case-control study was performed in the discovery stage (n=169) based on populations from Linqu, a known high-risk area for GC in China. We then conducted two-stage validation, including a cohort study from Linqu (n = 56), with prospective follow-up for progression of gastric lesions (280–473 days), and an independent case-control study from Beijing (n = 99). Findings: There was a clear distinction in proteomic features for precancerous gastric lesions and GC. We derived four molecular subtypes of gastric lesions and identified subtype-S4 with the highest progression risk. We found 104 positively-associated and 113 inversely-associated proteins for early GC, with APOA1BP, PGC, HPX and DDT associated with the risk of gastric lesion progression. Integrating these proteomic signatures, the ability to predict progression of gastric lesions was significantly strengthened (areas-under-the-curve=0.88 (95%CI: 0.78–0.99) vs. 0.56 (0.36–0.76), Delong's P = 0.002). Immunohistochemistry assays and examination at mRNA level validated the findings for four proteins. Interpretation: We defined proteomic signatures for progression of gastric lesions and risk of early GC, which may have translational significance for identifying particularly high-risk population and detecting GC at an early stage, improving potential for targeted GC prevention. Funding: The funders are listed in the Acknowledgement.

The structural design and operating strategy of a free piston expander–linear generator (FPE–LG) has a major impact on performance. In this paper, the simulation model of single–piston FPE–LG was built and verified by combining the structural parameters of the existing test rig with a set of kinetic and thermodynamic equations. On this basis, the influence of the design and operating parameters of the device on the performance was studied, while keeping other parameters fixed. Then, a sensitivity analysis of power output and operating frequency was carried out. The results show that within a certain range of external load and intake beginning position, increasing the diameter of the intake and exhaust pipes, or reducing the piston rod diameter can improve the power output. Within a certain range of frictional coefficient and intake time, increasing the cylinder diameter and intake pressure, or reducing the piston assembly mass and back electromotive force (EMF) constant can increase the operating frequency. Both the power output and the operating frequency are most sensitive to the cylinder diameter among the design parameters. Among the operating parameters, power output is the most sensitive to intake pressure, and operating frequency is the most sensitive to intake beginning position. The optimization of structural design and operation strategy in expander provides important guiding significance for ORC waste heat recovery system.

Urotensin II (UII) could increase blood pressure and heart rate via increased central reactive oxygen species (ROS) levels. We reported previously that hydrogen sulfide (H2S) exerts an antihypertensive effect by suppressing ROS production. The aim of the current study is to further examine the effects of endogenous and exogenous H2S on UII-induced cardiovascular effects by using an integrated physiology approach. We also use cell culture and molecular biological techniques to explore the inhibitory role of H2S on UII-induced cardiovascular effects. In this study, we found that cystathionine-β-synthase (CBS), the main H2S synthesizing enzyme in CNS, was expressed in neuronal cells of the rostral ventrolateral medulla (RVLM) area. Cellular distribution of CBS and urotensin II receptor (UT) in SH-SY5Y cells that are confirmed as glutamatergic were identified by immunofluorescent and Western blots assay. In Sprague–Dawley rats, administration of UII into the RVLM resulted in an increase in mean arterial pressure (MAP), heart rate (HR), ROS production, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and phosphorylation of p47phox, extracellular signal-regulated protein kinase (ERK)1/2 and p38MAPK, but not stress-activated protein kinase/Jun N-terminal kinase (SAPK/JNK). These effects of UII were attenuated by application into the RVLM of endogenous (L-cysteine, SAM) or exogenous (NaHS) H2S. These results were confirmed in SH-SY5Y cells. UII-induced cardiovascular effects were also significantly abolished by pretreatment with microinjection of Tempol, Apocynin, SB203580, or PD98059 into the RVLM. Preincubated SH-SY5Y cells with Apocynin before administration of UII followed by Western blots assay showed that ROS is in the upstream of p38MAPK/ERK1/2. Gao activation assay in SH-SY5Y cells suggested that H2S may exert an inhibitory role on UII-induced cardiovascular effects by inhibiting the activity of Gαo. These results suggest that both endogenous and exogenous H2S attenuate UII-induced cardiovascular effects via Gαo-ROS-p38MAPK/ERK1/2 pathway.

Chemical energy conversion strategies by photocatalysis and electrocatalysis are promising approaches to alleviating our energy shortages and environmental issues. Due to the 2D layer structure, adjustable composition, unique thermal decomposition and memory properties, abundant surface hydroxyl, and low cost, layered double hydroxides (LDHs) have attracted extensive attention in electrocatalysis, photocatalysis, and photoelectrocatalysis. This review summarizes the main structural characteristics of LDHs, including tunable composition, thermal decomposition and memory properties, delaminated layer, and surface hydroxyl. Next, the influences of the structural characteristics on the photo(electro)catalytic process are briefly introduced to understand the structure–performance correlations of LDHs materials. Recent progress and advances of LDHs in photocatalysis and photoelectrocatalysis applications are summarized. Finally, the challenges and future development of LDHs are prospected from the aspect of structural design and exploring structure-activity relationships in the photo(electro)catalysis applications.

Using a controlled optical bias and balanced geometry, we propose a new scheme for broadband terahertz detection by laser-gas interaction without high-voltage manipulation. Compared to the conventional optical bias scheme, the common noise is reduced and the dynamic range as well as the signal-to-noise ratio are doubled. It provides a simple alternative for coherent broadband terahertz detection. The influence of optical bias on terahertz waveform is also investigated, and the evolution of the terahertz-induced second harmonic with probe delay is further revealed. This new detection scheme for broadband terahertz will boost the application of terahertz time-domain spectroscopy for its miniaturization and integrability.

The brain has evolved in an environment where food sources are scarce, and foraging for food is one of the major challenges for survival of the individual and species. Basic and clinical studies show that obesity or overnutrition leads to overwhelming changes in the brain in animals and humans. However, the exact mechanisms underlying the consequences of excessive energy intake are not well understood. Neurons expressing the neuropeptide hypocretin/orexin (Hcrt) in the lateral/ perifonical hypothalamus (LH) are critical for homeostatic regulation, reward seeking, stress response, and cognitive functions. In this study, we examined adaptations in Hcrt cells regulating behavioral responses to salient stimuli in diet-induced obese mice. Our results demonstrated changes in primary cilia, synaptic transmission and plasticity, cellular responses to neurotransmitters necessary for reward seeking, and stress responses in Hcrt neurons from obese mice. Activities of neuronal networks in the LH and hippocampus were impaired as a result of decreased hypocretinergic function. The weakened Hcrt system decreased reward seeking while altering responses to acute stress (stress-coping strategy), which were reversed by selectively activating Hcrt cells with chemogenetics. Taken together, our data suggest that a deficiency in Hcrt signaling may be a common cause of behavioral changes (such as lowered arousal, weakened reward seeking, and altered stress response) in obese animals., Introduction The maintenance of energy balance is critical to survival. The brain has evolved to regulate energy intake and expenditure in vertebrate animals, supporting complex behaviors for seeking, securing, consuming, [...]

The pathogenesis of Alzheimer's disease is complex, and early-onset Alzheimer's disease (EOAD) is mostly influenced by genetic factors. Presenilin-1, presenilin-2 (PSEN2), and amyloid precursor protein are currently known as the three main causative genes for autosomal dominant EOAD, with the PSEN2 mutation being the rarest. In this study, we reported a 56-year-old Chinese Han proband who presented with prominent progressive amnesia, aphasia, executive function impairment, and depression 5 years ago. The 3-year follow-up showed that the patient experienced progressive brain atrophy displayed on magnetic resonance imaging (MRI) and dramatic cognitive decline assessed by neuropsychological evaluation. This patient was clinically diagnosed as EOAD based on established criteria. A heterozygous variant (NM_000447.2: c.1106T>C) of PSEN2 was identified for the first time in this patient and her two daughters. This mutation causing a novel missense mutation (p.Phe369Ser) in transmembrane domain 7 encoded by exon 11 had not been reported previously in 1000Genomes, ExAC, or ClinVar databases. This mutation was predicted by four in silico prediction programs, which all strongly suggested that it was damaging. Our results suggest that this novel PSEN2 Phe369Ser mutation may alter PSEN2 protein function and associate with EOAD.

Pentraxin 3 (PTX3), a potential biomarker of the severity and mortality of COVID-19 patients, is aberrantly expressed in human tumors. However, a comprehensive pan-cancer analysis of PTX3 remains to be elucidated. PTX3 data profiles and clinical information in TCGA cancers were obtained from different public databases to clarify the expression levels, genetic alterations, prognostic significance, underlying mechanisms, and the predicted role in immunotherapy of PTX3 across TCGA cancers. Our analyses showed that PTX3 was aberrantly expressed in most tumors and was significantly related to prognosis and tumor stage. Interaction network and enrichment analyses revealed that PTX3 participated in tumor immuno-related progression. In addition, PTX3 levels were critically associated with immune cell components and immune scores, and PTX3 strongly coexpressed with immune-related genes in TCGA cancers. Meanwhile, PTX3 expression was associated with immune checkpoint genes, and immunotherapy potential biomarkers in multiple cancers, predicting special immunotherapy responses in different tumor types. In kidney renal clear cell carcinoma (KIRC), PTX3 emerged as an independent prognostic factor through multivariable Cox regression analyses. Blocking PTX3 with siRNA could suppress the growth of KIRC cells and invasion. Conclusively, our study shows a comprehensive bioinformatic analysis of PTX3, which might serve as a pan-cancer prognostic biomarker.

The World Health Organization announced that COVID-19, with SARS-CoV-2 as its pathogen, had become a pandemic on 11 March 2020. Today, the global epidemic situation is still serious. With the development of research, cardiovascular injury in patients with COVID-19, such as arrhythmia, myocardial injury, and heart failure, is the second major symptom in addition to respiratory symptoms, and cardiovascular injury is related to the prognosis and mortality of patients. The incidence of arrhythmia in COVID-19 patients ranges from 10% to 20%. The potential mechanisms include viral infection-induced angiotensin-converting enzyme 2 expression change, myocarditis, cytokine storm, cardiac injury, electrophysiological effects, hypoxemia, myocardial strain, electrolyte abnormalities, intravascular volume imbalance, drug toxicities and interactions, and stress response caused by virus infection. COVID-19 complicated with arrhythmia needs to be accounted for and integrated in management. This article reviews the incidence, potential mechanisms, and related management measures of arrhythmia in COVID-19 patients.

The aim of this study was to obtain accurate angular positions and velocities from resolver signals; resolver-to-digital conversion (RDC) often adopts a phase-locked loop (PLL) as a demodulation algorithm. However, resolver signals often come with quadrature errors and harmonics, which lead to a severe reduction in PLL accuracy. The conventional PLL does not consider the impact of the quadrature error, and the bandwidth of the PLL is much larger than the fundamental frequency of resolver signals for pursuing a low dynamic error. These reasons render the retention of resolver harmonics in the demodulation results. In this paper, a disturbance-compensated PLL (DC-PLL) is proposed, which consists of a phase detector for suppressing quadrature error and harmonics (SQEH-PD) and a second-order observer. Firstly, since the quadrature error does not change with the angle velocity, the pre-estimated quadrature error is used in the SQEH-PD to compensate for the quadrature error in resolver signals. Secondly, although the frequency of the harmonics changes with the velocity, the amplitudes of the harmonics do not change. Therefore, the pre-estimated amplitudes of harmonics and estimated angular position are used in the SQEH-PD to compensate for the harmonics in resolver signals. Thirdly, a second-order observer is designed to estimate the angular position and velocity by regulating the phase detector error. Compared with the conventional PLL, the proposed DC-PLL has a stronger anti-disturbance ability against the quadrature error and harmonics by configurating the phase detector error and the estimated position error, which have a linear relation. Simulation and experimental results prove the effectiveness of the proposed method.

Inhomogeneous structures with carbon nanotubes (CNTs), reinforced with Cu composite foams as the reinforcing skeletons (CNTs/Cuf®Cu), have been designed to overcome the paradox between strength and ductility or conductivity in copper matrix composites. The interface between CNTs and the copper matrix is usually weak, due to poor wettability and interaction. In this study, nickel nanoparticles are decorated onto CNTs to improve interfacial bonding. The broader interface transition area between CNTs and copper with Ni3C interfacial products formed, and a combination of improved electrical conductivity (95.6% IACS), tensile strength (364.9 MPa), and elongation (40.6%) was achieved for the Ni-decorated CNTs/Cuf®Cu (Ni-CNTs/Cuf®Cu). In addition, the strengthening mechanisms are discussed in this study.

Thyroid cancer is the most common type of endocrine malignancy. Although the general prognosis is good, the treatment of advanced disease is still challenging. Exosomes are vesicle units containing specific components that transmit information between cells. In order to explore its role in papillary thyroid cancer (PTC), our study screened exosome enriched lncRNA SNHG9 by lncRNA chip and explored its biological function. We used lncRNA chips combined with bioinformatics analysis to screen lncRNA SNHG9 enriched in exosomes. GO analysis suggested its relationship with autophagy and apoptosis. Quantitative PCR showed SNHG9 was highly expressed in PTC cells and exosomes and its correlation with PTC tumor size was analyzed by clinical characteristics. SNHG9 could inhibit the protective cell autophagy induced by starvation of human normal thyroid epithelial cell line Nthy-ori-3 and promote its apoptosis through PTC cell exosomes. RNA-pull down combined with protein spectrum showed that SNHG9 could interact with YBOX3. Western blot and RNA immunoprecipitation further confirmed their interaction. Western blot showed that SNHG9 could induce degradation of YBOX3, thus interfering with the stability of P21 mRNA and inducing cell apoptosis. In conclusion, our study identified SNHG9 as a PTC cell exosome-enriched lncRNA. SNHG9 could inhibit cell autophagy and promote apoptosis of Nthy-ori-3 cell through YBOX3/P21 pathway.

Right heart thrombus accompanied by chronic thromboembolic pulmonary hypertension is a rare entity. Right heart thrombus may develop in the peripheral veins or in situ within the right heart chambers. The diagnosis of right heart thrombus is challenging, since its symptoms are typically non-specific and its imaging features resemble those of cardiac masses. Here, we report two cases of right heart thrombus with chronic thromboembolic pulmonary hypertension that presented as right ventricular masses initially. Both patients underwent simultaneous pulmonary endarterectomy and resection of the ventricular thrombi. Thus, when mass-like features are confirmed by imaging, right heart thrombus should be suspected in patients with chronic thromboembolic pulmonary hypertension, and simultaneous right heart thrombus resection is required along with pulmonary endarterectomy.

An amendment to this paper has been published and can be accessed via the original article.