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Abstract Background The outbreak of COVID-19 has resulted in serious concerns in China and abroad. To investigate clinical features of confirmed and suspected patients with COVID-19 in west China, and to examine differences between severe versus non-severe patients. Methods Patients admitted for COVID-19 between January 21 and February 11 from fifteen hospitals in Sichuan Province, China were included. Experienced clinicians trained with methods abstracted data from medical records using pre-defined, pilot-tested forms. Clinical characteristics between severe and non-severe patients were compared. Results Of the 169 patients included, 147 were laboratory-confirmed, 22 were suspected. For confirmed cases, the most common symptoms from onset to admission were cough (70·7%), fever (70·5%) and sputum (33·3%), and the most common chest CT patterns were patchy or stripes shadowing (78·0%); throughout the course of disease, 19·0% had no fever, and 12·4% had no radiologic abnormality; twelve (8·2%) received mechanical ventilation, four (2·7%) were transferred to ICU, and no death occurred. Compared to non-severe cases, severe ones were more likely to have underlying comorbidities (62·5% vs 26·2%, P = 0·001), to present with cough (92·0% vs 66·4%, P = 0·02), sputum (60·0% vs 27·9%, P = 0·004) and shortness of breath (40·0% vs 8·2%, P

Two novel 1,3,5-trisubstituted pyrazoline derivatives—1-acetyl-3-(4-methoxyphenyl)-5-(6-methoxy-2-naphthyl)-pyrazoline (2a) and 1-(4-nitrophenyl)-3-(4-methoxyphenyl)-5-(6-methoxy-2-naphtyl)-pyrazoline (2b)—were synthesized and their structures were determined by single crystal X-ray crystallography. Both of the two crystals exhibit twisted structures due to the large dihedral angles between the pyrazolinyl ring and the aromatic ring at the 5-position (88.09° for 2a and 71.26° for 2b). The optical⁻physical properties of the two compounds were investigated. The fluorescent emission of 2b arises from the 1,3-disubstituted pyrazoline chromophores and exhibits a red shift in polar solvents and solid-state, which could be attributed to photo-induced intramolecular charge transfer (ICT) from N1 to C3 in the pyrazoline moiety and the intermolecular interactions within the crystal. The fluorescent emissions of 2a (λmax 358⁻364 nm) in solvents and solid-state both come from 6-methoxy-2-naphthyl chromophores, which are fairly insensitive to the solvent polarity.

Cocrystal formation is a strategy used to modify the solid-state properties of a given molecule. In this study, a new cocrystal assembled by 1,4-Diiodotetrafluorobenzene (1,4-DITFB) and a pyrene derivative, 1-acetyl-3-phenyl-5-(1-pyrenyl)-pyrazoline (APPP), was synthesized. Due to the twisted structure of APPP, the crystal structure is greatly different with some large π-conjugated compounds, which exhibits edge-to-face π-stacked arrangement between 1,4-DITFB and pyrene rings, rather than the face-to-face π-stacked arrangement. Hirshfeld surface analysis and the shift of characteristic vibration band of the carbonyl group in FT-IR spectroscopy suggest the formation of a C=O···I halogen bond.

Astrocytes, characterized by complex spongiform morphology, participate in various physiological processes, and abnormal changes in their calcium (Ca2+) signaling are implicated in central nervous system disorders. However, medications targeting the control of Ca2+ have fallen short of the anticipated therapeutic outcomes in clinical applications. This underscores the fact that our comprehension of this intricate regulation of calcium ions remains considerably incomplete. In recent years, with the advancement of Ca2+ labeling, imaging, and analysis techniques, Ca2+ signals have been found to exhibit high specificity at different spatial locations within the intricate structure of astrocytes. This has ushered the study of Ca2+ signaling in astrocytes into a new phase, leading to several groundbreaking research achievements. Despite this, the comprehensive understanding of astrocytic Ca2+ signaling and their implications remains challenging area for future research.

Abstract Background Although microvascular dysfunction is a widespread phenomenon in type 2 diabetes (T2D) and is recognized as a main cause of T2D-aggravated ischemic stroke injury, the underlying mechanisms by which T2D-mediated exacerbation of cerebral damage after ischemic stroke is still largely uncharacterized. Here, we found that methylglyoxal-mediated miR-148a-3p decline can trigger blood-brain barrier dysfunction, thereby exacerbating cerebrovascular injury in diabetic stroke. Methods Using T2D models generated with streptozotocin plus a high-fat diet or db/db mice, and then inducing focal ischemic stroke through middle cerebral artery occlusion and reperfusion (MCAO/R), we established a diabetic stroke mouse model. RNA-sequencing was applied to identify the differentially expressed miRNAs in peri-cerebral infarction of diabetic stroke mice. RT-qPCR confirmed the potential miRNA in the plasma of ischemic stroke patients with or without T2D. Fluorescence in situ hybridization was used to image the localization of the miRNA. Brain pathology was analyzed using magnetic resonance imaging, laser-Doppler flowmetry, and transmission electron microscope in diabetic stroke mice. Immunofluorescence and immunoblotting were performed to elucidate the molecular mechanisms. Results miR-148a-3p level was downregulated in the peri-infarct cortex of stroke mice and this downregulation was even more enhanced in diabetic stroke mice. A similar decrease in miR-148a-3p expression was also confirmed in the plasma of ischemic stroke patients with T2D compared to patients with ischemic stroke only. This miR-148a-3p downregulation intensified the severity of BBB damage, infarct size, and neurological function impairment caused by stroke. Notably, the reduction in miR-148a-3p levels was primarily triggered by methylglyoxal, a toxic byproduct of glucose metabolism commonly associated with T2D. Furthermore, methylglyoxal somewhat replicated the influence of T2D in exacerbating BBB damage and increasing infarct size caused by ischemia. Mechanistically, we found that downregulation of miR-148a-3p de-repressed SMAD2 and activated matrix metalloproteinase 9 signaling pathway, promoting blood-brain barrier impairment, and exacerbating the cerebral ischemic injury. Conclusions Blood-brain barrier damage caused by methylglyoxal-mediated miR-148a-3p downregulation may provide a novel target for the therapeutic intervention for the treatment of stroke patients with diabetes.

Background: This study aimed to investigate the value of miR-671-5p in multiple myeloma (MM) in diagnostics and prognosis and developed a potential biomarker to improve the prognosis of MM. Methods: Plasma cells were isolated from bone marrow samples of 80 MM patients, in which miR-671-5p levels were determined. The correlation between miR-671-5p expression with serum creatinine, β-2-microglobulin, lactate dehydrogenase, bone lesions, International Staging System staging, chromosomal abnormalities, and albumin was analyzed. The association between miR-671-5p expression with progression-free survival and overall survival in MM patients was determined. Results: miR-671-5p expression was reduced and predicted an increased risk of MM. miR-671-5p expression was negatively correlated with serum creatinine, β-2-microglobulin, lactate dehydrogenase, bone lesions, International Staging System staging, and chromosomal abnormalities, and positively correlated with albumin. miR-671-5p expression was augmented in complete response patients and overall response rate patients, and differentiated CR and ORR patients from Non-CR and Non-ORR patients. Furthermore, miR-671-5p low expression was associated with unfavorable progression-free survival and overall survival in MM patients. Conclusions: In a word, miR-671-5p is associated with worsening clinical properties, increased ISS staging, unfavorable chromosomal abnormalities, and poor prognosis in MM patients. [ABSTRACT FROM AUTHOR]

Abstract A high efficiency simulation method for propagation-based phase-contrast imaging, called directional macro-wavefront (DMWF), is developed with the aim of simulating high-energy phase-contrast imaging. This method takes both Monte Carlo and wave optical propagation into consideration. Traditional wave-optics-based simulation methods for phase-contrast imaging encounter unacceptable computational complexity when high-energy radiation is used. In contrast, this method effectively addresses this issue by using macro-wavefront integration. Several simulation examples using typical parameters of inverse Compton scattering sources are presented to illustrate the excellent energy adaptability and efficiency of the DMWF method. This method provides a more efficient approach for phase-contrast imaging simulations, which will drive the advancement of high-energy phase-contrast imaging.

Abstract Deep learning models have been developed for various predictions in glioma; yet, they were constrained by manual segmentation, task-specific design, or a lack of biological interpretation. Herein, we aimed to develop an end-to-end multi-task deep learning (MDL) pipeline that can simultaneously predict molecular alterations and histological grade (auxiliary tasks), as well as prognosis (primary task) in gliomas. Further, we aimed to provide the biological mechanisms underlying the model’s predictions. We collected multiscale data including baseline MRI images from 2776 glioma patients across two private (FAHZU and HPPH, n = 1931) and three public datasets (TCGA, n = 213; UCSF, n = 410; and EGD, n = 222). We trained and internally validated the MDL model using our private datasets, and externally validated it using the three public datasets. We used the model-predicted deep prognosis score (DPS) to stratify patients into low-DPS and high-DPS subtypes. Additionally, a radio-multiomics analysis was conducted to elucidate the biological basis of the DPS. In the external validation cohorts, the MDL model achieved average areas under the curve of 0.892–0.903, 0.710–0.894, and 0.850–0.879 for predicting IDH mutation status, 1p/19q co-deletion status, and tumor grade, respectively. Moreover, the MDL model yielded a C-index of 0.723 in the TCGA and 0.671 in the UCSF for the prediction of overall survival. The DPS exhibits significant correlations with activated oncogenic pathways, immune infiltration patterns, specific protein expression, DNA methylation, tumor mutation burden, and tumor-stroma ratio. Accordingly, our work presents an accurate and biologically meaningful tool for predicting molecular subtypes, tumor grade, and survival outcomes in gliomas, which provides personalized clinical decision-making in a global and non-invasive manner.

Abstract Astrocytic processes minutely regulate neuronal activity via tripartite synaptic structures. The precision‐tuning of the function of astrocytic processes is garnering increasing attention because of its significance in promoting brain repair following ischemic stroke. Microdomain calcium (Ca2+) transients in astrocytic processes are pivotal for the functional regulation of these processes. However, the understanding of the alterations and regulatory mechanism of microdomain Ca2+ transients during stroke remains limited. In the present study, a fast high‐resolution, miniaturized two‐photon microscopy is used to show that the levels of astrocytic microdomain Ca2+ transients are significantly reduced in the peri‐infarct area of awake ischemic stroke mice. This finding correlated with the behavioral deficits shown by these mice under freely‐moving conditions. Mitochondrial Ca2+ activity is an important factor driving the microdomain Ca2+ transients. DEAD Box 1 (DDX1) bound to circSCMH1 (a circular RNA involved in vascular post‐stroke repair) facilitates the formation of membrane‐associated RNA‐containing vesicles (MARVs) and enhances the activity of astrocytic microdomain Ca2+ transients, thereby promoting behavioral recovery. These results show that targeting astrocytic microdomain Ca2+ transients is a potential therapeutic approach in stroke intervention.

Abstract Molecular pathways mediating systemic inflammation entering the brain parenchyma to induce sepsis-associated encephalopathy (SAE) remain elusive. Here, we report that in mice during the first 6 hours of peripheral lipopolysaccharide (LPS)-evoked systemic inflammation (6 hpi), the plasma level of adenosine quickly increased and enhanced the tone of central extracellular adenosine which then provoked neuroinflammation by triggering early astrocyte reactivity. Specific ablation of astrocytic Gi protein-coupled A1 adenosine receptors (A1ARs) prevented this early reactivity and reduced the levels of inflammatory factors (e.g., CCL2, CCL5, and CXCL1) in astrocytes, thereby alleviating microglial reaction, ameliorating blood-brain barrier disruption, peripheral immune cell infiltration, neuronal dysfunction, and depression-like behaviour in the mice. Chemogenetic stimulation of Gi signaling in A1AR-deficent astrocytes at 2 and 4 hpi of LPS injection could restore neuroinflammation and depression-like behaviour, highlighting astrocytes rather than microglia as early drivers of neuroinflammation. Our results identify early astrocyte reactivity towards peripheral and central levels of adenosine as an important pathway driving SAE and highlight the potential of targeting A1ARs for therapeutic intervention.

Abstract Immunotherapy, particularly immune checkpoint inhibitors (ICIs), such as anti-programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) therapy, has emerged as a pivotal treatment modality for solid tumors, including recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). Despite the advancements in the utilization of ICIs, there is still room for further improving patient outcomes. Another promising approach to immunotherapy for R/M-NPC involves adoptive cell therapy (ACT), which aims to stimulate systemic anti-tumor immunity. However, individual agent therapies targeting dendritic cells (DCs) appear to still be in the clinical trial phase. This current review underscores the potential of immunotherapy as a valuable adjunct to the treatment paradigm for R/M-NPC patients. Further research is warranted to enhance the efficacy of immunotherapy through the implementation of strategies such as combination therapies and overcoming immune suppression. Additionally, the development of a biomarker-based scoring system is essential for identifying suitable candidates for precision immunotherapy.

ObjectiveTo develop a guideline for selecting biomarkers in the diagnosis and assessment in patients with axial spondyloarthritis (axSpA).MethodA joint effort was carried out by the core team, the literature review team and the multidisciplinary voting panel to formulate recommendations regarding biomarkers in axSpA, using an evidence-based and consensus-based strategy. Certainty of evidence and strength of recommendation were determined, and levels of agreement within the voting panel were calculated.ResultsA total of 20 recommendations were formulated in this guideline, with levels of agreement ranging from 6.48 to 9.71. The two strong recommendations, HLA-B27 testing in patients suspected of axSpA and regular-interval monitoring of CRP/ESR represent the status quo of axSpA evaluation, while the 13 conditional recommendations represent the promising biomarkers with clinical utility in diagnosis, disease activity assessment, prediction of radiographic progression and therapeutic responses. This guideline does not dictate clinical choices of tests on axSpA, and decisions should be made based on comprehensive consideration of costs, accessibility, patients’ values and willingness as well as the objective of testing in the local context.ConclusionThis guideline addresses the interpretation of the clinical significance of biomarkers in axSpA, and the biomarkers endorsed in this guideline composed a clinical toolkit for healthcare professionals to choose from.

Abstract Genomics allows the tracing of origin and evolution of cancer at molecular scale and underpin modern cancer diagnosis and treatment systems. Yet, molecular biomarker‐guided clinical decision‐making encounters major challenges in the realm of individualized medicine, consisting of the invasiveness of procedures and the sampling errors due to high tumor heterogeneity. By contrast, medical imaging enables noninvasive and global characterization of tumors at a low cost. In recent years, radiomics has overcomes the limitations of human visual evaluation by high‐throughput quantitative analysis, enabling the comprehensive utilization of the vast amount of information underlying radiological images. The cross‐scale integration of radiomics and genomics (hereafter radiogenomics) has the enormous potential to enhance cancer decoding and act as a catalyst for digital precision medicine. Herein, we provide a comprehensive overview of the current framework and potential clinical applications of radiogenomics in patient care. We also highlight recent research advances to illustrate how radiogenomics can address common clinical problems in solid tumors such as breast cancer, lung cancer, and glioma. Finally, we analyze existing literature to outline challenges and propose solutions, while also identifying future research pathways. We believe that the perspectives shared in this survey will provide a valuable guide for researchers in the realm of radiogenomics aiming to advance precision oncology.

Abstract Systemic lupus erythematosus (SLE) is characterized by disruptions in cell death pathways and impaired clearance of apoptotic cells, resulting in immune dysregulation and tissue damage. This review explores the complex interplay of regulated cell death (RCD) mechanisms, including apoptosis, necroptosis, pyroptosis, NETosis, autophagy, and ferroptosis, in the pathogenesis of SLE. These pathways release autoantigens and danger signals, triggering autoimmune reactions and inflammation. Six various RCDs have mutual associates to support immune dysregulation and are associated with SLE. Apoptosis intrinsically induces immune tolerance by packaging dying cells into immunologically inert fragments. Deficiencies in apoptotic clearance will result in impaired tolerance. Necroptosis, pyroptosis, NETosis, and ferroptosis lead to cell membrane destruction, production of intracellular immunostimulatory components, and triggering a strong inflammatory immune reaction. Abnormal autophagic activity affects the development, differentiation, function, and metabolism of many immune cell subpopulations. Investigating the interconnections between cell death pathways and SLE sheds light on the disease's underlying mechanisms and provides opportunities for novel therapeutic interventions. The convergence of precision medicine and innovative strategies targeting these intricate pathways holds promise for expanding the landscape of SLE treatment.

Abstract Acute lung injury (ALI) is one of the life-threatening complications of sepsis, and macrophage polarization plays a crucial role in the sepsis-associated ALI. However, the regulatory mechanisms of macrophage polarization in ALI and in the development of inflammation are largely unknown. In this study, we demonstrated that macrophage polarization occurs in sepsis-associated ALI and is accompanied by mitochondrial dysfunction and inflammation, and a decrease of PRDX3 promotes the initiation of macrophage polarization and mitochondrial dysfunction. Mechanistically, PRDX3 overexpression promotes M1 macrophages to differentiate into M2 macrophages, and enhances mitochondrial functional recovery after injury by reducing the level of glycolysis and increasing TCA cycle activity. In conclusion, we identified PRDX3 as a critical hub integrating oxidative stress, inflammation, and metabolic reprogramming in macrophage polarization. The findings illustrate an adaptive mechanism underlying the link between macrophage polarization and sepsis-associated ALI.

While autonomous vehicles are vital components of intelligent transportation systems, ensuring the trustworthiness of decision-making remains a substantial challenge in realizing autonomous driving. Therefore, we present a novel robust reinforcement learning approach with safety guarantees to attain trustworthy decision-making for autonomous vehicles. The proposed technique ensures decision trustworthiness in terms of policy robustness and collision safety. Specifically, an adversary model is learned online to simulate the worst-case uncertainty by approximating the optimal adversarial perturbations on the observed states and environmental dynamics. In addition, an adversarial robust actor-critic algorithm is developed to enable the agent to learn robust policies against perturbations in observations and dynamics. Moreover, we devise a safety mask to guarantee the collision safety of the autonomous driving agent during both the training and testing processes using an interpretable knowledge model known as the Responsibility-Sensitive Safety Model. Finally, the proposed approach is evaluated through both simulations and experiments. These results indicate that the autonomous driving agent can make trustworthy decisions and drastically reduce the number of collisions through robust safety policies.

Reactive arthritis(ReA), a form of arthritis occurring post-infection, manifests with antecedent infection symptoms, arthritis, and extra-articular manifestations, categorizing it as spondyloarthritis. “Keratoderma blennorrhagicum” (characterized by pustular hyperkeratosis on palms and soles, resembling pustular psoriasis) represents the most typical skin manifestation of ReA, occurring in acute or chronic phases. Severe lesions necessitate systemic disease modifying anti-rheumatic drugs (DMARDs) or biologic therapies. This article reports a case of ReA with sacroiliitis and widespread pustular eruptions following a urinary tract infection. Treatment with sulfasalazine and thalidomide significantly improved sacroiliitis, but the skin rash remained persistent and recurring. Subsequent use of adalimumab and secukinumab resulted in worsening skin rash, prompting a switch to tofacitinib, leading to a remarkable improvement in pustular eruptions after 20 days of treatment. This case demonstrates successful application of tofacitinib in treating severe keratoderma blennorrhagicum refractory to conventional DMARDs and biologics, offering insights into JAK inhibition for challenging rheumatic diseases with skin involvement.

Summary: Here, we present a protocol for 3D printing heart tissues using thiol-norbornene photoclick collagen (NorCol). We describe steps for synthesizing NorCol, preparing bioink and the support bath, and cell-laden printing. We then detail procedures for the loading of C2C12 cells into NorCol, ensuring structural integrity and cell viability after printing. This protocol is adaptable to various cell lines and allows for the printing of diverse complex structures, which can be used in drug screening and disease modeling. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Background Optimal medical therapy (OMT) for uncomplicated type B aortic dissection (uTBAD) provides excellent short-term outcomes during follow up; however, its long-term therapeutic effectiveness is unsatisfactory. This study evaluated the predictive value of systemic immune-inflammation index (SII) for adverse events among patients with acute uTBAD undergoing OMT. Methods We performed a retrospective analysis of a prospectively maintained database between 2013 and 2020. The primary end point in this study was composite outcomes including aortic intervention, all-cause mortality, retrograde type A aortic dissection (rTAAD) and aortic diameter growth > 5 mm. The patients were divided into high and low SII groups according to the optimal cut-off value of SII as determined using the receiver operating characteristic curve. Cox proportional hazards models were constructed to estimate the hazards ratios and identify the predictors of composite outcomes. Results A total of 124 patients with acute uTBAD who underwent OMT were enrolled. One patient died during hospitalisation. At the end of a mean follow-up duration of 51 ± 23 months, 53 (43.1%) patients experienced composite outcomes, 15 patients (12.2%) died, 31 (25.2%) underwent aortic intervention, 21 (17.1%) exhibited diameter growth of > 5 mm, and 2 developed rTAAD. The patients were divided into low SII group (n = 78, 62.9%) and high SII group (n = 46, 37.1%) as per the optimal cut-off SII value of 1449. The incidence of composite outcomes in high SII group was significantly higher than that in low SII (28 [60.9%] vs. 26[33.3%], p 1449 at the time of diagnosis is an independent predictor of OMT failure.

Abstract Background Abdominal aortic aneurysms (AAAs) can result in high mortality upon rupture but are usually undiagnosed because of the absence of symptoms in the early stage. Ultrasound screening is regarded as an impactful way to prevent the AAA-related death but cannot be performed efficiently; therefore, a target population, especially in Asia, for this procedure is lacking. Additionally, although dyslipidaemia and atherosclerosis are associated with AAA. However, it remains undetermined whether the non-high-density lipoprotein-cholesterol to high-density lipoprotein-cholesterol ratio (NHHR) is associated with AAA. Therefore, this study was aimed at examining whether NHHR is associated with AAA. Method A total of 9559 participants who underwent AAA screening at Guangdong Provincial People’s Hospital and through screening in two communities in Dongguan, from June 2019 to June 2021 joined in this screening program. The diagnosis of AAA was confirmed by the ultrasound examination of the abdominal aorta rather than any known or suspected AAA. Clinical and laboratory data of participants were collected. The participants were separated into a normal group and an AAA group according to the abdominal aortic status. To eliminate confounding factors, a propensity score matching (PSM) approach was utilized. The independent relationship between NHHR and AAA was assessed through the utilization of multivariable logistic regression analysis. In addition, internal consistency was evaluated through subgroup analysis, which controlled for significant risk factors. Results Of all the participants, 219 (2.29%) participants were diagnosed with AAA. A significant elevation in NHHR was identified in the AAA group when contrasted with that in the normal group (P

Polarized x rays or gamma rays generated from inverse Compton scattering (ICS) sources are high-brightness, quasimonochromatic, and polarization-tunable and are widely applied in medical imaging, material science, and nuclear physics research. In this paper, to simulate ICS between electron beams and polarized laser beams, a Monte Carlo simulation code has been developed and implemented based on the geant4 toolkit. This code considers the polarization as well as the bandwidth of incident laser beams. The code is benchmarked by comparing its simulation results with those from the well-known Monte Carlo tool called cain and experimental results. The comparisons show that this code accurately reproduces the scattered photons, demonstrating its potential for various ICS-based applications.

A light source project named very compact inverse Compton scattering gamma-ray source (VIGAS) is under development at Tsinghua University. VIGAS aims to generate monochromatic high-energy gamma rays by colliding 350-MeV electron beams with 400-nm laser photons within a 12-m beamline. To produce a high-energy electron beam in such a compact space, the system consists of an S-band high-brightness injector and six X-band high-gradient accelerating structures. The goal of the X-band structure is to operate at a high gradient of 80 MV/m. Therefore, we adopts the constant gradient traveling wave approach, where the iris from the first cell to the end cell is tapered. The structure has 72 cells, including 70 cells and 2 couplers, so we named it XT72. The frequency of XT72 is selected to 11.424 GHz, and the 2π/3 mode is adopted. In this paper, we present a comprehensive study covering the detailed design, fabrication, rf tuning, and high-power test results of the first XT72. Additionally, we compare the performance of this structure to that of the previous constant impedance structure. Our results demonstrate that the XT72 is capable of operating at an 80-MV/m gradient with a lower breakdown rate. This advancement paves the way for the development of VIGAS project and contributes to the wider application of X-band room-temperature high-gradient structures in compact accelerator facilities.

The stability of hydrogen fuel cell system power generation is affected by key variables such as oxygen excess ratio (OER), electric stack temperature, and cathode–anode differential pressure. To increase the fuel cell’s stability, a sliding mode integral separation proportional–integral–derivative (SMC−IS−PID) control strategy was proposed by combining the four−segment integral separation PID (IS−PID) control with the switching control in the sliding mode control (SMC). The control mode is selected through the system variable error and the current variable value; if there are significant systematic variable errors, the switching control in the SMC adopts the four−segment integral separation PID control, which determines the values of the segmentation thresholds and controls the integral weights to reduce the amount of overshoot. When the error of the system variables is small, the switching control in the SMC adopts the improved convergence law control, which introduces the hyperbolic tangent exponential power term, the nonlinear function term, and the saturation function term to improve the convergence law and decrease the control’s convergence time. Experimentally verifying the effectiveness of the control strategy above, the results show that for the OER, the SMC−IS−PID overshoots 0 and realizes no overshooting with a regulation time of 5.019 s. For the temperature of the stack, the SMC−IS−PID overshoots only 0.134% with a regulation time of 40.521 s. For the pressure of the stack, the SMC−IS−PID realizes the system is basically free of oscillation.

Abstract Background Patients with omphalocele, a midline abdominal wall defect at the umbilical cord base, have a low survival rate. However, the long-term outcomes of fetuses with prenatally diagnosed omphalocele have scarcely been studied. Therefore, we investigated the ultrasonographic features, genetic characteristics, and maternal and fetal outcomes of fetuses with omphalocele and provided a reference for the perinatal management of such cases. Methods A total of 120 pregnant females with fetal omphalocele were diagnosed using prenatal ultrasonography at the Fujian Provincial Maternity and Child Health Hospital from January 2015 to March 2022. Amniotic fluid or cord blood samples were drawn at different gestational weeks for routine karyotype analysis, chromosomal microarray analysis (CMA) detection, and whole exome sequencing (WES). The maternal and fetal outcomes were followed up. Results Among the 120 fetuses, 27 were diagnosed with isolated omphalocele and 93 with nonisolated omphalocele using prenatal ultrasonography. Cardiac anomalies were the most observed cause in 17 fetuses. Routine karyotyping and CMA were performed on 35 patients, and chromosomal abnormalities were observed in five patients, trisomy 18 in three, trisomy 13 in one, and chromosome 8–11 translocation in one patient; all were non-isolated omphalocele cases. Six nonisolated cases had normal CMA results and conventional karyotype tests, and further WES examination revealed one pathogenic variant and two suspected pathogenic variants. Of the 120 fetuses, 112 were successfully followed up. Eighty of the 112 patients requested pregnancy termination. Seven of the cases died in utero. A 72% 1-year survival rate was observed from the successful 25 live births. Conclusion The prognosis of fetuses with nonisolated omphalocele varies greatly, and individualized analysis should be performed to determine fetal retention carefully. Routine karyotyping with CMA testing should be provided for fetuses with omphalocele. WES is an option if karyotype and CMA tests are normal. If the fetal karyotype is normal and no associated abnormalities are observed, fetuses with omphalocele could have a high survival rate, and most will have a good prognosis.

Introduction: China is a large country of REE resources and production, supplying more than 90% of the world’s rare earth consumption market, China’s traditional REE resources, although rich, but reserves are also declining, in recent years, scholars have shown that the REEs in the specific geological conditions in the coals can be enriched, and even reach the industrial grade, the search for more REE mineral resources will be of great strategic significance.Methods: The article has selected the Zibo, Taozao, Huainan, Datong, Huozhou, Jungar, and Weibei coalfields in North China as the research objects. Based on inductively coupled plasma mass spectrometry (ICP-MS) analyses, the study provides a detailed analysis of the enrichment rules and distribution patterns of rare earth elements (REEs) in coal under different geological conditions.Results: The REE distribution patterns in Late Palaeozoic coals in North China are characterized by enrichment of LREEs, deficit of HREEs with gentle changes, and obvious negative anomalies of Eu, the enrichment of REE in coal is controlled by provenance and volcanism, and is related to distance of transport terrigenous material and the sedimentary environment. The REEs concentrations in North China indicates that Late Palaeozoic coals in the mining areas of the north, northwest, and western parts of North China are significantly enriched in REEs. In addition, REEs in Late Palaeozoic coals in the southeastern mining areas are relatively enriched, and the central and eastern regions are significantly depleted.Discussion: Large coal-type rare earth deposits are expected to be developed in North China, particularly the Datong coalfield, Jungar coal mine and the Weibei coal mine in the eastern margin of the Ordos Basin, and the Zibo coalfield.

IntroductionAn accurate inverse dynamics model of manipulators can be effectively learned using neural networks. However, further research is required to investigate the impact of spatiotemporal variations in manipulator motion sequences on network learning. In this work, the Velocity Aware Spatial-Temporal Attention Residual LSTM neural network (VA-STA-ResLSTM) is proposed to learn a more accurate inverse dynamics model, which uses a velocity-aware spatial-temporal attention mechanism to extract dynamic spatiotemporal features selectively from the motion sequence of the serial manipulator.MethodsThe multi-layer perception (MLP) attention mechanism is adopted to capture the correlation between joint position and velocity in the motion sequence, and the state correlation between hidden units in the LSTM network to reduce the weight of invalid features. A velocity-aware state fusion approach of LSTM network hidden units' states is proposed, which utilizes variation in joint velocity to adapt to the temporal characteristics of the manipulator dynamic motion, improving the generalization and accuracy of the neural network.ResultsComparative experiments have been conducted on two open datasets and a self-built dataset. Specifically, the proposed method achieved an average accuracy improvement of 61.88% and 43.93% on the two different open datasets and 71.13% on the self-built dataset compared to the LSTM network. These results demonstrate a significant advancement in accuracy for the proposed method.DiscussionCompared with the state-of-the-art inverse dynamics model learning methods of manipulators, the modeling accuracy of the proposed method in this paper is higher by an average of 10%. Finally, by visualizing attention weights to explain the training procedure, it was found that dynamic modeling only relies on partial features, which is meaningful for future optimization of inverse dynamic model learning methods.

Abstract Introduction Agents that can be used for the treatment of neuropsychiatric lupus (NPSLE) are lacking in the therapeutic armamentarium. Belimumab is a monoclonal antibody targeting the B‐cell activating factor (BAFF) and is approved by the US Food and Drug Administration as an additional treatment for systemic lupus erythematosus patients with persistent disease activity and lupus nephritis (LN); however, severe active central nervous system manifestations were excluded. Case Report We report on a treatment‐naïve LN patient with refractory NPSLE complicated with progressive posterior reversible encephalopathy syndrome (PRES) who was successfully treated via the combination of mycophenolate and belimumab, resulting in reversal of persistent headache and neuroradiologic manifestations. Conclusion Research on this topic could be relevant for identifying a possible correlation between BAFF and psychiatric NPSLE manifestations.

Background: Malnutrition is a poor prognostic factor in a wide range of diseases. Nevertheless, there is a lack of data investigating the association between malnutrition and outcomes of patients with type B aortic dissection (TBAD) undergoing thoracic endovascular aortic repair (TEVAR). Therefore, the aim of the present study was to report the prevalence and clinical impact of malnutrition assessed by the controlling nutritional status (CONUT) score in TBAD patients undergoing TEVAR. Methods: The retrospective study indicated that a total of 881 patients diagnosed with TBAD and treated with TEVAR from January 2010 to December 2017 were categorized into subgroups based on their CONUT score (low ≤5 vs. high >5). To assess the correlation between malnutrition and early and follow-up outcomes of TBAD patients, logistic and Cox regression analysis were utilized, incorporating inverse probability weighting. Results: Malnutrition was present in 20.3% of patients according to the CONUT score. Multivariate logistic regression analysis revealed that pre-operative CONUT score modeled as a continuous variable was an independent risk factor for prolonged intensive care unit stay (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.02–1.17; p = 0.015), 30-day death (OR, 1.43; 95% CI, 1.19–1.72; p < 0.001), delirium (OR, 1.11; 95% CI, 1.01–1.23; p = 0.035) and acute kidney injury (OR, 1.09; 95% CI, 1.01–1.16; p = 0.027). During a median follow-up of 70.8 (46.1–90.8) months, 102 (11.8%) patients died (high CONUT group: 21.8% vs. low CONUT group: 9.0%; p < 0.001). Multivariable Cox proportional-hazards models showed that malnutrition was an independent predictor for follow-up mortality (hazard ratio, 1.68; 95% CI, 1.11–2.53; p = 0.014). Results remained consistent across various sensitivity analyses. Conclusions: Malnutrition assessed by the CONUT score could profoundly affect the early and follow-up prognosis in patients undergoing TEVAR. Routine pre-intervention nutritional evaluation might provide valuable prognostic information.

All-fiber coherent beam combiners based on the self-imaging effect can achieve a near-perfect single laser beam, which can provide a promising way to overcome the power limitation of a single-fiber laser. One of the key points is combining efficiency, which is determined by various mismatches during fabrication. A theoretical model has been built, and the mismatch error is analyzed numerically for the first time. The mismatch errors have been numerically studied with the beam quality and combining efficiency being chosen as the evaluation criteria. The tolerance of each mismatch error for causing 1% loss is calculated to guide the design of the beam combiners. The simulation results are consistent with the experimental results, which show that the mismatch error of the square-core fiber is the main cause of the efficiency loss. The results can provide useful guidance for the fabrication of all-fiber coherent beam combiners.

In this study, we propose a physical design of a compact all-optical terahertz (THz)-driven electron source. The 300-mm accelerator beamline, powered by a Joule-level laser system, can be easily integrated into the tabletop scale. A THz-driven electron gun, a tapered dielectric-loaded cylindrical waveguide, THz-driven bunch compressors, and permanent magnetic solenoids (PMSs) have been designed and optimized. Dynamic simulations show that the electron source can deliver 19 fC electron beams at 3 MeV, with a normalized transverse emittance of 0.079 π.mm.mrad. A minimum relative energy spread of 0.04% or a minimum root-mean-square (RMS) bunch length of 6.1 fs can be achieved. Sensitivity analysis shows that the THz-driven electron source can effectively work with a laser power jitter within 1.5%. Simulation studies also reveal the potential of the designed THz-driven electron source for achieving high-quality ultrafast electron diffraction (UED). Prototype THz-driven electron guns have been fabricated and are currently under testing, and more comprehensive results will be reported in future works.

Abstract Background Although the pressure of pulmonary vein increases before pulmonary artery in pulmonary hypertension due to left heart disease (PH-LHD), only a few studies have assessed pulmonary vein smooth muscle cells (PVSMCs) because of the lack of a simple and feasible isolation method. Methods In this study, we introduced a simple method to obtain PVSMCs. Primary pulmonary veins were removed by puncture needle cannula guidance. Then, PVSMCs were cultured by the tissue explant method and purified by the differential adhesion method. The cells were characterized by hematoxylin-eosin (HE) staining, immunohistochemistry, western blotting, and immunofluorescence to observe the morphology and verify the expression of alpha-smooth muscle actin (α-SMA). Results The HE staining results showed that the pulmonary vein media was thinner than the pulmonary artery, the intima and adventitia of the pulmonary vein were removed by this method, and the obtained cells with good activity exhibited morphological characteristics of smooth muscle cells. In addition, higher α-SMA expression was observed in the cells obtained by our isolation method than in the traditional method. Conclusion This study established a simple and feasible method to isolate and culture PVSMCs that might facilitate the cytological experiments for PH-LHD.

Abstract Background Idiopathic pulmonary fibrosis is a chronic progressive, lethal disease in which ectopic lung fibroblast (LF) activation plays a vital part. We have previously shown that alamandine (ALA) exerts anti-fibrosis effects via the MAS-related G-protein coupled receptor D (MrgD). Here, we further investigate how it moderates transforming growth factor β1 (TGF-β1)-induced LF activation by regulating glucose metabolism and mitochondria autophagy (mitophagy). Methods In vitro, we examined glycolysis-related protein hexokinase 2 (HK2), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), and lactic acid in cells treated with TGF-β1. The oxygen consumption rate and the extracellular acidification rate were detected using Seahorse assays. Then, mitophagy was evaluated using transmission electron microscopy, mt-Keima, and the co-localization of Parkin and COX IV with LC3 and LAMP1, respectively. The autophagic degradation of HK2 and PFKFB3 was detected by 3MA and bafilomycin A1 and assessed by their co-localization with LC3 and LAMP1, respectively. The effects of ALA on LF activation markers collagen I and α-SMA were detected. The effects of ALA on glucose metabolism, mitophagy, and the activation of LF were also investigated in vivo. Results We found that the ALA/MrgD axis improved TGF-β1-mediated LF activation by repressing glycolysis by downregulating HK2 and PFKFB3 expression. Lactic acid sustained positive feedback between glycolysis and LF activation by maintaining the expression of HK2 and PFKFB3. We also showed that glycolysis enhancement resulted from blocking the autophagic degradation of HK2 and PFKFB3 while upregulated mRNA levels by TGF-β1, while all of those improved by ALA adding. Importantly, we determined that moderation of Parkin/LC3-mediated mitophagy by TGF-β1 also promotes glycolysis but is reversed by ALA. Furthermore, we proved that ALA counteracts the effects of bleomycin on HK2, PFKFB3, LC3, Parkin, and LF activation in vivo. Conclusion In this study, we show that the ALA/MrgD axis prevents TGF-β1-mediated fibroblast activation via regulation of aerobic glycolysis and mitophagy.

Abstract Background Fibronectin glomerulopathy is a rare, familial glomerular disease characterized by mesangial fibronectin deposition in the glomeruli. It is caused by the genetic defect in fibronectin and does not involve the activation of the immune system. Therefore, glomerular immunoglobulin and complement staining is generally absent or weak. Monoclonal gammopathy (MG) is an increasing cause of renal lesion, featured by light chain (κ or λ) and/or heavy chain restriction in glomeruli. Herein, we report a case of fibronectin glomerulopathy presenting as strong IgA and C3 immunostaining in renal biopsy, concomitant with monoclonal gammopathy (monoclonal IgA κ). Case presentation A 44-year-old female was admitted to our hospital for one-month pedal edema. The serum albumin of 19.6 g/l, and the 24-h urine protein was 15.092 g. Immunofixation electrophoresis displayed monoclonal IgA. The renal biopsy showed the mesangial deposits positive for IgA (3+) and C3 (3+) and also for IgG (2+), IgM (2+), and C1q (2+) IF microscopy. In addition, the staining intensity of light chain κ was slight greater than that of light chain λ. The glomerular deposits were strongly positive by FN by immuohistochemistry. The patient was treated with bortezomib, dexamethasone in combination with cyclophosphamide and gained partial remission. Conclusion We present the first FNG patient with strong IgA and C3 immunostaining in the context of monoclonal IgA κ in the circulation. Perhaps FNG, monoclonal IgA κ and immune activation are potentially interplayed and eventually induce renal injuries.

IntroductionConsiderable evidence indicates that some trees are more vulnerable than others during bamboo (Phyllostachys edulis) expansion, which can affect plant community structure and alter the environment, but there has been insufficient research on the growth status of surviving individuals in colonized forests.MethodsIn this study, we compared the annual growth increment, growth rate, and onset, cessation, and duration of radial growth of Alniphyllum fortunei, Machilus pauhoi, and Castanopsis eyrei in a bamboo-expended broadleaf forest (BEBF) and a bamboo-absent broadleaf forest (BABF) using high-resolution point dendrometers.ResultsWe found that the annual radial growth of A. fortunei, M. pauhoi, and C. eyrei was 22.5%, 172.2%, and 59.3% greater in BEBF than in BABF, respectively. The growth rates of M. pauhoi and C. eyrei in BEBF were significantly higher than in BABF by13.9 μm/d and 19.6 μm/d, whereas A. fortunei decreased significantly by 7.9 μm/d from BABF to BEBF. The onset and cessation of broad-leaf tree growth was later, and the growth duration was longer in BEBF compared to BABF. For example, A. fortunei and M. pauhoi in BEBF had more than one month longer growth duration than in BABF. Additionally, the nighttime growth rates of some surviving broad-leaf trees in BEBF was significantly higher than that in BABF.DiscussionThese results suggest that the surviving trees have plasticity and can adapt to atmospheric changes and competitive relationships after expansion of bamboo in one of two ways: by increasing their growth rates or by modifying onset and cessation of growth to extend the growth duration of trees or avoid the period of intense competition with bamboo, thereby growing better. Our research reveals for the first time how the growth of surviving broad-leaf trees adjusts to bamboo expansion. These results provide insights into how biological expansions impact primary production and have implications for forest management in the Anthropocene.

Background: Lupus nephritis (LN) frequently manifests as a significant complication in systemic lupus erythematosus (SLE) patients, with emerging research indicating a plausible correlation between subclinical retinal involvement and renal manifestations. This study aims to investigate the relationship between the neutrophil-to-C3 ratio (NC3R) and both LN as well as retinal microvasculature damage among SLE patients. Methods: In this cross-sectional study, a cohort of 220 participants was recruited, consisting of 78 LN patients and 142 patients without LN. We assessed clinical indicators and organ involvement and conducted correlation analyses between NC3R and markers of lupus activity. Additionally, we analyzed the diagnostic performance of NC3R in diagnosing LN and constructing ROC curves. Logistic regression analysis was performed to investigate the impact of NC3R on LN. We further examined the influence of NC3R on retinal vasculature density based on its cutoff value and conducted correlation analyses accordingly. Results: The LN group exhibited a significant increase in NC3R compared to the group without LN (5.9 vs 4.5, P=0.007). NC3R demonstrated positive correlations with 24-hour proteinuria (R=0.329, P

Background: In systemic lupus erythematosus (SLE), retinopathy is connected to severe disease and poorer prognosis. This study aimed to investigate changes in retinal vascular density (VD) in SLE and lupus nephritis (LN) patients and to examine the effects of Belimumab and hydroxychloroquine (HCQ) on retinal VD in these patients. Methods: This cross-sectional study enrolled 54 SLE patients (21 with LN and 33 without LN). A comprehensive ophthalmological evaluation using optical coherence tomography angiography (OCTA) was conducted on SLE patients. Rheumatological evaluations were performed through the collection of relevant clinical and laboratory data, as well as the assessment of rheumatological treatment. Results: We found that the mean VD in the superficial capillary plexus (SCP-VD) of most regions showed a significant decrease in the LN group. Further analysis revealed that LN patients using Belimumab exhibited a reduction in SCP-VD and deep capillary plexus VD (DCP-VD) (P

Abstract There has been significant progress in hydrocarbon exploration of the eastern Kuqa Depression, Tarim Basin, whose Jurassic reservoir is a key area for abundant hydrocarbon with poorly understood accumulation mechanism. This study conducts an integrated investigation comprising petrographic observations, microthermometry measurements, and fluorescence spectroscopy analyses on fluid inclusions to reconstruct hydrocarbon accumulation history in the Jurassic reservoir. These conclusions are combined with biomarker characteristics to reveal the burial history and thermal evolution of the study area. The results show that (1) there were two episodes of oil charging that occurred at 6~4 Ma and 4~2 Ma, respectively. The QGF experiment response and yellow fluorescent oil inclusions indicated that low-maturity medium crude oil from the Triassic source rocks was expelled into the upper Ahe Formation. In the second charging stage, some mature oil generated from Jurassic source rocks was charged into the reservoir of the Kezilenuer and Yangxia formations, while the condensate from the Triassic source rocks was migrated upward to the Jurassic reservoir, consistent with smaller QGF-E intensity values and blue-white fluorescent petroleum inclusions. (2) There were two kinds of hydrocarbon accumulation models including the lower-generation and upper-storage and the self-generated and self-stored models. (3) It was noted that active faults were developed under the compression stress to provide channels for hydrocarbon vertical migration. Moreover, the early reservoir was destroyed resulting from the strata denudation and a large amount of crude oil was escaped to the surface. The findings of this study can help for better understanding of hydrocarbon accumulation mechanism in the eastern Kuqa Depression and provide theoretical guidance for further oil and gas exploration.

Abstract Elevated extrachromosomal circular DNA (eccDNA) has been reported to accelerate tumor pathogenesis. Although the eccDNA profiles of other tumors have been established, the landscape of the eccDNA of acute myeloid leukemia (AML) has not been revealed. Our study first depicted the eccDNA profile of normal hematopoiesis and AML evolution by exploiting the ATAC-seq and RNA-seq data from nine healthy donors and 12 AML patients, which contained a total of 137 cell samples and 96 RNA-seq samples (including 16 blood cell types of the normal hematopoietic and AML hierarchies). We found the number of eccDNAs generally increased with the evolution of normal hematopoiesis and AML. The ecDNAs and ring chromosomes were found to reappear both in normal hematopoiesis and AML cells. Furthermore, we compared the eccDNAs of AML with normal cells. There were almost 300 AML-specific genes, including the known oncogenes NRAS, MCL1, EVI1, GATA2, WT1, and PAK1. And the ecDNA (chr11: 58668376-58826008) occurred in five out of 17 AML evolution-related cells, which was associated with the high expression of the GLYATL1 gene and the high expressed GLYATL1 was a poor prognostic factor. In conclusion, the eccDNA profiles of normal hematopoiesis and AML evolution were depicted and the recurrent eccDNAs we revealed might be utilized in the treatment of AML as biomarkers.

Abstract Background Cigarette smoking (CS) is a strong risk factor for idiopathic pulmonary fibrosis (IPF). It can activate lung fibroblasts (LF) by inducing redox imbalance. We previously showed that clearing mitochondrial reactive oxygen species (mtROS) protects against CS-induced pulmonary fibrosis. However, the precise mechanisms of mtROS in LF need further investigation. Here we focused on mtROS to elucidate how it was regulated by CS in LF and how it contributed to LF activation. Methods We treated cells with 1% cigarette smoking extract (CSE) and examined mtROS level by MitoSOX™ indicator. And the effect of CSE on expression of SIRT1, SOD2, mitochondrial NOX4 (mtNOX4), fatty acid oxidation (FAO)-related protein PPARα and CPT1a and LF activation marker Collagen I and α-SMA were detected. Nile Red staining was performed to show cellular lipid content. Then, lipid droplets, autophagosome and lysosome were marked by Bodipy 493/503, LC3 and LAMP1, respectively. And lipophagy was evaluated by the colocalization of lipid droplets with LC3 and LAMP1. The role of autophagy on lipid metabolism and LF activation were explored. Additionally, the effect of mitochondria-targeted ROS scavenger mitoquinone and SIRT1 activator SRT1720 on mitochondrial oxidative stress, autophagy flux, lipid metabolism and LF activation were investigated in vitro and in vivo. Results We found that CS promoted mtROS production by increasing mtNOX4 and decreasing SOD2. Next, we proved mtROS inhibited the expression of PPARα and CPT1a. It also reduced lipophagy and upregulated cellular lipid content, suggesting lipid metabolism was disturbed by CS. In addition, we showed both insufficient FAO and lipophagy resulted from blocked autophagy flux caused by mtROS. Moreover, we uncovered decreased SIRT1 was responsible for mitochondrial redox imbalance. Furthermore, we proved that both SRT1720 and mitoquinone counteracted the effect of CS on NOX4, SOD2, PPARα and CPT1a in vivo. Conclusions We demonstrated that CS decreased SIRT1 to activate LF through dysregulating lipid metabolism, which was due to increased mtROS and impaired autophagy flux. These events may serve as therapeutic targets for IPF patients.