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Abstract Objectives The main purpose of this study is to evaluate the efficacy of polyetheretherketone (PEEK) as a material for prefabricated crown restorations in pediatric dentistry, particularly for restoring primary tooth structure defects. Materials and methods This study analyzed the effects of three surface treatment modalities on PEEK’s surface morphology, wettability (as measured by contact angle), and shear bond strength. These treatments included alumina (Al2O3) sandblasting alone, and in conjunction with a 98% sulfuric acid pretreatment. Subsequently, an evaluation was conducted to assess the compressive and fatigue properties of self-fabricated PEEK preformed crowns, preformed metal crowns, and preformed zirconia crowns. Results Al2O3 sandblasting followed by sulfuric acid pretreatment significantly enhanced the bond strength of PEEK. PEEK crowns, when compared with stainless steel and zirconia crowns, showed similar compressive and fatigue strengths to zirconia crowns but lower than metal alternatives. Additionally, PEEK crowns required less extensive modification of dental abutments compared to zirconia crowns. Conclusions The study concludes that PEEK prefabricated crown, especially after alumina (Al2O3) sandblasting in conjunction with a 98% sulfuric acid pretreatment, exhibits improved bond strength and favorable material characteristics for use in pediatric dental restorations. Clinical relevance The findings highlight the potential of PEEK prefabricated crowns in pediatric dentistry as a viable option for the aesthetic restoration of primary teeth, offering benefits over traditional materials like stainless steel and zirconia in terms of preferable compressive and fatigue strengths and ideal reduction of dental abutments.

Abstract Different strains of identical species can vary substantially in terms of their spectrum of biomedically relevant phenotypes. Reconstructing the genomes of microbial communities at the level of their strains poses significant challenges, because sequencing errors can obscure strain-specific variants. Next-generation sequencing (NGS) reads are too short to resolve complex genomic regions. Third-generation sequencing (TGS) reads, although longer, are prone to higher error rates or substantially more expensive. Limiting TGS coverage to reduce costs compromises the accuracy of the assemblies. This explains why prior approaches agree on losses in strain awareness, accuracy, tendentially excessive costs, or combinations thereof. We introduce HyLight, a metagenome assembly approach that addresses these challenges by implementing the complementary strengths of TGS and NGS data. HyLight employs strain-resolved overlap graphs (OG) to accurately reconstruct individual strains within microbial communities. Our experiments demonstrate that HyLight produces strain-aware and contiguous assemblies at minimal error content, while significantly reducing costs because utilizing low-coverage TGS data. HyLight achieves an average improvement of 19.05% in preserving strain identity and demonstrates near-complete strain awareness across diverse datasets. In summary, HyLight offers considerable advances in metagenome assembly, insofar as it delivers significantly enhanced strain awareness, contiguity, and accuracy without the typical compromises observed in existing approaches.

Abstract Background Primary cardiac tumors, while rare, present significant clinical challenges due to their diverse pathology and presentation. Lung cancer frequently metastasizes to the heart; however, cases involving primary cardiac tumors of different origins alongside primary lung cancer are exceedingly rare in the literature. Case presentation We report the case of a 53-year-old female who presented with hemoptysis and was subsequently diagnosed with a left atrial myxoma, pulmonary squamous cell carcinoma, and a thymic cyst. This coexistence of multiple non-homologous tumors in a single patient is exceedingly rare. Conclusion This case underscores the complexity of diagnosing and managing patients with multiple distinct tumors. The simultaneous occurrence of a primary cardiac myxoma, pulmonary squamous cell carcinoma, and thymic cyst is unprecedented, providing valuable insights for future clinical practice.

ObjectiveTo understand the status and influencing factors of first aid-related health literacy among urban residents in Jiangsu province and and to provide a reference for improving the health literacy in the population. MethodsUsing a multistage stratified cluster sampling method and a self-designed questionnaire, we conducted a face-to-face survey among 2 804 urban residents aged 10 years and above in three cities of Jiangsu province from July to September 2022 to collect the residents’ information on first aid-related health literacy. T-test, analysis of variance, and chi-squared test were used for univariate analysis, and a decision tree algorithm model was created for multivariate analysis. ResultsThe participants’ mean score for overall first aid-related health literacy was 14.40 ± 7.965 out of a total score of 45, and only 7.99% of the participants were classified as having qualified literacy (scored 27 points and above). The proportion of individuals with qualified dimension-specific first aid-related health literacy (scoring ≥ 60% of the total score) was 17.58% for cardiopulmonary resuscitation, 22.47% for trauma care, 16.01% for accidental injury care, 5.53% for critical care, and 34.91% for emergency response, with significant differences in the proportions among participants in different cities, at different ages, with different levels of education, and in different occupations (all P < 0.05). The decision tree model analysis showed that the importance of factors influencing first aid-related health literacy were, in descending order, occupation, education level, city, and age. ConclusionFirst aid-related health literacy is relatively low among urban residents in Jiangsu province, with particularly low levels of critical care, accidental injury management, and cardiopulmonary resuscitation, suggesting that targeted first aid education needs to be promoted among the population.

BackgroundBystander Cardiopulmonary Resuscitation (CPR) can significantly improve the rate of return of spontaneous circulation in patients with cardiac arrest. Since first year students with no specific academic background are energetic and quick to learn, many Chinese schools offer first-aid training course including CPR to them before they start school. However, data on CPR knowledge, training, and willingness among first year students are lacking in most regions of China, which makes the effectiveness of CPR training unknown.ObjectivesTo evaluate first year students’ knowledge level, training experience and rescue willingness for CPR of first year students in Xuzhou, and to analyze the influencing factors of CPR knowledge level and rescue willingness of first year students in Xuzhou.DesignA cross-sectional study.ParticipationsA total of 9,887 first year students from three universities in Xuzhou city were selected by multi-stage random cluster sampling method.MethodsA self-designed five-part structured questionnaire was used to investigate the knowledge, training and willingness of CPR among first year students. Independent sample t-test, χ2-test and Logistic regression were used for data analysis.ResultsThe average score of CPR knowledge was 2.44 (±1.60), 99.13% of the respondents were willing to participate in CPR training, and 66.25% had received CPR training. Respondents with rural household registration, relatives who had suffered from serious diseases, relatives engaged in the medical profession, good self-rated quality of life, CPR training, and willing to CPR training had higher CPR knowledge levels. 76.77% of the respondents were willing to perform bystander CPR. Women, those who had received CPR training, and those who were willing to receive CPR training were more willing to help patients with sudden cardiac arrest. Lack of first aid knowledge and skills (82.61%) was the biggest obstacle hindering respondents from performing rescue.ConclusionMost of the first year students of Xuzhou University in China have CPR training experience and have a strong willingness to train. Most are willing to perform bystander CPR, but have a low knowledge level. Colleges and universities can adopt diversified training methods, make plans for regular CPR retraining and other strategies to improve the quality and effect of CPR training for college students.

Abstract Thermoelectrics have great potential for use in waste heat recovery to improve energy utilization. Moreover, serving as a solid-state heat pump, they have found practical application in cooling electronic products. Nevertheless, the scarcity of commercial Bi2Te3 raw materials has impeded the sustainable and widespread application of thermoelectric technology. In this study, we developed a low-cost and earth-abundant PbS compound with impressive thermoelectric performance. The optimized n-type PbS material achieved a record-high room temperature ZT of 0.64 in this system. Additionally, the first thermoelectric cooling device based on n-type PbS was fabricated, which exhibits a remarkable cooling temperature difference of ~36.9 K at room temperature. Meanwhile, the power generation efficiency of a single-leg device employing our n-type PbS material reaches ~8%, showing significant potential in harvesting waste heat into valuable electrical power. This study demonstrates the feasibility of sustainable n-type PbS as a viable alternative to commercial Bi2Te3, thereby extending the application of thermoelectrics.

It is believed that DNA double-strand breaks induced by Zika virus (ZIKV) infection in pregnant women is a main reason of brain damage (e.g. microcephaly, severe brain malformation, and neuropathy) in newborn babies [1,2], but its underlying mechanism is poorly understood. In this study, we report that the depletion of ERp57, a member of the protein disulphide isomerase (PDI) family, leads to the limited production of ZIKV in nerve cells. ERp57 knockout not only suppresses viral induced reactive oxygen species (ROS) mediated host DNA damage, but also decreases apoptosis. Strikingly, DNA damage depends on ERp57-bridged complex formation of viral protein NS2B/NS3. LOC14, an ERp57 inhibitor, restricts ZIKV infection and virus-induced DNA damage. Our work reveals an important role of ERp57 in both ZIKV propagation and virus-induced DNA damage, suggesting a potential target against ZIKV infection.

A positive-sense (+) single-stranded RNA (ssRNA) virus (e.g. enterovirus A71, EV-A71) depends on viral polypeptide translation for initiation of virus replication after entry. We reported that EV-A71 hijacks Hsp27 to induce hnRNP A1 cytosol redistribution to initiate viral protein translation, but the underlying mechanism is still elusive. Here, we show that phosphorylation-deficient Hsp27-3A (Hsp27S15/78/82A) and Hsp27S78A fail to translocate into the nucleus and induce hnRNP A1 cytosol redistribution, while Hsp27S15A and Hsp27S82A display similar effects to the wild type Hsp27. Furthermore, we demonstrate that the viral 2A protease (2Apro) activity is a key factor in regulating Hsp27/hnRNP A1 relocalization. Hsp27S78A dramatically decreases the IRES activity and viral replication, which are partially reduced by Hsp27S82A. However, Hsp27S15A displays the same activity as the wild-type Hsp27. Peptide S78 potently suppresses EV-A71 protein translation and reproduction through blockage of EV-A71-induced Hsp27 phosphorylation and Hsp27/hnRNP A1 relocalization. A point mutation (S78A) on S78 impairs its inhibitory functions on Hsp27/hnRNP A1 relocalization and viral replication. Taken together, we demonstrate the importance of Ser78 phosphorylation of Hsp27 regulated by virus infection in nuclear translocation, hnRNP A1 cytosol relocation, and viral replication, suggesting a new path (such as peptide S78) for target-based antiviral strategy.

Abstract Aims To identify the gestational weight gain (GWG) patterns in women with gestational diabetes mellitus (GDM) and evaluate their association with offspring weight status from birth to 40 months. Materials and methods This study included 2,723 GDM-mother–child pairs from the Beijing Birth Cohort Study. The association between GWG trajectories identified by the latent class model and offspring weight outcomes from birth to 40 months were evaluated, after adjustment for maternal age, parity, pre-pregnancy body mass index, maternal height, and blood glucose levels. Results Three GWG rate groups, including the non-excessive GWG group (1,994/2,732), excessive GWG group (598 /2,732), and excessive early GWG group (140/2,732), were identified in women with GDM, respectively. Compared to the non-excessive GWG group, the adjusted OR (aOR) and 95% CI were 1.83 (1.35–2.47) and 1.79 (1.06–3.01) for macrosomia, 1.33 (1.07–1.66) and 1.48 (1.01–2.17) for large for gestational age (LGA) in the excessive GWG group and excessive early GWG group. Excessive GWG was also associated with an increased risk of BMI-for-age at 40 months (aOR = 1.66, 95% CI 1.14–2.42). Conclusions Both excessive GWG and excessive early GWG increased the risk of macrosomia and LGA in women with GDM, but only the excessive GWG was associated with childhood overweight/obesity. The results suggest the long-term impact of GWG on offspring weight status in women with GDM and the potential benefits of GWG restriction after GDM diagnosis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was responsible for causing the COVID-19 pandemic. Intensive research has illuminated the complex biology of SARS-CoV-2 and its continuous evolution during and after the COVID-19 pandemic. While much attention has been paid to the structure and functions of the viral spike protein and the entry step of viral infection, partly because these are targets for neutralizing antibodies and COVID-19 vaccines, the later stages of SARS-CoV-2 replication, including the assembly and egress of viral progenies, remain poorly characterized. This includes insight into how the activities of the viral structural proteins are orchestrated spatially and temporally, which cellular proteins are assimilated by the virus to assist viral assembly, and how SARS-CoV-2 counters and evades the cellular mechanisms antagonizing virus assembly. In addition to becoming infectious, SARS-CoV-2 progenies also need to survive the hostile innate and adaptive immune mechanisms, such as recognition by neutralizing antibodies. This review offers an updated summary of the roles of SARS-CoV-2 structural proteins in viral assembly, the regulation of assembly by viral and cellular factors, and the cellular mechanisms that restrict this process. Knowledge of these key events often reveals the vulnerabilities of SARS-CoV-2 and aids in the development of effective antiviral therapeutics.

Abstract Background Acute exposures to high levels of air pollutants are thought to be associated with hospitalization of patients with lung infection, while relatively little is known about the association between air pollutants and HOSPITAL ADMISSIONS FOR pulmonary sepsis. Objectives To assess the correlation between low-level exposure to air pollutants and the hospitalizations for pulmonary sepsis in elderly patients. Methods A total of 249 elderly patients with pulmonary sepsis from January 2018 to December 2020 in Shenzhen people’s hospital were included. The data regarding hospitalizations for pulmonary sepsis, meteorological factors, and daily average levels of air pollutants on single-day lags (Lag0 to Lag7) in Shenzhen were collected. Low-level exposure was defined as the annual means of air pollutants below the levels of the Ambient Air Quality Standard (AAQS) in China (NO. GB3095-2012) and/or Global Air Quality Guidelines (AQG). A time-stratified case-crossover study design approach was used to evaluate the associations between exposure to air pollutants and incidence of the disease, univariate and multivariate logistic regression analysis to analyze the association between levels of air pollutants and hospitalizations for pulmonary sepsis in elderly patients. Results Exposure to PM1(P = 0.007, Lag 2 day; P = 0.038, Lag6 day), PM2.5(P = 0.046, Lag2 day), PM10(P = 0.048, Lag4 day), and O3(P = 0.044, Lag6 day) was positively correlated with elevated risk of hospitalizations for pulmonary sepsis. In addition, logistic regression analysis revealed that exposure to PM1 (OR = 1.833, 95%CI:1.032 ~ 3.256, Lag6 day) and O3 (OR = 2.091, 95%CI:1.019 ~ 4.289, Lag6 day) were the independent risk factors of pulmonary sepsis in elderly patients. Conclusion Our results demonstrate that short-term low-level exposure to PM1 and O3 could elevate the risk of hospitalizations for pulmonary sepsis in elderly patients in Shenzhen, providing evidence for developing early warning and screening systems for pulmonary sepsis.

Abstract The crucial role of interferon (IFN) signaling is well known in the restriction or eradication of pathogen invasion. Viruses take a variety of ways to antagonize host defense through eliminating IFN-signaling intracellularly for decades. However, the way by viruses target IFN-signaling extracellularly has not been discovered. Infection by both coronavirus SARS-CoV-2 and enterovirus 71 (EV71 or EV-A71) can cause severe diseases such as neurological disorders and even death in children.1–3 Here, we show evidence that the protease of SARS-CoV-2 (3CLpro) and EV71 (2Apro) upregulates the expression and secretion of LDL-receptor-related protein-associated protein 1 (LRPAP1). As a ligand, the N-terminus of secreted LRPAP1 binds with the extracellular domain of IFNAR1 that triggers the receptor ubiquitination and degradation and promotes virus infection both in vitro, ex vivo in the mouse brain, and in vivo in newborn mice. A small peptide from the N-terminus of LRPAP1 effectively binds and causes IFNAR1 degradation that enhances both DNA and RNA viral infections, including herpesvirus HSV-1, hepatitis B virus (HBV), EV71, and beta-coronavirus HCoV-OC43; whereas α2M, a LRPAP1 inhibitor, arrests virus infections by stabilizing IFNAR1. Our study demonstrates a new mechanism used by viruses for evading host cell immunity, supporting a strategy for developing pan-antiviral drugs.

In this work, a permanent connection of a high-nitrogen steel plate is achieved by using layer-by-layer powder-filled laser welding of high-nitrogen steel powder, and the stability levels of the welding process, microstructures and mechanical properties are analyzed. Compared with other processes, powder-filled laser welding is smooth without bursts and spatters, and the nitrogen content of the welding seam is obviously improved. The welding seam consists mainly of austenite, with few ferrite and manganese oxides. There is a nitrogen concentration gradient between the inside and the upper part of the melt pool, which leads to nitrogen escape. Laser remelting exacerbates this process, resulting in more severe nitrogen loss in the bottom layer than in the upper layer of the welding seam. The differences in the nitrogen solubilities in austenite and ferrite and the high-nitrogen content in the melt pool are the main reasons for the formation of micropores. Tensile experiments and impact experiments are conducted on the welding joint. The average tensile strength and elongation of the welding joint are 1032.36 MPa and 19.70%, respectively, contributing to 94% and 53.4% of the total values for the base metal. The grain refinement and relatively high nitrogen content are the reasons for the better tensile strength relative to other processes. The average impact energy of the welding joint is 24.68 J, which is approximately 63.74% of the base metal. Pores are the main reason for the reduced impact energy of the welding joint.

Guanylate binding protein 5 (GBP5) is an emerging immune component that has been increasingly recognized for its involvement in autoimmune diseases, particularly inflammatory bowel disease (IBD). IBD is a complex disease involving inflammation of the gastrointestinal tract. Here, we explored the functional significance of GBP5 using Gbp5 knockout mice and wildtype mice exposed to dextran sulfate sodium (DSS) to generate chronic colitis model. We found that Gbp5 deficiency protected mice from DSS-induced chronic colitis. Transcriptome analysis of colon tissues showed reduced immune responses in Gbp5 knockout mice compared to those in corresponding wildtype mice. We further observed that after repeated DSS exposure, the gut microbiota was altered, both in wildtype mice and Gbp5 knockout mice; however, the gut microbiome health index was higher in the Gbp5 knockout mice. Notably, a probiotic murine commensal bacterium, Dubosiella, was predominantly enriched in these knockout mice. Our findings suggest that GBP5 plays an important role in promoting inflammation and dysbiosis in the intestine, the prevention of which might therefore be worth exploring in regards to IBD treatment.

BackgroundNeuroinflammation is a common feature of many neurological diseases, and remains crucial for disease progression and prognosis. Activation of microglia and astrocytes can lead to neuroinflammation. However, little is known about the role of lncRNA xist and miR-122-5p in the pathogenesis of sepsis-associated neuroinflammation (SAN). This study aims to investigate the role of lncRNA xist and miR-122-5p in the pathogenesis of SAN.MethodsLevels of miR-122-5p and proinflammatory mediators were detected in the cerebrospinal fluid (CSF) of patients with intracranial infection (ICI) by ELISA and qRT-PCR. miRNA expression in the periventricular white matter (PWM) in rats was analyzed by high-throughput sequencing. Levels of lncRNA xist, miR-122-5p and proinflammatory mediators in the PWM were measured using qRT-PCR and western blot. Bioinformatics analysis was used to predict the upstream and downstream of miR-122-5p. The interaction between miR-122-5p and its target protein was validated using luciferase reporter assay. BV2 and astrocytes were used to detect the expression of lncRNA xist, miR-122-5p.ResultsThe level of miR-122-5p was significantly decreased in the CSF of ICI patients, while the expression of IL-1β and TNF-α were significantly upregulated. Furthermore, it was found that the expression of IL-1β and TNF-α were negatively correlated with the level of miR-122-5p. A high-throughput sequencing analysis showed that miR-122-5p expression was downregulated with 1.5-fold changes in the PWM of CLP rats compared with sham group. Bioinformatics analysis found that lncRNA xist and PKCη were the upstream and downstream target genes of miR-122-5p, respectively. The identified lncRNA xist and PKCη were significantly increased in the PWM of CLP rats. Overexpression of miR-122-5p or knockdown of lncRNA xist could significantly downregulate the level of PKCη and proinflammatory mediators from activated microglia and astrocytes. Meanwhile, in vitro investigation showed that silencing lncRNA xist or PKCη or enhancing the expression of miR-122-5p could obviously inhibit the release of proinflammatory mediators in activated BV2 cells and astrocytes.ConclusionLncRNA xist could regulate microglia and astrocytes activation in the PWM of CLP rats via miR-122-5p/PKCη axis, further mediating sepsis associated neuroinflammation.

Magnesium is generally known to degrade in aqueous environments by an electrochemical reaction. The corrosion products of magnesium include hydrogen gas, Mg2+, and Mg(OH)2. Here, we summarize the published literature describing the corrosion characteristics of magnesium, and the antitumor properties of magnesium-associated corrosion products, aiming to induce the therapeutic properties of magnesium and magnesium alloys in solid tumors. The therapeutic potential of corrosion products of magnesium is enormous. Hydrogen gas exhibits antioxidant and anti-inflammatory properties, which amount to potential anti-tumor characteristics. Mg(OH)2, which creates a localized alkaline microenvironment, represents a second approach for anti-tumor therapy with magnesium metal. Upregulated concentrations of Mg2+ ions in the local tumor microenvironment remodelling are considered a third approach for anti-tumor therapy. Therefore, we speculate about the different physical forms of magnesium that could create an anti-tumor microenvironment upon tumor interventional therapy, a technique that precisely places anti-tumor implants like particles and stents. Finally, we present our viewpoints on the potential use of magnesium in diverse solid tumor therapies to inhibit tumor progression.

To obtain precise positional information, in this study, we propose an adaptive expectation–maximization (EM)-based Kalman filter (KF)/finite impulse response (FIR) integrated filter for inertial navigation system (INS)-based posture capture of human upper limbs. Initially, a data fusion model for wrist and elbow position is developed. Subsequently, the Mahalanobis distance is utilized to evaluate the performance of the filter. The integrated filter employs the EM-based KF to enhance noise estimation accuracy when the performance of KF declines. Conversely, upon deterioration in the performance of the EM-based KF, which is evaluated using the Mahalanobis distance, the FIR filter is employed to maintain the effectiveness of the data fusion filter. This research utilizes the proposed EM-based KF/FIR integrated filter to ascertain wrist and elbow positions. The empirical results demonstrate the proficiency of the proposed approach in estimating these positions, thereby overcoming the challenge and highlighting its inherent effectiveness.

Alzheimer’s disease (AD) is a complex degenerative disease of the central nervous system that is clinically characterized by a progressive decline in memory and cognitive function. The pathogenesis of AD is intricate and not yet fully understood. Neuroinflammation, particularly microglial activation-mediated neuroinflammation, is believed to play a crucial role in increasing the risk, triggering the onset, and hastening the progression of AD. Modulating microglial activation and regulating microglial energy metabolic disorder are seen as promising strategies to intervene in AD. The application of anti-inflammatory drugs and the targeting of microglia for the prevention and treatment of AD has emerged as a new area of research interest. This article provides a comprehensive review of the role of neuroinflammation of microglial regulation in the development of AD, exploring the connection between microglial energy metabolic disorder, neuroinflammation, and AD development. Additionally, the advancements in anti-inflammatory and microglia-regulating therapies for AD are discussed.

Primary cardiac tumors are exceptionally rare, with malignant tumor occurrences ranging from 0.0017% to 0.28%. Among these, primary cardiac angiosarcoma (PCA) stands as the most prevalent malignancy, primarily impacting the right cardiac system. In this case report, we present the instance of a 44-year-old woman who recently exhibited acute chest discomfort and was subsequently diagnosed with a microangiosarcoma within the right atrium and superior vena cava. Diagnostic modalities including chest x-rays, CT, MRI, and PET-CT were instrumental in pinpointing the tumor's location and nature. Surgical excision followed by pathological and immunological examinations confirmed the diagnosis. The patient's recovery post-surgery has been encouraging, with successful follow-up chemoradiotherapy administered. Despite advancements, devising optimal strategies for enhancing patient survival and quality of life in angiosarcoma cases remains a pressing research challenge.

BackgroundTuberous Sclerosis Complex (TSC) is a hereditary condition that leads to the development of non-malignant neoplasms in various organs, including cardiac rhabdomyomas, which can cause significant complications.Case presentationThis report describes the case of a 15-day-old male neonate who was hospitalized due to intracardiac masses and brain lesions, despite the absence of TSC gene mutations. The patient's mother exhibited facial angiofibromas, a common feature of TSC. Over a 2-year follow-up period, spontaneous regression of the cardiac tumor was observed.ConclusionsThis case illustrates that not all TSC cases exhibit detectable TSC gene mutations. Current treatment strategies, such as mTOR inhibitors, offer potential effectiveness in managing associated cardiac rhabdomyomas. Further research should focus on evaluating the therapeutic potential of these inhibitors.

Congenital coronary artery fistula (CAF) represents a remarkable rarity within the realm of cardiovascular anomalies, characterized by an aberrant connection between coronary arteries and either cardiac chambers or major vessels. Clinical manifestations of CAFs often remain unspecified or may even be entirely absent, posing diagnostic challenges. Notably, patients harboring substantial CAFs may exhibit symptoms such as palpitations, chest tightness, and dyspnea. Although right-sided congenital CAFs are relatively prevalent, the occurrence of a CAF accompanied by a colossal pseudoaneurysm imposing compression upon the pulmonary vein is an exceedingly rare phenomenon. This exceptional case report delineates a singular fistula originating from the right coronary artery, extending its course to the right atrium, and remarkably featuring a substantial pseudoaneurysm exerting compression upon the right superior pulmonary vein. Therapeutic intervention encompassed surgical closure of the proximal artery and excision of the pseudoaneurysm, underscoring the complexity and criticality of managing such intricate cardiac anomalies to ensure optimal patient outcomes.

Abstract Main goal of the JUNO experiment is to determine the neutrino mass ordering using a 20 kt liquid-scintillator detector. Its key feature is an excellent energy resolution of at least 3% at 1 MeV, for which its instruments need to meet a certain quality and thus have to be fully characterized. More than 20,000 20-inch PMTs have been received and assessed by JUNO after a detailed testing program which began in 2017 and elapsed for about four years. Based on this mass characterization and a set of specific requirements, a good quality of all accepted PMTs could be ascertained. This paper presents the performed testing procedure with the designed testing systems as well as the statistical characteristics of all 20-inch PMTs intended to be used in the JUNO experiment, covering more than fifteen performance parameters including the photocathode uniformity. This constitutes the largest sample of 20-inch PMTs ever produced and studied in detail to date, i.e. 15,000 of the newly developed 20-inch MCP-PMTs from Northern Night Vision Technology Co. (NNVT) and 5000 of dynode PMTs from Hamamatsu Photonics K. K.(HPK).

Abstract The Taishan Antineutrino Observatory (TAO or JUNO-TAO) is a satellite experiment of the Jiangmen Underground Neutrino Observatory (JUNO). Located near a reactor of the Taishan Nuclear Power Plant, TAO will measure the reactor antineutrino energy spectrum with an unprecedented energy resolution of $$

The Nuclear Pore Complex (NPC) represents a critical passage through the nuclear envelope for nuclear import and export that impacts nearly every cellular process at some level. Recent technological advances in the form of Auxin Inducible Degron (AID) strategies and Single-Point Edge-Excitation sub-Diffraction (SPEED) microscopy have enabled us to provide new insight into the distinct functions and roles of nuclear basket nucleoporins (Nups) upon nuclear docking and export for mRNAs. In this paper, we provide a review of our recent findings as well as an assessment of new techniques, updated models, and future perspectives in the studies of mRNA’s nuclear export.

The physics potential of detecting ^8 B solar neutrinos will be exploited at the Jiangmen Underground Neutrino Observatory (JUNO), in a model-independent manner by using three distinct channels of the charged current (CC), neutral current (NC), and elastic scattering (ES) interactions. Due to the largest-ever mass of ^13 C nuclei in the liquid scintillator detectors and the expected low background level, ^8 B solar neutrinos are observable in the CC and NC interactions on ^13 C for the first time. By virtue of optimized event selections and muon veto strategies, backgrounds from the accidental coincidence, muon-induced isotopes, and external backgrounds can be greatly suppressed. Excellent signal-to-background ratios can be achieved in the CC, NC, and ES channels to guarantee the observation of the ^8 B solar neutrinos. From the sensitivity studies performed in this work, we show that JUNO, with 10 yr of data, can reach the 1 σ precision levels of 5%, 8%, and 20% for the ^8 B neutrino flux, ${\sin }^{2}{\theta }_{12}$ , and ${\rm{\Delta }}{m}_{21}^{2}$ , respectively. Probing the details of both solar physics and neutrino physics would be unique and helpful. In addition, when combined with the Sudbury Neutrino Observatory measurement, the world's best precision of 3% is expected for the measurement of the ^8 B neutrino flux.

O3 poses a significant threat to human health and the ecological environment. In recent years, O3 pollution has become increasingly serious, making it difficult to accurately control O3 precursor emissions. Satellite indicator methods, such as the FNR (formaldehyde-to-nitrogen dioxide ratio (HCHO/NO2 ratio)), provide an effective way to identify ozone pollution control areas on a large geographical scale due to their simple acquisition of datasets. This can help determine the primary factors contributing to O3 pollution and assist in managing it. Based on TROPOMI data from May 2018 to December 2022, combined with ground-based monitoring data from the China National Environmental Monitoring Centre, we explored the uncertainty associated with using the HCHO/NO2 ratio (FNR) as an indicator in ozone control area determination. We focused on the four representative regions in China: Jing-Jin-Ji-Lu-Yu (JJJLY), Jiang-Zhe-Hu-Wan (JZHW), Chuan-Yu (CY), and South China. By using the statistical curve-fitting method, we found that the FNR thresholds were 3.5–5.1, 2.0–4.0, 2.5–4.2, and 1.7–3.5, respectively. Meanwhile, we analyzed the spatial and temporal characteristics of the HCHO, NO2, and O3 control areas. The HCHO concentrations and NO2 concentrations had obvious cyclical patterns, with higher HCHO column densities occurring in summer and higher NO2 concentrations in winter. These high values always appeared in areas with dense population activities and well-developed economies. The distribution characteristics of the ozone control areas indicated that during O3 pollution periods, the urban areas with industrial activities and high population densities were primarily controlled by VOCs, and the suburban areas gradually shifted from VOC-limited regimes to transitional regimes and eventually reverted back to VOC-limited regimes. In contrast, the rural and other remote areas with relatively less development were mainly controlled by NOx. The FNR also exhibited periodic variations, with higher values mostly appearing in summer and lower values appearing in winter. This study identifies the main factors contributing to O3 pollution in different regions of China and can serve as a valuable reference for O3 pollution control.

The surge in deep learning-driven EMR research has centered on harnessing diverse data forms. Yet, the amalgamation of diverse modalities within time series data remains an underexplored realm. This study probes a multimodal fusion approach, merging temporal and non-temporal clinical notes along with tabular data. We leveraged data from 1271 myocardial infarction and 6450 stroke inpatients at a Beijing tertiary hospital. Our dataset encompassed static, and time series note data, coupled with static and time series table data. The temporal data underwent a preprocessing phase, padding to a 30-day interval, and segmenting into 3-day sub-sequences. These were fed into a long short-term memory (LSTM) network for sub-sequence representation. Multimodal attention gates were implemented for both static and temporal subsequence representations, culminating in fused representations. An attention-backtracking module was introduced for the latter, adept at capturing enduring dependencies in temporal fused representations. The concatenated results were channeled into an LSTM to yield the ultimate fused representation. Initially, two note modalities were designated as primary modes, and subsequently, the proposed fusion model was compared with comparative models including recent models such as Crossformer. The proposed model consistently exhibited superior predictive prowess in both tasks. Removing the attention-backtracking module led to performance decline. The proposed model consistently shows excellent predictive capabilities in both tasks. The proposed method not only effectively integrates data from the four modalities, but also has a good understanding of how to handle irregular time series data and lengthy clinical texts. An effective method is provided, which is expected to be more widely used in multimodal medical data representation.

Traditional textile dyeing uses chemical pigments and dyes, which consumes a large amount of water and causes serious environmental pollution. Structural color is an essential means of achieving green dyeing of textiles, and thin-film interference is one of the principles of structural coloring. In the assembly of structural color films, it is necessary to introduce dark materials to suppress light scattering and improve the brightness of the fabric. In this study, the conditions for the generation of nanofilms of catechin (CC) at the gas–liquid interface were successfully investigated. At the same time, environmentally friendly colored silk fabrics were novelly prepared using polycatechin (PCC) structural color films. In addition, it was found that various structural colors were obtained on the surface of silk fabrics by adjusting the time. Meanwhile, the color fastness of the structural colored fabrics was improved by introducing polyvinylpyrrolidone (PVP) to form a strong hydrogen bond between the fabric and catechin. PCC film is uniform and smooth, with a special double-layer structure, and can be attached to the surface of silk fabrics, giving the fabrics special structural colors. Through the thin-film interference formed between the visible light and the PCC film, the silk fabrics obtain bright, controllable, and uniform structural colors. This method is easy to operate and provides a new way of thinking for environmental-protection-oriented coloring of fabrics.

BackgroundNon-suicidal self-injury (NSSI) is a significant predictor of completed suicide and is increasingly recognized as a serious public health concern. Multiple factors, including social, familial, mental, and genetic factors could influence the occurrence of this behavior. Identifying the early risk factors is important for screening and preventing this behavior.MethodsHere, we recruited a total of 742 adolescent inpatient participants from a mental health center and conducted a series of diagnostic interviews and questionnaires to assess NSSI behavior and other events. Bivariate analysis was used to detect differences between groups in NSSI and non-NSSI. Then, binary logistic regression was fitted to identify predictors of NSSI as a function of these questionnaire scores.ResultsOf the 742 adolescents examined, a total of 382 (51.5%) participants engaged in NSSI. Bivariate analysis showed that age, gender, depression, anxiety, insomnia, and childhood trauma was significantly associated with NSSI. Logistic regression results suggested that females had 2.43 higher odds of engaging in NSSI when compared to their male counterparts (OR = 3.43, 95%CI = 2.09–5.74, p = 1.70 × 10−6). Depression was a primary risk predictor for NSSI with each additional increase in symptoms of depression increasing the odds of engaging in NSSI by 18% (OR = 1.18, 95%CI = 1.12–1.25, p = 2.25 × 10−8).ConclusionMore than half of the adolescent inpatients with psychiatric disorders have NSSI experience. Depression and gender were the risk factors for NSSI. Age at a specific range had a high prevalence of NSSI.

IntroductionTea is one of the most widely consumed beverages around the world. Larvae of the moth, Ectropis obliqua Prout (Geometridae, Lepidoptera), are one of the most destructive insect pests of tea in China. E. obliqua is a polyphagus insect that is of increasing concern due to the development of populations resistant to certain chemical insecticides. Microbial biological control agents offer an environmentally friendly and effective means for insect control that can be compatible with “green” and organic farming practices.MethodsTo identify novel E. obliqua biological control agents, soil and inset cadaver samples were collected from tea growing regions in the Fujian province, China. Isolates were analyzed morphologically and via molecular characterization to identity them at the species level. Laboratory and greenhouse insect bioassays were used to determine the effectiveness of the isolates for E. obliqua control.ResultsEleven isolates corresponding to ten different species of Metarhizium were identified according to morphological and molecular analyses from soil and/or insect cadavers found on tea plants and/or in the surrounding soil sampled from eight different regions within the Fujian province, China. Four species of Metarhizium including M. clavatum, M. indigoticum, M. pemphigi, and M. phasmatodeae were documented for the first time in China, and the other species were identified as M. anisopliae, M. brunneum, M. lepidiotae, M. majus, M. pinghaense, and M. robertsii. Insect bioassays of the eleven isolates of Metarhizium revealed significant variation in the efficacy of each isolate to infect and kill E. obliqua. Metarhizium pingshaense (MaFZ-13) showed the highest virulence reaching a host target mortality rate of 93% in laboratory bioassays. The median lethal concentration (LC50) and median lethal time (LT50) values of M. pingshaense MaFZ-13 were 9.6 × 104 conidia/mL and 4.8 days, respectively. Greenhouse experiments and a time-dose-mortality (TDM) models were used to further evaluate and confirm the fungal pathogenic potential of M. pingshaense MaFZ-13 against E. obliqua larvae.DiscussionIsolation of indigenous microbial biological control agents targeting specific pests is an effective approach for collecting resources that can be exploited for pest control with lowered obstacles to approval and commercialization. Our data show the presence of four different previously unreported Metarhizium species in China. Bioassays of the eleven different Metarhizium strains isolated revealed that each could infect and kill E. obliqua to different degrees with the newly isolated M. pingshaense MaFZ-13 strain representing a particularly highly virulent isolate potentially applicable for the control of E. obliqua larvae.

Abstract Background Health insurance plays a significant role in reducing the financial burden for lung cancer patients. However, limited research exists regarding the differences in medical costs for lung cancer patients with different insurance schemes across different cities. We aimed to assess disparities in lung cancer patients’ costs by insurance type and city–specific insurance type. Methods Claim data of China Urban Employees’ Basic Medical Insurance (UEBMI) and Urban Residents’ Basic Medical Insurance (URBMI) between 2010 and 2016 were employed to investigate differences in medical costs. This study primarily applied descriptive analysis and a generalized linear model with a gamma distribution and a log link. Results In total, 92,856 lung cancer patients with inpatient records were identified, with Renminbi (RMB) 11,276 [6322–20,850] (median [interquartile range]) medical costs for the UEBMI group and RMB 8303 [4492–14,823] for the URBMI group. Out–of–pocket (OOP) expenses for the UEBMI group was RMB 2143 [1108–4506] and RMB 2975 [1367–6275] for the URBMI group. The UEBMI group also had significantly higher drug costs, medical service costs, and medical consumable costs, compared to the URBMI group. Regarding city-specific insurances, medical costs for the UEBMI and the URBMI lung cancer patients in Shanghai were RMB 9771 [5183–16,623] and RMB 9741 [5924–16,067], respectively. In Xianyang, the medical costs for UEBMI and URBMI patients were RMB 11,398 [6880–20,648] and RMB 9853 [5370–24,674], respectively. The regression results showed that the UEBMI group had 27.31% fewer OOP expenses than the URBMI group did, while patients in Xiangyang and Xianyang had 39.53 and 35.53% fewer OOP expenses, respectively, compared to patients in Shanghai. Conclusions Compared with the URBMI patients, the UEBMI lung cancer patients obtained more or even better health services and had reduced financial burden. The differences in insurances among cities were greater, compared to those among insurances within cities, and the differences in OOP expenses between cities were greater compared to those between UEBMI and URBMI. Our results called for further reform of China’s fragmented insurance schemes.

Abstract The global pandemic of COVID-19 has caused huge causality and unquantifiable loss of social wealth. The innate immune response is the first line of defense against SARS-CoV-2 infection. However, strong inflammatory response associated with dysregulation of innate immunity causes severe acute respiratory syndrome (SARS) and death. In this review, we update the current knowledge on how SARS-CoV-2 modulates the host innate immune response for its evasion from host defense and its corresponding pathogenesis caused by cytokine storm. We emphasize Type I interferon response and the strategies of evading innate immune defense used by SARS-CoV-2. We also extensively discuss the cells and their function involved in the innate immune response and inflammatory response, as well as the promises and challenges of drugs targeting excessive inflammation for antiviral treatment. This review would help us to figure out the current challenge questions of SARS-CoV-2 infection on innate immunity and directions for future studies.

Prior studies reported inconsistent results on the altered gut microbial composition in patients with Crohn’s disease (CD), likely under the influences of many confounding factors including genetic, life style and environmental variations among different study cohorts. This study aims to examine the gut microbiota of CD patients with particular efforts to minimize the impact of the confounding factors. For this purpose, the healthy relatives of the patients were enrolled as control subjects so that the paired study subjects may have similar genetic background, dietary habits, and household environment. The fecal microbiota of the study subjects were examined by 16S rRNA sequencing. After the identification of the differential bacterial genera, multivariate regression analysis was performed to adjust the results for the impact of confounding factors. We found that the microbiota of the CD patients were featured with reduced short chain fatty acid (SCFA) producing bacteria and elevated opportunistic pathogen Escherichia-Shigella. Correlation analysis indicated that the elevation in Escherichia-Shigella and the reduction in SCFA-producing bacteria usually occur simultaneously. These differential genera exhibited a high capacity in distinguishing between CD and healthy controls achieving an area under curve of 0.89, and were correlated with the changes in inflammation related blood biochemical markers. Consistent with the reduction in SCFA-producing bacteria in CD, metabolomics analysis revealed decreased blood level of SCFAs in the patients. The differential genera identified in this study demonstrated outstanding capability to serve as diagnosis markers for CD and are potential targets for intervention.

BackgroundSmall non-functional neuroendocrine tumors (NF-PNETs) are a heterogeneous subset of tumors with controversy regarding their optimal management. We aimed to analyze the prognostic factors of patients with small NF-PNETs and create a risk score for lymph node metastasis (LNM).MethodsData of 751 patients with NF-PNETs ≤ 2 cm were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate survival analysis was performed to analyze the prognostic factors. Logistic regression was used to identify risk factors for LNM.ResultsOf the 751 patients, 99 (13.2%) were confirmed to have LNM. In multivariate survival analysis, LNM (hazard ratio [HR], 2.12; 95% CI, 1.04–4.32, p = 0.040) was independently associated with disease-specific survival. Logistic regression identified that tumor location in the head of the pancreas (odds ratio [OR], 4.33; 95% CI, 2.75–6.81; p < 0.001), size ≥ 1.5–2 cm (OR, 1.84; 95% CI, 1.17–2.87; p = 0.009), and grade III–IV (OR, 7.90; 95% CI, 1.79–34.90; p = 0.006) were independent risk factors of LNM. According to the OR value, the risk of LNM was scored as follows: a score of 1 for tumors located in the body/tail of the pancreas and 4 for those located in the head; a score of 1 for tumors

Alkaline sphingomyelinase (alk-SMase) is phospholipase that creates ceramides and inactivates platelet activating factors during metabolism, and is linked to digestion and cancer prevention. There have been few studies that completely investigate the linked function and identify the genes related to alk-SMase. In this work, RNA sequencing was performed to investigate the function of alk-SMase. Using RNA-seq data, we discovered 95 differentially expressed genes in the liver of wild type (WT) mice and alk-SMase (gene NPP7) knockout (KO) mice. Differentially expressed genes were functionally associated with the inflammatory response, steroid metabolic process and TNF signaling pathway related terms, regulation of carbohydrate biosynthetic process, and Cytochrome P450-arranged by substrate type using Metascape, according to the results of gene ontology functional enrichment analysis. In addition, an integrated PPI and KEGG network was used to investigate the relationship of differentially expressed genes, It was discovered that one module, which contained 21 nodes and 23 interactions, was significantly related to Cytochrome P450 family, which as mediator of phospholipase. To corroborate the RNAseq results, we identified 12 important genes with high expression levels and significant differences in RNAseq for quantitative real-time polymerase chain reaction (qPCR) verification; 7 genes showed difference significantly (P

NLRP3 inflammasome is implicated in the pathogenesis of inflammatory bowel diseases (IBD). Since guanylate-binding protein 5 (GBP5) induces the NLRP3 inflammasome activity, we aim to investigate the potential role of GBP5 in IBD pathogenesis. The expression of GBP5, NLRP3 inflammasome, and related cytokines and chemokines was examined in two cohorts of IBD patients and healthy controls, by microarray transcriptome analysis and quantitative real-time PCR. Cellular localization of GBP5 in colonic biopsies was examined by immunohistochemistry and immunofluorescence with confocal microscopy. For functional studies, GBP5 was induced by interferon γ or silenced by siRNA or CRISPR/CAS9 technique, and inflammatory activities were evaluated at mRNA and protein levels. We found that the expression of GBP5 was elevated in colonic mucosa in two geographically and culturally distinct IBD cohorts. In colonic tissues of IBD patients, GBP5 expression was mainly confined to immune cells and the levels of GBP5 expression were correlated with those of the inflammatory cytokines and chemokines. In cultured T and macrophage cells, the expression of proinflammatory cytokines and chemokines was increased when GBP5 was induced, while GBP5 deficiency leads to decreased expression of proinflammatory mediators including gasdermin D, caspase 1, cytokines, and chemokines. We conclude that GBP5 is required in the expression of many proinflammatory cytokines and chemokines in intestinal immune cells. In addition, GBP5 may upregulate inflammatory reactions through an inflammasome-mediated mechanism. Since GBP5 plays a proinflammatory role at the early steps of the inflammatory cascades of IBD pathogenesis, and is implicated in IBD patients of distinct genetic and environmental backgrounds, targeting GBP5 could be an effective strategy for the management of IBD.

Summary: Hsp70 is a key molecular chaperone in the protein quality control system to safeguard protein homeostasis in cells. Previous studies have shown that Hsp70 chaperones TDP-43, a pathogenic protein associated with amyotrophic lateral sclerosis (ALS), in nuclear bodies and prevents it from the pathological aggregation. In this work, we report that Hsp70 undergoes liquid-liquid phase separation, chaperones FUS, another ALS-linked pathogenic protein, in stress granules (SGs), and prevents condensed FUS from amyloid aggregation. Knock-down of Hsp70 does not influence SG assembly but results in the liquid-to-solid transition in SGs. NMR experiments further reveal Hsp70 predominantly uses its C-terminal substrate-binding domain to interact with the low complexity domain of FUS, which represents a mechanism distinct from that interacting with TDP-43. These findings suggest that Hsp70 is widely involved in chaperoning the physiological dynamics of various membrane-less organelles and adopts different mechanisms to prevent the pathological aggregation of different proteins.

Most cancer‐related deaths result from the progressive growth of metastases. Patients with peritoneal metastatic (PM) colorectal cancer have reduced overall survival. Currently, it is still unclear why colorectal cancer (CRC) cells home to and proliferate inside the peritoneal cavity, and there is no effective consolidation therapy for improved survival. Using a proteomic approach, we found that key enzymes of fatty acid oxidation (FAO) were decreased in patients with PM colorectal cancer. Furthermore, we confirmed that carnitine palmitoyltransferase IA (CPT1A), a rate‐limiting enzyme of FAO, was expressed at significantly low levels in patients with PM colorectal cancer, as determined by RT‐qPCR, IHC, and GEO dataset analysis. However, lipidomics revealed no difference in FFA levels between PM and non‐PM primary tumors. Here, we showed that cancer‐associated fibroblasts (CAFs) promote the proliferation, migration, and invasion of colon cancer cells via upregulating CPT1A to actively oxidize FAs and conduct minimal glycolysis. In addition, coculture‐induced glycolysis increased in cancer cells while fatty acid catabolism decreased with lower adiponectin levels. Importantly, inhibition of glycolysis significantly reduced the survival of CRC cells after incubation with conditioned medium from CAFsCPT1A‐OE in vitro and impaired the survival and growth of organoids derived from CRC‐PM. Finally, we found that directly blocking FAO in CAFsCPT1A‐OE with etomoxir inhibits migration and invasion in vitro and decreases tumor growth and intraperitoneal dissemination in vivo, revealing a role for CAF CPT1A in promoting tumor growth and invasion. In conclusion, our results suggest the possibility of testing FAO inhibition as a novel approach and clinical strategy against CAF‐induced colorectal cancer with peritoneal dissemination/metastases.

Abstract Associations between gut microbiota and colorectal cancer (CRC) have been widely investigated. However, the replicable markers for early-stage adenoma diagnosis across multiple populations remain elusive. Here, we perform an integrated analysis on 1056 public fecal samples, to identify adenoma-associated microbial markers for early detection of CRC. After adjusting for potential confounders, Random Forest classifiers are constructed with 11 markers to discriminate adenoma from control (area under the ROC curve (AUC) = 0.80), and 26 markers to discriminate adenoma from CRC (AUC = 0.89), respectively. Moreover, we validate the classifiers in two independent cohorts achieving AUCs of 0.78 and 0.84, respectively. Functional analysis reveals that the altered microbiome is characterized with increased ADP-l-glycero-beta-d-manno-heptose biosynthesis in adenoma and elevated menaquinone-10 biosynthesis in CRC. These findings are validated in a newly-collected cohort of 43 samples using quantitative real-time PCR. This work proves the validity of adenoma-specific markers across multi-populations, which would contribute to the early diagnosis and treatment of CRC.

In this study, the physiological and thermal responses of 54 healthy elderly adults during horticultural activities with various intensities (low, moderate, and high) in three typical open spaces were investigated through meteorological measurements, questionnaires, and physiological monitoring. Physiological equivalent temperature (PET), blood pressure, heart rate, oxygen saturation, and ear canal temperature were used as physiological evaluation indices. The results showed that: (1) the proportional changes before and after thermal sensation vote (TSV) and thermal comfort vote (TCV) activities were positively correlated with the spatial characteristics and metabolic levels of outdoor activities in summer; (2) physiological indices were almost constant during low-intensity horticultural activities and significantly different before and after moderate-intensity and vigorous-intensity horticultural activities; (3) when the intensity of horticultural activities changed from low to moderate, the neutral PET (NPET) decreased to 25.29 and 26.82 °C, respectively, whereas the NPET increased to 23.97 °C during vigorous intensity; (4) heart rate (HR) and diastolic blood pressure (SBP) were positively correlated with metabolic rate for the elderly; (5) a moderate sky view factor space was more suitable for the elderly to participate in during outdoor horticultural activities in summer.

Background: The pathological differences between Crohn’s disease (CD) and ulcerative colitis (UC) are substantial and unexplained yet. Here, we aimed to identify potential regulators that drive different pathogenesis of CD and UC by causal inference analysis of transcriptome data.Methods: Kruskal–Wallis and Dunnett’s tests were performed to identify differentially expressed genes (DEGs) among CD patients, UC patients, and controls. Subsequently, differentially expressed pathways (DEPs) between CD and UC were identified and used to construct the interaction network of DEPs. Causal inference was performed to identify IBD subtype-regulators. The expression of the subtype-regulators and their downstream genes was validated by qRT-PCR with an independent cohort.Results: Compared with the control group, we identified 1,352 and 2,081 DEGs in CD and UC groups, respectively. Multiple DEPs between CD and UC were closely related to inflammation-related pathways, such as NOD-like receptor signaling, IL-17 signaling, and chemokine signaling pathways. Based on the priori interaction network of DEPs, causal inference analysis identified IFNG and GBP5 as IBD subtype-regulators. The results with the discovery cohort showed that the expression level of IFNG, GBP5, and NLRP3 was significantly higher in the CD group than that in the UC group. The regulation relationships among IFNG, GBP5, and NLRP3 were confirmed with transcriptome data from an independent cohort and validated by qRT-PCR.Conclusion: Our study suggests that IFNG and GBP5 were IBD subtype-regulators that trigger more intense innate immunity and inflammatory responses in CD than those in UC. Our findings reveal pathomechanical differences between CD and UC that may contribute to personalized treatment for CD and UC.

Summary: Numerous proteins can undergo liquid-liquid phase separation (LLPS) in various biological processes. However, it remains a challenge to systematically evaluate the LLPS ability of proteins. Here, we develop a high-throughput protein phase separation (HiPPS) profiling method to delineate LLPS ability of proteins, which we term as the LLPS space of proteins. We next apply HiPPS to explore LLPS space of more than 30 different proteins including RNA-binding proteins, chaperones, amyloid proteins, and enzymes. Our results demonstrate that (1) LLPS is a common property of both unstructured and well-folded proteins; (2) LLPS space of protein can be dynamically reshaped by protein-protein interaction, post-translational modification, and genetic mutation; and (3) multi-component co-LLPS mixture decreases the threshold concentration of individual proteins for LLPS. We anticipate that the HiPPS method may effectively characterize LLPS of individual proteins or protein mixtures in vitro, which is valuable for understanding its role in biological processes.

Abstract Background Prior studies reported that 5 ~ 32% COVID-19 patients were critically ill, a situation that poses great challenge for the management of the patients and ICU resources. We aim to identify independent risk factors to serve as prediction markers for critical illness of SARS-CoV-2 infection. Methods Fifty-two critical and 200 non-critical SARS-CoV-2 nucleic acid positive patients hospitalized in 15 hospitals outside Wuhan from January 19 to March 6, 2020 were enrolled in this study. Multivariable logistic regression and LASSO logistic regression were performed to identify independent risk factors for critical illness. Results Age older than 60 years, dyspnea, respiratory rate > 24 breaths per min, leukocytosis > 9.5 × 109/L, neutrophilia > 6.3 × 109/L, lymphopenia 3.53, fibrinogen > 4 g/L, d-dimer > 0.55 μg/mL, blood urea nitrogen > 7.1 mM, elevated aspartate transaminase, elevated alanine aminotransferase, total bilirubin > 21 μM, and Sequential Organ Failure Assessment (SOFA) score ≥ 2 were identified as risk factors for critical illness. LASSO logistic regression identified the best combination of risk factors as SOFA score, age, dyspnea, and leukocytosis. The Area Under the Receiver-Operator Curve values for the risk factors in predicting critical illness were 0.921 for SOFA score, 0.776 for age, 0.764 for dyspnea, 0.658 for leukocytosis, and 0.960 for the combination of the four risk factors. Conclusions Our findings advocate the use of risk factors SOFA score ≥ 2, age > 60, dyspnea and leukocytosis > 9.5 × 109/L on admission, alone or in combination, to determine the optimal management of the patients and health care resources.

The contribution of central and peripheral channels of nuclear pores to transport of transmembrane proteins is unclear. Here the authors show that most inner nuclear membrane proteins use only peripheral channels, but some extend nuclear localization signals into the central channel for directed nuclear transport.

As the proportion of new energy sources in the grid increases and the structure of the ultra-high-voltage grid becomes more complicated, the variability of the external environment and the complexity of the grid itself bring many new challenges to the power system reserve configuration problem. The multilevel and multitime scale characteristics of the grid reserve are analyzed in this paper, and the reserve is classified according to the response time characteristics combined with the system function. We establish a demand-side response participation system reserve configuration optimization model, including synchronous generator generation and reserve models, demand-side scheduling and reserve models, grid power generation planning and reserve optimization mathematical models. Based on the idea of decomposition coordination, the current power generation plan and reserve optimization problem are decomposed into a finite fault state safety constraint unit combination subproblem, Monte Carlo secondary negative reserve constraint check subproblem, frequency safety constraint checking subproblem based on large-disturbance long-process time domain simulation analysis, and fault state static safety constraint check subproblem based on minimum load shedding. Considering the demand side response to the reserve configuration of the system, combined with the problem of previous unit association, the optimal allocation of the reserve coal consumption units is realized by determining the start and stop status of the unit and the unit output.

Discovery of novel pharmacological effects of berberine hydrochloride (BH) has made its clinical application valuable. However, further development and applications of BH are hampered by its short half-life and the side effects associated with its intravenous (iv) injection. To improve the hypolipidemia efficacy and reduce side effects, we encapsulated BH into biocompatible red blood cells (RBCs) to explore its sustained-release effect by hypotonic pre-swelling method. From in vitro evaluation, BH loaded RBCs (BH-RBCs) presented similar morphology and osmotic fragility to native RBCs (NRBCs). After the loading process, the BH-RBCs maintained around 69% of Na+/K+-ATPase activity of NRBCs and phosphatidylserine externalization value of BH-RBCs was about 26.1 ± 2.9%. The survival test showed that the loaded cells could circulate in plasma for over 9 d. For in vivo evaluation, a series of tests including pharmacokinetics study and hypolipidemic effect were carried out to examine the long-acting effect of BH-RBCs. The results showed that the release of BH in the loaded cells could last for about 5 d and the hypolipidemic effect can still be observed on 5 d after injection. BH-loaded autologous erythrocytes seem to be a promising sustained releasing delivery system with long hypolipidemic effect.

Hindered casing strings are often encountered in unconventional oil and gas exploration during the casing running process. This not only increases the operating costs and time but can also lead to downhole accidents and even abandonment in serious cases. Due to various assumptions, the calculation results of the existing soft models and hard models are different, which causes confusion for field operators when taking friction reduction measures. Moreover, a lowering force is often applied to assist hindered casing string running in a drilling field. However, its application is mainly based on work experience and lacks mechanistic analysis and theoretical guidance. Thus, in this study, a simulation model for the analysis of casing string tripability in a directional well was established and the model was combined with the continuous beam-column theory and buckling theory. The model was used to study how various factors including the friction coefficient, drilling fluid density, and casing diameter could affect the lowering force required when a casing string was hindered by buckling. The results showed that the maximum lowering force and the maximum effective lowering force decreased with the increase in the friction coefficient and the performance of the drilling fluid could be adjusted rapidly, which would be beneficial for ensuring that the casing string could be tripped smoothly by applying a lowering force. The increase in the drilling fluid density caused the maximum lowering force and the maximum effective lowering force to decrease, which was not conducive to hindered casing string running. The larger the casing diameter was, the greater the maximum lowering force and the maximum effective lowering force were. It was more convenient to apply a lowering force for a casing with a large diameter. In addition, the improved model could identify whether the casing string was in contact with the upper or lower borehole walls. Through finite element method verification, the prediction was in line with the actual casing running operation and the improved model has the smallest prediction error, i.e., 6.58%, compared with the existing models. Therefore, the improved model might provide necessary theoretical guidance for casing running operations in directional wells.

Summary: FUS is a multifunctional nuclear protein which undergoes liquid–liquid phase separation in response to stress and DNA damage. Dysregulation of FUS dynamic phase separation leads to formation of pathological fibril closely associated with neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal dementia. In this study, we determined the cryo-EM structure of a cytotoxic fibril formed by the low-complexity (LC) domain of FUS at 2.9 Å resolution. The fibril structure exhibits a new and extensive serpentine fold consisting of three motifs incorporating together via a Tyr triad. FUS LC employs 91 residues to form an enlarged and stable fibril core via hydrophilic interaction and hydrogen bonds, which is distinct from most of previously determined fibrils commonly stabilized by hydrophobic interaction. Our work reveals the structural basis underlying formation of a cytotoxic and thermostable fibril of FUS LC and sheds light on understanding the liquid-to-solid phase transition of FUS in disease.

The incorporation of steel fibers into the natural soil is generally considered to be a novel and effective way to reduce the amount of frost heave induced by an artificial freezing process in underground engineering. In order to analyze the frost heave behavior of the steel fiber improved soil, a one-dimensional frost heave test under the open recharge system was conducted in this paper, focusing on the influence of steel fiber content, size, and soil properties. The results show that small amounts of steel fibers in the soil will not significantly affect the freezing process and temperature distribution, while the water-conducting properties of the steel fibers and the effect of limiting the ice lens growth can reduce the frost heave rate of the samples incorporated with 0.5% steel fibers by 26.93%. At the same time, the reduction effect of the frost heave rate increases linearly with the increase of steel fiber content and length but weakens with the increase of steel fiber diameter. In terms of soil property influence, the frost heave rate of the clay samples was reduced by 14.31% compared to the silt samples, while the water migration was reduced by 11.99%. In addition, the cementation of the steel fibers with the soil will also inhibit the growth of the ice lens and reduce the external water migration, thus significantly lowering the frost heave rate. The results can provide a reference for the research of the frost deformation of similar modified soils.