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Abstract To prolong the network lifetime of energy harvesting-cognitive radio sensor networks (EH-CRSNs), this paper integrates active intelligent reflecting surface (IRS) to support both downlink EH and uplink data transmissions and formulates a constrained non-convex optimization problem that maximizes the net energy gain. To solve this problem, a joint passive beamforming and IRS deployment mechanism is proposed to determine the optimal deployment location of the active IRS and optimally configure the IRS reflection coefficient matrices. Specifically, the net energy gain maximization problem at a specified location is divided into two sub-problems according to its characteristics: maximizing the cumulative energy harvested by all CRSNs nodes in the downlink and minimizing the energy consumption of cluster heads in uplink data transmissions, with each sub-problem being solved independently. Furthermore, this paper explores how factors such as the number of active reflecting elements and the amplification power budget influence the optimal deployment location of the active IRS. The findings from this investigation can guide the design of active IRS-assisted EH-CRSNs under specified parameters. Simulation results confirm the aforementioned conclusions and highlight the benefits of the proposed joint mechanism in enhancing net energy gain over various benchmark mechanisms.

Abstract BAP1, BRCA1-Associated Protein 1, serves as a novel tumor suppressor through the deubiquitination of monoubiquitination of H2A and subsequent gene transcriptional regulation. Regulated cell death like apoptosis or ferroptosis is considered an essential mechanism mediating tumor suppression. Previous reports, including ours, have demonstrated that BAP1 could promote apoptosis and ferroptosis to inhibit tumor development. Whether BAP1 regulated additional types of cell death remains unclear. Disulfidptosis is a recently identified novel cell death mode characterized by aberrant accumulation of intracellular disulfide (e.g., cystine) and depletion of NADPH. In this study, we first demonstrated that BAP1 could significantly protect disulfidptosis induced by glucose starvation, which is validated by various cell death inhibitors and the accumulation of disulfide bonds in the cytoskeleton proteins. BAP1 is known to inhibit SLC7A11 expression. We found that the protective effect of BAP1 against disulfidptosis was counteracted when overexpressing SLC7A11 or adding additional cystine. Conversely, BAP1-mediated suppression of disulfidptosis was largely abrogated when SLC7A11-mediated cystine uptake was inhibited by the knockout of SLC7A11 or erastin treatment. Besides, high BAP1 expression showed lower NADP+/NADPH levels, which might confer resistance to disulfidptosis. Consistent with these observations, the expression level of BAP1 was also positively correlated with NADPH-related genes in KIRC patients, though the underlying mechanism mediating NADPH regulation remains further investigation. In summary, our results revealed the role of BAP1 in the regulation disulfidptosis and provided new insights into the understanding of disulfidptosis in tumor development.

Abstract Endo-periodontal lesions (EPLs) involve both the periodontium and pulp tissue and have complicated etiologies and pathogenic mechanisms, including unique anatomical and microbiological characteristics and multiple contributing factors. This etiological complexity leads to difficulties in determining patient prognosis, posing great challenges in clinical practice. Furthermore, EPL-affected teeth require multidisciplinary therapy, including periodontal therapy, endodontic therapy and others, but there is still much debate about the appropriate timing of periodontal therapy and root canal therapy. By compiling the most recent findings on the etiology, pathogenesis, clinical characteristics, diagnosis, therapy, and prognosis of EPL-affected teeth, this consensus sought to support clinicians in making the best possible treatment decisions based on both biological and clinical evidence.

Abstract The Wnt receptor Frizzled3 (FZD3) is important for brain axonal development and cancer progression. We report structures of FZD3 in complex with extracellular and intracellular binding nanobodies (Nb). The crystal structure of Nb8 in complex with the FZD3 cysteine-rich domain (CRD) reveals that the nanobody binds at the base of the lipid-binding groove and can compete with Wnt5a. Nb8 fused with the Dickkopf-1 C-terminal domain behaves as a FZD3-specific Wnt surrogate, activating β-catenin signalling. The cryo-EM structure of FZD3 in complex with Nb9 reveals partially resolved density for the CRD, which exhibits positional flexibility, and a transmembrane conformation that resembles active GPCRs. Nb9 binds to the cytoplasmic region of FZD3 at the putative Dishevelled (DVL) or G protein-binding site, competes with DVL binding, and inhibits GαS coupling. In combination, our FZD3 structures with nanobody modulators map extracellular and intracellular interaction surfaces of functional, and potentially therapeutic, relevance.

ABSTRACT Adult severe caries (ASC) brings severe oral dysfunction and treatment difficulties to patients, and yet no clear pathogenic mechanism for it has been found. This study is focused on the composition of dental plaque microbiome profiles in order to identify disease-relevant species and to investigate into their interactions with the S. mutans. Samples of dental plaque were collected for metagenomic analysis. The acidification, aciduricity, oxidative stress tolerance, and gtf (glucosyltransferase) gene expression of S. mutans cocultured with V. parvula which was identified as ASC-related dominant bacterium. The biofilm formation and extracellular exopolysaccharide (EPS) synthesis of dual-strain were analyzed with scanning electron microscopy (SEM), crystal violet (CV) staining, live/dead bacterial staining, and confocal laser scanning microscopy (CLSM). Furthermore, rodent model experiments were performed to validate the in vivo cariogenicity of the dual-species biofilm. The most significantly abundant taxon found associated with ASC was V. parvula. In vitro experiments found that V. parvula can effectively promote S. mutans mature biofilm formation with enhanced acid resistance, hydrogen peroxide detoxicity, and biofilm virulence. Rodent model experiments revealed that V. parvula was incapable of causing disease on its own, but it significantly heightened the biofilm virulence of S. mutans when being co-infected and augmented the progression, quantity, and severity of dental caries. Our findings demonstrated that V. parvula may act as a synergistic pathobiont to modulate the metabolic activity, spatial structure, and pathogenicity of biofilms of S. mutans in the context of ASC.IMPORTANCEAdult severe caries (ASC), as a special type of acute caries, is rarely reported and its worthiness of further study is still in dispute. Yet studies on the etiology of severe caries in adults have not found a clear pathogenic mechanism for it. Knowledge of the oral microbiota is important for the treatment of dental caries. We discovered that the interaction between V. parvula and S. mutans augments the severity of dental caries in vivo, suggesting V. parvula may act as a synergistic pathobiont exacerbating biofilm virulence of S. mutans in ASC. Our findings may improve the understanding of ASC pathogenesis and are likely to provide a basis for planning appropriate therapeutic strategies.

Background/Aims: Early diagnosis of gastric cancer can improve the prognosis of patients, especially for those with early gastric cancer (EGC), but only 15% of patients, or less, are diagnosed with EGC and precancerous lesions. Magnifying endoscopy with narrow-band imaging (ME-NBI) can improve diagnostic accuracy. We assess the efficacy of ME-NBI in diagnosing ECG and precancerous lesions, especially some characteristics under NBI+ME. Materials and Methods: This was a retrospective analysis of 131 patients with EGC or gastric intraepithelial neoplasia (IN) who had undergone endoscopic submucosal dissection and were pathologically diagnosed with EGC or IN according to 2019 WHO criteria for gastrointestinal tract tumors. We studied the characteristics of lesions under ME-NBI ,compared the diagnostic efficacy of ME-NBI and white light endoscopy (WLI) plus biopsy, and investigated the effect of Helicobacter pylori infection on microvascular and microsurface pattern. Results: The diagnostic accuracy of ME-NBI for EGC, high-grade IN (HGIN), and low-grade IN (LGIN) was 76.06%, 77.96%, and 77.06%, respectively. The accuracy of WLI plus biopsy in diagnosing the above lesions was 69.7%, 57.5%, and 60.53%, respectively. The rate of gyrus-like tubular pattern was highest in LGIN (60.46%), whereas the highest rate of papillary pattern was 57.14% in HGIN and villous tubular pattern was 52% in EGC. Demarcation lines have better sensitivity for differentiating EGC from IN (92.06%). Conclusion: The ME-NBI has higher diagnostic accuracy for EGC than WLI plus biopsy. Demarcation lines and villous and papillary-like microsurface patterns are more specific as EGC and HGIN characteristics. The cerebral gyrus-like microsurface pattern is more specific for LGIN.

Abstract Background Oral squamous cell carcinoma (OSCC) remains a rampant oral cavity neoplasm with high degree of aggressiveness. Aldo–keto reductase 1B10 (AKR1B10) that is an oxidoreductase dependent on nicotinamide adenine dinucleotide phosphate (NADPH) has been introduced to possess prognostic potential in OSCC. The present work was focused on specifying the involvement of AKR1B10 in the process of OSCC and its latent functional mechanism. Methods AKR1B10 expression in OSCC tissues and cells were detected by RT-qPCR and Western blot analysis. CCK-8 method, EdU staining, wound healing and transwell assays respectively assayed cell viability, proliferation, migration and invasion. Immunofluorescence staining and Western blot evaluated epithelial mesenchymal transition (EMT). Adenosine triphosphate (ATP) contents, glucose consumption and extracellular acidification rate (ECAR) were measured by relevant commercially available kits and Seahorse XF96 Glycolysis Analyzer, severally. The expressions of proteins associated with metastasis and glycolysis were examined with Western blot. Co-IP assay confirmed the binding between AKR1B10 and hexokinase 2 (HK2). Results It was observed that AKR1B10 expression was increased in OSCC tissues and cells. After AKR1B10 was knocked down, the proliferation, migration, invasion and EMT of OSCC cells were all hampered. Additionally, AKR1B10 silencing suppressed glycolysis and bound to HK2 in OSCC cells. Up-regulation of HK2 partially abolished the hampered glycolysis, proliferation, migration, invasion and EMT of AKR1B10-silenced OSCC cells. Conclusion To sum up, AKR1B10 could bind to HK2 to accelerate glycolysis, thereby facilitating the proliferation, migration, invasion and EMT of OSCC cells.

Abstract Background Caspase Recruitment Domain-containing protein 9 (CARD9) expressed in myeloid cells has been demonstrated to play an antifungal immunity role in protecting against disseminated candidiasis. Hereditary CARD9 ablation leads to fatal disseminated candidiasis. However, the myeloid cell types and molecular mechanisms implicated in CARD9 protecting against disseminated candidiasis remain wholly elusive. Methods The role of CARD9 ablation in exacerbating disseminated candidiasis was determined in vivo and in vitro. The molecular mechanism by which CARD9 ablation promotes acute kidney injury in disseminated candidiasis was identified by RNA-sequencing analysis. The expression of mitochondrial proteins and ferroptosis-associated proteins were measured by Quantitative real-time PCR and western blot. Results CARD9 ablation resulted in a reduced proportion of myeloid-derived suppressor cells (MDSCs) and a substantially lower expression of solute carrier family 7 member 11 (SLC7A11) in the kidneys, which increased susceptibility to acute kidney injury and renal ferroptosis during disseminated Candida tropicalis (C. tropicalis) infection. Moreover, CARD9-deficient MDSCs were susceptible to ferroptosis upon stimulation with C. tropicalis, which was attributed to augmented mitochondrial oxidative phosphorylation (OXPHOS) caused by reduced SLC7A11 expression. Mechanistically, C-type lectin receptors (CLRs)-mediated recognition of C. tropicalis promoted the expression of SLC7A11 which was transcriptionally manipulated by the Syk-PKCδ-CARD9-FosB signaling axis in MDSCs. FosB enhanced SLC7A11 transcription by binding to the promoter of SLC7A11 in MDSCs stimulated with C. tropicalis. Mitochondrial OXPHOS, which was negatively regulated by SLC7A11, was responsible for inducing ferroptosis of MDSCs upon C. tropicalis stimulation. Finally, pharmacological inhibition of mitochondrial OXPHOS or ferroptosis significantly increased the number of MDSCs in the kidneys to augment host antifungal immunity, thereby attenuating ferroptosis and acute kidney injury exacerbated by CARD9 ablation during disseminated candidiasis. Conclusions Collectively, our findings show that CARD9 ablation enhances mitochondria-mediated ferroptosis in MDSCs, which negatively regulates antifungal immunity. We also identify mitochondria-mediated ferroptosis in MDSCs as a new molecular mechanism of CARD9 ablation-exacerbated acute kidney injury during disseminated candidiasis, thus targeting mitochondria-mediated ferroptosis is a novel therapeutic strategy for acute kidney injury in disseminated candidiasis.

Abstract This study assesses the reliability and limitations of the Geostationary Lightning Mapper (GLM) in detecting continuing currents by comparing observations from ground‐based high‐speed cameras with GLM‐16 data. Our findings show that the GLM's one‐group detection efficiency (DE_1) is 53%, while the more stringent five‐consecutive‐group detection efficiency (DE_5) is 10%. Optical signals detected by the GLM predominantly occur during the early stages of continuing currents. Additionally, there is a notable disparity in detection efficiencies between positive and negative continuing currents, with positive continuing currents being detected more frequently. The application of the logistic regression model developed by Fairman and Bitzer (2022) further illustrates the limitations in continuing current identification. The study underscores the challenges of relying solely on satellite data to monitor and analyze continuing currents, emphasizing the need for advancements in detection technologies and methodologies to reliably detect continuing current at a large spatial scale.

Abstract Objective The purpose of this study was to assess the composition of the oral microbial flora of adults with rampant caries in China to provide guidance for treatment. Patients and methods Sixty human salivary and supragingival plaque samples were collected. They were characterized into four groups: patients with rampant caries with Sjogren’s syndrome (RC-SS) or high-sugar diet (RC-HD), common dental caries (DC), and healthy individuals (HP). The 16S rRNA V3-V4 region of the bacterial DNA was detected by Illumina sequencing. PCoA based on OTU with Bray–Curtis algorithm, the abundance of each level, LEfSe analysis, network analysis, and PICRUSt analysis were carried out between the four groups and two sample types. Clinical and demographic data were compared using analysis of variance (ANOVA) or the nonparametric Kruskal–Wallis rank-sum test, depending on the normality of the data, using GraphPad Prism 8 (P

Abstract Background and Objective While earlier studies have focused on the relationship between stress and obesity, there was a gap in understanding the potential impact of positive psychological factors, such as resilience, on obesity. By investigating the role of psychological resilience with obesity, this study aimed to address this gap and tackle obesity through a positive psychological framework. Methods Participants consisted of 2445 community residents from Shenzhen, China, with a mean age of 41.09 ± 13.72 years, comprising 846 males and 1599 females. Psychological resilience was measured using the Brief Resilience Scale; gender, age, marital status, education level, smoking status, alcohol consumption, frequency of physical exercise, and perceived stress were considered potential confounding factors. The relationship between psychological resilience and body mass index (BMI) was examined through multiple linear regression and logistic regression analyses. Results The participants had an average psychological resilience score of 3.46 (standard deviation [SD] = 0.62) and an average BMI of 22.59 (SD = 3.35), with 104 individuals (4.3%) identified with obesity. In the fully adjusted multiple linear regression model, a higher psychological resilience score was associated with a higher BMI (β = 0.507, 95% CI:0.283, 0.731). In the logistic regression model, higher psychological resilience scores were linked to increased obesity risk, with a more significant association observed among males (odds ratio [OR] = 2.169, 95% CI:1.155, 4.073), while psychological resilience acted as a protective factor against underweight among females (OR = 0.528, 95% CI:0.376, 0.816). Conclusion The study demonstrated a significant link between higher psychological resilience and elevated BMI, emphasizing the complex relationship between psychological fortitude and weight management. Interventions targeting socioeconomic status, education, lifestyle habits, and physiological well‐being might offer a promising strategy for enhancing psychological resilience and promoting healthier weight. Emphasizing self‐efficacy and coping skills at the individual level could contribute to balanced weight and comprehensive health outcomes, addressing the global challenge of obesity.

Abstract KMT2A-rearranged acute myeloid leukemia (KMT2Ar-AML) is an aggressive subtype of AML with poor response and prognosis. KMT2Ar-AML has been demonstrated to be sensitive to BCL2 inhibitor venetoclax (VEN), but these patients are unable to benefit from current VEN-based regimen (VEN plus azacitidine or low dose-cytarabine), so a novel and KMT2A rearrangement-specific targeting partner is required, and MENIN inhibitor (MEN1i) is a promising one. Herein, we investigated the effect and mechanism of VEN plus MEN1i in KMT2Ar-AML. Our results showed that VEN and MEN1i exhibited a striking synergistic effect in KMT2Ar-AML cell lines (in vitro), primary KMT2Ar-AML cells (ex vivo), and MOLM13 xenotransplantation model (in vivo). Furthermore, we found that VEN plus MEN1i significantly enhanced apoptotic induction in KMT2Ar-AML cell lines. VEN or MEN1i monotherapy disrupted balance of BCL-2/BCL-XL or down-regulated HOXA9/MEIS1, respectively, but these mechanisms were not further strengthened by their combination. RNA-Sequencing identified that HDAC9 was specifically repressed by VEN plus MEN1i rather than monotherapy. We demonstrated that HDAC9 was indispensable for KMT2Ar-AML proliferation and its repression contributed to proliferation inhibition of VEN plus MEN1i. Moreover, we found that hypoxia induced HDAC9 expression in KMT2Ar-AML, and VEN plus MEN1i inhibited hypoxia pathway, especially HIF-1A, and its target HDAC9. As our results indicated, VEN plus MEN1i-mediated HDAC9 down-regulation was partially dependent on HIF-1A repression in KMT2Ar-AML. Hypoxia induction sensitized KMT2Ar-AML to VEN plus MI-503-mediated proliferation inhibition and apoptosis induction. Therefore, repressing HIF-1A-induced HDAC9 contributed to the synergistic effect of VEN and MEN1i in KMT2Ar-AML.

Abstract Porcine reproductive and respiratory syndrome (PRRS) is a serious infectious disease and one of the major causes of death in the global pig industry. PRRS virus (PRRSV) strains have complex and diverse genetic characteristics and cross-protection between strains is low, which complicates vaccine selection; thus, the current vaccination strategy has been greatly compromised. Therefore, it is necessary to identify effective natural compounds for the clinical treatment of PRRS. A small molecule library composed of 720 natural compounds was screened in vitro, and we found that Sanggenon C (SC) was amongst the most effective natural compound inhibitors of PRRSV infection. Compared with ribavirin, SC more significantly inhibited PRRSV infection at both the gene and protein levels and reduced the viral titres and levels of protein expression and inflammatory cytokine secretion to more effectively protect cells from PRRSV infection and damage. Mechanistically, SC inhibits activation of the NF-κB signalling pathway by promoting TRAF2 expression, thereby reducing PRRSV replication. In conclusion, by screening natural compounds, we found that SC suppresses PRRSV infection by regulating the TRAF2/NF-κB signalling pathway. This study contributes to a deeper understanding of the therapeutic targets and pathogenesis of PRRSV infection. More importantly, our results demonstrate that SC has potential as a candidate for the treatment of PRRS.

Abstract The structure of chromatin plays pivotal roles in regulating gene transcription, DNA replication and repair, and chromosome segregation. This structure, however, remains elusive. Here, using cryo-FIB and cryo-ET, we delineate the 3D architecture of native chromatin fibres in intact interphase human T-lymphoblasts and determine the in situ structures of nucleosomes in different conformations. These chromatin fibres are not structured as uniform 30 nm one-start or two-start filaments but are composed of relaxed, variable zigzag organizations of nucleosomes connected by straight linker DNA. Nucleosomes with little H1 and linker DNA density are distributed randomly without any spatial preference. This work will inspire future high-resolution investigations on native chromatin structures in situ at both a single-nucleosome level and a population level under many different cellular conditions in health and disease.

The fractal theory can effectively describe the complexity and multi-scale of concrete under impact load and provide a scientific basis for evaluating concrete’s impact resistance. Therefore, based on the fractal theory, this study carried out the fragmentation size analysis by weighing the quality of SFRRAC fragments, disclosed the distribution characteristics of impact fragmentation size of steel fiber reinforced recycled aggregate concrete (SFRRAC) specimens under different recycled coarse aggregate (RCA) replacement ratio, different steel fiber (SF) contents and different impact pressures. The results indicate that the fractal dimension can describe the degree of fragmentation of the specimen. The greater the fractal dimension, the more the amount of fragmentation of the specimen subjected to impact load, the lesser the fragmentation size, and the greater the degree of fragmentation. Under the impact load, the fractal dimension of SFRRAC is between 1.36 and 2.28. As the impact pressure increases, the energy consumption increases, and the fractal dimension decreases. With the growth in replacement ratio, the fractal dimension gradually increases, and the energy consumption is negatively correlated with the fractal dimension. Along with the growth of SF content, the energy consumption gradually increases, and the fractal dimension continuously decreases. A new metric angle is provided to explore the inherent law between the impact-crushing characteristics of SFRRAC and the dynamic load, thereby offering foundational support for the application of SFRRAC in practical engineering.

Abstract Carboxysomes are a paradigm of self-assembling proteinaceous organelles found in nature, offering compartmentalisation of enzymes and pathways to enhance carbon fixation. In α-carboxysomes, the disordered linker protein CsoS2 plays an essential role in carboxysome assembly and Rubisco encapsulation. Its mechanism of action, however, is not fully understood. Here we synthetically engineer α-carboxysome shells using minimal shell components and determine cryoEM structures of these to decipher the principle of shell assembly and encapsulation. The structures reveal that the intrinsically disordered CsoS2 C-terminus is well-structured and acts as a universal “molecular thread” stitching through multiple shell protein interfaces. We further uncover in CsoS2 a highly conserved repetitive key interaction motif, [IV]TG, which is critical to the shell assembly and architecture. Our study provides a general mechanism for the CsoS2-governed carboxysome shell assembly and cargo encapsulation and further advances synthetic engineering of carboxysomes for diverse biotechnological applications.

Importance: Chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) have been linked to shorter telomere length (TL). While understanding this association has critical clinical implications for respiratory diseases, previous studies exploring these associations were conducted in European populations. The present study aims to investigate this relationship in an Asian population. Objective: To examine the causal relationship between leukocyte TL and COPD and ILD in an Asian population. Design: Setting, and Participants: We used a genome-wide association study summary statistics-based two-sample Mendelian randomization (MR) design to investigate the association between leukocyte TL, genetically predicted by nine single-nucleotide polymorphisms and the risk of COPD and ILD. Participants were Japanese individuals enrolled in the Biobank Japan Project, including 3315 COPD patients and 806 ILD patients. Exposure: Leukocyte TL was genetically predicted by nine single-nucleotide polymorphisms. Results: The inverse-variance weighted estimates showed a significant inverse association between leukocyte TL and COPD (odds ratio [OR] = 0.78; 95 % confidence interval [CI]: 0.64, 0.95; P = 0.01) and ILD (OR = 0.29; 95 % CI: 0.14, 0.61; P = 0.001), respectively. All sensitivity analyses yielded consistent results. The MR-Egger regression intercept test showed no evidence of horizontal pleiotropy (Pintercept: COPD, 0.56; ILD: 0.70). Conclusion: and Relevance: Our findings suggest that leukocyte telomere shortening may causally increase the risk of COPD and ILD. These results highlight the potential importance of TL for these respiratory diseases.

In this paper, we study the improved block splitting (IBS) iteration method and its accelerated variant, the accelerated improved block splitting (AIBS) iteration method, for solving linear systems of equations stemming from the discretization of the complex Helmholtz equation. We conduct a comprehensive convergence analysis and derive optimal iteration parameters aimed at minimizing the spectral radius of the iteration matrix. Through numerical experiments, we validate the efficiency of both iteration methods.

The catalytic oxidation of alcohols is an important transformation in the chemical industry. Carbon materials with a large surface area and N doping show great promise as metal-free catalysts for the reaction. In this study, a rich N-containing covalent triazine framework polymerized by cyanuric chloride and p-phenylenediamine was used to synthesize N-doped porous carbon with the assistance of a pore-forming agent—NaCl. First, the mass ratio of the polymer/NaCl was optimized to 1:9. Then, the influence of the pyrolysis temperatures (700–1000 °C) on the materials was studied in detail. It was found that the carbon materials were gradually exfoliated by molten salt at high temperatures. XRD and Raman characterizations showed them with a certain graphitization. The optimal doped carbon CNN-1-9-900 achieved the highest surface area of 199.03 m2g−1 with the largest pore volume of 0.29 cm3g−1. Furthermore, it had a high N content of 9.9 at% with the highest relative proportion of pyridinic/graphitic N. Due to the synergistic effect between the surface area and pyridinic/graphitic N, CNN-1-9-900 showed the best performance for benzyl alcohol oxidation with TBHP at moderate conditions, and the process also worked for its derivatives.

Summary: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been proven to be an effective means of decreasing COVID-19 mortality, hospitalization rates, and transmission. One of the vaccines deployed worldwide is ChAdOx1 nCoV-19, which uses an adenovirus vector to drive the expression of the original SARS-CoV-2 spike on the surface of transduced cells. Using cryo-electron tomography and subtomogram averaging, we determined the native structures of the vaccine product expressed on cell surfaces in situ. We show that ChAdOx1-vectored vaccines expressing the Beta SARS-CoV-2 variant produce abundant native prefusion spikes predominantly in one-RBD-up conformation. Furthermore, the ChAdOx1-vectored HexaPro-stabilized spike yields higher cell surface expression, enhanced RBD exposure, and reduced shedding of S1 compared to the wild type. We demonstrate in situ structure determination as a powerful means for studying antigen design options in future vaccine development against emerging novel SARS-CoV-2 variants and broadly against other infectious viruses.

Unsupervised domain adaptation (UDA) is an emerging research topic in the field of machine learning and pattern recognition, which aims to help the learning of unlabeled target domain by transferring knowledge from the source domain. To perform UDA, a variety of methods have been proposed, most of which concentrate on the scenario of single source and the single target domain (1S1T). However, in real applications, usually single source domain with multiple target domains are involved (1SmT), which cannot be handled directly by those 1S1T models. Unfortunately, although a few related works on 1SmT UDA have been proposed, nearly none of them model the source domain knowledge and leverage the target-relatedness jointly. To overcome these shortcomings, we herein propose a more general 1SmT UDA model through transferring both the source-knowledge and target-relatedness, UDA-SKTR for short. In this way, not only the supervision knowledge from the source domain but also the potential relatedness among the target domains are simultaneously modeled for exploitation in the process of 1SmT UDA. In addition, we construct an alternating optimization algorithm to solve the variables of the proposed model with a convergence guarantee. Finally, through extensive experiments on both benchmark and real datasets, we validate the effectiveness and superiority of the proposed method.

Abstract Background Alexithymia is a common psychological disorder. However, few studies have investigated its prevalence and predictors in patients with chronic obstructive pulmonary disease (COPD). Therefore, we aimed to determine the prevalence and predictors of alexithymia in Chinese patients. Methods This cross-sectional study included 842 COPD patients to assess the prevalence and predictors of alexithymia using the 20-item Toronto Alexithymia Scale (TAS-20). We used the Hospital Anxiety and Depression Scale (HADS) to assess anxiety and depression, the modified British Medical Research Council dyspnea Rating Scale (mMRC) to assess dyspnea, St. George's Respiratory Questionnaire (SGRQ) to assess quality of life, and the age-adjusted Charlson comorbidity index (ACCI) to assess comorbidities. Alexithymia-related predictors were identified using univariate and multivariate logistic regression analyses. Results The prevalence of alexithymia in COPD patients was 23.6% (199/842). Multivariate analysis showed that age [odds ratio (OR) 0.886; 95% confidence interval (CI) 0.794–0.998], body mass index (OR 0.879; 95% CI 0.781–0.989), HADS-anxiety (OR 1.238; 95% CI 1.097–1.396), HADS-depression (OR 1.178; 95% CI 1.034–1.340), mMRC (OR 1.297; 95% CI 1.274–1.320), SGRQ (OR 1.627; 95% CI 1.401–1.890), ACCI (OR 1.165; 95% CI 1.051–1.280), and GOLD grade (OR 1.296; 95% CI 1.256–1.337) were independent predictors for alexithymia in patients with COPD. Conclusions The prevalence of alexithymia was high in Chinese COPD patients. Anxiety, depression, dyspnea, quality of life, comorbidities, and disease severity are independent risk factors, and age and BMI are predictive factors for alexithymia in COPD patients.

Abstract m6A is an important RNA methylation in progression of various human cancers. As the m6A reader protein, YTHDF1 is reported to accelerate m6A-modified mRNAs translation in cytoplasm. It is highly expressed in various human cancers and contributes to the progression and metastasis of cancers. YTHDF1 was closely associated with poor prognosis and also used as a molecular marker for clinical diagnosis or therapy in human cancers. It has been reported to promote chemoresistance to Adriamycin, Cisplatin and Olaparib by increasing mRNA stability of its target molecule. Moreover, it contributes to CSC-like characteristic of tumor cells and inducing the antitumor immune microenvironment. Here, we reviewed the clinical diagnostic and prognostic values of YTHDF1, as well as the molecular mechanisms of YTHDF1 in progression and metastasis of human cancers.

Positive lightning discharges are rare and not well understood. Here, the authors present observations from three positive discharges and demonstrate unexpected luminosity dips in the channel to ground, as well as transient coupling to a negative discharge nearby.

Enterotoxigenic Escherichia coli (ETEC) is the major diarrhoea-causing pathogen world-wide. Fimbria–receptor recognition is the primary step when attachment of ETEC to the intestine occurs. This study aims to evaluate the potential of some traditional foods, particularly those rich in β-glucans, as analogues for fimbriae or receptors in reducing ETEC colonisation. The adhesion test (AT) demonstrated that aqueous extracts of highland barley (EHB), black rice (EBR) and little millet (ELT) at concentrations of 2% and 1% could attach to more ETEC K88ac (p < 0.001), as well as aqueous extracts of shiitake (EST) (p < 0.01). The competition test (CT) revealed that EHB and EST significantly prevented ETEC K88ac from adhering to intestinal epithelial cells (IPEC-J2) at 2% (p < 0.01) and 1% (p < 0.05). In the Exclusion Test (ET) and the displacement test (DT), the food samples were unable to impair ETEC colonisation in terms of blocking receptors or removing attached pathogens. These results demonstrate how some traditional foods such as highland barley and shiitake contain bioactive compounds that interfere with the attachment of ETEC to the intestinal epithelium, and their potential in the prevention and treatment of ETEC diarrhoea.

BACKGROUND: The study aimed to find out the association between sleep duration and psychological resilience in a population-based survey. MATERIALS AND METHODS: A cross-sectional survey was conducted in August 2022, employing a cluster random sampling method to recruit community residents at Futian District in Shenzhen, China. A total of 2,445 participants aged 18 years and over were included in the study. The Brief Resilience Scale (BRS) was utilized to measure psychological resilience, and sleep duration was classified according to the American Heart Association’s sleep duration categories. Multivariable linear regression was used to analyze the relationship between psychological resilience and sleep duration after adjusting for gender, age, smoking status, physical exercise frequency, body mass index (BMI), and education level. RESULTS: The participants displayed moderate levels of psychological resilience, with a mean resilience score of 3.46 (standard deviation [SD] = 0.62) and a mean sleep duration of 7.04 h (SD = 1.10). After adjusting for covariates, longer sleep duration was associated with higher psychological resilience (β = 0.047, P < 0.05), indicating that participants with a long sleep duration had higher resilience scores than those with a short sleep duration. CONCLUSION: Longer sleep duration is positively associated with higher psychological resilience in community residents. These findings suggest that improving sleep duration may be a promising approach to enhancing psychological resilience, preventing psychological problems, and promoting overall physical and mental health development.

Abstract The combination of rituximab, lenalidomide, and Bruton’s tyrosine kinase inhibitor (BTKi) ibrutinib, followed by chemotherapy, has shown high efficacy in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) in Smart Start trial. We aimed to evaluate the efficacy, safety of SMART (rituximab + lenalidomide + BTKi) regimen and SMART–START regimen as a first-line treatment in elderly or unfit DLBCL patients. 31 patients were included, 17 used SMART regimen, with median age 82 years, 14 unfit patients received SMART–START regimen. 14/16 (87.5%) patients in SMART group achieved overall response (OR), with 10/16 (62.5%) achieved complete response (CR). 12/13 (92.3%) patients in SMART–START group achieved OR, with 8/13 (61.5%) achieved CR. With a median follow-up of 15.4 (3–29.1) months, median progression-free survival (PFS) and overall survival (OS) have not been reached, 1-year PFS was 81% in SMART group and 84% in SMART–START group. Common grade 3–4 adverse events (AEs) during SMART regimen were neutropenia (8 [25.8%]), infection (6 [19.4%]) and skin rash (3 [9.7%]). Our study shows that SMART regimen is an effective and safe therapy for elderly DLBCL patients, and SMART–START regimen can be used in unfit patients who could not tolerate intensive chemotherapy in the onset.

Particulate methane monooxygenase (pMMO) is the main enzyme used by methanotrophs. Here, the authors determined the native structure of pMMO by cryo-electron tomography, revealing lipid-stabilized features and a higher-order hexagonal array arrangement in intact cells.

Carboxysomes are bacterial microcompartments encapsulating Rubisco and carbonic anhydrase for carbon fixation. Here, authors determine the organization of Rubisco and its interaction with the linker protein CsoS2 within two distant α-carboxysomes.

Abstract Sepsis is characterized by systemic inflammation, it’s caused by primary infection of pathogenic microorganisms or secondary infection of damaged tissue. In this study, we focus on sepsis-induced intestine barrier functional disturbalice, presenting as increased permeability of intestinal epithelium. We observed that the phenotype of LPS-induced sepsis was exacerbated in Card9 −/− mice, especially displaying more serious intestinal inflammation and gut barrier dysfunction. Next, we found the hyperactivation of NLRP3 inflammasome in the intestinal macrophages of Card9 −/− -sepsis mice. Moreover, Card9 over-expression decreased NLRP3 inflammasome activation in macrophages. Furthermore, we found that Card9 inhibited NLRP3 inflammasome activation by recruiting Ripk2. The competitive binding between Ripk2 with Caspase-1, instead of ASC with Caspase-1, inhibited the NLRP3 inflammasome activation. Over-expression of Ripk2 alleviated septic intestinal injury caused by Card9 deficiency. Taken together, we suggested Card9 acts as a negative regulation factor of NLRP3 inflammasome activation, which protects against intestinal damage during sepsis. Therefore, maintaining Card9-Ripk2 signaling homeostasis may provide a novel therapy of septic intestinal damage.

Introduction: Hepatocellular carcinoma (HCC) is the sixth most commonly diagnosed cancer and the third leading cause of cancer death worldwide. While there has been rapid evolution in the treatment paradigm of HCC across the past decade, the extent to which these newly approved therapies are utilised in clinical practice in the real world is however, unknown. The INSIGHT study was an investigator-initiated, multi-site longitudinal cohort study conducted to reflect real-world epidemiology and clinical practice in Asia-Pacific in the immediate 7-year period after the conclusion of the BRIDGE study. Methods: Data was collected both retrospectively (planned 30% of total cohort size) and prospectively (planned 70%) from January 2013 to December 2019 from eligible patients newly diagnosed with HCC from 33 participating sites across 9 Asia-Pacific countries. Results: A total of 2,533 newly diagnosed HCC patients (1052 in retrospective cohort and 1481 in prospective cohort) were enrolled. The most common risk factor was hepatitis B in all countries except Japan, Australia and New Zealand, where the prevalence of Hepatitis C and diabetes were more common. The top three comorbidities reported in the INSIGHT study include cirrhosis, hypertension and diabetes. We observe high heterogeneity in the first-line treatment recorded across countries and across disease stage, which significantly affects survival outcomes. Stratification by factors such as etiologies, tumor characteristics, presence of extrahepatic metastases or macrovascular invasion and the use of subsequent lines of treatment were performed. Conclusion: The INSIGHT study describes a wide spectrum of clinical management practices in HCC, where patient demographics, differential costs and patient access to therapies may lead to wide geographical variations through the patient’s treatment cycle, from diagnosis to clinical outcome. The high heterogeneity in patient outcomes demonstrates the need for more robust and clinical management strategies to be designed and adopted to bring about better patient outcomes.

Abstract Background “Overlap syndrome” refers to obstructive sleep apnea (OSA) combined with chronic obstructive pulmonary disease (COPD), and has poorer outcomes than either condition alone. We aimed to evaluate the prevalence and possible predictors of overlap syndrome and its association with clinical outcomes in patients with COPD. Methods We assessed the modified Medical Research Council dyspnea scale (mMRC), Epworth sleepiness scale (ESS), COPD assessment test (CAT), Hospital Anxiety and Depression Scale (HADS), Charlson Comorbidity Index (CCI), and STOP-Bang questionnaire (SBQ) and performed spirometry and full overnight polysomnography in all patients. An apnea–hypopnea index (AHI) ≥ 5 events per hour was considered to indicate OSA. Risk factors for OSA in COPD patients were identified by univariate and multivariate logistic regression analyses. Results A total of 556 patients (66%) had an AHI ≥ 5 events per hour. There were no significant differences in age, sex ratio, mMRC score, smoking index, number of acute exacerbations and hospitalizations in the last year, and prevalence of cor pulmonale between the two groups (all p > 0.05). Body mass index (BMI), neck circumference, CAT score, CCI, ESS, HADS, and SBQ scores, forced expiratory volume (FEV)1, FEV1% pred, FEV1/forced vital capacity ratio, and prevalence of hypertension, coronary heart disease, and diabetes were all significantly higher and the prevalence of severe COPD was significantly lower in the COPD-OSA group compared with the COPD group (p

Fusarium crown rot (FCR) on wheat is a soil-borne disease that affects the yield and quality of the produce. In 2020, 297 Fusarium pseudograminearum isolates were isolated from diseased FCR wheat samples from eight regional areas across Hebei Province in China. Baseline sensitivity of F. pseudograminearum to fludioxonil (0.0613 ± 0.0347 μg/mL) and tebuconazole (0.2328 ± 0.0840 μg/mL) were constructed based on the in vitro tests of 71 and 83 isolates, respectively. The resistance index analysis showed no resistance isolate to fludioxonil but two low-resistance isolates to tebuconazole in 2020. There was an increased frequency of resistant isolates from 2021 to 2022 based on the baseline sensitivity for tebuconazole. There was no cross-resistance between fludioxonil and tebuconazole. This study provides a significant theoretical and practical basis for monitoring the resistance of F. pseudograminearum to fungicides, especially the control of FCR.

Abstract Background Norovirus (NoV) is the main cause of non-bacterial acute gastroenteritis (AGE) outbreaks worldwide. From September 2015 through August 2018, 203 NoV outbreaks involving 2500 cases were reported to the Shenzhen Center for Disease Control and Prevention. Methods Faecal specimens for 203 outbreaks were collected and epidemiological data were obtained through the AGE outbreak surveillance system in Shenzhen. Genotypes were determined by sequencing analysis. To gain a better understanding of the evolutionary characteristics of NoV in Shenzhen, molecular evolution and mutations were evaluated based on time-scale evolutionary phylogeny and amino acid mutations. Results A total of nine districts reported NoV outbreaks and the reported NoV outbreaks peaked from November to March. Among the 203 NoV outbreaks, 150 were sequenced successfully. Most of these outbreaks were associated with the NoV GII.2[P16] strain (45.3%, 92/203) and occurred in school settings (91.6%, 186/203). The evolutionary rates of the RdRp region and the VP1 sequence were 2.1 × 10–3 (95% HPD interval, 1.7 × 10–3–2.5 × 10–3) substitutions/site/year and 2.7 × 10–3 (95% HPD interval, 2.4 × 10–3–3.1 × 10–3) substitutions/site/year, respectively. The common ancestors of the GII.2[P16] strain from Shenzhen and GII.4 Sydney 2012[P16] diverged from 2011 to 2012. The common ancestors of the GII.2[P16] strain from Shenzhen and previous GII.2[P16] (2010–2012) diverged from 2003 to 2004. The results of amino acid mutations showed 6 amino acid substitutions (*77E, R750K, P845Q, H1310Y, K1546Q, T1549A) were found only in GII.4 Sydney 2012[P16] and the GII.2[P16] recombinant strain. Conclusions This study illustrates the molecular epidemiological patterns in Shenzhen, China, from September 2015 to August 2018 and provides evidence that the epidemic trend of GII.2[P16] recombinant strain had weakened and the non-structural proteins of the recombinant strain might have played a more significant role than VP1.

Cigarette smoking is one of the major risk factors for the occurrence and progression of oral squamous cell carcinoma (OSCC). Receptor-interacting protein 2 (RIP2) has been involved in mucosal immunity and homeostasis via a positive regulation of nuclear factor κB (NF-κB) transcription factor activity. Caspase-12 can bind to RIP2 and dampen mucosal immunity. However, the roles of RIP2/NF-κB and caspase-12 in OSCC induced by cigarette smoking remain unknown. Herein, we investigated the effects of cigarette smoking on the RIP2/NF-κB and caspase-12 in human OSCC tissues and OSCC cell lines (HSC-3). We first observed that RIP2 mediated NF-κB activation and caspase-12 upregulation in OSCC patients with cigarette smoking and cigarette smoke extract (CSE)-treated HSC-3 cells, respectively. Moreover, we confirmed that the downregulation of RIP2 by siRNA resulted in the reduction of caspase-12 expression and NF-κB activity in the presence of CSE treatment in vitro. In summary, our results indicated that cigarette smoking induced the activation of the RIP2/caspase-12/NF-κB axis and it played an important role in the development of OSCC. The RIP2/caspase-12/NF-κB axis could be a target for OSCC prevention and treatment in the future.

Recurrent aphthous ulcer (RAU), one of the most common diseases in humans, has an unknown etiology and is difficult to treat. Thalidomide is an important immunomodulatory and antitumor drug and its effects on the gut microbiota still remain unclear. We conducted a metagenomic sequencing study of fecal samples from a cohort of individuals with RAU, performed biochemical assays of cytokines, immunoglobulins and antimicrobial peptides in serum and saliva, and investigated the regulation effects of thalidomide administration and withdrawal. Meanwhile we constructed the corresponding prediction models. Our metagenome-wide association results indicated that gut dysbacteriosis, microbial dysfunction and immune imbalance occurred in RAU patients. Thalidomide regulated gut dysbacteriosis in a species-specific manner and had different sustainable effects on various probiotics and pathogens. A previously unknown association between gut microbiota alterations and RAU was found, and the specific roles of thalidomide in modulating the gut microbiota and immunity were determined, suggesting that RAU may be affected by targeting gut dysbacteriosis and modifying immune imbalance. In-depth insights into sophisticated networks consisting of the gut microbiota and host cells may lead to the development of emerging treatments, including prebiotics, probiotics, synbiotics, and postbiotics.

Fibre-reinforced composites have shown a growing interest in pressure-resistant materials for deep-sea use due to their excellent properties. This paper presents the influence of the moisture absorption on the mechanical properties and damage mechanisms of three-dimensional six-directional (3D6D) braided composites under hydrostatic pressure. The bisphenol A epoxy resin, bisphenol F epoxy resin, and hydrogenated bisphenol A epoxy resin, are chosen. SEM and X-ray Micro-CT are employed to investigate the moisture absorption, tensile and compressive damage before and after subjecting to the hydrostatic pressure. Results show that the bisphenol F carbon/epoxy composite has the lowest porosity at 0.082% among the three composite materials. The average moisture absorption was the lowest at 0.3755%. Furthermore, moisture is mainly transported along micro cracks in the matrix and the fiber-matrix interface under hydrostatic pressure. After the composites absorb moisture, the average tensile strength retention rates of bisphenol A carbon/epoxy composite, bisphenol F carbon/epoxy composite, and hydrogenated bisphenol A carbon/epoxy composites drop to 88.282%, 76.34%, and 66.43%, respectively. Moreover, their average compressive strength retention rates drop to 53.15%, 74.26%, and 83.45%, respectively. The tensile and compressive strengths of the 3D6D braided composites decreased significantly after moisture absorption, mainly due to fiber-matrix debonding and matrix cracking.

Abstract This study aimed to construct a widely accepted prognostic nomogram in Chinese high-grade osteosarcoma (HOS) patients aged ≤ 30 years to provide insight into predicting 5-year overall survival (OS). Data from 503 consecutive HOS patients at our centre between 12/2012 and 05/2019 were retrospectively collected. Eighty-four clinical features and routine laboratory haematological and biochemical testing indicators of each patient at the time of diagnosis were collected. A prognostic nomogram model for predicting OS was constructed based on the Cox proportional hazards model. The performance was assessed by the concordance index (C-index), receiver operating characteristic curve and calibration curve. The utility was evaluated by decision curve analysis. The 5-year OS was 52.1% and 2.6% for the nonmetastatic and metastatic patients, respectively. The nomogram included nine important variables based on a multivariate analysis: tumour stage, surgical type, metastasis, preoperative neoadjuvant chemotherapy cycle, postoperative metastasis time, mean corpuscular volume, tumour-specific growth factor, gamma-glutamyl transferase and creatinine. The calibration curve showed that the nomogram was able to predict 5-year OS accurately. The C-index of the nomogram for OS prediction was 0.795 (range, 0.703–0.887). Moreover, the decision curve analysis curve also demonstrated the clinical benefit of this model. The nomogram provides an individualized risk estimate of the 5-year OS in patients with HOS aged ≤ 30 years in a Chinese population-based cohort.

Abstract Oral immunosuppression caused by smoking creates a microenvironment to promote the occurrence and development of oral mucosa precancerous lesions. This study aimed to investigate the role of metabolism and macrophage polarization in cigarette-promoting oral leukoplakia. The effects of cigarette smoke extract (CSE) on macrophage polarization and metabolism were studied in vivo and in vitro. The polarity of macrophages was detected by flow cytometric analysis and qPCR. Liquid chromatography-mass spectrometry (LC-MS) was used to perform a metabolomic analysis of Raw cells stimulated with CSE. Immunofluorescence and flow cytometry were used to detect the polarity of macrophages in the condition of glutamine abundance and deficiency. Cell Counting Kit-8 (CCK-8), wound-healing assay, and Annexin V-FITC (fluorescein isothiocyanate)/PI (propidium iodide) double-staining flow cytometry were applied to detect the growth and transferability and apoptosis of Leuk-1 cells in the supernatant of Raw cells which were stimulated with CSE, glutamine abundance and deficiency. Hyperkeratosis and dysplasia of the epithelium were evident in smoking mice. M2 macrophages increased under CSE stimulation in vivo and in vitro. In total, 162 types of metabolites were detected in the CSE group. The metabolites of nicotine, glutamate, arachidic acid, and arginine changed significantly. The significant enrichment pathways were also selected, including nicotine addiction, glutamine and glutamate metabolism, and arginine biosynthesis. The results also showed that the supernatant of Raw cells stimulated by CSE could induce excessive proliferation of Leuk-1 and inhibit apoptosis. Glutamine abundance can facilitate this process. Cigarette smoke promotes oral leukoplakia via regulating glutamine metabolism and macrophage M2 polarization.

Abstract Distant metastasis is the main cause of death for cancer patients. Recently, the newly discovered programmed cell death includes necroptosis, pyroptosis, and ferroptosis, which possesses an important role in the process of tumor metastasis. At the same time, it is widely reported that non-coding RNA precisely regulates programmed death and tumor metastasis. In the present review, we summarize the function and role of necroptosis, pyrolysis, and ferroptosis involving in cancer metastasis, as well as the regulatory factors, including non-coding RNAs, of necroptosis, pyroptosis, and ferroptosis in the process of tumor metastasis.

Acute myelocytic leukemia (AML) is a malignancy of the stem cell precursors of the myeloid lineage. CD4+ and CD8+ T cells play pivotal roles in influencing AML progression but are functionally suppressed in the bone marrow microenvironment. We aimed to find hub genes related to T cell exhaustion and suppression, thereby providing evidence for immunotherapy. In this study, gene transcriptome expression data from TCGA and TARGET databases were utilized to find key genes. Firstly, CIBERSORT immune cell infiltration algorithm and WGCNA method were used to identify CD4+ and CD8+ T cells-related genes. Univariate and multivariate cox regression analyses were then introduced to construct the overall survival prognosis model and included hub genes. The ESTIMATE and ssGSEA scoring methods were used to analyze the correlation between the hub genes and immune activity. Single-cell transcriptome analysis was applied to detect the immune cells expressing hub genes, hence, to detect exact mechanisms. Consequently, FLT3LG and IFITM3P6 were determined to be positively correlated with patients’ overall survival and microenvironment immune activity. Further study suggested FLT3-FLT3LG and IFITM3P6-miR-6748-3p-CBX7 signaling axes were involved in CD4+ and CD8+ T cells activation. This may be one of the mechanisms of T cells suppression in AML.

BackgroundThe sporadic coronavirus disease (COVID-19) epidemic has placed enormous psychological stress on people, especially clinicians. The objective of this study was to examine depression, anxiety, quality of life (QOL), and related social psychological factors among young front-line clinicians in high-risk areas during the COVID-19 sporadic epidemic in China and to provide a reference for formulating reasonable countermeasures.MethodsIn this cross-sectional study, demographic information, COVID-19-related questions, anxiety (Generalized Anxiety Disorder-7, GAD-7), depression (Patient Health Questionnaire-9, PHQ-9), insomnia (Insomnia Severity Index, ISI), stress (Perceived Stress Scale-10, PSS-10), and QOL (World Health Organization Quality of Life-brief version, WHOQOL-BREF) were collected. Binary logistic regression analysis was used to test the relationships between anxiety and/or depression and other related problems. Multiple linear regression analysis was used to test the relationships among factors influencing QOL.ResultsA total of 146 young front-line clinicians were included. The prevalence rates of depression, anxiety, and anxiety-depression comorbidity were 37.7% (95% CI = 29.7–45.6%), 26.0% (95% CI = 18.8–33.2%), and 24.0% (95% CI = 17.0–31.0%), respectively. Severe stress (OR = 1.258, 95% CI = 1.098–1.442, P < 0.01) and insomnia (OR = 1.282, 95% CI = 1.135–1.447, P < 0.01) were positively correlated with depression. Severe stress (OR = 1.487, 95% CI = 1.213–1.823, P < 0.01) and insomnia (OR = 1.131, 95% CI = 1.003–1.274, P < 0.05) were positively correlated with anxiety. Severe stress (OR = 1.532, 95% CI = 1.228–1.912, P < 0.01) was positively correlated with anxiety-depression comorbidity. However, insomnia (OR = 1.081, 95% CI = 0.963–1.214, P > 0.05) was not correlated with anxiety-depression comorbidity. The belief that the vaccine will stop the COVID-19 pandemic (OR = 0.099, 95% CI = 0.014–0.715, P < 0.05) was negatively correlated with anxiety and anxiety-depression comorbidity (OR = 0.101, 95% CI = 0.014–0.744, P < 0.05). Severe stress (B = −0.068, 95% CI = −0.129 to −0.007, P < 0.05) and insomnia (B = −0.127, 95% CI = −0.188 to −0.067, P < 0.01) were negatively correlated with QOL. The belief that the vaccine could provide protection (B = 1.442, 95% CI = 0.253–2.631, P < 0.05) was positively correlated with QOL.ConclusionsThe prevalence of depression, anxiety, and even anxiety-depression comorbidity was high among young front-line clinicians in high-risk areas during the COVID-19 sporadic epidemic in China. Various biological and psychological factors as well as COVID-19-related factors were associated with mental health issues and QOL. Psychological intervention should evaluate these related factors and formulate measures for these high-risk groups.

Background and objective: This study was performed to investigate the effect of expressive art therapy (EAT) on the health status of patients with chronic obstructive pulmonary disease (COPD). Methods: This community-based cluster randomized controlled trial involved patients with COPD from 16 communities in China. Participants received either EAT plus usual care (UC) or UC only. General practitioners were trained in EAT before the intervention. The primary outcomes were depression and anxiety symptoms, measured with the Hospital Anxiety and Depression Scale (HADS) and expressed as the HADS score for depression or anxiety (HADS-D or HADS-A, respectively). The secondary outcomes were the quality of life and dyspnoea, measured with the COPD assessment test (CAT). Dyspnoea was assessed using the modified Medical Research Council (mMRC) dyspnoea scale. Lung function was expressed as the forced expiratory volume in 1 s as a percentage of the predicted value [FEV 1 (% pred)]. Outcome data were collected from all participants at baseline, 2 and 6 months. Results: In total, 360 participants with COPD and comorbid depression were included in the analysis with the control group of 181 receiving UC only and the intervention group of 179 receiving EAT plus UC. The EAT group showed significantly greater improvement in the HADS-D and HADS-A scores than the UC group at 2 months ( p

With the deep development of domestic and international oil and gas fields, due to the complicated and harsh medium conditions, high density polyethylene (HDPE) lining technology becomes one of the important measures to control the corrosion leakage of the surface gathering & transportation system and water injection system in oil and gas fields and to extend the service life of pipelines. With the lining principle of isodiametric compression for HDPE liner and in accordance with the domestic and foreign standards and specifications, the material performance requirements of HDPE liner, the applicable conditions of HDPE lining technology, the fitness of liner with the base pipe and the design principles for vents were proposed from the 3 aspects of design, construction and economy. Moreover, the wall thickness of HDPE liner was determined based on the minimum thickness for installation & storage, the stability and the collapse resistance of liner, and through comparative analysis on the joint type of different HDPE liner technologies, it was proposed to consider the flange joint preferably. In addition, the construction & installation process of HDPE liner and the lining form of hot induction bend were introduced, the key points and requirements of construction quality control were summarized, and the economic efficiency of different material selection schemes for pipeline in oil and gas field was compared, so as to advance the application of HDPE liner technology in oil and gas fields and to solve the problem of pipeline corrosion leakage in the oil and gas fields.

AbstractBackground Circular RNA microarray analysis showed hsa_circ_0010235 (circ_0010235) was highly upregulated in non-small-cell lung cancer (NSCLC) patients; however, its role in carcinogenesis and development of NSCLC cells was unrevealed. Here, we intended to investigate role and mechanism of circ_0010235 in NSCLC proliferation, migration and invasion.Methods and results Expression of circ_0010235, microRNA (miR)-338-3p and kinesin family member 2A (KIF2A) was detected by quantitative real-time PCR, western blotting and immunohistochemistry (IHC). Cell progression was measured by cell-counting kit-8 assay, 5-ethynyl-2-deoxyuridine (EdU) assay, flow cytometry, transwell assay, western blotting, IHC and xenograft experiment. The relationship among circ_0010235, miR-338-3p and KIF2A was determined by dual-luciferase reporter assay, RNA immunoprecipitation and Pearson’s correlation analysis. Expression of circ_0010235 was increased in human NSCLC tissues and cells, accompanied with miR-338-3p downregulation and KIF2A upregulation. Essentially, circ_0010235 could sponge miR-338-3p via target binding, and miR-338-3p downstream targeted KIF2A. Functionally, exhaustion of circ_0010235 induced apoptosis rate of NSCLC cells and curbed cell viability, EdU incorporation, migration rate and invasion rate, accompanied with higher E-cadherin and lower N-cadherin expression. Additionally, re-expression of miR-338-3p prompted above similar effects in NSCLC cells in vitro. Contrarily, miR-338-3p blockage partially counteract the effects of circ_0010235 exhaustion; plus, restoration of KIF2A could attenuate miR-338-3p role, as well. Notably, interfering circ_0010235 delayed tumour growth of NSCLC cells by promoting miR-338-3p and E-cadherin expression, and depressing KIF2A, ki-67 and N-cadherin expression.Conclusions circ_0010235 could be a novel identified oncogenic circRNA in NSCLC, and targeting miR-338-3p/KIF2A axis was one regulatory mechanism underlying circ_0010235.KEY MESSAGECirc_0010235 was an upregulated circRNA in NSCLC patients and cells.Interfering circ_0010235 restrained NSCLC cell proliferation and metastasis in vitro and in vivo.miR-338-3p per se suppressed NSCLC in vitro and its downregulation diminished the tumour-suppressive role of circ_0010235 blockage in NSCLC cells.miR-338-3p could downstream target KIF2A and be sponged by circ_0010235.

Background: Presbyopia has become a global disease affecting the world's aging population. Among various treatments, cataract extraction and intraocular lens (IOL) implantation have become the most popular and common methods of presbyopia correction. During the twentieth century, IOLs have underwent significant innovation and advancements to meet the patients' high demands for functional vision at all distances. Main Text: To meet the increasing needs for excellent near and intermediate vision for daily activities, some premium IOLs with more than one focus have been developed, for example, the refractive MfIOLs, diffractive MfIOLs, extended depth of field (EDOF) IOLs, and accommodating IOLs (AIOLs) were introduced to meet this need. In addition, the add-on MfIOLs have been explored as promising supplementary IOLs for pseudophakic presbyopia. When selecting the MfIOLs, the IOLs' features, patients’ characteristics, preoperative eye conditions, and treatment expectations should be considered. Conclusions: In this review, we focus on the multifocal IOLs (MfIOLs) commonly used for presbyopia correction and systematically summarized their optical designs and clinical outcomes. More evidence-based studies are required to provide guidelines for MfIOL selection, provide maximum visual benefits, and develop personalized visual solutions in the future.

Abstract IKZF1 belongs to the IKAROS family of transcription factors, and its deletion/mutation frequently affects acute lymphoblastic leukemia. In acute myeloid leukemia, IKZF1 deletion has been demonstrated recurrent, but whether IKZF1 mutation also exists in AML remained largely unknown. Herein, we analyzed the IKZF1 mutation in AML. In our cohort, the frequency of IKZF1 mutation was 2.6% (5/193), and 5 frameshift/nonsense mutations as well as 2 missense mutations were identified in total. Molecularly, IKZF1 mutation was absent in fusion gene-positive AML, but it was demonstrated as the significant concomitant genetic alteration with SF3B1 or bi-allele CEBPA mutation in AML. Clinically, two IKZF1, PTPN11 and SF3B1-mutated AML patients exhibited one aggressive clinical course and showed primary resistant to chemotherapy. Furthermore, we confirmed the recurrent IKZF1 mutation in AML with cBioPortal tool from OHSU, TCGA and TARGET studies. Interestingly, OHSU study also showed that SF3B1 mutation was the significant concomitant genetic alteration with IKZF1 mutation, indicating their strong synergy in leukemogenesis. In conclusion, IKZF1 mutation recurrently affected AML.

Abstract Background Femtosecond laser assisted cataract surgery (FLACS) combined with implantable collamer lenses (ICLs) extraction has been shown to be a feasible method for patients developing cataracts after the ICL implantation. All reported cases had shallow vaults, ranging from 47 μm (μm) to 100 μm. We report for the first time, a case in which the FLACS was performed on the “0” vault eye. Case presentation A 38-year-old man with anterior subcapsular cataracts underwent the FLACS combined with ICLs extraction 6 years after ICLs implantation in both eyes. In his left eye, the ICL touched the anterior capsule, existing “0” vault. During the capsulotomy, cavitation bubbles were trapped in the shallow space beneath the ICL, developing from small bubbles into big ones, which resulted in the incomplete capsulotomy. Comparatively, in the right eye, the ICL vault was measured 72 μm, and the capsulotomy was complete and no big cavitation bubbles formed. In both eyes, capsulotomy zones were manually assigned to the anterior capsule surface in the process of laser identification. However, the nuclear pre-fragmentations were unsuccessful in both eyes. Other steps of surgeries were performed uneventfully. Depending on the design of monovision, the uncorrected distance visual acuity (UDVA) was 20/32, and the near uncorrected visual acuity (UCVA) was 20/25 in both eyes postoperatively. Conclusions This case suggested that the surgeon should pay attention to the incomplete laser capsulotomy when using a femtosecond laser in cataractous cases with “0” vaulted ICLs, and manual adjustment was required in the process of laser identification.

Diabetic cardiomyopathy (DCM) is characterized by microvascular pathology and interstitial fibrosis that leads to progressive heart failure. The mechanisms underlying DCM pathogenesis remain obscure, and no effective treatments for the disease have been available. In the present study, we observed that STK35, a novel kinase, is decreased in the diabetic human heart. High glucose treatment, mimicking hyperglycemia in diabetes, downregulated STK35 expression in mouse cardiac endothelial cells (MCEC). Knockdown of STK35 attenuated MCEC proliferation, migration, and tube formation, whereas STK35 overexpression restored the high glucose-suppressed MCEC migration and tube formation. Angiogenesis gene PCR array analysis revealed that HG downregulated the expression of several angiogenic genes, and this suppression was fully restored by STK35 overexpression. Intravenous injection of AAV9-STK35 viral particles successfully overexpressed STK35 in diabetic mouse hearts, leading to increased vascular density, suppression of fibrosis in the heart, and amelioration of left ventricular function. Altogether, our results suggest that hyperglycemia downregulates endothelial STK35 expression, leading to microvascular dysfunction in diabetic hearts, representing a novel mechanism underlying DCM pathogenesis. Our study also emerges STK35 is a novel gene therapeutic target for preventing and treating DCM.