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Abstract Background Puccinia striiformis f. sp. tritici (Pst) causes wheat stripe (yellow) rust disease, which is one of the most destructive diseases affecting wheat worldwide. ATPases, a class of membrane proteins, play an important role in material exchange and signal transduction both within and outside biological cells by transporting ions and phospholipids. In plant pathogens, P-type ATPases primarily participate in pathogen development and virulence regulation. However, the P-type ATPase of subfamily IIIA (PMA) has not yet been identified in Pst. To investigate the potential functions of the PMA gene family in Pst, we conducted a genome-wide bioinformatics analysis and examined the expression profiles of the PMA gene family. Results Six PMA genes were identified in the genome of P. striiformis f. sp. tritici (CYR34 race). The PMA proteins encoded by these genes ranged in length from 811 to 960 amino acids (aa). Each of the six PMA genes contained a typical ATPase IIIA H superfamily domain and was distributed across four chromosomes. Thirty-six major cis-regulatory elements were detected within the PMA gene family members. Elements such as the CGTCA-motif and TGACG-motif play significant roles in responding to environmental stresses and hormone signals. Quantitative PCR analysis revealed that the expression of the PMA04 gene was generally higher at 9 °C under various temperature stresses. The PMA06 gene typically exhibited higher expression levels at 16 °C. During the infection of Pst, the expression levels of PMA04, PMA05, and PMA06 were elevated at 72 h post treatment. Conclusions Our results indicate that the PMA gene family in the CYR34 strain comprises six PMA genes, which are crucial for managing temperature stress and pathogen infection, and exhibit a distinctive splicing pattern. This study not only identifies a target and direction for the development of new, efficient, and environmentally friendly control agents for wheat stripe rust but also establishes a foundation for analyzing its pathogenic mechanisms.

Background Japanese encephalitis (JE) is a severe infectious disease of the central nervous system. Vaccination with Vero cell culture-derived vaccines may effectively reduce JE incidence.Research Design and Methods In this single-center, randomized, blinded, positive-controlled clinical trial in China involving 600 healthy infants aged 6–11 months, participants were divided into experimental and control groups administered JEV-PI and JEV-LI, respectively. Antibody titers were determined after 0- and 7-day immunization schedules. A booster dose followed 12 months later.Results After primary vaccination and before booster vaccination, the positive conversion rate, geometric mean titer (GMT), and geometric mean increase (GMI) of JEV-PI-neutralizing antibodies exceeded those of JEV-LI. After booster immunization, the GMT and GMI of JEV-PI were higher than those of JEV-LI. After primary immunization, the local, systemic, and overall adverse reactions were of grades 1 and 2, with a low incidence of grade 3. After booster immunization, these differences were mainly grades 1 and 2, with no differences between JEV-PI and JEV-LI.Conclusion JEV-PI is a promising vaccine as infants acquired long-lasting and highly neutralizing immune antibodies after inoculation with JEV-PI.Trial Registration The trial was registered in the Chinese Clinical Trial Registry (https://www.chictr.org.cn/showproj.html?proj = 203130; registration number: ChiCTR2300074692; registration date: 14/08/2023).

Abstract Background Delirium is one of the most common neurological complications after cardiac surgery. The purpose of our study was to assess the relationship between perioperative blood pressure variability (BPV) and postoperative delirium (POD) in the patients undergoing cardiac surgery. Methods Adult patients received cardiac surgery and stayed in Cardiovascular Intensive Care Unit (ICU) for more than 24 h after surgery during the study period between June 2019 and December 2022 were included in this study. Baseline characteristics, perioperative hemodynamic variables and postoperative laboratory results of the cardiac patients were collected and analyzed. Perioperative BPV was quantified by calculating the standard deviation (SD) and average real variability (ARV) of blood pressure. Assessment of delirium was based on the mental status of the patients and CAM-positive. The relationship between perioperative BPV and POD was analyzed by LASSO and logistic regression using R (R package, 4.3.2). Results The incidence of POD was 15.0% (324/2164) in the patients receiving cardiac surgery, and the average day for POD occurred at day 3 after surgery. Patients with POD had statistically lower levels of intraoperative mean blood pressure (P = 0.015) and blood pressure ARV (P

The paper analyzed the current state of China's grain supply chain in 2023, highlighting the continuous innovations in various aspects, including production, import and export, storage, transportation, processing, and sales. It summarized the exploration of various supply chain models in practice, such as the futures market, group enterprises, wholesale markets (National Grain Trade Centers), logistics companies, new retail enterprises, digital technology companies, production bases, fertilizer companies, exhibitions, "grain logistics channels," provincial regional brands, and the grain logistics supply chain, etc. The paper analyzed the existing problems in China's grain supply chain innovation and application, and identified seven major trends in the development of the grain supply chain, namely digitalization, greening, safety, globalization, coordination, intelligence, and standardization. It also put forward policy recommendations for China's grain supply chain innovation.

Abstract Background Primary screening for high-risk human papillomavirus (hrHPV) with cytological triage for women with non-16/18 hrHPV-positive status has become popular in China. However, cytology relies on the subjective judgment of pathologists, leading to inconsistent clinical performance. Methods A total of 657 hrHPV-positive women aged 25–64 years were enrolled in this cross-sectional study. All participants underwent colposcopic biopsy after cytology triage, with cytology residual specimens undergoing DNA methylation testing. CIN2+ and CIN3+ sensitivity and specificity were compared between the different triage strategies (n=487): PAX1 methylation (PAX1 m ) , Glycophorin C methylation (GYPC m ), cytology, and combinations between them or with HPV16/18. Results The area under the receiver operating characteristic curves (AUCs) for PAX1 m and GYPC m in detecting CIN2 or worse (CIN2+) were 0.867 (95% confidence interval [CI]: 0.796–0.937) and 0.873 (95% CI: 0.808–0.938), respectively. The sensitivities of PAX1 m and GYPC m were consistent with those of cytology for both CIN2+ and CIN3+ detection. The relative specificities of PAX1 m and GYPC m for CIN2+ detection compared to cytology were 2.83 (95% CI: 2.33–2.45) and 3.09 (95% CI: 2.40–3.98), respectively. The relative specificities of combining HPV 16/18 with PAX1 m and GYPC m for CIN2+ detection compared to cytology were 3.38 (95% CI: 2.96–3.86) and 3.67 (95% CI: 3.15–4.27), respectively. Compared to low levels of DNA methylation, high levels of PAX1 m and GYPC m resulted in odd ratios (ORs) of 57.66 (95% CI: 13.57–409.12, p < 0.001) and 23.87 (95% CI: 6.49–115.42, p < 0.001) for CIN3+, adjusted for HPV 16/18 and cytology results. Conclusions PAX1 m and GYPC m demonstrated superior ability to identify cervical precancerous lesions and cervical cancer, with AUC values exceeding 0.85. For detecting CIN2+/CIN3+ in women with hrHPV-positive status, DNA methylation (combined with HPV 16/18) showed higher specificity than cytology (combined with HPV 16/18) and is a potential molecular biomarker for detecting cervical (pre)cancer.

Abstract Despite the pivotal role of stannum doping in achieving ultrahigh piezoelectric performance in barium titanate-based ceramics, the fundamental mechanisms underlying this enhancement remain elusive. Here, we introduce a single variable nonstoichiometric stannum strategy in lead-free barium titanate-based ceramics with giant piezoelectricity, revealing that stannum doping contributes intrinsically and extrinsically to enhance piezoelectricity. Density functional theory calculations elucidate the intrinsic enhancement of polarization arising from lattice distortion and increased space for titanium-oxygen bonds induced by optimal stannum doping, which is corroborated by Rayleigh analysis. A phase transition from ferroelectric multiphase coexistence to paraelectric phase is observed, alongside a rapid miniaturized and eventually disappeared domains with increasing stannum doping. This evolution in phase structure and domain configuration induces a nearly vanishing polarization anisotropy and low domain wall energy, facilitating easy polarization rotation and domain wall motion, thereby significantly contributing to the extrinsic piezoelectric response. Consequently, the origins of ultrahigh performance can be attributed to the synergistic effect of stannum-induced intrinsic and extrinsic contributions in barium titanate-based ceramics. This study provides fundamental insights into the role of doping elements and offers guidance for the design of high-performance piezoelectrics.

Abstract Background Transcatheter arterial chemoembolization (TACE) combined with targeted therapy and immunotherapy can significantly improve the prognosis of patients with hepatocellular carcinoma (HCC). T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) is a novel immunosuppressive molecule. This study aimed to analyze the clinical correlation between TIGIT expression on T cells and patients with HCC. Methods Clinical data from 140 patients with HCC were retrospectively collected, and TIGIT expression on T cells was examined in each patient. Patients were subsequently divided into high- and low-expression groups, and their prognosis was analyzed. Results Patients with a high TIGIT expression on their T cells at baseline had a larger tumor volume, later staging, higher proportion of regulatory T cells, higher blood concentrations of interleukin (IL)-6 and IL-10, and lower interferon-γ concentrations. Following TACE, CD155 concentration decreased; however, TACE did not affect TIGIT expression on T cells. Additionally, among patients receiving TACE combined with apatinib and camrelizumab treatment, patients with a high TIGIT expression on T cells had significantly shorter progression-free survival (PFS) and overall survival times than those of patients in the low-expression group. Patients receiving TACE combined with apatinib and camrelizumab treatment with higher TIGIT expression have shorter PFS time than those receiving TACE combined with apatinib treatment. Conclusions Patients with HCC that have a high TIGIT expression on their T cells exhibited poorer baseline characteristics, immunosuppressive status, and prognosis after receiving TACE combined with apatinib and camrelizumab and maybe more suited to receive TACE combined with apatinib treatment instead.

Abstract Background The risk of cervical cancer progression in high-risk human papillomavirus (HR-HPV)-positive women is associated with cervical lesion severity and molecular heterogeneity. Classification systems based on p16 and Ki67 expression cumulative scores (0–3 each)—p16/Ki67 collectively known as an immunoscore [IS]—are an accurate and reproducible method for grading cervical intraepithelial neoplasia (CIN) lesions. Meanwhile, DNA methylation is an early event in the development of cervical cancer. Hence, this study evaluated the relationship among CIN, p16/Ki-67 IS, and PAX1/ZNF582 methylation. Methods In this study, 414 HPV-positive paraffin-embedded specimens were collected, and PAX1/ZNF582 methylation and the p16/ki67 IS were determined. A total of 43 invalid samples were excluded and 371 were included in the statistical analyses. There were 103 cervicitis, 95 CIN1, 71 CIN2, 89 CIN3, and 13 squamous cell carcinoma (SCC) cases. The association between PAX1/ZNF582 methylation and p16/Ki6 immunohistochemical staining scores was analyzed. Results The ΔCp of PAX1 m (PAX1 methylation) and ZNF582 m (ZNF582 methylation) decreased with cervical lesion severity (Cuzick trend test, all P

Abstract Background Acute kidney injury (AKI) is a major complication following cardiac surgery. We explored the clinical utility of iron metabolism indexes for identification of patients at risk for AKI after cardiac surgery. Methods This prospective observational study included patients who underwent cardiac surgery between March 2023 and June 2023. Iron metabolism indexes were measured upon admission to the intensive care unit. Multivariable logistic regression analyses were performed to explore the relationship between iron metabolism indexes and cardiac surgery-associated AKI (CSA-AKI). Receiver operating characteristic (ROC) curve was used to assess the predictive ability of iron, APACHE II score and the combination of the two indicators. Restricted cubic splines (RCS) was used to further confirm the linear relationship between iron and CSA-AKI. Results Among the 112 recruited patients, 38 (33.9%) were diagnosed with AKI. Multivariable logistic regression analysis indicated that APACHE II score (odds ratio [OR], 1.208; 95% confidence interval [CI], 1.003–1.455, P = 0.036) and iron (OR 1.069; 95% CI 1.009–1.133, P = 0.036) could be used as independent risk factors to predict CSA-AKI. ROC curve analysis showed that iron (area under curve [AUC] = 0.669, 95% CI 0.572–0.757), APACHE II score (AUC = 0.655, 95% CI 0.557–0.744) and iron and APACHE II score combination (AUC = 0.726, 95% CI 0.632–0.807) were predictive indicators for CSA-AKI. RCS further confirmed the linear relationship between iron and CSA-AKI. Conclusions Elevated iron levels were independently associated with higher risk of CSA-AKI, and there was a linear relationship between iron and CSA-AKI.

BackgroundHuman papillomavirus (HPV) infection is a worldwide reproductive system disease. Baofukang suppository, a traditional herbal preparation that includes curdione and borneol, has been reported to treat bacterial vaginosis (BV) and HPV infection in China. However, the therapeutic mechanism is still unknown. This study aims to explore the molecular mechanisms of curdione and borneol in treating HPV infection.MethodsWe conducted a retrospective cohort analysis of medical records from a single-center study involving 205 HPV patients, focusing on the correlation between HPV clearance and co-infection with other pathogens, confirming the efficacy of Baofukang suppository. Bioinformatics and network pharmacology approaches were employed to identify therapeutic targets of Baofukang suppository for BV/HPV co-infections. qRT-PCR, Western blot, immunofluorescence staining, and flow cytometry were utilized to validate the therapeutic targets of curdione and borneol, along with the associated immune molecular changes. Finally, the molecular mechanisms and therapeutic efficacy of curdione and borneol were confirmed in vivo using an LPS/TC-1 cervical orthotopic injection model.ResultsCurdione and borneol selectively inhibit the secretion of interleukin-6 (IL-6) and interleukin-1β (IL-1β) by macrophages. The reduction in IL-6 and IL-1β levels effectively inhibits the expression of CD274 (Programmed death ligand 1, PD-L1) in infected epithelial cells by inhibiting STAT3 phosphorylation, thereby suppressing their immune evasion capabilities. Furthermore, curdione and borneol enhance the expression of tumor necrosis factor α (TNF-α) and caspase 1 (CASP1) in macrophages, as well as the expression of interleukin 12 (IL-12) and interleukin 23 (IL-23) in dendritic cells (DCs). The expression of these inflammatory factors effectively promotes the migration and differentiation of T cells to the site of infection, completing the clearance of infected epithelial cells.ConclusionThe main components of Baofukang suppository, curdione and borneol, inhibit the progression of HPV infection and the occurrence of cervical cancer by modulating the communication between innate and adaptive immunity, promoting the recruitment and recognition of CD8+ T cells to eliminate HPV-infected epithelial cells.

Abstract Background Delirium is a common disorder affecting patients’ psychiatric illness, characterized by a high rate of underdiagnosis, misdiagnosis, and high risks. However, previous studies frequently excluded patients with psychiatric illness, leading to limited knowledge about risk factors and optimal assessment tools for delirium in psychiatric settings. Objectives The scoping review was carried out to (1) identify the risk factors associated with delirium in patients with psychiatric illness; (2) synthesize the performance of assessment tools for detecting delirium in patients with psychiatric illness in psychiatric settings. Design Scoping review. Data sources PubMed, Web of Science, and Embase were searched to identify primary studies on delirium in psychiatric settings from inception to Dec 2023 inclusive. Two independent reviewers screened eligible studies against inclusion criteria. A narrative synthesis of the included studies was conducted. Results A final set of 36 articles meeting the inclusion criteria, two main themes were extracted: risk factors associated with delirium in patients with psychiatric illness and assessment tools for detecting delirium in psychiatric settings. The risk factors associated with delirium primarily included advanced age, physical comorbid, types of psychiatric illness, antipsychotics, anticholinergic drug, Electroconvulsive therapy, and the combination of lithium and Electroconvulsive therapy. Delirium Rating Scale-Revised-98, Memorial Delirium Assessment Scale, and Delirium Diagnostic Tool-Provisional might be valuable for delirium assessment in patients with psychiatric illness in psychiatric settings. Conclusions Delirium diagnosis in psychiatric settings is complex due to the overlapping clinical manifestations between psychiatric illness and delirium, as well as their potential co-occurrence. It is imperative to understand the risk factors and assessment methods related to delirium in this population to address diagnostic delays, establish effective prevention and screening strategies. Future research should focus on designing, implementing, and evaluating interventions that target modifiable risk factors, to prevent and manage delirium in patients with psychiatric illness.

Abstract Background Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery. However, the predictive value of single indictor still remains controversial. This study aimed to assess the predictive value of combining preoperative left atrial volume index (LAVI) and postoperative interleukin-6 (IL-6) for POAF in the patients receiving cardiac surgery. Methods Patients who admitted to Nanjing First Hospital during the study period between December 2022 and June 2023, and underwent open-heart surgery without a history of atrial fibrillation (AF) were enrolled. The relationships between predictors and POAF were investigated using logistic regression analysis. We determined the combined predictive value of LAVI and IL-6 for POAF by measuring the changes in the area under the receiver operating characteristic curve (AUC) and calculating the net reclassification improvements (NRIs) and integrated discrimination improvement (IDIs). Results 102 patients were enrolled in this study, and 50 participants developed POAF (49.0%). Patients who experienced POAF had higher levels of preoperative LAVI and postoperative IL-6 than those who did not. Regression analysis revealed that larger LAVI and higher level of IL-6 were independently associated with increased risk of POAF. The combined addition of LAVI and IL-6 to the predictive model resulted in an evident increase in the AUC. Incorporating both LAVI and IL-6 increased IDIs in all models. Conclusion Our results demonstrated that combined LAVI and IL-6 achieved a higher prediction performance for POAF.

BackgroundTuberculosis (TB) is a leading cause of death worldwide from a single infectious agent. In China the most common extra-pulmonary TB (EPTB) is pleural tuberculosis (PLTB). An important clinical feature of PLTB is that the lymphocytes associated with TB will accumulate in the pleural fluid. The adaptive immune repertoires play important roles in Mycobacterium tuberculosis (Mtb) infection.MethodsIn this study, 10 PLTB patients were enrolled, and their Peripheral Blood Mononuclear Cells(PBMCs) and Pleural Effusion Mononuclear Cells(PEMCs) were collected. After T cells were purified from PBMCs and PEMCs, high-throughput immunosequencing of the TCRβ chain (TRB), TCRγ chain(TRG), and B cell receptor(BCR) immunoglobulin heavy chain (IGH) were conducted on these samples.ResultsThe TRB, TRG, and BCR IGH repertoires were characterized between the pleural effusion and blood in PLTB patients, and the shared clones were analyzed and collected. The binding activity of antibodies in plasma and pleural effusion to Mtb antigens was tested which indicates that different antibodies responses to Mtb antigens in plasma and pleural effusion in PLTB patients. Moreover, GLIPH2 was used to identify the specificity groups of TRB clusters and Mtb-specific TRB sequences were analyzed and collected by VJ mapping.ConclusionWe characterize the adaptive immune repertoires and identify the shared clones and Mtb-specific clones in pleural effusion and blood in PLTB patients which can give important clues for TB diagnosis, treatment, and vaccine development.

Abstract Despite the dominance of lead-based piezoelectric materials with ultrahigh electric-field-induced strain in actuating applications, seeking eco-friendly substitutes with an equivalent performance remains an urgent demand. Here, a strategy of regulating the irreversible non-180° domain via phase engineering is introduced to optimize the available strain (the difference between the maximum strain and the remnant strain in a unipolar strain curve) in the lead-free potassium–sodium niobate-based piezoelectric ceramics. In situ synchrotron X-ray diffraction and Rayleigh analysis reveal the contribution of the non-180° domain to available strain in the tetragonal–orthorhombic–rhombohedral phase boundary. The reducing orthorhombic phase and increasing rhombohedral/tetragonal phase accompanied by the reduced irreversible non-180° domain are obtained with increasing doping of Sb5+, resulting in an enlarged available strain due to the significantly lowered remnant strain. This optimization is mainly attributed to the reduced irreversible non-180° domain wall motion and the increased lattice distortion, which are beneficial to decrease extrinsic contribution and enhance intrinsic contribution. The mesoscopic structure of miniaturized nanosized domain with facilitated domain switching also contributes to the enhancement of available strain due to the improved random field and decreased energy barrier. The study will shed light on the design of lead-free high-performance piezoelectric ceramics for actuator applications.

Chlorogenic acid (CGA) has strong antioxidant properties. In order to improve the low maturation rate and poor vitrification freezing effect of sheep oocytes caused by oxidative stress. In this study, oocytes from 200 2–3-year-old Kazakh sheep were collected, and different concentrations of CGA were added to the maturation medium and vitrification freezing solution to study the effects of CGA on the maturation rate, cleavage rate, blastocyst rate, reactive oxygen species (ROS) and glutathione (GSH) levels, mitochondrial membrane potential, and the expression levels of oxidation and apoptosis-related genes in sheep oocytes. The results showed that adding 40 μmol/L CGA to the oocyte in vitro maturation solution significantly increased the maturation rate of oocytes, adding 50 μmol/L CGA to the vitrification cryopreservative solution significantly increased the cleavage and blastocyst rates of mature oocytes activated by parthenogenetic activation after freezing. During in vitro maturation and vitrification freezing in sheep oocytes, CGA significantly reduced the level of ROS and the expression of apoptosis-related genes (Caspase-3 and Bax/Bcl-2), and significantly increased the level of glutathione (GSH), mitochondrial membrane potential, and the expression of antioxidant and anti-apoptosis-related genes (SOD-2 and GPX-3). In addition, CGA significantly increased the expression of the anti-apoptotic gene (AKT) and anti-stress gene (FOXO) during vitrification freezing of sheep oocytes. In conclusion, 40 μmol/L CGA improves the maturation rate of sheep oocytes, and 50 μmol/L CGA improves the quality of parthenogenetic activation embryos after vitrification freezing of mature oocytes in sheep. These results provide a basis for the production of sheep in vitro embryos and the establishment of a germplasm resource bank.

Abstract Background Nursing interns often experience lots of challenges during their clinical nursing internships, which can adversely affect career decisions and result in a squandering of nursing education resources. Patient safety attitudes, professional identity and climate of caring may affect nursing interns’ clinical experience. However, more evidence is requested to validate these relationships for nursing educators to develop effective education programs and facilitate interns’ successful transition. Methods This was a cross-sectional study, which used a convenience sampling method to recruit 387 nursing interns during December 2022 to April 2023 in university affiliated hospital in Hunan province, China. Data were collected using standardized scales. Spearman correlation and multiple regression analysis were employed to examine the relationship between transition shock, patient safety attitudes, professional identity, and climate of caring. Results Nursing interns experienced transition shock at a moderate level and the highest levels of transition shock in response to overwhelming practicum workloads, with the second being related to the conflict between theory and practice. Transition shock was negatively correlated with patient safety attitudes, professional identity and climate of caring among nursing interns. Conclusions Nursing managers and educators need to value the transition shock experienced by nursing interns. Our study suggests that developing a strong sense of professional identity and a positive attitude toward patient safety can be effective in reducing the level of transition shock among nursing interns. In addition, a caring climate within the nursing unit can significantly enhance the overall experience of nursing interns. This can be achieved by enhancing the support of clinical mentors, providing patient safety-focused education, and facilitating team communication among nurses.

Abstract Background This study used next‐generation sequencing (NGS) to investigate the genetic profiles in cerebrospinal fluid (CSF), plasma, and tumor tissue to explore alternative detection methods for anaplastic lymphoma kinase (ALK) rearrangement status and potential resistance mechanisms to ALK inhibitors. Methods From January 2016 to January 2021, 19 non‐small cell lung cancer (NSCLC) patients with brain metastases (BMs) and ALK‐positive primary tumors were enrolled at Beijing Chest Hospital. CSF, plasma, and primary tumor samples from patients with BMs of NSCLC were tested using NGS with a 168‐gene panel. The intracranial response and prognosis were also investigated. Results The study included 19 patients, seven females and 12 males, aged between 29 and 68 (median age 44). CSF cytology was negative in all cases. NGS results showed ALK fusion genes detected in 26.3% (5/19) of CSF cfDNA samples, 78.9% (15/19) of plasma samples, and 89.5% (17/19) of tumor samples from ALK‐positive patients. ALK‐positive CSF samples had significantly higher allele fractions in CSF cfDNA compared with the other two sample types. In five patients with ALK‐positive in CSF, after receiving ALK inhibitors ± local treatment, one case achieved an intracranial complete response, and two had an intracranial partial response. In CSF samples, the intracranial median progression‐free survival was 8.0 and 18.0 months for ALK‐positive (n = 5) and ALK‐negative (n = 14), respectively (p = 0.077). Conclusion CSF may serve as a liquid biopsy for ALK‐positive lung cancer with BMs by detecting cfDNA within CSF to characterize driver and resistant genes.

Abstract In patients with unresectable non-small cell lung cancer, histological diagnosis is frequently based on small biopsy specimens unsuitable for histological diagnosis when they are severely crushed and do not retain their morphology. Therefore, establishing a novel diagnostic method independent of tissue morphology or conventional immunohistochemistry (IHC) markers is required. We analyzed the lipid profiles of resected primary lung adenocarcinoma (ADC) and squamous cell carcinoma (SQCC) specimens using liquid chromatography-tandem mass spectrometry. The specimens of 26 ADC and 18 SQCC cases were evenly assigned to the discovery and validation cohorts. Non-target screening on the discovery cohort identified 96 and 13 lipid peaks abundant in ADC and SQCC, respectively. Among these 109 lipid peaks, six and six lipid peaks in ADC and SQCC showed reproducibility in target screening on the validation cohort. Finally, we selected three and four positive lipid markers for ADC and SQCC, demonstrating high discrimination abilities. In cases difficult to diagnose by IHC staining, [cardiolipin(18:2_18:2_18:2_18:2)-H]− and [triglyceride(18:1_17:1_18:1) + NH4]+ showed the excellent diagnostic ability for ADC (sensitivity: 1.00, specificity: 0.89, accuracy: 0.93) and SQCC (sensitivity: 0.89, specificity: 0.83, accuracy: 0.87), respectively. These novel candidate lipid markers may contribute to a more accurate diagnosis and subsequent treatment strategy for unresectable NSCLC.

Skull base surgery is an important branch of neurosurgery that focuses on the surgical treatment of skull base lesions. This field requires a high degree of specialization and a high technical level. Skull base surgeons must be skilled and experienced while maintaining high ethical standards to ensure patients receive the best results. This article intends to systematically illustrate how to become an excellent skull base surgeon based on the update and progress of technology and equipment in the field of skull base surgery, combined with own experience.

Hypophthalmichthys nobilis are widely distributed in the Yangtze River basin and its related lakes. They are an important economic fish species and are a famous cultured species known as the “Four Famous Domestic Fishes” in China. Currently, with the fishing ban in the Yangtze River basin, fishing for H. nobilis in the natural water bodies of the Yangtze River basin has been completely prohibited. In order to identify the sources of H. nobilis appearing in the market, further control and accountability is necessary to trace the sources of H. nobilis in the Yangtze River basin and its related water bodies. Therefore, this study identified and traced different sources of H. nobilis through muscle element fingerprint analysis (EFA). The results show that H. nobilis from different stations have characteristic element compositions. The characteristic element of H. nobilis from Wuhan (WH) is Pb, which is significantly higher than that in other stations; the characteristic element from Anqing (AQ) is Hg, which is significantly higher than that in other stations; and the characteristic element from Taihu (TH) is Al, which is significantly higher than that in other water areas. Multivariate analysis selected different spatial distribution patterns in four discriminative element ratios (Pb/Ca, Cr/Ca, Na/Ca, and Al/Ca) in the muscle of H. nobilis in the Yangtze River basin and its related lakes. This study suggests that the screened discriminative elements can be used to visually distinguish different sources of H. nobilis and to quickly trace and verify the origin of newly emerging samples. Therefore, the use of selected discriminative element fingerprint features to trace the origin of new samples has been proven to be feasible. By further discriminating and verifying the muscle element fingerprints of new samples, the discrimination rate is high. Therefore, a multivariate analysis of muscle element fingerprints can be used for tracing the origins of samples of unknown origin in market supervision.

Feature selection is a basic and important step in real applications, such as face recognition and image segmentation. In this paper, we propose a new weakly supervised multi-view feature selection method by utilizing pairwise constraints, i.e., the pairwise constraint-guided multi-view feature selection (PCFS for short) method. In this method, linear projections of all views and a consistent similarity graph with pairwise constraints are jointly optimized to learning discriminative projections. Meanwhile, the l2,0-norm-based row sparsity constraint is imposed on the concatenation of projections for discriminative feature selection. Then, an iterative algorithm with theoretically guaranteed convergence is developed for the optimization of PCFS. The performance of the proposed PCFS method was evaluated by comprehensive experiments on six benchmark datasets and applications on cancer clustering. The experimental results demonstrate that PCFS exhibited competitive performance in feature selection in comparison with related models.

Background: There are limited population studies on the neurodevelopmental effects of bisphenol F (BPF), a substitute for bisphenol A. Furthermore, the role of placental estradiol as a potential mediator linking these two factors remains unclear. Objective: To examine the association between maternal prenatal BPF exposure and infant neurodevelopment in a prospective cohort study and to explore the mediating effects of placental estradiol between BPF exposure and neurodevelopment in a nested case-control study. Methods: The prospective cohort study included 1077 mother-neonate pairs from the Wuhu city cohort study in China. Maternal BPF was determined using the liquid/liquid extraction and Ultra-performance liquid chromatography tandem mass spectrometry method. Children's neurodevelopment was assessed at ages 3, 6, and 12 months using Ages and Stages Questionnaires. The nested case-control study included 150 neurodevelopmental delay cases and 150 healthy controls. Placental estradiol levels were measured using enzyme-linked immunosorbent assay kits. Generalized estimating equation models and robust Poisson regression models were used to examine the associations between BPF exposure and children's neurodevelopment. In the nested case-control study, causal mediation analysis was conducted to assess the role of placental estradiol as a mediator in multivariate models. Results: In the prospective cohort study, the pregnancy-average BPF concentration was positively associated with developmental delays in gross-motor, fine-motor, and problem-solving ( ORtotal ASQ: 1.14(1.05, 1.25), ORgross-motor: 1.22(1.10, 1.36), ORfine-motor: 1.19(1.07, 1.31), ORproblem-solving: 1.11(1.01, 1.23)). After sex-stratified analyses, pregnancy-average BPF concentration was associated with an increased risk of neurodevelopmental delays in the gross-motor (ORgross-motor:1.30(1.12, 1.51)) and fine-motor (ORfine-motor: 1.22(1.06, 1.40)) domains in boys. In the nested case-control study, placental estradiol mediated 16.6% (95%CI: 4.4%, 35.0%) of the effects of prenatal BPF exposure on developmental delay. Conclusions: Our study supports an inverse relationship between prenatal BPF exposure and child neurodevelopment in infancy, particularly in boys. Decreased placental estradiol may be an underlying biological pathway linking prenatal BPF exposure to neurodevelopmental delay in offspring.

ABSTRACTObjective To explore the clinical outcomes and characteristics of TP53-mutated primary myelodysplastic syndromes (MDS).Methods A total of 74 de novo primary MDS patients who were diagnosed and treated in the Department of Hematology of our hospital from January 2018 and September 2021 were analyzed retrospectively. All patients had evaluable blood cell counts, mean corpuscular volume (MCV), lactate dehydrogenase (LDH), bone marrow (BM) morphology, biopsy, and MDS-related 20-gene mutations sequencing. In addition, 69 of 74 patients had complete cytogenetic analysis through conventional chromosome analysis and fluorescence in-situ hybridization.Results Patients were divided into two cohorts, the TP53-mutated type (TP53Mut) group (n = 19) and TP53 wild type (TP53WT) group (n = 55). Compared with the TP53WT group, patients in the TP53Mut group had higher ratios of cytogenetic abnormalities (82.4% vs. 30.8%, P

Abstract We provide an approach for compiling quantum simulation circuits that appear in Trotter, qDRIFT and multi-product formulas to Clifford and non-Clifford operations that can reduce the number of non-Clifford operations. The total number of gates, especially CNOT, reduce in many cases. We show that it is possible to implement an exponentiated sum of commuting Paulis with at most m (controlled)-rotation gates, where m is the number of distinct non-zero eigenvalues (ignoring sign). Thus we can collect mutually commuting Hamiltonian terms into groups satisfying one of several symmetries identified in this work. This allows an inexpensive simulation of the entire group of terms. We further show that the cost can in some cases be reduced by partially allocating Hamiltonian terms to several groups and provide a polynomial time classical algorithm that can greedily allocate the terms to appropriate groupings.

Abstract Background Anxiety and depression are common psychological comorbidities in patients with chronic pancreatitis (CP). There is still a lack of epidemiological studies on anxiety and depression in Chinese CP patients. This study aimed to identify the incidence and related factor of anxiety and depression among East Chinese CP patients and explore the relationship between anxiety, depression, and coping styles. Methods This prospective observational study was conducted from June 1, 2019 to March 31, 2021 in Shanghai, China. Patient diagnosed with CP were interviewed using the sociodemographic and clinical characteristics questionnaire, Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), and Coping Style Questionnaire (CSQ). Multivariate logistic regression analysis was conducted to identify the related factors of anxiety and depression. Correlation test was preformed to analyze the correlation between anxiety, depression, and coping styles. Results The incidence of anxiety and depression in East Chinese CP patients was 22.64% and 38.61%, respectively. Patients’ previous health status, level of disease coping, frequency of abdominal pain episodes, and pain severity were significantly associated with anxiety and depression. Mature coping styles (Problem solving, Seeking for help) had a positive impact on anxiety and depression, while immature coping styles (Self-blame, Fantasy, Repression, Rationalization) had negative effects on anxiety and depression. Conclusion Anxiety and depression were common in patients with CP in China. The factors identified in this study may provide references for the management of anxiety and depression in CP patients.

Computational Fluid Dynamics (CFD) and Fluid-Structure Interaction (FSI) are increasingly used to predict the hemodynamic and structural behaviors of cerebral aneurysms (CAs) whilst a less-pursued method is the static structural analysis (SSA) using the finite element method. In this paper, hemodynamic parameters including the flow velocity and wall shear stress predicted by CFD and FSI are compared whilst structural parameters including the wall displacement and wall stress predicted by SSA and FSI are compared for four patient-specific CA models under different systolic/diastolic pressures. The predicted distribution patterns of the same parameters for the same CA model under different pressures are similar. However, the percentage differences of the maximum hemodynamic parameters increase with increasing pressure. Conversely, the percentage differences of the maximum structural parameters decrease from a few to less than 1.5% when the systolic/diastolic pressure changes from 120/80 to 180/110 mmHg. The ratio of the computation times for CFD, SSA and FSI is typically 75:1:165. If the maximum wall stress under either ongoing or temporary hypertension is the most critical factor for immediate rupture and, thus, clinical treatment of CAs, SSA can provide a low cost and efficient predictions close to those of FSI for assessing the rupture risk.

IntroductionMoral injury, predominantly studied in military populations, has garnered increased attention in the healthcare setting, in large part due to the psychological and emotional consequences of the COVID-19 pandemic. The measurement of moral injury with instrumentation adapted from military settings and validated by frontline healthcare personnel is essential to assess prevalence and guide intervention. This study aimed to validate the Moral Injury Outcome Scale (MIOS) in the population of acute care.MethodsA sample of 309 acute care nurses completed surveys regarding moral injury, depression, anxiety, burnout, professional fulfillment, spiritual wellbeing, and post-traumatic stress disorder symptoms. Confirmatory factor analysis was conducted as well as an assessment of reliability and validity.ResultsThe internal consistency of the 14-item MIOS was 0.89. The scale demonstrated significant convergent and discriminant validity, and the test of construct validity confirmed the two-factor structure of shame and trust violations in this clinical population. Regression analysis indicated age, race, and marital status-related differences in the experience of moral injury.DiscussionThe MIOS is valid and reliable in acute care nursing populations and demonstrates sound psychometric properties. Scores among nurses diverge from those of military personnel in areas that may inform distinctions in interventions to address moral injury in these populations.

Abstract Background This study aimed to analyze associations between genetic variants and plasma concentrations along with clinical outcomes in dabigatran in patients with non-valvular atrial fibrillation (NVAF). Methods We conducted a prospective study and enrolled NVAF patients treated with dabigatran in the real world. A total of 86 patients treated with 110 mg DE twice daily were recruited for this study. Blood samples were obtained from each patient and used for genotyping and determination of plasma dabigatran concentration. All bleeding and thromboembolic complications were recorded during the 1.5 years of follow-up. Results Eighty-three patients provided samples at the trough plasma level of dabigatran, and 58 patients provided samples at the peak plasma level of dabigatran. There was a significant association between the CES1 SNP rs8192935 and trough plasma concentrations of dabigatran (P = 0.013). Our results showed that the CES1 SNP rs8192935 significantly influenced dabigatran trough concentrations in the Chinese population, and carriers of the G allele had increased trough plasma concentrations of dabigatran compared to noncarriers. The ABCB1 SNP c.2482-2236G > A (rs4148738) was associated with major bleeding events in the addictive model (P = 0.046, OR = 3.29) and dominant model (P = 0.040, OR = 8.17). Additionally, the ABCB1 SNP c.3435 C > T (rs1045642) was associated with the incidence of major bleeding events in the addictive model (P = 0.043, OR = 3.34) and dominant model (P = 0.046, OR = 7.77). However, no significant associations were found between all the SNPs and the incidence of minor bleeding events. Conclusion Our results indicated that the CES1 polymorphism rs8192935 was associated with trough plasma concentrations of dabigatran. Carriers of the G allele had increased trough plasma concentrations of dabigatran compared to noncarriers. The ABCB1 polymorphisms rs4148738 and rs1045642 were associated with an increased risk for major bleeding events for the first time in a Chinese population.

For relaxor ferroelectrics, correlating their properties and local structures is challenging. Here, the authors correlate the atomic-scale structure and the large dynamic electromechanical property in Bi0.5Na0.5TiO3-based relaxor ferroelectrics.

Image classification is vital and basic in many data analysis domains. Since real-world images generally contain multiple diverse semantic labels, it amounts to a typical multi-label classification problem. Traditional multi-label image classification relies on a large amount of training data with plenty of labels, which requires a lot of human and financial costs. By contrast, one can easily obtain a correlation matrix of concerned categories in current scene based on the historical image data in other application scenarios. How to perform image classification with only label correlation priors, without specific and costly annotated labels, is an important but rarely studied problem. In this paper, we propose a model to classify images with this kind of weak correlation prior. We use label correlation to recapitulate the sample similarity, employ the prior information to decompose the projection matrix when regressing the label indication matrix, and introduce the ℓ2,1 norm to select features for each image. Finally, experimental results on several image datasets demonstrate that the proposed model has distinct advantages over current state-of-the-art multi-label classification methods.

BackgroundIt has been reported that inflammatory bowel disease (IBD) is associated with an increased risk of malignancies, including lymphoma. A number of large observational studies have been devoted to exploring the causal link between IBD and malignant lymphoma. However, no consensus exists on whether there is a causal relationship between IBD and malignant lymphoma.MethodsThe summary dataset of the IBD and lymphoma genome-wide association studies (GWAS) was obtained from the OPEN GWAS website. Single-nucleotide polymorphisms (SNPs) were selected as genetic instrumental variants (IVs) for fulling P < 5 × 10-8 and linkage disequilibrium (LD) of r2 = 0.001 in the IBD GWAS. The proxy SNPs with LD of r2 > 0.8 were identified. Palindromic SNPs and outlier SNPs were excluded. The assessments of sensitivity employed the Cochran’s Q test, Mendelian randomization (MR)-Egger intercept test, and leave-one-out analysis.ResultsThe MR analysis results proved the causality of IBD on diffuse large B-cell lymphoma (DLBCL). The risk of developing DLBCL is increased by 28.6% in patients with IBD [odds ratio (OR)IVW = 1.286, 95% confidence interval (CI) 1.066–1.552, P = 0.009]. The results of the subgroup analysis showed that Crohn’s disease (ORIVW = 1.218, 95% CI 1.030–1.441, P = 0.021) rather than ulcerative colitis (ORIVW = 1.206, 95% CI 0.984–1.478, P = 0.072) had a causal effect on DLBCL. No horizontal and directional pleiotropy was observed in the MR studies.ConclusionsThe above MR study concluded that IBD itself is causally responsible for DLBCL, especially Crohn’s disease. Further investigations are needed to elucidate the mechanism underlying this direct causal link.

Phytoremediation techniques have been widely used in the treatment of heavy metal contaminated soils in recent years, but there is no effective post-treatment method for plant tissues containing heavy metals after remediation. Elsholtzia Harchowensis is a copper hyperaccumulator, commonly distributed in copper mining areas and often used for soil remediation of mine tailings. Moreover, copper-based catalysts are widely used in electrocatalytic reduction of carbon dioxide, which aims to convert carbon dioxide into useful fuels or chemicals. In this study, copper-modified biochar was prepared from Elsholtzia Harchowensis. Its specific surface area can reach as high as 1202.9 m2/g, with a certain porous structure and even distribution of copper on the amorphous carbon. Various products (such as carbon monoxide, methane, ethanol, and formic acid) could be obtained from the electrolytic reduction of carbon dioxide by using the as-prepared catalyst. Instantaneous current density of up to 15.3 mA/cm2 were achieved in 1.0 M KHCO3 solution at a potential of −0.82 V (vs. RHE). Electrolysis at a potential of −0.32 V (vs. RHE) for 8 h resulted in a stable current of about 0.25 mA/cm2, and the Faraday efficiency (FE) of carbon monoxide can reach as high as 74.6%. In addition, electrolysis at a potential of −0.52 V (vs. RHE) for 8 h led to a stable current of about 2.2 mA/cm2 and a FE of 8.7% for the C2 product. The rich variety of elements in plants leads to catalysts with complex structural and elemental characteristics as well, which facilitates the electrolytic reduction of carbon dioxide with a variety of useful products.

IntroductionMyxococcus sp. PT13 is a wild strain with multiple predatory properties that prey on multiple model microorganisms preserved in the laboratory. However, the lysis spectrum of PT13 on typical soil bacteria and its driving effect on soil microecosystems are still unclear.MethodsIn this study, the lawn predation method was used to determine the predation diameter of 62 typical soil bacteria by myxobacteria PT13 and analyze their lysis spectra.Results and DiscussionThe results showed that PT13 had a predation diameter greater than 15 mm against typical soil microorganisms such as Aeromonas, Bacillus, Brevibacterium, Fictibacillus, Glutamicibacter, Herbaspirillum, and Leifsonia and had an outstanding lysis effect but a significant preference (p

In the present study, the effects of Humulus scandens extract on growth performance, antioxidant responses and intestinal microflora of Yellow River carp (Cyprinus carpio) were investigated. 240 carps were assigned to four treatments received diets supplemented with 0 (control), 0.5, 1 and 2 g/kg Humulus scandens extract for 8 weeks. At end of the trial, the final body weight, specific growth rate (SGR) and intestinal body index of the 1.0 g/kg and 2.0 g/kg group were significantly higher than those of the control group (P

Abstract Background Micronucleus (MN) is an abnormal fragment in a human cell caused by disorders in the mechanism regulating chromosome segregation. It can be used as a biomarker for genotoxicity, tumor risk, and tumor malignancy. The in vitro micronucleus assay is a commonly used method to detect micronucleus. However, it is time-consuming and the visual scoring can be inconsistent. Methods To alleviate this issue, we proposed a computer-aided diagnosis method combining convolutional neural networks and visual attention for micronucleus recognition. The backbone of our model is AlexNet without any dense layers and it is pretrained on the ImageNet dataset. Two attention modules are applied to extract cell image features and generate attention maps highlighting the region of interest to improve the interpretability of the network. Given the problems in the data set, we leverage data augmentation and focal loss to alleviate the impact. Results Experiments show that the proposed network yields better performance with fewer parameters. The AP value, F1 value and AUC value reach 0.932, 0.811 and 0.995, respectively. Conclusion In conclusion, the proposed network can effectively recognize micronucleus, and it can play an auxiliary role in clinical diagnosis by doctors.

Objectives The association between remnant lipoprotein cholesterol (RLP-C) levels and the incidence of non-alcoholic fatty liver disease (NAFLD) is unclear, especially in non-obese populations.Setting We used data from a health assessment database. The assessment was conducted at the Wenzhou Medical Center from January 2010 to December 2014. The patients were divided into low, middle and high RLP-C groups according to tertiles of RLP-C, and baseline metabolic parameters were compared among the three groups. Kaplan-Meier analysis and Cox proportional hazards regression were used to evaluate the relationship between RLP-C and NAFLD incidence. Additionally, sex-specific associations between RLP-C and NAFLD were examined.Participants 16 173 non-obese participants from the longitudinal healthcare database.Outcome measure NAFLD was diagnosed using abdominal ultrasonography and clinical history.Results Participants with higher RLP-C levels tended to have higher blood pressure, liver metabolic index and lipid metabolism index than those with middle or low RLP-C (p

Abstract Introduction Anaplastic lymphoma kinase (ALK) gene rearrangements, have been identified in approximately 2-7% of patients with lung adenocarcinoma (LUAD). However, co-occurrence of double ALK fusions in one patient was rare. Herein, we reported two Chinese female LUAD patients with confirmed double ALK fusion variants by next generation sequencing. Case presentation Case 1, a 38-year-old female was diagnosed as peripheral LUAD in left upper lobe with synchronous multiple intrapulmonary metastases (pT2N0M1b, stage IVa). And case 2, a 58-year-old female had left lower lobe primary LUAD and synchronous multiple lung metastases (pT4N2M1b, stage IVa). In both patients, tumor cells displayed strong expression of ALK protein. Genetic profiling by next generation sequencing showed both patients concurrently harbored two types of ALK rearrangements. Case 1 had an unreported ALK-SSH2/EML4-ALK double fusions, and case 2 had an another novel ARID2-ALK/EML4‐ALK double fusions. Both of these patients responded to ALK inhibitor crizotinib. Conclusions Our study reported two novel ALK fusion partners never reported, which expands the knowledge of ALK fusion spectrum and provides insight into therapeutic options for patients with double ALK fusions.

Abstract Background To reduce disease recurrence after radical surgery for lung squamous cell carcinomas (SQCCs), accurate prediction of recurrent high-risk patients is required for efficient patient selection for adjuvant chemotherapy. Because treatment modalities for recurrent lung SQCCs are scarce compared to lung adenocarcinomas (ADCs), accurately selecting lung SQCC patients for adjuvant chemotherapy after radical surgery is highly important. Predicting lung cancer recurrence with high objectivity is difficult with conventional histopathological prognostic factors; therefore, identification of a novel predictor is expected to be highly beneficial. Lipid metabolism alterations in cancers are known to contribute to cancer progression. Previously, we found that increased sphingomyelin (SM)(d35:1) in lung ADCs is a candidate for an objective recurrence predictor. However, no lipid predictors for lung SQCC recurrence have been identified to date. This study aims to identify candidate lipid predictors for lung SQCC recurrence after radical surgery. Methods Recurrent (n = 5) and non-recurrent (n = 6) cases of lung SQCC patients who underwent radical surgery were assigned to recurrent and non-recurrent groups, respectively. Extracted lipids from frozen tissue samples of primary lung SQCC were analyzed by liquid chromatography-tandem mass spectrometry. Candidate lipid predictors were screened by comparing the relative expression levels between the recurrent and non-recurrent groups. To compare lipidomic characteristics associated with recurrent SQCCs and ADCs, a meta-analysis combining SQCC (n = 11) and ADC (n = 20) cohorts was conducted. Results Among 1745 screened lipid species, five species were decreased (≤ 0.5 fold change; P

PurposeTo search for adaptive response molecules that affect the efficacy of transcatheter arterial chemoembolization (TACE), analyze their clinical correlation with and prognostic value for hepatocellular carcinoma (HCC), and explore their impact on cell biological behavior and their mechanisms of action.MethodsHCC tissue gene sequencing was used to identify differentially expressed genes. The expression of proteoglycan 4 (PRG4) in the serum of 117 patients with HCC who received TACE was detected by enzyme-linked immunosorbent assay. Serum-free medium mimicked TACE-induced nutrient deprivation. Cells with stable knockdown of PRG4 (shPRG4) were constructed to verify the effect and mechanism of PRG4 on the biological behavior of HCC cells in vitro.ResultsThe expression of PRG4 was significantly elevated under TACE-induced starvation conditions. Low PRG4 expression was associated with worse response to TACE treatment, shorter survival time, and stronger HCC migration ability. Furthermore, in vitro experiments showed that knockdown of PRG4 promoted HCC cell migration by enhancing epithelial–mesenchymal transition (EMT) while did not affect proliferation. When PRG4 expression was low, starvation treatment impaired the migratory ability of HCC cells and reduced the chemosensitivity of HCC cells to epirubicin.ConclusionsPRG4 expression predicts survival and TACE treatment response in patients with HCC. Furthermore, knockdown of PRG4 enhanced EMT, leading to HCC cell migration. PRG4 may serve as a biomarker for HCC patients receiving TACE.

Purpose Cognitive impairment (CI) is very common in patients with chronic obstructive pulmonary disease (COPD). Cerebral structural and functional abnormalities have been reported in cognitively impaired patients with COPD, and the neurovascular coupling changes are rarely investigated. To address this issue, arterial spin labeling (ASL) and resting-state blood oxygenation level dependent (BOLD) fMRI techniques were used to determine whether any neurovascular changes in COPD patients. Methods Forty-five stable COPD patients and forty gender- and age-matched healthy controls were recruited. Furthermore, resting-state BOLD fMRI and ASL were acquired to calculate degree centrality (DC) and cerebral blood flow (CBF) respectively. The CBF-DC coupling and CBF/DC ratio were compared between the two groups. Results COPD patients showed abnormal CBF, DC and CBF/DC ratio in several regions. Moreover, lower CBF/DC ratio in the left lingual gyrus negatively correlated with naming scores, lower CBF/DC ratio in medial frontal cortex/temporal gyrus positively correlated with the Montreal Cognitive Assessment (MoCA), visuospatial/executive and delayed recall scores. Conclusion These findings may provide new potential insights into neuropathogenesis of cognition decline in stable COPD patients.

Abstract Mutant isocitrate dehydrogenase 1/2 (mIDH1/2) gain a novel function for the conversion of α-ketoglutarate (α-KG) to oncometabolite R-2-hydroxyglutarate (R-2-HG). Two molecular entities namely enasidenib (AG-221) and ivosidenib (AG-120) targeting mIDH2 and mIDH1 respectively, have already been approved by FDA for the treatment of relapsed/refractory acute myeloid leukemia (R/R AML). However, the low responses, drug-related adverse effects, and most significantly, the clinically-acquired resistance of AG-221 and AG-120 has shown great influence on their clinical application. Therefore, searching for novel therapeutic strategies to enhance tumor sensitivity, reduce drug-related side effects, and overcome drug resistance have opened a new research field for defeating IDH-mutated cancers. As the effective methods, synthetic lethal interactions and synergetic therapies are extensively investigated in recent years for the cure of different cancers. In this review, the molecules displaying synergetic effects with mIDH1/2 inhibitors, as well as the targets showing relevant synthetic lethal interactions with mIDH1/2 are described emphatically. On these foundations, we discuss the opportunities and challenges for translating these strategies into clinic to combat the defects of existing IDH inhibitors.

Experimentally manipulating bubble domains remains elusive especially in the bulk form of ferroelectrics. Here, the authors achieve self-confined bubble domains with multiple polar topologies in bulk Bi0.5Na0.5TiO3 ferroelectrics, demonstrating reversible and donut-like domain morphology evolution.

Abstract Background ALK rearrangement is a very rare subset of squamous cell carcinoma (SCC) and one of the clinical features in patients is lack of data. Here, we report eight patients diagnosed with SCC of the lung harboring ALK rearrangement. Methods We collected primary NSCLC samples at the Beijing Chest Hospital between January 2012 and December 2018 for Ventana (D5F3) immunohistochemical detection. Among the 148 patients was diagnosed ALK‐rearranged non small cell lung cancer (NSCLC), only eight cases was SCC. We collected patients information from electronic patent records (EPRs). Results The eight cases of SCC were diagnosed by immunohistochemistry (IHC). Two were given crizotinib as second‐line therapy. One patient had stable disease (SD) and progression‐free survival (PFS) of six months. The other patient had progressive disease (PD) but PFS was only one month. The side effects were tolerable. This report identified 31 cases of ALK rearrangement in SCC patients from a literature search (including the eight patients in this study). These fusion genes are often seen in a younger age group (mean age: 55.6 years) and non‐smokers (18/31, 58.1%). A total of 20 cases received an ALK inhibitor as first‐ or second‐line treatment which included 11 with a partial response (PR), four with SD, and five with PD. The DCR and ORR was 75.0% (15/20) and 55.0% (11/20), respectively. The median duration time of therapy was 6.4 ± 4.4 months. Conclusions Patients with ALK‐rearranged SCC obtained clinical benefit from ALK‐inhibitor therapy, especially those who were non‐smokers and whose tumors had been identified by IHC+/FISH+.

BackgroundThis study aimed to develop machine learning models to predict Low Cardiac Output Syndrome (LCOS) in patients following cardiac surgery using machine learning algorithms.MethodsThe clinical data of cardiac surgery patients in Nanjing First Hospital between June 2019 and November 2020 were retrospectively extracted from the electronic medical records. Six conventional machine learning algorithms, including logistic regression, support vector machine, decision tree, random forest, extreme gradient boosting and light gradient boosting machine, were employed to construct the LCOS predictive models with all predictive features (full models) and selected predictive features (reduced models). The discrimination of these models was evaluated by the area under the receiver operating characteristic curve (AUC) and the calibration of the models was assessed by the calibration curve. Shapley Additive explanation (SHAP) and Local Interpretable Model-Agnostic Explanations (LIME) were used to interpret the predictive models.ResultsData from 1,585 patients [982 (62.0%) were male, aged 18 to 88, 212 (13.4%) with LCOS] were employed to train and validate the LCOS models. Among the full models, the RF model (AUC: 0.909, 95% CI: 0.875–0.943; Sensitivity: 0.849, 95% CI: 0.724–0.933; Specificity: 0.835, 95% CI: 0.796–0.869) and the XGB model (AUC: 0.897, 95% CI: 0.859–0.935; Sensitivity: 0.830, 95% CI: 0.702–0.919; Specificity: 0.809, 95% CI: 0.768–0.845) exhibited well predictive power for LCOS. Eleven predictive features including left ventricular ejection fraction (LVEF), first post-operative blood lactate (Lac), left ventricular diastolic diameter (LVDd), cumulative time of mean artery blood pressure (MABP) lower than 65 mmHg (MABP < 65 time), hypertension history, platelets level (PLT), age, blood creatinine (Cr), total area under curve above threshold central venous pressure (CVP) 12 mmHg and 16 mmHg, and blood loss during operation were used to build the reduced models. Among the reduced models, RF model (AUC: 0.895, 95% CI: 0.857–0.933; Sensitivity: 0.830, 95% CI: 0.702–0.919; Specificity: 0.806, 95% CI: 0.765–0.843) revealed the best performance. SHAP and LIME plot showed that LVEF, Lac, LVDd and MABP < 65 time significantly contributed to the prediction model.ConclusionIn this study, we successfully developed several machine learning models to predict LCOS after surgery, which may avail to risk stratification, early detection and management of LCOS after cardiac surgery.

Abstract Introduction Stress‐related brain disorders can be associated with glucocorticoid disturbance and hippocampal alteration. However, it remains largely unknown how cortisol affects the structure and function of hippocampus. Cushing's disease (CD) provides a unique “hyperexpression model” to explore the effects of excessive cortisol on hippocampus as well as the relation between these effects and neuropsychological deficits. Methods We acquired high‐resolution T1‐weighted and resting‐state functional magnetic resonance imaging in 47 CD patients and 53 healthy controls. We obtained the volume and functional connectivity of the hippocampal rostral and caudal subregions in both groups. Relationships between hippocampal alterations, neuroendocrine, and neuropsychological assessments were identified. Results Relative to control subjects, the CD patients had smaller volumes of all four hippocampal subregions. Furthermore, whole brain resting‐state functional connectivity analyses with these four different hippocampal regions as seeds revealed altered hippocampal functional connectivity with high‐order networks, involving the DMN, frontoparietal, and limbic networks in CD patients. The intrinsic hippocampal functional connectivity was associated with the quality of life of the CD patients. Conclusions Our findings elucidate the cumulative effect of excess cortisol on the morphology and function of hippocampus and reinforce the need for effective interventions in stress‐related brain disease to halt potential hippocampal damage.

Among various types of brain computer interfaces (BCIs), steady state visually evoked potential (SSVEP) based BCIs can provide high information transfer rate (ITR), however the users could suffer serious fatigue that may induce discomfort, health hazards and deterioration of system performance. To overcome the fatigue obstacle, the first step is to detect the fatigue accurately, reliably and quickly. This paper proposes an approach based on the wavelet entropy of the measured EEG to fatigue detection in real time when using an SSVEP-BCI. Specifically, the wavelet analysis is first applied to the EEG, resulting in the approximation and detail components at different levels. The sample entropy values of these components are then calculated to generate features for classification. Experimental results identified the entropy of the lower frequency components (0 – 4.6875Hz) as the most important feature. The proposed wavelet entropy improved the fatigue detection accuracy to 87.7% from 65.1% by the traditional entropy method, when distinguishing subjects’ mental states between alert (before task) and fatigue (after task). Furthermore, the detection accuracy based on the state of art multiple conventional fatigue indices can be improved from 91.9% to 96.5% by replacing the delta band amplitude with the new wavelet entropy feature.

Abstract In order to ensure the safe usage of silver nanoparticles (nAgs) in cosmetics, it is necessary to reveal the physical properties of nAgs inside the skin, as these properties may change during the process of percutaneous absorption. In this study, we aimed to establish an analytical system based on single particle inductively coupled plasma mass spectrometry (sp-ICP-MS) to determine the physical properties of nAgs in the skin. First, we optimized a pretreatment method for solubilizing the skin samples and then showed that most of the nAgs were recovered by sodium hydroxide treatment while remaining in particle form. For separating the skin into the epidermis and dermis, we screened several conditions of microwave irradiation. The sp-ICP-MS analysis indicated that the application of 200 W for 30 s was optimal, as this condition ensured complete separation of skin layers without changing the physical properties of the majority of nAgs. Finally, we evaluated the in vivo application by analyzing the quantity as well as the physical properties of Ag in the epidermis, dermis, and peripheral blood of mice after exposing the skin to nAgs or Ag+. Subsequent sp-ICP-MS analysis indicated that nAgs could be absorbed and distributed into the deeper layers in the ionized form, whereas Ag+ was absorbed and distributed without a change in physical properties. This study indicates that in order to obtain a comprehensive understanding of the response of skin following exposure to nAgs, it is essential to consider the distribution and particle size of not only nAgs but also Ag+ released from nAgs into the skin.

Purpose: To explore the molecular genetic mechanisms underlying different responsiveness to Enterovirus 71 (EV71) vaccine. Methods: We recruited 10,245 healthy children into a phase 3 clinical trial to evaluate the efficacy of EV71 vaccine in 2012. Fifty subjects from the trial were divided into the potent immune response group (20 subjects) and the ineffective immune response group (30 subjects). Whole-exome sequencing was performed for these 50 samples and we conducted bioinformatics analyses based on online public database. Results: A total of 222,180 germline variants were detected across 50 subjects. Single nucleotide variant (SNV)-based screening of the subjects with potent or ineffective immune response allowed the identification of a potentially detrimental heterozygous missense variant (c.3784C>T) in EEA1. We also retained TRIM59 and ABCA7 genes that contain different loss of function (LoF) variants shared in two cases and involved in the immune response process. Then, we conducted high-resolution typing of 9 classical HLA genes, HLA-DRB1*03:01, HLA-DQA1*05:01 and HLA-DQB1*02:01 alleles were frequently (recurrence ≥5) observed only in ineffective immune responders. Conclusions: Our study is a meaningful attempt on the comparison of genomic profiles between potent and ineffective immune responders induced by EV71 vaccine, and several candidate potentially detrimental genes were identified.

Abstract Background To improve the postoperative prognosis of patients with lung cancer, predicting the recurrence high-risk patients is needed for the efficient application of adjuvant chemotherapy. However, predicting lung cancer recurrence after a radical surgery is difficult even with conventional histopathological prognostic factors, thereby a novel predictor should be identified. As lipid metabolism alterations are known to contribute to cancer progression, we hypothesized that lung adenocarcinomas with high recurrence risk contain candidate lipid predictors. This study aimed to identify candidate lipid predictors for the recurrence of lung adenocarcinoma after a radical surgery. Methods Frozen tissue samples of primary lung adenocarcinoma obtained from patients who underwent a radical surgery were retrospectively reviewed. Recurrent and non-recurrent cases were assigned to recurrent (n = 10) and non-recurrent (n = 10) groups, respectively. Extracted lipids from frozen tissue samples were subjected to liquid chromatography-tandem mass spectrometry analysis. The average total lipid levels of the non-recurrent and recurrent groups were compared. Candidate predictors were screened by comparing the folding change and P-value of t-test in each lipid species between the recurrent and non-recurrent groups. Results The average total lipid level of the recurrent group was 1.65 times higher than that of the non-recurrent group (P

This study is aimed to examine the impact of mindfulness in the relationship between social isolation, job and financial insecurity, and stress during the lockdown period of the COVID-19 pandemic. Drawing on Conservation of Resources theory, Psychological Contract theory, Mindfulness theory, and Awareness notion, we propose that lockdown job insecurity partially mediates the link from lockdown social isolation to lockdown financial insecurity, and that the relationship between lockdown social isolation and lockdown stress is mediated as follows: first, simple partial mediation through both lockdown job and financial insecurity and second, sequential mediation through lockdown job and financial insecurity, respectively. Moreover, we assume that mindfulness moderates the relationship between lockdown financial insecurity and lockdown stress. The results from our SEM analyses, using a sample of 1,356 respondents in China, support all the research hypotheses. Based on this empirical work, this study concludes that mindfulness, which is considered by many people to play a role in reducing stress during the COVID-19 lockdown period, is de facto endangering their mental health (that is, they experience more stress) instead. Theoretical and practical implications, as well as limitations and proposals for future research are discussed.