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An analysis of the J/ψ→ηη′γ decay by the BESIII collaboration claims the observation of an exotic state η1(1855) with IGJPC=0+1−+. To establish its C-parity partner η1′(1855) in the picture of the KK¯1(1400) molecular state, we propose that J/ψ→η1′(1855)η(′) receives the main contributions from the final state interaction of KK⁎(K+K⁎−, K−K⁎+, K0K¯⁎0, and K¯0K⁎0). Specifically, K and K⁎ in J/ψ→KK⁎ decays transform as η1′(1855)η(′), by exchanging a K1(1400). We predict B(J/ψ→η1′(1855)η)=(6.3−3.5+12.6)×10−6, and B(J/ψ→η1′(1855)η′)=(6.5−4.6+6.6)×10−6, which can be studied in the J/ψ→K⁎K¯⁎η(′) decays.

Transcription factors are protein molecules that act as regulators of gene expression. Aberrant protein activity of transcription factors can have a significant impact on tumor progression and metastasis in tumor patients. In this study, 868 immune-related transcription factors were identified from the transcription factor activity profile of 1823 ovarian cancer patients. The prognosis-related transcription factors were identified through univariate Cox analysis and random survival tree analysis, and two distinct clustering subtypes were subsequently derived based on these transcription factors. We assessed the clinical significance and genomics landscape of the two clustering subtypes and found statistically significant differences in prognosis, response to immunotherapy, and chemotherapy among ovarian cancer patients with different subtypes. Multi-scale Embedded Gene Co-expression Network Analysis was used to identify differential gene modules between the two clustering subtypes, which allowed us to conduct further analysis of biological pathways that exhibited significant differences between them. Finally, a ceRNA network was constructed to analyze lncRNA-miRNA-mRNA regulatory pairs with differential expression levels between two clustering subtypes. We expected that our study may provide some useful references for stratifying and treating patients with ovarian cancer.

Abstract Malnutrition is a state of altered body composition and body cell mass due to inadequate intake or utilization of energy or nutrients, leading to physical and mental dysfunction and impaired clinical outcomes. As one of the most common geriatric syndromes, malnutrition in the elderly is a significant risk factor for poor clinical outcomes, causing a massive burden on medical resources and society. The risk factors for malnutrition in the elderly are diverse and include demographics, chronic diseases, and psychosocial factors. Presently, recommendations for the prevention and intervention of malnutrition in the elderly are not clear or consistent in China. This consensus is based on the latest global evidence and multiregional clinical experience in China, which aims to standardize the prevention and intervention of malnutrition in the elderly in China and improve the efficacy of clinical practice and the prognosis of elderly patients.

In the context of new power system construction and the increasingly severe risks of urban security， urban power supply security has now become a top priority of urban security. Firstly， the risks faced by urban power grid in the context of new power system are analyzed. Then， major urban power supply accidents at home and abroad in recent years are sorted out， and the causes of each accident are analyzed. Then， the concept of risk transmission chain is put forward. Based on the evolution and conduction theory of the proposed risk chain， major urban power supply accidents at home and abroad in recent years are deduced， a detailed risk blocking scheme is formulated， and the grid risk assessment process and risk blocking deduction framework are put forward. Finally， the main measures and suggestions for improving the safety level of urban power supply are put forward. The proposed risk transmission chain and risk blocking measures have practical significance for consolidating urban power supply security in building a new power system.

Purpose: Proton therapy is an emerging therapy for several malignancies owing to its favorable therapeutic ratio. There are very limited data on the use of proton therapy in the management of thyroid carcinoma. Our objective was to review the safety, feasibility, and outcomes of proton therapy for patients with thyroid cancer treated to the head and neck. Methods: From our institution's proton database from 2012 to 2021, we identified 22 patients with thyroid cancer treated with proton beam therapy. We evaluated outcomes and toxicities. Results: Median follow-up was 26 months. Of the 22 patients, 50% were female. The mean age was 65 years. Three patients had anaplastic cancer; 13, papillary carcinoma; 2, follicular carcinoma; and 2, poorly differentiated carcinoma. Forty-six percent had T4 disease. Primary targets were the central neck compartment, level VI, and upper mediastinum. Radiation dose was 60 GyRBE adjuvantly, and 70 GyRBE for gross disease (range, 6000-7600 GyRBE). Eight patients underwent upfront adjuvant radiation, and 3 received definitive radiation for unresectable disease upfront. Eleven patients received either salvage or palliative radiation. Fifty-nine percent of patients had extrathyroidal extension, and 64% of patients had gross disease in the neck before treatment. Fifty percent of patients had metastatic disease before treatment. Sixteen patients received concurrent chemotherapy, 63% of these patients received doxorubicin. For all patients, 1-year local regional recurrence (LRR) was 0%, and overall survival (OS) was 90%. Acute grade 3+ toxicities occurred in 27% of patients, the most frequent being dermatitis (27%). Three patients required a percutaneous endoscopic gastrostomy tube after radiation therapy (RT), 2 owing to progression. There were no grade 4+ toxicities. Conclusions: Proton therapy for thyroid cancer appears feasible and effective with minimal toxicities. Prospective studies comparing proton therapy with intensity-modulated RT, to evaluate the clinical efficacy of using proton therapy to reduce toxicities in patients undergoing radiation for thyroid cancer, are warranted.

Cryptococcus neoformans causes opportunistic infection and potentially lethal immunopathology but therapeutic options are limited. Here the authors implicate myeloid derived suppressor cells during C. neoformans infection and suggest targeting arginase-1 production as a potential therapeutic strategy.

Abstract Extensive research have been devoted to the exploration of multifunctional theranostic agents for cancer, but the poor tumor specificity and unsatisfactory treatment efficacy are some of the critical obstacles for their clinical translations. Herein, ferrocene‐carbon dot‐crosslinked nanoparticles (Fc‐CD NPs) were designed and fabricated for achieving highly specific and photothermal‐augmented chemodynamic therapy (CDT). The Fc‐CD NPs were found not only to inherit the immanent fluorescence, photoacoustic, and photothermal properties of carbon dots (CDs), but also be endowed with CDT that could occur selectively in tumor microenvironment (TME) due to the presence of Fc for triggering Fenton reaction. Moreover, the enlarged particle size of Fc‐CD NPs facilitated their effective accumulation at tumor sites, thus realizing great improvement for antitumor treatment outcomes. Once docking at tumor and being exposed to 660 nm laser irradiation, significantly amplified CDT effect of Fc‐CD NPs was observed due to heat‐accelerating generation of reactive oxygen species (ROS). More interestingly, since the produced ROS could in turn alleviate the thermal‐resistance of photothermal therapy (PTT), the therapeutic efficiency of integrated PTT and CDT was synergized to the maximum extent. This study on the one hand provides a facile approach to fabricate CDs‐based multifunctional theranostic nanoplatform with enhanced tumor accumulation and specificity, on the other hand emphasizes the merits of synergizing mutually beneficial therapeutic modalities for more efficient cancer therapy.

Abstract Hair conditions, such as hair loss and graying, are prevalent human conditions. But they are often poorly controlled due to our insufficient understanding of human scalp hair follicle (hsHF) in health and disease. Here we describe a comprehensive single-cell RNA-seq (scRNA-seq) analysis on highly purified black and early-stage graying hsHFs. Based on these, a concise single-cell atlas for hsHF and its early graying changes is generated and verified using samples from multiple independent individuals. These data reveal the lineage trajectory of hsHF in unprecedented detail and uncover its multiple unexpected features not found in mouse HFs, including the presence of an innerbulge like compartment in the growing phase, lack of a discrete companion layer, and enrichment of EMT features in HF stem cells (HFSCs). Moreover, we demonstrate that besides melanocyte depletion, early-stage human hair graying is also associated with specific depletion of matrix hair progenitors but not HFSCs. The hair progenitors’ depletion is accompanied by their P53 pathway activation whose pharmaceutical blockade can ameliorate hair graying in mice, enlightening a promising therapeutic avenue for this prevalent hair condition.

Abstract Seamounts are isolated elevations in the seafloor with circular or elliptical plans, comparatively steep slopes, and relatively small summit area (Menard, 1964). The vertical gravity gradient (VGG), which is the curvature of the ocean surface topography derived from satellite altimeter measurements, has been used to map the global distribution of seamounts (Kim & Wessel, 2011, https://doi.org/10.1111/j.1365-246x.2011.05076.x). We used the latest grid of VGG to update and refine the global seamount catalog; we identified 19,325 new seamounts, expanding a previously published catalog having 24,643 seamounts. Seven hundred thirty‐nine well‐surveyed seamounts, having heights ranging from 421 to 2,500 m, were used to estimate the typical radially symmetric seamount morphology. First, an Empirical Orthogonal Function (EOF) analysis was used to demonstrate that these small seamounts have a basal radius that is linearly related to their height—their shapes are scale invariant. Two methods were then used to compute this characteristic base to height ratio: an average Gaussian fit to the stack of all profiles and an individual Gaussian fit for each seamount in the sample. The first method combined the radial normalized height data from all 739 seamounts to form median and median‐absolute deviation. These data were fit by a 2‐parameter Gaussian model that explained 99.82% of the variance. The second method used the Gaussian function to individually model each seamount in the sample and further establish the Gaussian model. Using this characteristic Gaussian shape we show that VGG can be used to estimate the height of small seamounts to an accuracy of ∼270 m.

The study aims to develop a decision pathway based on HEAR score and 0 h high-sensitivity cardiac troponin T (hs-cTnT) to safely avoid a second troponin test for suspected non-ST elevation myocardial infarction (NSTEMI) in emergency departments. A HEAR score consists of history, electrocardiogram, age, and risk factors. A HEAR pathway is established using a Bayesian approach based on a predefined safety threshold of NSTEMI prevalence in the rule-out group. In total, 7131 patients were retrospectively enrolled, 582 (8.2%) with index visit NSTEMI and 940 (13.2%) with 180-day major adverse cardiovascular events (MACE). For patients with a low-risk HEAR score (0 to 2) and low 0 h hs-cTnT (

The stress phase angle (SPA), defined as the temporal phase angle between circumferential stress (CS) in the arterial wall and wall shear stress (WSS), is utilized to investigate the interactions between CS and WSS. SPA serves as an important parameter for the early diagnosis of cardiovascular disease. In this study, we proposed a novel method for measuring SPA using spectral domain optical coherence tomography (SD-OCT). The multi-M-mode scan strategy is adopted for interference spectrum acquisition. The phases of CS and WSS are extracted from the corresponding structural and flow velocity images of SD-OCT. The method is validated by measuring SPA in the outflow tract (OFT) of chick embryonic hearts and the common carotid artery of mice. To the best of our knowledge, this is the first time that OCT has been used for SPA measurement.

Background Heart failure with recovered ejection fraction (HFrecEF) has been a newly recognized entity since 2020. However, the concept has primarily focused on left ventricular ejection fraction improvement, with less focus on the recovery of the left atrium. In this study, we investigated changes in left atrial (LA) echocardiographic indices in HFrecEF. Methods and Results An inpatient cohort with heart failure with reduced ejection fraction (HFrEF) was identified retrospectively and followed up prospectively in a single tertiary hospital. The enrolled patients were classified into HFrecEF and persistent HFrEF groups. Alternations in LA parameters by echocardiography were calculated. The primary outcome was a composite of cardiovascular death or heart failure rehospitalization. A total of 699 patients were included (HFrecEF: n=228; persistent HFrEF: n=471). Compared with persistent HFrEF, the HFrecEF group had greater reductions in LA diameter, LA transverse diameter, LA superior–inferior diameter, LA volume, and LA volume index but not in LA sphericity index. Cox regression analysis showed that the HFrecEF group experienced lower risks of prespecified end points than the persistent HFrEF group after adjusting for confounders. Additionally, 136 (59.6%) and 62 (13.0%) patients showed LA reverse remodeling (LARR) for the HFrecEF and persistent HFrEF groups, respectively. Among the HFrecEF subgroup, patients with LARR had better prognosis compared with those without LARR. Multivariate logistic analysis demonstrated that age and coronary heart disease were 2 independent negative predictors for LARR. Conclusions In HFrecEF, both left ventricular systolic function and LA structure remodeling were improved. Patients with HFrecEF with LARR had improved clinical outcomes, indicating that the evaluation of LA size provides a useful biomarker for risk stratification of heart failure.

IntroductionGastric cancer (GC) remains the major constituent of cancer-related deaths and a global public health challenge with a high incidence rate. Helicobacter pylori (HP) plays an essential role in promoting the occurrence and progression of GC. Cancer-associated fibroblasts (CAFs) are regarded as a significant component in the tumor microenvironment (TME), which is related to the metastasis of GC. However, the regulation mechanisms of CAFs in HP-related GC are not elucidated thoroughly.MethodsHP-related genes (HRGs) were downloaded from the GSE84437 and TCGA-GC databases. The two databases were combined into one cohort for training. Furthermore, the consensus unsupervised clustering analysis was obtained to sort the training cohort into different groups for the identification of differential expression genes (DEGs). Weighted correlation network analysis (WGCNA) was performed to verify the correlation between the DEGs and cancer-associated fibroblasts which were key components in the tumor microenvironment. The least absolute shrinkage and selection operator (LASSO) was executed to find cancer-associated fibroblast-related differential expression genes (CDEGs) for the further establishment of a prognostic model.Results and discussionIn this study, 52 HP-related genes (HRGs) were screened out based on the GSE84437 and TCGA-GC databases. A total of 804 GC samples were analyzed, respectively, and clustered into two HP-related subtypes. The DEGs identified from the two subtypes were proved to have a relationship with TME. After WGCNA and LASSO, the CAFs-related module was identified, from which 21 gene signatures were confirmed. Then, a CDEGs-Score was constructed and its prediction efficiency in GC patients was conducted for validation. Overall, a highly precise nomogram was established for enhancing the adaptability of the CDEGs-Score. Furthermore, our findings revealed the applicability of CDEGs-Score in the sensitivity of chemotherapeutic drugs. In general, our research provided brand-new possibilities for comprehending HP-related GC, evaluating survival, and more efficient therapeutic strategies.

ObjectiveTo determine whether intraoperative transfusion of allogeneic or autologous blood is associated with an increased incidence of postoperative delirium (POD) after total knee arthroplasty (TKA) and total hip arthroplasty (THA).MethodsThe medical records of 1,143 older (≥65 years old) patients who received an intraoperative blood transfusion while undergoing total knee or hip arthroplasty at the First Medical Center of Chinese PLA General Hospital from 2014 to 2019 were reviewed; of these patients, 742 (64.92%) received allogeneic blood, while 401 (35.08%) received autologous blood. Patients who received autologous transfusion were paired with those received allogeneic transfusion using 1:1 propensity score matching method. The primary outcome was POD. The secondary outcomes were postoperative complications, including heart failure, deep vein thrombosis, myocardial infarction, stroke, and lung infection. Multivariable nominal logistic regression was used to identify any independent associations between intraoperative blood transfusions and POD, and secondary postoperative complications, respectively.ResultsPostoperative delirium occurred in 6.6% (49/742) of patients who had received an allogeneic blood transfusion and in 2.0% (8/401) of patients who had received an autologous blood transfusion. It is noteworthy that the multivariable logistic regression demonstrated a significant association between intraoperative allogeneic blood transfusion and POD (odds ratio [OR]: 4.11; 95% confidence interval [CI]: 1.95–9.77; p

Summary: A high point of Tibetan Plateau (TP) civilization, the expansive Tubo Empire (618–842 AD) wielded great influence across ancient western China. However, whether the Tubo expansion was cultural or demic remains unclear due to sparse ancient DNA sampling. Here, we reported ten ancient genomes at 0.017- to 0.867-fold coverages from the Dulan site with typical Tubo archaeological culture dating to 1308–1130 BP. Nine individuals from three different grave types have close relationship with previously reported ancient highlanders from the southwestern Himalayas and modern core-Tibetan populations. A Dulan-related Tubo ancestry contributed overwhelmingly (95%–100%) to the formation of modern Tibetans. A genetic outlier with dominant Eurasian steppe-related ancestry suggesting a potential population movement into the Tubo-controlled regions from Central Asia. Together with archeological evidence from burial styles and customs, our study suggested the impact of the Tubo empire on the northeast edge of the TP involved both cultural and demic diffusion.

Inconsistent training programs for public health emergency (PHE) have been criticized as a contributing factor in PHE's managerial weak points. In response, to analyze the relevant discrepancies among the medical students in the class of 2021 from Xiangya School of Medicine of Central South University, the present study conducted an online questionnaire survey using convenience sampling. The questionnaire comprised four sections, including the basic information, the subjective cognition in PHE, the rescue knowledge and capabilities of PHE, and the mastery of PHE regulations and psychological intervention abilities. To compare the abovementioned aspects, related data were collected from 235 medical students divided into two groups, namely, clinical medical students (Group A) and preventive medical students (Group B). We found a more positive attitude in PHE (P = 0.014) and a better grasp of the PHE classification (P = 0.027) and the reporting system in group B compared with group A. In addition, even if group B showed the same response capability in communicable diseases as group A, the former had less access to clinical practice, resulting in poorer performance in the noncommunicable diseases during a fire, flood, and traffic accidents (P = 0.002, P = 0.018, P = 0.002). The different emphasis of each training program contributed to the uneven distribution of abilities and cognition. Meanwhile, the lack of an integrated PHE curriculum led to unsystematic expertise. Hence, to optimize the PHE management system, equal attention should be paid to medical students with diverse majors along with a complete integrated PHE curriculum.

ObjectiveOveractive bladder (OAB) is a disease that seriously affects patients’ quality of life and mental health. To address this issue, more and more researchers are examining the relationship between OAB treatment and urinary microecology. In this study, we sought to determine whether differences in treatment efficacy were related to microbiome diversity and composition as well as the abundance of specific genera. Machine learning algorithms were used to construct predictive models for urine microbiota-based treatment of OAB.MethodsUrine samples were obtained from 64 adult female OAB patients for 16S rRNA gene sequencing. Patients’ overactive bladder symptom scores (OABSS) were collected before and after mirabegron treatment and patients were divided into effective and ineffective groups. The relationship between the relative abundance of certain genera and OABSS were analyzed. Three machine learning algorithms, including random forest (RF), supporting vector machine (SVM) and eXtreme gradient boosting (XGBoost) were utilized to predict the therapeutic effect of mirabegron based on the relative abundance of certain genera in OAB patients’ urine microbiome.ResultsThe species composition of the two groups differed. For one, the relative abundance of Lactobacillus was significantly higher in the effective group than in the ineffective group. In addition, the relative abundance of Gardnerella and Prevotella in the effective group was significantly lower than in the ineffective group. Alpha-diversity and beta-diversity differed significantly between the two groups. LEfSe analysis revealed that Lactobacillus abundance increased while Prevotella and Gardnerella abundance decreased in the effective group. The Lactobacillus abundance ROC curve had high predictive accuracy. The OABSS after treatment was negatively correlated with the abundance of Lactobacillus, whereas the relationship between OABSS and Prevotella and Gardnerella showed the opposite trend. In addition, RF, SVM and XGBoost models demonstrated high predictive ability to assess the effect of mirabegron in OAB patients in the test cohort.ConclusionsThe results of this study indicate that urinary microbiota might influence the efficacy of mirabegron, and that Lactobacillus might be a potential marker for evaluating the therapeutic efficacy of mirabegron in OAB patients.

Abstract Background Postoperative acute kidney injury (AKI) is associated with poor clinical outcomes. Early identification of high-risk patients of developing postoperative AKI can optimize perioperative renal management and facilitate patient survival. The present study aims to develop and validate a nomogram to predict postoperative AKI after liver resection in older patients. Methods A retrospective observational study was conducted involving data from 843 older patients scheduled for liver resection at a single tertiary high caseload general hospital between 2012 and 2019. The data were randomly divided into training (70%, n = 599) and validation (30%, n = 244) datasets. The training cohort was used to construct a predictive nomogram for postoperative AKI with the logistic regression model which was confirmed by a validation cohort. The model was evaluated by receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis in the validation cohort. A summary risk score was also constructed for identifying postoperative AKI patients. Results Postoperative AKI occurred in 155 (18.4%) patients and was highly associated with in-hospital mortality (5.2% vs. 0.7%, P

Abstract Retinal segmentation is a prerequisite for quantifying retinal structural features and diagnosing related ophthalmic diseases. Canny operator is recognized as the best boundary detection operator so far, and is often used to obtain the initial boundary of the retina in retinal segmentation. However, the traditional Canny operator is susceptible to vascular shadows, vitreous artifacts, or noise interference in retinal segmentation, causing serious misdetection or missed detection. This paper proposed an improved Canny operator for automatic segmentation of retinal boundaries. The improved algorithm solves the problems of the traditional Canny operator by adding a multi-point boundary search step on the basis of the original method, and adjusts the convolution kernel. The algorithm was used to segment the retinal images of healthy subjects and age-related macular degeneration (AMD) patients; eleven retinal boundaries were identified and compared with the results of manual segmentation by the ophthalmologists. The average difference between the automatic and manual methods is: 2–6 microns (1–2 pixels) for healthy subjects and 3–10 microns (1–3 pixels) for AMD patients. Qualitative method is also used to verify the accuracy and stability of the algorithm. The percentage of “perfect segmentation” and “good segmentation” is 98% in healthy subjects and 94% in AMD patients. This algorithm can be used alone or in combination with other methods as an initial boundary detection algorithm. It is easy to understand and improve, and may become a useful tool for analyzing and diagnosing eye diseases.

The spatial variability is an inherent uncertainty of soils. The random field theory is used to represent the spatial variability of soils, and the random field discretization is performed by the Karhunen-Loève (KL) expansion method. Using the slope upper bound analysis based on the discrete mechanism, the discretization results of the internal friction angle random field at each point in the space are considered when generating the velocity discontinuity surface. And the strength reduction technique, bisection searching, and sequential quadratic programming method are combined to solve the safety factor of slopes. The first-order reliability method (FORM) and subset simulation (SS) are employed for slope reliability analysis. Given the characteristics of SS and the shear strength reduction technique, an optimization algorithm coupling the two is proposed to improve computational efficiency. By calculating and analyzing an earth slope, the similarities and differences between FORM and SS based on the KL expansion method in solving the slope reliability index and failure consequence are clarified. The influence of the coefficient of variation of soil strength parameters on the slope reliability index and failure consequence is investigated, providing a theoretical basis for risk analysis and prevention of slopes.

Abstract We study $$D_{s}^{+}\rightarrow \rho ^{0(+)}a^{+(0)}_{0}$$ D s + → ρ 0 ( + ) a 0 + ( 0 ) , $$D_{s}^{+}\rightarrow \omega a^{+}_{0}$$ D s + → ω a 0 + , and the resonant $$D_{s}^{+}\rightarrow \rho a_0$$ D s + → ρ a 0 , $$a_{0}\rightarrow \eta \pi (KK)$$ a 0 → η π ( K K ) decays. In the final state interaction, where $$D_s^+\rightarrow (\eta ^{(\prime )}\pi ^+,K^+{{\bar{K}}}^0)$$ D s + → ( η ( ′ ) π + , K + K ¯ 0 ) are followed by the $$(\eta ^{(\prime )}\pi ^+,K^+{{\bar{K}}}^0)$$ ( η ( ′ ) π + , K + K ¯ 0 ) to $$\rho ^{0(+)}a^{+(0)}_{0}$$ ρ 0 ( + ) a 0 + ( 0 ) rescatterings, we predict $$\mathcal{B}(D_{s}^{+}\rightarrow \rho ^{0(+)}a^{+(0)}_{0})=(3.0\pm 0.3\pm 1.0)\times 10^{-3}$$ B ( D s + → ρ 0 ( + ) a 0 + ( 0 ) ) = ( 3.0 ± 0.3 ± 1.0 ) × 10 - 3 . Due to the cancellation of the rescattering effects and the suppressed short-distance W annihilation contribution, we expect that $${{\mathcal {B}}}(D_{s}^{+}\rightarrow \omega a^{+}_{0}) \simeq \mathcal{B}(D_s^+\rightarrow \pi ^+\pi ^0)

Abstract Background Kluyveromyces marxianus is a promising cell factory for producing bioethanol and that raised a demand for a high yield of heterologous proteins in this species. Expressions of heterologous proteins usually lead to the accumulation of misfolded or unfolded proteins in the lumen of the endoplasmic reticulum (ER) and then cause ER stress. To cope with this problem, a group of ER stress response target genes (ESRTs) are induced, mainly through a signaling network called unfolded protein response (UPR). Characterization and modulation of ESRTs direct the optimization of heterologous expressions. However, ESRTs in K. marxianus have not been identified so far. Results In this study, we characterized the ER stress response in K. marxianus for the first time, by using two ER stress-inducing reagents, dithiothreitol (DTT) and tunicamycin (TM). Results showed that the Kar2–Ire1–Hac1 pathway of UPR is well conserved in K. marxianus. About 15% and 6% of genes were upregulated during treatment of DTT and TM, respectively. A total of 115 upregulated genes were characterized as ESRTs, among which 97 genes were identified as UPR target genes and 37 UPR target genes contained UPR elements in their promoters. Genes related to carbohydrate metabolic process and actin filament organization were identified as new types of UPR target genes. A total of 102 ESRTs were overexpressed separately in plasmids and their effects on productions of two different lignocellulolytic enzymes were systematically evaluated. Overexpressing genes involved in carbohydrate metabolism, including PDC1, PGK and VID28, overexpressing a chaperone gene CAJ1 or overexpressing a reductase gene MET13 substantially improved secretion expressions of heterologous proteins. Meanwhile, overexpressing a novel gene, KLMA_50479 (named ESR1), as well as overexpressing genes involved in ER-associated protein degradation (ERAD), including HRD3, USA1 andYET3, reduced the secretory expressions. ESR1 and the aforementioned ERAD genes were deleted from the genome. Resultant mutants, except the yet3Δ mutant, substantially improved secretions of three different heterologous proteins. During the fed-batch fermentation, extracellular activities of an endoxylanase and a glucanase in hrd3Δ cells improved by 43% and 28%, respectively, compared to those in wild-type cells. Conclusions Our results unveil the transcriptional scope of the ER stress response in K. marxianus and suggest efficient ways to improve productions of heterologous proteins by manipulating expressions of ESRTs.

Abstract Background Hemicellulose acts as one factor contributing to the recalcitrance of lignocellulose that prevents cellulases to degrade the cellulose efficiently even in low quantities. Supplement of hemicellulases can enhance the performance of commercial cellulases in the enzymatic hydrolyses of lignocellulose. Kluyveromyce marxianus is an attractive yeast for cellulosic ethanol fermentation, as well as a promising host for heterologous protein production, since it has remarkable thermotolerance, high growth rate, and broad substrate spectrum etc. In this study, we attempted to coordinately express multiple hemicellulases in K. marxianus through a 2A-mediated ribosome skipping to self-cleave polyproteins, and investigated their capabilities for saccharification and ethanol production from corncobs. Results Two polycistronic genes IMPX and IMPαX were constructed to test the self-cleavage of P2A sequence from the Foot-and-Mouth Disease virus (FMDV) in K. marxianus. The IMPX gene consisted of a β-mannanase gene M330 (without the stop codon), a P2A sequence and a β-xylanase gene Xyn-CDBFV in turn. In the IMPαX gene, there was an additional α-factor signal sequence in frame with the N-terminus of Xyn-CDBFV. The extracellular β-mannanase activities of the IMPX and IMPαX strains were 21.34 and 15.50 U/mL, respectively, but the extracellular β-xylanase activity of IMPαX strain was much higher than that of the IMPX strain, which was 136.17 and 42.07 U/mL, respectively. Subsequently, two recombinant strains, the IXPαR and IMPαXPαR, were constructed to coordinately and secretorily express two xylantic enzymes, Xyn-CDBFV and β-D-xylosidase RuXyn1, or three hemicellulolytic enzymes including M330, Xyn-CDBFV and RuXyn1. In fed-batch fermentation, extracellular activities of β-xylanase and β-xylosidase in the IXPαR strain were 1664.2 and 0.90 U/mL. Similarly, the IMPαXPαR strain secreted the three enzymes, β-mannanase, β-xylanase, and β-xylosidase, with the activities of 159.8, 2210.5, and 1.25 U/mL, respectively. Hemicellulolases of both strains enhanced the yields of glucose and xylose from diluted acid pretreated (DAP) corncobs when acted synergistically with commercial cellulases. In hybrid saccharification and fermentation (HSF) of DAP corncobs, hemicellulases of the IMPαXPαR strain increased the ethanol yield by 8.7% at 144 h compared with the control. However, both ethanol and xylose yields were increased by 12.7 and 18.2%, respectively, at 120 h in HSF of aqueous ammonia pretreated (AAP) corncobs with this strain. Our results indicated that coordinate expression of hemicellulolytic enzymes in K. marxianus promoted the saccharification and ethanol production from corncobs. Conclusions The FMDV P2A sequence showed high efficiency in self-cleavage of polyproteins in K. marxianus and could be used for secretory expression of multiple enzymes in the presence of their signal sequences. The IMPαXPαR strain coexpressed three hemicellulolytic enzymes improved the saccharification and ethanol production from corncobs, and could be used as a promising strain for ethanol production from lignocelluloses.

Reputation evaluation is an effective measure for maintaining secure Internet of Things (IoT) ecosystems, but there are still several challenges when applied in IoT-enabled pumped storage power stations (PSPSs), such as the limited resources of intelligent inspection devices and the threat of single-point and collusion attacks. To address these challenges, in this paper we present ReIPS, a secure cloud-based reputation evaluation system designed to manage intelligent inspection devices’ reputations in IoT-enabled PSPSs. Our ReIPS incorporates a resource-rich cloud platform to collect various reputation evaluation indexes and perform complex evaluation operations. To resist single-point attacks, we present a novel reputation evaluation model that combines backpropagation neural networks (BPNNs) with a point reputation-weighted directed network model (PR-WDNM). The BPNNs objectively evaluate device point reputations, which are further integrated into PR-WDNM to detect malicious devices and obtain corrective global reputations. To resist collusion attacks, we introduce a knowledge graph-based collusion device identification method that calculates behavioral and semantic similarities to accurately identify collusion devices. Simulation results show that our ReIPS outperforms existing systems regarding reputation evaluation performance, particularly in single-point and collusion attack scenarios.

During the harvesting of cut-stem vegetables, the structural parameters of cutters have an important influence on the harvesting effect. Structural parameters of stalks directly affect the cutting effect of the cutter. The thickness of the stalk xylem has a strong influence on the cutting stability and cutting surface effect of the cutter. In this paper, the effect of the broccoli stalk xylem on conventional toothless cutters was investigated using broccoli stalks as the cutting object. It was found that a thicker xylem leads to shear force fluctuations, which in turn affects the smooth operation of the cutting device. Taking locust mouthparts as the research object, a bionic multi-tooth cutting method is proposed in this paper to obtain the contour curve based on the locust upper jaw cutting tooth lobe. By establishing the regression equation, the contour curve of the cutting teeth is fitted accurately. The cutter edge is designed with the locust’s maxillary incisive lobe as the bionic object. ANSYS software was used to simulate the cutting of a double disc cutter and broccoli stalk. The effect of each factor was analyzed by response-surface regression to determine the optimal cutter speed, machine forward speed, cutting inclination, blade overlap, and optimal cutting position. The cutting test is verified via broccoli stalks and a cutting test bench to further determine the cutting device operating parameters. The optimal operating parameters of the cutting device were 0.239 m/s forward speed, 30.974-degree cutting edge angle, 10.066 mm blade overlap, and 467.511 rpm.

Abstract Background Osteosarcoma (OS) is the most common aggressive bone tumor in children and teenagers. Doxorubicin (DOX) is a chemotherapeutic drug for OS. This study aims to reveal the effects and underneath mechanism of DOX treatment in OS progression. Methods The expression of circular_0000006 (circ_0000006), microRNA-646 (miR-646) and brain-derived neurotrophic factor (BDNF) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). BDNF protein expression was determined by western blot. Cell proliferation was illustrated by cell counting kit-8 (CCK-8) and cell colony formation assays. Cell migration and invasion were revealed by transwell migration and wound-healing assays and transwell invasion assay, respectively. Cell apoptosis was demonstrated by flow cytometry analysis. The binding relationship of miR-646 and circ_0000006 or BDNF was predicted by circRNA interactome and targetscan online database, respectively, and verified by dual-luciferase reporter assay. The effects of circ_0000006 knockdown on tumor growth in vivo were manifested by in vivo tumor formation assay. Results Circ_0000006 expression and the mRNA and protein levels of BDNF were dramatically upregulated, and miR-646 expression was effectively downregulated in OS tissues or cells compared with control groups. Circ_0000006 expression and BDNF protein expression were lower, and miR-646 expression was higher in DOX treatment groups than in control groups in OS cells. Circ_0000006 knockdown repressed cell proliferation, migration and invasion, whereas promoted cell apoptosis under DOX treatment in OS cells; however, these effects were attenuated by miR-646 inhibitor. Additionally, circ_0000006 sponged miR-646 to bind to BDNF. Circ_0000006 silencing suppressed tumor growth in vivo. Conclusion Circ_0000006 knockdown promoted DOX-mediated effects on OS development by miR-646/BDNF pathway, which provided a theoretical basis in treating OS with DOX.

The three-dimensional carbon fiber fabric was densified by chemical vapor infiltration and precursor impregnation cracking composite process, and the high thermal conductivity 3D C/C composite material with density of 1.95 g/cm3 was obtained. Using SEM, XRD, thermal conductivity test, linear expansion coefficient test and three-point bending experiment to study the effect of different heat treatment temperatures of 2350,2550,2850℃ on the microscopic morphology,structure, thermal conductivity, linear expansion coefficient and bending performance of 3D C/C composites. The results show that with the increase of the heat treatment temperature, the mesophase pitch-based carbon fiber graphite sheet structure becomes more obvious, the order of the pyrolytic carbon sheets evenly wrapped around the carbon fiber increases, and the arrangement between the sheets becomes more dense; the graphitization and thermal conductivity of 3D C/C composite materials improve; in the test temperature range of 250-1400℃, the linear expansion coefficient increases slightly with the increase of the test temperature, and the 3D C/C composite after different heat treatment temperatures. The linear expansion coefficient of the materials is -1×10-6-2×10-6℃-1, showing good "zero expansion". In addition, when the heat treatment temperature increases, the bonding of the carbon fiber and the matrix of the 3D C/C composite materials are weakened, resulting in the decrease in the bending strength and flexural modulus of the materials. A large number of long fibers are pulled out on the bending fracture surface of the materials after the high temperature heat treatment at 2850℃. In general, the fracture after three different heat treatment temperatures shows "pseudoplastic" fracture characteristics.

Summary: Gold nanoclusters (AuNCs) have become a promising material for bioimaging detection because of their tunable photoluminescence, large Stokes shift, low photobleaching, and good biocompatibility. Last decade, great efforts have been made to develop AuNCs for enhanced imaging contrast and multimodal imaging. Herein, an updated overview of recent advances in AuNCs was present for visible fluorescence (FL) imaging, near-infrared fluorescence (NIR-FL) imaging, two-photon near-infrared fluorescence (TP-NIR-FL) imaging, computed tomography (CT) imaging, positron emission tomography (PET) imaging, magnetic resonance imaging (MRI), and photoacoustic (PA) imaging. The justification of AuNCs applied in bioimaging mentioned above applications was discussed, the performance location of different AuNCs were summarized and highlighted in an unified parameter coordinate system of corresponding bioimaging, and the current challenges, research frontiers, and prospects of AuNCs in bioimaging were discussed. This review will bring new insights into the future development of AuNCs in bio-diagnostic imaging.

Summary: We present here a detailed protocol for PANINI (protein and nucleic acid in situ imaging), a technique that enables the concurrent staining of protein and nucleic acids in archival tissue sections. PANINI utilizes an optimized antigen retrieval strategy that forgoes protease treatment while retaining high sensitivity of nucleic acid detection down to single genomic events. While the protocol here is geared toward standard fluorescent microscopes with 3–4 available channels, PANINI is compatible with many commercial multiplexed tissue imaging modalities.For complete details on the use and execution of this protocol, please refer to Jiang et al. (2022). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

K. marxianus is a promising cell factory for producing heterologous proteins. Oxidative stresses were raised during overexpression of heterologous proteins, leading to the shift of the redox state. How to measure the redox state of live K. marxianus cells without perturbing their growth remains a big challenge. Here, a fluorescence lifetime imaging (FLIM)-based method was developed in live K. marxianus cells. During the early exponential growth, K. marxianus cells exhibited an increased mean fluorescence lifetime (τ-mean) of NAD(P)H compared with Saccharomyces cerevisiae cells, which was consistent with the preference for respiration in K. marxianus cells and that for fermentation in S. cerevisiae cells. Upon oxidative stresses induced by high temperature or H2O2, K. marxianus cells exhibited an increased τ-mean in company with decreased intracellular NAD(P)H/NAD(P)+, suggesting a correlation between an increased τ-mean and a more oxidized redox state. The relationship between τ-mean and the expression level of a heterologous protein was investigated. There was no difference between the τ-means of K. marxianus strains which were not producing a heterologous protein. The τ-mean of a strain yielding a high level of a heterologous protein was higher than that of a low-yielding strain. The results suggested the potential application of FLIM in the non-invasive screen of high-yielding cells.

This study intended to explore the current status of psychological problems of preschool teachers in Southwest China 1 year after the COVID-19 pandemic and to assess the association between mental health education and psychological problems and symptoms of psychopathology. A total of 614 preschool teachers from Southwest China were enrolled to complete the questionnaires of the Chinese Symptom Checklist (SCL-90). Notably, 60% of the respondents reported psychological distress with GSI T-scores ≥ 63, especially the high score was reported on obsessive-compulsive disorder, interpersonal sensitivity, and phobic anxiety. Although less than half of the respondents have received mental health education last year, the teachers who received the mental health education reported lower GSI T-scores(β = −1.303, 95% CI: −2.208, −0.397). The results demonstrated the significance of constructing the education of promoting mental health of preschool teachers, and enlightening government or managers of kindergartens to relieve the psychological problems of preschool teachers through mental health education, especially for those with the pressure of overtime. It is recommended that local governments or kindergartens should organize more mental health education for kindergarten teachers to improve their mental health as well as their teaching professionalism.

Han/non-Han interactions were engrained among the border regions of ancient Imperial China. Yet, little is known about either the genetic origins or the lifeways of these border peoples. Our study applies tools from ancient deoxyribonucleic acid (DNA) and stable isotope analysis to the study of a Han dynasty population at the Shichengzi site in modern-day Xinjiang. Isotopic analysis (δ13C and δ15N) of human (n = 8), animal (n = 26), and crop remains (n = 23) from Shichengzi indicated that dietary patterns among site inhabitants could be split among agro-pastoral and agricultural groups based on differences in the collagen 15N ratios. DNA analysis divided the four Shichengzi samples into two groups, with one group primarily harboring the ancient Northeast Asian (ANA) related ancestry, while the other showed a dominant Late Neolithic Yellow River (YR_LN) related ancestry. Both ancient DNA and stable isotope evidence point to the Northeast Asian origins of pastoralists and East Asian origins of Han agriculturalists, who, nonetheless, shared a single burial space at Shichengzi. This study thus provides clear evidence for the multiple origins and identities of populations across the porous border represented by the Han Empire and surrounding regions and proposes a new model for the interpretation of border culture in early Imperial China.

We propose a high-speed all-optic dual-modal system that integrates spectral-domain optical coherence tomography and photoacoustic microscopy (PAM). A [Formula: see text] coupler-based interferometer is used to remotely detect the surface vibration caused by photoacoustic (PA) waves. Three outputs of the interferometer are acquired simultaneously with a multi-channel data acquisition card. One channel data with the highest PA signal detection sensitivity is selected for sensitivity compensation. Experiment on the phantom demonstrates that the proposed method can successfully compensate for the loss of intensity caused by sensitivity variation. The imaging speed of the PAM is improved compared to our previous system. The total time to image a sample with [Formula: see text] pixels is [Formula: see text][Formula: see text]s. Using the proposed system, the microvasculature in the mouse auricle is visualized and the blood flow state is accessed.

This study explored the application of Kluyveromyces marxianus and Saccharomyces cerevisiae (commercial and wild type) in the alcoholic fermentation of Fuji apple juice under static conditions. Metabolome analyses revealed that ethyl esters, including ethyl hexanoate, ethyl decanoate, ethyl octanoate, octanoic acid and decanoic acid, were the dominant components in ciders fermented by the Saccharomyces yeasts. In the K. marxianus ciders, ethyl acetate, hexyl acetate, propyl acetate and acetic acid were the most abundant volatiles, suggesting that the cider fermented by K. marxianus might have a fruitier smell. Transcriptome analyses were adapted to gain insight into the differential metabolite patterns between K. marxianus and S. cerevisiae during cider fermentation. GO and KEGG enrichments revealed that the metabolic pathways of glucose, organic acids and amino acids during cider fermentation were quite different between these two yeasts. The K. marxianus strain exhibited a higher rate of glycolysis and ethanol fermentation than did Saccharomyces yeasts under oxygen-limited conditions. It also reduced the metabolic flux of acetate into acetyl-CoA and then into the TCA cycle, increasing the syntheses of ethyl acetate and relevant esters, which may affect its cell growth under anaerobic conditions but enriched the taste and variety of aromas in apple cider.

The relationship between archeological culture and ethnicity is invariably complex. This is especially the case for periods of national division and rapid inter-ethnic exchange, such as China’s Sixteen Kingdoms (304–439 CE) and Northern and Southern Dynasties (420–589 CE). Going by tomb shape and grave goods, the Foyemiaowan cemetery at Dunhuang exhibits a typical third–tenth century Han style. Despite this, the ethnic makeup of the Foyemiaowan population has remained unclear. We therefore analyzed 485 Y-chromosomal SNPs and entire mitochondrial genomes of 34 Foyemiaowan samples. Our study yielded the following discoveries: (1) principal component analysis revealed that the Foyemiaowan population was closely clustered with Tibeto-Burman populations on the paternal side and close to Mongolic-speaking populations on the maternal side; (2) lineage comparisons at the individual level showed that the Foyemiaowan population consisted of primarily Tibeto-Burman and Han Chinese related lineages (Oα-M117, 25%;Oβ-F46, 18.75%), partially Altaic speaking North Eurasian lineages (N-F1206, 18.75%) and a slight admixture of southern East Asian lineages (O1b1a2-Page59, 6.25%; O1b1a1-PK4, 3.13%). Similarly, the maternal gene pool of Foyemiaowan contained northern East Asian (A, 4.17%; CZ, 16.67%; D, 20.83%; G, 4.17%; M9, 4.17%), southern East Asian (B, 12.51%; F, 20.83%) and western Eurasian (H, 4.17%; J, 4.17%) related lineages; (3) we discovered a relatively high genetic diversity among the Foyemiaowan population (0.891) in our ancient reference populations, indicating a complex history of population admixture. Archeological findings, stable isotope analysis and historical documents further corroborated our results. Although in this period China’s central government had relinquished control of the Hexi Corridor and regional non-Han regimes became the dominant regional power, Foyemiaowan’s inhabitants remained strongly influenced by Han culture.

Lung adenocarcinoma is increasingly harmful to society and individuals as cancer with an inferior prognosis and insensitive to chemotherapy. Previous studies have demonstrated that oxidative stress and lncRNAs play a vital role in many biological processes. Therefore, we explored the role of lncRNAs associated with oxidative stress in the prognosis and survival of LUAD patients. We examined the expression profiles of lncRNAs and oxidative stress genes in this study. A prognosis prediction model and a nomogram were built based on oxidative stress-related lncRNAs. Functional and drug sensitivity analyses were also performed depending on oxidative stress-related lncRNA signature. Moreover, we investigated the relationship between immune response and immunotherapy. The results showed that a risk scoring model based on 16 critical oxidative stress lncRNAs was able to distinguish the clinical status of LUAD and better predict the prognosis and survival. Additionally, the model demonstrated a close correlation with the tumor immune system, and these key lncRNAs also revealed the relationship between LUAD and chemotherapeutic drug sensitivity. Our work aims to provide new perspectives and new ideas for the treatment and management of LUAD.

Abstract The growth and tolerance of Kluyveromyces marxianus at high temperatures decreased significantly in the synthetic medium (SM), which is commonly used in industrial fermentations. After 100 days of adaptive laboratory evolution, a strain named KM234 exhibited excellent tolerance at a high temperature, without loss of its growth ability at a moderate temperature. Transcriptomic analysis revealed that the KM234 strain decreased the expression of the ammonium (NH4+) transporter gene MEP3 and increased the synthesis of the amino acid carbon backbone, which may contribute greatly to the high‐temperature growth phenotype. High NH4+ content in SM significantly increased the reactive oxygen species (ROS) production at high temperatures and thus caused toxicity to yeast cells. Replacing NH4+ with organic nitrogen sources or increasing the concentration of potassium ions (K+) in the medium restored the growth of the wild‐type K. marxianus at a high temperature in SM. We also showed that the NH4+ toxicity mitigated by K+ might closely depend on the KIN1 gene. Our results provide a practical solution to industrial fermentation under high‐temperature conditions.

Purpose: Radiation treatment plans undergo peer review during chart rounds, but changes to treatment volumes would require replanning. Our group implemented weekly head and neck cancer “volume rounds” to peer review all target volumes for head and neck cancer before radiation therapy (RT) planning and chart rounds. Methods and Materials: We analyzed modifications made to planning target volumes (PTVs) at volume rounds for consecutive nonproton head and neck cancer cases from May 2020 to May 2021. Nine head and neck radiation oncologists participated in weekly volume rounds during this time. Recommendations were categorized as no changes, minor changes, major changes, additional workup (eg, biopsy or imaging), and consultation or tumor board discussion needed before the start of RT. Minor changes to PTVs generally did not require a second review before treatment planning while major changes did. Results: PTVs for 511 cases involving 432 patients underwent peer review and 298 (58.3%) of these cases did not require any modifications before treatment planning. Minor and major changes were recommended in 75 (14.7%) and 86 (16.8%) cases, respectively. Forty-five (8.8%) cases were recommended to have additional workup and 23 (4.5%) required additional consultation with nonradiation surgeons or medical oncologists. Of the 45 cases that were recommended for additional workup, 40 underwent biopsy or imaging. Positive findings on imaging or biopsy occurred in 13 patients, leading to a significant change in management, including 4 patients who underwent additional surgery after positive findings before the start of RT. Conclusions: Prospective peer review during head and neck cancer volume rounds led to frequent minor and major alterations to PTVs. Significant changes in the overall treatment plan, such as additional surgery before start of RT, occurred in a minority of patients.

ObjectiveWe sought to find a bedside prognosis prediction model based on clinical and image parameters to determine the in-hospital outcomes of acute aortic dissection (AAD) in the emergency department.MethodsPatients who presented with AAD from January 2010 to December 2019 were retrospectively recruited in our derivation cohort. Then we prospectively collected patients with AAD from January 2020 to December 2021 as the validation cohort. We collected the demographics, medical history, treatment options, and in-hospital outcomes. All enrolled patients underwent computed tomography angiography. The image data were systematically reviewed for anatomic criteria in a retrospective fashion by three professional radiologists. A series of radiological parameters, including the extent of dissection, the site of the intimal tear, entry tear diameter, aortic diameter at each level, maximum false lumen diameter, and presence of pericardial effusion were collected.ResultsOf the 449 patients in the derivation cohort, 345 (76.8%) were male, the mean age was 61 years, and 298 (66.4%) had a history of hypertension. Surgical repair was performed in 327 (72.8%) cases in the derivation cohort, and the overall crude in-hospital mortality of AAD was 10.9%. Multivariate logistic regression analysis showed that predictors of in-hospital mortality in AAD included age, Marfan syndrome, type A aortic dissection, surgical repair, and maximum false lumen diameter. A final prognostic model incorporating these five predictors showed good calibration and discrimination in the derivation and validation cohorts. As for type A aortic dissection, 3-level type A aortic dissection clinical prognosis score (3ADPS) including 5 clinical and image variables scored from −2 to 5 was established: (1) moderate risk of death if 3ADPS is

Optical coherence tomography (OCT) attenuation imaging is a technique that uses the optical attenuation coefficient (OAC) to distinguish the types or pathological states of tissues and has been increasingly used in basic research and clinical diagnosis. With the increasing application of swept-source OCT, scholars are increasingly inclined to explore deep tissues. Unfortunately, the accuracy of OAC calculation when exploring deep tissues has yet to be improved. Existing methods generally have the following problems: overestimation error, underestimation error, severe fluctuation, or stripe artifacts in the OAC calculation of the OCT tail signal. The main reason for this is that the influence of the noise floor on the OCT weak signal at the tail-end is not paid enough attention. The noise floor can change the attenuation pattern of the OCT tail signal, which can lead to severe errors in the OAC. In this paper, we proposed a Kalman filter-based OAC optimal algorithm to solve this problem. This algorithm can not only eliminate the influence of the noise floor, but can also effectively protect the weak signal at the tail-end from being lost. The OAC of deep tissues can be calculated accurately and stably. Numerical simulation, phantom, and in vivo experiments were tested to verify the algorithm’s effectiveness in this paper. This technology is expected to play an essential role in disease diagnosis and in the evaluation of the effectiveness of treatment methods.

Two important phenomena of the solar wind–magnetosphere–ionosphere coupling are auroral particle precipitation and the formation of ions flowing upward from the ionosphere. They have opposite transport directions of energy and substance. Based on the observations of particle precipitation and ion drift from the DMSP F13 satellite in January and July 2005, the ionospheric ion upflows in dayside auroral oval (0600–1800 MLT) can be divided into five types according to the velocity of ion upflows and the spectrum characteristics of auroral particle precipitation, and the distribution for different types of ion upflows is studied. The results show that the ion upflows mainly occur in the geomagnetic latitude (MLAT) range of 70–80°.The main magnetospheric source region of ion upflows (type A and D) caused by the accelerated electron (mainly the soft electron) corresponds to Low Latitude Boundary Layer (LLBL) and Cusp, and ion upflows of type B and C (related to the process of ambipolar diffusion caused by electron acceleration) mainly occur in LLBL and Boundary Plasma Sheet (BPS), while ion upflows of type E without electron acceleration mainly occur in the central plasma sheet (CPS).The dawn–dusk asymmetry is obvious in the winter season, with the ion upflows mainly occurring on the dawn/dusk side ionosphere. However, the ion upflows in summer mainly occur at the magnetic noon, with a symmetric distribution centered at the magnetic noon. The occurrence of ion upflow in winter is significantly higher than that in summer, and it is significantly enhanced during the period of moderate geomagnetic activity. The upward region expands to the lower latitude when the geomagnetic activity is enhanced. The effect of interplanetary magnetic field (IMF) components has also been studied in this paper. When IMF Bx is negative, the upflow occurrence increases in the region of 1500–1800 MLT and 0600–0900 MLT, with the MLAT range below 70°. The direction of IMF By may lead to the high-incidence area reverse at the prenoon or postnoon region. The occurrence of ion upflows with the MLAT range below 75° increases significantly when IMF is southward. Type A ion upflow has the highest velocity of ion upflows, followed by type E, and type D has the lowest. The average velocity of ion upflows in winter is significantly higher than that in summer.

Abstract An effective feature representation can boost recognition tasks in the sketch domain. Due to an abstract and diverse structure of the sketch relatively with a natural image, it is complex to generate a discriminative features representation for sketch recognition. Accordingly, this article presents a novel scheme for sketch recognition. It generates a discriminative features representation as a result of integrating asymmetry essential information from deep features. This information is kept as an original feature‐vector space for making a final decision. Specifically, five different well‐known pre‐trained deep convolutional neural networks (DCNNs), namely, AlexNet, VGGNet‐19, Inception V3, Xception, and InceptionResNetV2 are fine‐tuned and utilised for feature extraction. First, the high‐level deep layers of the networks were used to get multi‐features hierarchy from sketch images. Second, an entropy‐based neighbourhood component analysis was employed to optimise the fusion of features in order of rank from multiple different layers of various deep networks. Finally, the ranked features vector space was fed into the support vector machine (SVM) classifier for sketch classification outcomes. The performance of the proposed scheme is evaluated on two different sketch datasets such as TU‐Berlin and Sketchy for classification and retrieval tasks. Experimental outcomes demonstrate that the proposed scheme brings substantial improvement over human recognition accuracy and other state‐of‐the‐art algorithms.

Abstract Background Although postoperative delirium is a frequent complication of surgery, little is known about risk factors for delirium occurring in the post-anaesthesia care unit (PACU). The aim of this study was to determine pre- and intraoperative risk factors for the development of recovery room delirium (RRD) in patients undergoing elective non-cardiovascular surgery. Methods RRD was diagnosed according to the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). We collected perioperative data in 228 patients undergoing elective non-cardiovascular surgery under general anaesthesia and performed univariate and multivariate logistic regression to identify risk factors related to RRD. PACU and postoperative events were recorded to assess the outcome of RRD. Results Fifty-seven patients (25%) developed RRD. On multivariate analysis, maintenance of anaesthesia with inhalation anaesthetic agents (OR = 6.294, 95% CI 1.4–28.8, corrected p = 0.03), malignant primary disease (OR = 3.464, 95% CI = 1.396–8.592, corrected p = 0.018), American Society of Anaesthesiologists Physical Status (ASA-PS) III–V (OR = 3.389, 95% CI = 1.401–8.201, corrected p = 0.018), elevated serum total or direct bilirubin (OR = 2.535, 95% CI = 1.006–6.388, corrected p = 0.049), and invasive surgery (OR = 2.431, 95% CI = 1.103–5.357, corrected p = 0.035) were identified as independent risk factors for RRD. RRD was associated with higher healthcare costs (31,428 yuan [17,872–43,674] versus 16,555 yuan [12,618–27,788], corrected p = 0.002), a longer median hospital stay (17 days [12–23.5] versus 11 days [9–17], corrected p = 0.002), and a longer postoperative stay (11 days [7–15] versus 7 days [5–10], corrected p = 0.002]). Conclusions Identifying patients at high odds for RRD preoperatively would enable the formation of more timely postoperative delirium management programmes.

Abstract Background Although the immune function of neutrophils in sepsis has been well described, the heterogeneity of neutrophils remains unclear during the process of sepsis. Methods In this study, we used a mouse CLP model to simulate the clinical scenario of patients with sepsis, neutrophil infiltration, abnormal distribution and dysfunction was analyzed. LPS was used to stimulate neutrophils in vitro to simulate sepsis; single-cell gene sequencing technology was used to explore the immunological typing. To explore the immunological function of immunosuppressive neutrophils, PD-L1 knockout neutrophils were cocultured with lymphocytes from wild-type mice. Results We found that neutrophils presented variant dysfunction at the late stage of sepsis, including inhibition of apoptosis, seriously damaged chemotaxis and extensive infiltration into the tissues. Single-cell RNA sequencing revealed that multiple subclusters of neutrophils were differentiated after LPS stimulation. The two-dimensional spatial distribution analysis showed that Foxp3+ T cells were much closer to Ly-6G than the CD4+ and CD8+ cells, indicating that infiltrated neutrophils may play immunomodulatory effect on surrounding T-regs. Further observations showed that LPS mediates PD-L1 over expression through p38α-MSK1/-MK2 pathway in neutrophils. The subsets of highly expressed PD-L1 exert immunosuppressive effect under direct contact mode, including inhibition of T cell activation and induction of T cell apoptosis and trans-differentiation. Conclusions Taken together, our data identify a previously unknown immunosuppressive subset of neutrophils as inhibitory neutrophil in order to more accurately describe the phenotype and characteristics of these cells in sepsis.

Scaffold protein Ste5 and associated kinases, including Ste11, Ste7, and Fus3, are core components of the mating pheromone pathway, which is required to induce a mating response. Orthologs of these proteins are widely present in fungi, but to which extent one protein can be replaced by its ortholog is less well understood. Here, interspecies complementation was carried out to evaluate the functional homology of Ste5 and associated kinases in Kluyveromyces lactis, K. marxianus, and Saccharomyces cerevisiae. These three species occupy important positions in the evolution of hemiascomycetes. Results indicated that Ste5 and associated kinases in K. lactis and K. marxianus could be functionally replaced by their orthologs to different extents. However, the extent of sequence identity, either between full-length proteins or between domains, did not necessarily indicate the extent of functional replaceability. For example, Ste5, the most unconserved protein in sequence, achieved the highest average functional replaceability. Notably, swapping Ste5 between K. lactis and K. marxianus significantly promoted mating in both species and the weakened interaction between the Ste5 and Ste7 might contribute to this phenotype. Consistently, chimeric Ste5 displaying a higher affinity for Ste7 decreased the mating efficiency, while chimeric Ste5 displaying a lower affinity for Ste7 improved the mating efficiency. Furthermore, the length of a negatively charged segment in the Ste7-binding domain of Ste5 was negatively correlated with the mating efficiency in K. lactis and K. marxianus. Extending the length of the segment in KlSte5 improved its interaction with Ste7 and that might contribute to the reduced mating efficiency. Our study suggested a novel role of Ste5-Ste7 interaction in the negative regulation of the pheromone pathway. Meanwhile, Ste5 mutants displaying improved mating efficiency facilitated the breeding and selection of Kluyveromyces strains for industrial applications.