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Abstract Drug resistance is vital for the poor prognosis of acute myeloid leukemia (AML) patients, but the underlying mechanism remains poorly understood. Given the unique microenvironment of bone marrow, we reasoned that drug resistance of AML might rely on distinct metabolic processes. Here, we identify succinate dehydrogenase (SDH) deficiency and over-cumulative succinate as typical features in AML, with a marked function in causing the resistance of AML cells to various anti-cancer therapies. Mechanistically, succinate promotes the accumulation of oncogenic proteins in a manner that precedes transcriptional activation. This function is mediated by succinate-triggered upregulation of ubiquitin-conjugating enzyme E2M (UBC12) phosphorylation, which impairs its E2 function in cullins neddylation. Notably, decreasing succinate by fludarabine can restore the sensitivity of anti-cancer drugs in SDH-deficient AML. Together, we uncover the function of succinate in driving drug resistance by regulating p-UBC12/cullin activity, and indicate reshaping succinate metabolism as a promising treatment for SDH-deficient AML.

Abstract Here we define and report the relationship between the maximum seismic magnitude (M) and injection volume (ΔV) through fluid-injection fault-reactivation experiments and analysis. This relationship incorporates the in situ shear modulus (G) and fault pre-stress as a fraction of the strength drop (c), expressed as M = c/(1-c) GΔV. Injection response defines a sigmoidal relation in $$M-\Delta {V}$$ M − Δ V space with unit gradient limbs linked by an intermediate up-step. Both laboratory observations and analysis for a rigid fault with slip limited to the zone of pressurization show trajectories of cumulative $$M-\Delta {V}$$ M − Δ V that evolve at a gradient of unity, are offset in order of increasing pre-stress and are capable of step changes in moment with shear reactivation at elevated critical-stresses – key features apparent in field observations. The model and confirmatory laboratory observations explain the occurrence of some triggered earthquakes at EGS sites significantly larger than expected relative to injection volumes and based on previous models.

Precisely capturing and manipulating microparticles is the key to exploring microscopic mysteries. Optical tweezers play a crucial role in facilitating these tasks. However, existing optical tweezers are limited by their dependence on specific beam modes, which restrict their ability to flexibly switch and manipulate optical traps, thereby limiting their application in complex scientific challenges. Here, we propose a new method to achieve type switching and manipulation of optical traps using a single structured beam via optical coherence engineering. A conjugate-model random structured beam with a switch is designed. By altering the state of the switch, we can change the type of optical cage, enabling the capture of different particle types. Furthermore, the range, strength, and position of the optical trap can be controlled by adjusting the initial beam parameters. We hope that optical coherence engineering will extend the capabilities of existing structured optical tweezers, paving the way for advances in future optical tweezers applications.

Multiple myeloma (MM) is the second most prevalent hematological malignancy. Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy. This study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy, which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes, termed T-PB@M. The results from our investigations highlight the considerable bone affinity of T-PB@M, both in vitro and in vivo. Additionally, this material demonstrated a capability for drug release triggered by low pH conditions. Moreover, T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose) polymerase 1 (PARP1)–Caspase-3–B-cell lymphoma-2 (Bcl-2) pathway in MM cells. Notably, T-PB@M preferentially targeted bone-involved sites, thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic mice. Therefore, this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM.

Abstract We link changes in crustal permeability to informative features of microearthquakes (MEQs) using two field hydraulic stimulation experiments where both MEQs and permeability evolution are recorded simultaneously. The Bidirectional Long Short-Term Memory (Bi-LSTM) model effectively predicts permeability evolution and ultimate permeability increase. Our findings confirm the form of key features linking the MEQs to permeability, offering mechanistically consistent interpretations of this association. Transfer learning correctly predicts permeability evolution of one experiment from a model trained on an alternate dataset and locale, which further reinforces the innate interdependency of permeability-to-seismicity. Models representing permeability evolution on reactivated fractures in both shear and tension suggest scaling relationships in which changes in permeability ( $$\Delta k$$ Δ k ) are linearly related to the seismic moment ( $$M$$ M ) of individual MEQs as $$\Delta k\propto M$$ Δ k ∝ M . This scaling relation rationalizes our observation of the permeability-to-seismicity linkage, contributes to its predictive robustness and accentuates its potential in characterizing crustal permeability evolution using MEQs.

BackgroundCerebral radiation necrosis (RN), a severe complication of stereotactic radiotherapy (SRT), has been shown to significantly decrease patient survival time and quality of life. The purpose of this study was to analyze whether bevacizumab can prevent or reduce the occurrence of SRT-induced cerebral RN in non-small cell lung cancer (NSCLC) patients with brain metastases.Materials and methodsWe retrospectively reviewed the clinical records of NSCLC patients with brain metastases from March 2013 to June 2023 who were treated with SRT. Patients were divided into two groups: those in the bevacizumab group received SRT with four cycles of bevacizumab, and patients in the control group received SRT only. Inverse probability of treatment weighting (IPTW) was performed based on a multinomial propensity score model to balance the baseline characteristics. The chi-square test was used. A Cox model was used to evaluate overall survival (OS).ResultsA total of 80 patients were enrolled, namely, 28 patients in the bevacizumab group and 52 patients in the control group. The possibility of developing cerebral RN and/or symptomatic edema (RN/SE) was significantly decreased in patients treated with bevacizumab compared to those who did not receive bevacizumab before IPTW (p=0.036) and after IPTW (p=0.015) according to chi-square analysis. The IPTW-adjusted median OS was 47.7 months (95% CI 27.4-80.8) for patients in the bevacizumab group and 44.1 months (95% CI 36.7-68.0) (p=0.364) for patients in the control group.ConclusionThe application of bevacizumab concurrent with SRT may prevent or reduce the occurrence of cerebral RN in NSCLC patients with brain metastases.

Abstract Objective To construct and validate a model based on the dual-energy computed tomography (DECT) quantitative parameters and radiological features to predict Ki-67 expression levels in pancreatic ductal adenocarcinoma (PDAC). Materials and methods Data from 143 PDAC patients were analysed. The variables of clinic, radiology and DECT were evaluated. In the arterial phase and portal venous phase (PVP), the normalized iodine concentration (NIC), normalized effective atomic number and slope of the spectral attenuation curves were measured. The extracellular volume fraction (ECVf) was measured in the equilibrium phase. Univariate analysis was used to screen independent risk factors to predict Ki-67 expression. The Radiology, DECT and DECT–Radiology models were constructed, and their diagnostic effectiveness and clinical applicability were obtained through area under the curve (AUC) and decision curve analysis, respectively. The nomogram was established based on the optimal model, and its goodness-of-fit was assessed by a calibration curve. Results Computed tomography reported regional lymph node status, NIC of PVP, and ECVf were independent predictors for Ki-67 expression prediction. The AUCs of the Radiology, DECT, and DECT–Radiology models were 0.705, 0.884, and 0.905, respectively, in the training cohort, and 0.669, 0.835, and 0.865, respectively, in the validation cohort. The DECT–Radiology nomogram was established based on the DECT–Radiology model, which showed the highest net benefit and satisfactory consistency. Conclusions The DECT–Radiology model shows favourable predictive efficacy for Ki-67 expression, which may be of value for clinical decision-making in PDAC patients. Critical relevance statement The DECT–Radiology model could contribute to the preoperative and non-invasive assessment of Ki-67 expression of PDAC, which may help clinicians to screen out PDAC patients with high Ki-67 expression. Key points • Dual-energy computed tomography (DECT) can predict Ki-67 in pancreatic ductal adenocarcinoma (PDAC). • The DECT–Radiology model facilitates preoperative and non-invasive assessment of PDAC Ki-67 expression. • The nomogram may help screen out PDAC patients with high Ki-67 expression. Graphical Abstract

PurposeTo evaluate the capability of dual-layer detector spectral CT (DLCT) quantitative parameters in conjunction with clinical variables to detect malignant lesions in cytologically indeterminate thyroid nodules (TNs).Materials and methodsData from 107 patients with cytologically indeterminate TNs who underwent DLCT scans were retrospectively reviewed and randomly divided into training and validation sets (7:3 ratio). DLCT quantitative parameters (iodine concentration (IC), NICP (IC nodule/IC thyroid parenchyma), NICA (IC nodule/IC ipsilateral carotid artery), attenuation on the slope of spectral HU curve and effective atomic number), along with clinical variables, were compared between benign and malignant cohorts through univariate analysis. Multivariable logistic regression analysis was employed to identify independent predictors which were used to construct the clinical model, DLCT model, and combined model. A nomogram was formulated based on optimal performing model, and its performance was assessed using receiver operating characteristic curve, calibration curve, and decision curve analysis. The nomogram was subsequently tested in the validation set.ResultsIndependent predictors associated with malignant TNs with indeterminate cytology included NICP in the arterial phase, Hashimoto’s Thyroiditis (HT), and BRAF V600E (all p < 0.05). The DLCT-clinical nomogram, incorporating the aforementioned variables, exhibited superior performance than the clinical model or DLCT model in both training set (AUC: 0.875 vs 0.792 vs 0.824) and validation set (AUC: 0.874 vs 0.792 vs 0.779). The DLCT-clinical nomogram demonstrated satisfactory calibration and clinical utility in both training set and validation set.ConclusionThe DLCT-clinical nomogram emerges as an effective tool to detect malignant lesions in cytologically indeterminate TNs.

Metastatic choriocarcinoma during viable pregnancy is rare worldwide, and neonate survival following pregnancy termination in the second trimester is uncommon. Here, we report the successful delivery of a pregnancy by a patient with metastatic choriocarcinoma, who received three courses of etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA-CO) chemotherapy in the second trimester. After multidisciplinary discussions, she was administered paclitaxel and carboplatin (TC) chemotherapy. Regular contractions occurred during her first paclitaxel infusion, and a healthy infant was delivered by cesarean section at 26+4 gestational weeks. Choriocarcinoma was not detected in the placenta. Following delivery of the pregnancy, the patient underwent total treatment comprising one cycle of TC, seven cycles of EMA-CO, and five courses of etoposide, cisplatin, methotrexate, and dactinomycin chemotherapy; her serum level of beta–human chorionic gonadotropin gradually fell after chemotherapy. Uterine and pulmonary metastases shrank, and no distant metastasis or recurrence were found until the eighth course of maintenance treatment with immunotherapy. The patient received periodic chemotherapy for recurrence at the time of publishing this case report. The child was disease-free 15+ months after delivery. Despite serious metastases and complications, metastatic choriocarcinoma diagnosed in the second trimester of pregnancy can be successfully treated with minimal delay by multidisciplinary medical and nursing management.

Abstract Objective The prognosis of aneurysmal subarachnoid hemorrhage (aSAH) survivors is concerning. The goal of this study was to investigate and demonstrate the relationship between the neutrophil-to-albumin ratio (NAR) and long-term mortality of aSAH survivors. Methods A retrospective observational cohort study was conducted at Sichuan University West China Hospital between January 2009 and June 2019. The investigation of relationship between NAR and long-term mortality was conducted using univariable and multivariable Cox regression models. To demonstrate the predictive performance of different biomarkers over time, time-dependent receiver operating characteristic curve (ROC) analysis and decision curve analysis (DCA) were created. Results In total, 3173 aSAH patients were included in this study. There was a strong and continuous relationship between NAR levels and long-term mortality (HR 3.23 95% CI 2.75–3.79, p 0.28: adjusted HR 1.74 95% CI 1.30–2.32). Results in survivors were found to be still robust. Moreover, out of all the inflammatory markers studied, NAR demonstrated the highest correlation with long-term mortality. Conclusions A high level of NAR was associated with increased long-term mortality among patients with aSAH. NAR was a promising inflammatory marker for long-term mortality of aSAH.

With the continuous development and progress of society, age estimation based on deep learning has gradually become a key link in human-computer interaction. Widely combined with other fields of application, this paper performs a gradient division of human fall behavior according to the age estimation of the human body, a complete priority detection of the key population, and a phased single aggregation backbone network VoVNetv4 was proposed for feature extraction. At the same time, the regional single aggregation module ROSA module was constructed to encapsulate the feature module regionally. The adaptive stage module was used for feature smoothing. Consistent predictions for each task were made using the CORAL framework as a classifier and tasks were divided in binary. At the same time, a gradient two-node fall detection framework combined with age estimation was designed. The detection was divided into a primary node and a secondary node. In the first-level node, the age estimation algorithm based on VoVNetv4 was used to classify the population of different age groups. A face tracking algorithm was constructed by combining the key point matrices of humans, and the body processed by OpenPose with the central coordinates of the human face. In the secondary node, human age gradient information was used to detect human falls based on the AT-MLP model. The experimental results show that compared with Resnet-34, the MAE value of the proposed method decreased by 0.41. Compared with curriculum learning and the CORAL-CNN method, MAE value decreased by 0.17 relative to the RMSE value. Compared with other methods, the method in this paper was significantly lower, with a biggest drop of 0.51.

At present, there are few studies exploring the impact of market-based environmental regulation on ESG performance based on the perspective of carbon emission trading scheme (CETS). This paper aims to supplement this research field through empirical analysis. Taking Shanghai-Shenzhen A-share listed companies from 2012 to 2022 as the research object, this paper studies the impact of CETS, a market-based environmental regulation tool, on the ESG performance of enterprises by constructing a time-varying DID model and examines the mediating roles of green technology innovation, agency cost and analyst attention. The results show that the implementation of CETS can significantly boost ESG performance, and green technology innovation, agency cost, and analyst attention play a partial intermediary role between the two, while the mediating effects of green total factor productivity and green total factor energy efficiency are not significant. In terms of heterogeneity analysis, the study shows that CETS implementation has a more substantial promotion effect on ESG performance in non-state-owned enterprises, non-politically connected enterprises and non-high-tech enterprises. In this paper, the robustness test was carried out through PSM-DID, placebo test and replacement of explained variables, and the test results further supported the hypothesis in this paper. This study enriched the research on the impact of market-based environmental regulation on ESG from the perspective of CETS. It provided enlightenment for enterprises to improve ESG performance to a strategic level, improve the level of green technology innovation, and the government to implement differentiated environmental governance policies.

We introduce a general and effective strategy for selecting and controlling nonuniform coherence structures to further improve fiber-coupling efficiency (FCE) of nonuniformly randomly structured beams in turbulence. Our results show that adjusting the weight distribution of such beams is the key to mastering the strategy. Selecting the beams with weight distribution concentrated at short/long focal length modes possess higher/lower maximum FCE, which is suitable for short/long-distance transmission situations. Furthermore, adjusting the initial coherence length and beam order of the selected beam will help users further improve the FCE.

Network security situational awareness (NSSA) aims to capture, understand, and display security elements in large-scale network environments in order to predict security trends in the relevant network environment. With the internet’s increasingly large scale, increasingly complex structure, and gradual diversification of components, the traditional single-layer network topology model can no longer meet the needs of network security analysis. Therefore, we conduct research based on a multi-layer network model for network security situational awareness, which is characterized by the three-layer network structure of a physical device network, a business application network, and a user role network. Its network characteristics require new assessment methods, so we propose a multi-layer network link importance assessment metric: the multi-layer-dependent link entropy (MDLE). On the one hand, the MDLE comprehensively evaluates the connectivity importance of links by fitting the link-local betweenness centrality and mapping entropy. On the other hand, it relies on the link-dependent mechanism to better aggregate the link importance contributions in each network layer. The experimental results show that the MDLE has better ordering monotonicity during critical link discovery and a higher destruction efficacy in destruction simulations compared to classical link importance metrics, thus better adapting to the critical link discovery requirements of a multi-layer network topology.

ABSTRACT: In the study, 336 broiler chickens were selected to explore dietary effects of different β-hydroxy-β-methylbutyrate (HMB) levels (0 (control), 0.05, 0.10, and 0.15%) on the compositions of fatty acids and free amino acids, and lipid metabolism in the different muscles of broilers. In the breast muscle, dietary HMB supplementation hardly affected the free amino acid composition (P > 0.05). Compared to the control group, dietary 0.10 and 0.15% HMB supplementation decreased the content of C18:1n9c and thus the monounsaturated fatty acid (MUFA), and dietary 0.15% HMB supplementation increased the sum of saturated fatty acids (SFA) (P < 0.05). Moreover, compared to the control group, dietary 0.05 and 0.10% HMB increased the mRNA expression of proliferator activated receptor-γ and the activity of fatty acid synthase (FAS), and dietary 0.10% HMB increased the acetyl-CoA carboxylase activity (P < 0.05). In the leg muscle, dietary 0.10 and 0.15% HMB increased the MUFA content and decreased the polyunsaturated fatty acid (PUFA) content, the PUFA to SFA ratio, the mRNA expression of sterol regulatory element binding proteins-1c, and the activities of acyl-CoA oxidase 1 and acetyl-CoA synthetase (P < 0.05). Moreover, dietary 0.10% HMB decreased the activities of hydroxy-3-methylglutaryl-CoA synthase 1 and FAS in comparison to the control group (P < 0.05). Dietary 0.05% HMB decreased the contents of essential amino acids and nonessential amino acids (NEAA), and dietary 0.15% HMB decreased the NEAA content (P < 0.05). In summary, dietary 0.10% HMB supplementation had superior efficiency on lipogenesis in the breast muscle of broilers. However, dietary HMB supplementation, especially at the level of 0.05 and 0.15%, decreased meat nutritional values and the lipogenesis in leg muscles.

Abstract Purpose To analyse the predictive effect of a nomogram combining dual-layer spectral computed tomography (DSCT) quantitative parameters with typical radiological features in distinguishing benign micro-nodule from thyroid microcarcinoma (TMC). Methods Data from 342 instances with thyroid micro-nodules (≤1 cm) who underwent DSCT (benign group: n = 170; malignant group: n = 172) were reviewed. Typical radiological features including micro-calcification and enhanced blurring, and DSCT quantitative parameters including attenuation on virtual monoenergetic images (40 keV, 70 keV and 100 keV), the slope of the spectral HU curve (λHU), normalized iodine concentration (NIC), and normalized effective atomic number (NZeff) in the arterial phase (AP) and venous phase (VP), were measured and compared between the benign and malignant groups. The receiver operating characteristic (ROC) curve was used to assess the diagnostic performance of significant quantitative DSCT parameters or the models combining DSCT parameters respectively and typical radiological features based on multivariate logistic regression (LR) analysis. A nomogram was developed using predictors with the highest diagnostic performance in the above model, as determined by multivariate LR analysis. Results The DSCT parameter APλHU showed the greatest diagnostic efficiency in identifying patients with TMC, with an area under the ROC curve (AUC) of 0.829, a sensitivity and specificity of 0.738 and 0.753, respectively. Then, APλHU was combined with the two radiological features to construct the DSCT-Radiological nomogram, which had an AUC of 0.858, a sensitivity of 0.791 and a specificity of 0.800. The calibration curve of the nomogram demonstrated that the prediction result was in good agreement with the actual observation. The decision curve revealed that the nomogram can result in a greater net benefit than the all/none-intervention strategy for all threshold probabilities. Conclusion As a valid and visual noninvasive prediction tool, the DSCT-Radiological nomogram incorporating DSCT quantitative parameters and radiological features shows favourable predictive efficiency for identifying benign and malignant thyroid micro-nodules.

Abstract Objective In quantitative reverse transcription‐polymerase chain reaction (RT‐qPCR) studies, the selection and validation of reference genes are crucial for the accurate analysis of MicroRNAs (miRNAs) expression. In this work, the optimal reference genes for RT‐qPCR normalisation in plasma samples of rat middle cerebral artery occlusion (MCAO) models were identified. Methods Six rat MCAO models were established. Blood samples were collected before modelling and approximately 16–24 h after modelling. Two commonly used reference genes (U6 and 5S) and three miRNAs (miR‐24, miR‐122 and miR‐9a) were selected as candidate reference genes, and the expression of these genes was detected with RT‐qPCR. The acquired data were analysed using geNorm, Normfinder, BestKeeper, RefFinder and comparative delta threshold cycle statistical models. Results The analysed results consistently showed that miR‐24 was the most stably expressed reference gene. The ‘optimal combination’ calculated by geNorm was miR‐24, U6 and5S. The expression level of the target gene miR124 was similar when the most stable reference gene miR‐24 or the ‘optimal combination’ was used as a reference gene. However, compared with miR24 or the ‘optimal combination’, the less stable reference genes influenced the fold change and the data accuracy with a large standard deviation. Conclusion These results confirmed the importance of selecting suitable reference genes for normalisation to obtain reliable results in RT‐qPCR studies and demonstrated that the identified reference gene miR‐24 or the ‘optimal combination’ could be used as an internal control for gene expression analysis in the rat MCAO model.

Both coherence and polarization are important inherent properties of light [...]

ObjectiveMany peripheral inflammatory markers were reported to be associated with the prognosis of aneurysmal subarachnoid hemorrhage (aSAH). We aimed to identify the most promising inflammatory factor that can improve existing predictive models.MethodsThe study was based on data from a 10 year retrospective cohort study at Sichuan University West China Hospital. We selected the well-known SAFIRE and Subarachnoid Hemorrhage International Trialists’ (SAHIT) models as the basic models. We compared the performance of the models after including the inflammatory markers and that of the original models. The developed models were internally and temporally validated.ResultsA total of 3,173 patients were included in this study, divided into the derivation cohort (n = 2,525) and the validation cohort (n = 648). Most inflammatory markers could improve the SAH model for mortality prediction in patients with aSAH, and the neutrophil-to-albumin ratio (NAR) performed best among all the included inflammatory markers. By incorporating NAR, the modified SAFIRE and SAHIT models improved the area under the receiver operator characteristics curve (SAFIRE+NAR vs. SAFIRE: 0.794 vs. 0.778, p = 0.012; SAHIT+NAR vs. SAHIT: 0.831 vs. 0.819, p = 0.016) and categorical net reclassification improvement (SAFIRE+NAR: 0.0727, p = 0.002; SAHIT+NAR: 0.0810, p

BackgroundSmoking is associated with increased mortality in patients with cancer. However, there are limited data on the impact of smoking on the survival of patients with brain metastases. Therefore, this study aimed to evaluate whether smoking was associated with survival and whether smoking cessation was beneficial to these patients.MethodsThis study used lung cancer with a brain metastasis cohort of the West China Hospital of Sichuan University from 2013 to 2021. Patients were stratified according to smoking history; the distribution, clinical characteristics, and survival data of each group were estimated. Kaplan-Meier analysis and risk analysis were performed for the survival endpoint.ResultsOf the 2,647 patients included in the analysis, the median age was 57.8 years, and 55.4% were men. Among them, 67.1% had no smoking history, 18.9% still smoked, and 14% reported quitting smoking. Compared with never smokers, current smokers [HR, 1.51 (95% CI, 1.35-1.69), p < 0.01] and former smokers [HR, 1.32 (95% CI, 1.16-1.49), p

Abstract Background To investigate the long-term surgical outcomes and prognostic factors of foveal detachment (FD) in pathological myopia. Methods This retrospective observational study included 59 patients with FD (61 eyes) who underwent pars plana vitrectomy at Shanghai General Hospital between June 2017 and July 2018 with follow-up for at least 24 months. Comprehensive ophthalmic examinations, including best-corrected visual acuity (BCVA) and swept-source optical coherence tomography, were assessed. Preoperative myopic maculopathy was evaluated according to the ATN classification. Results FD completely resolved in 59 of 61 eyes (96.7%). Mean duration of retinal reattachment was 12.10 ± 8.10 months. Mean logMAR BCVA improved from 1.34 ± 0.52 to 0.83 ± 0.43 at 24 months postoperatively (P

Bacterial leaf blight caused by Xanthomonas oryzae pv. oryzae (Xoo) has always been considered to be one of the most severe worldwide diseases in rice. Xoo strains usually use the highly conserved type III secretion system (T3SS) to deliver virulence effectors into rice cells and further suppress the host’s immunity. Previous studies reported that different Xanthomonas outer protein (Xop) effectors include XopZ from one strain appear to share functional redundancies on suppressing rice PAMP-triggered immunity (PTI). But only xopZ, except other xop genes, could significantly impaire Xoo virulence when individually deleting in PXO99 strains. Thus, the XopZ effector should not only suppress rice PTI pathway, but also has other unknown indispensable pathological functions in PXO99–rice interactions. Here, we also found that ∆xopZ mutant strains displayed lower virulence on Nipponbare leaves compared with PXO99 strains. We identified an oxysterol-binding related protein, ORP1C, as a XopZ-interacting protein in rice. Further studies found that rice ORP1C preliminarily played a positive role in regulating the resistance to PXO99 strains, and XopZ–ORP1C interactions cooperated to regulate the compatible interactions of PXO99-Nipponbare rice. The reactive oxygen species (ROS) burst and PTI marker gene expression data indicated that ORP1C were not directly relevant to the PTI pathway in rice. The deeper mechanisms underlying XopZ–ORP1C interaction and how XopZ and ORP1C cooperate for regulating the PXO99–rice interactions require further exploration.

We investigate the behavior of the orbital angular momentum (OAM) flux density of partially coherent vortex (PCV) beams in atmospheric turbulence. It is shown that for PCV beams with different spatial coherence structures, the OAM flux density distribution exhibits rich variations along the propagation path. Our findings provide insight into the use of the OAM in free-space optical communications when turbulence effects are significant.

Glutamine is the most abundant amino acid in blood and tissues, and the most important nutrient except for glucose in cancer cells. Over the past years, most studies have focused on the role of Gln metabolism in supporting energy metabolism rather than maintaining oxidative homeostasis. In fact, Gln is an important factor in maintaining oxidative homeostasis of cancer cells, especially in “Glutamine addicted” cancer cells. Here, this paper will review the recent scientific literature about the link between Gln metabolism and oxidative homeostasis, with an emphasis on the potential role of Gln metabolism in different cancers. Given that oxidative homeostasis is of critical importance in cancer, understanding the impacts of a Gln metabolism on oxidative homeostasis, gaining great insights into underlying molecular mechanisms, and developing effective therapeutic strategies are of great importance.

ObjectivesTo investigate the potential value of a contrast enhanced computed tomography (CECT)-based radiological-radiomics nomogram combining a lymph node (LN) radiomics signature and LNs’ radiological features for preoperative detection of LN metastasis in patients with pancreatic ductal adenocarcinoma (PDAC).Materials and methodsIn this retrospective study, 196 LNs in 61 PDAC patients were enrolled and divided into the training (137 LNs) and validation (59 LNs) cohorts. Radiomic features were extracted from portal venous phase images of LNs. The least absolute shrinkage and selection operator (LASSO) regression algorithm with 10-fold cross-validation was used to select optimal features to determine the radiomics score (Rad-score). The radiological-radiomics nomogram was developed by using significant predictors of LN metastasis by multivariate logistic regression (LR) analysis in the training cohort and validated in the validation cohort independently. Its diagnostic performance was assessed by receiver operating characteristic curve (ROC), decision curve (DCA) and calibration curve analyses.ResultsThe radiological model, including LN size, and margin and enhancement pattern (three significant predictors), exhibited areas under the curves (AUCs) of 0.831 and 0.756 in the training and validation cohorts, respectively. Nine radiomic features were used to construct a radiomics model, which showed AUCs of 0.879 and 0.804 in the training and validation cohorts, respectively. The radiological-radiomics nomogram, which incorporated the LN Rad-score and the three LNs’ radiological features, performed better than the Rad-score and radiological models individually, with AUCs of 0.937 and 0.851 in the training and validation cohorts, respectively. Calibration curve analysis and DCA revealed that the radiological-radiomics nomogram showed satisfactory consistency and the highest net benefit for preoperative diagnosis of LN metastasis.ConclusionsThe CT-based LN radiological-radiomics nomogram may serve as a valid and convenient computer-aided tool for personalized risk assessment of LN metastasis and help clinicians make appropriate clinical decisions for PADC patients.

We use the extended Huygens–Fresnel integral to analyze the propagation properties of a class of partially coherent beams with Laguerre non-uniform coherence properties (called Laguerre non-uniformly correlated beams) in free space and in a turbulent atmosphere. We focus on how different initial beam orders and coherence lengths affect the propagation behavior of the beams, such as the evolution of intensity, degree of coherence, propagation factor, and beam wander. Our results show that non-uniform coherence properties play a role in resisting the degrading effects of turbulence. Furthermore, adjusting the initial beam parameter of the non-uniform coherence structure, i.e., increasing the beam order and decreasing the coherence, can further improve the turbulence resistance of the beams. Our results have potential applications in free-space optical communications.

BackgroundThe prognostic role of body mass index (BMI) in patients with brain metastases is controversial. We aim to investigate the impact of BMI on prognosis and anti-cancer therapy effectiveness in brain metastases.MethodsPatients diagnosed with brain metastases between Oct 2010 and July 2019 were followed for mortality through April 2021. The prognostic role of BMI on overall survival was assessed by a restricted cubic spline (RCS) using a flexible model to visualize the relationship between the BMI values and hazard ratios of all-cause mortality, followed by a cox regression model. The disparity of survival outcomes in patients receiving anti-cancer therapies or those did not was evaluated according to the classification of BMI.ResultsA total of 2,466 patients were included in the analysis, including 241 in the underweight (BMI < 18.5 kg/m2) group, 1,503 in the normal weight group (BMI 18.5–23.9 kg/m2), and 722 in the overweight (BMI ≥ 24 kg/m2) group. Relative to the normal weight group, underweight patients were associated with poor prognosis (adjusted HR 1.25, 95% CI 1.07–1.46, p = 0.005). However, those in the overweight group showed similar overall survival when compared to the normal-weight group. Patients with weight loss were associated with a higher risk of mortality compared with patients without significant weight loss. In underweight patients, there was an insignificant difference in survival outcomes whether they received anti-cancer therapies or not.ConclusionUnderweight and significant weight loss were associated with poor prognosis in brain metastases. Meanwhile, anti-cancer therapies did not significantly improve overall survival in patients with underweight. These findings suggest that improving nutrition to maintain body weight is critical for patients with brain metastases.

Abstract Pectin is a kind of natural and complex carbohydrates which is extensively used in food, chemical, cosmetic, and pharmaceutical industries. Fresh sunflower (Helianthus annuus L.) heads were utilized as a novel source of pectin extracted by ammonium oxalate. The conditions of the extraction process were optimized implementing the response surface methodology. Under optimal extraction parameters (extraction time 1.34 h, liquid–solid ratio 15:1 mL/g, ammonium oxalate concentration 0.76% (w/v)), the maximum experimental yield was 7.36%. The effect of spray-drying and freeze-drying on the physiochemical properties, structural characteristics, and antioxidant activities was investigated by FT-IR spectroscopy, high performance size exclusion chromatography, and X-ray diffraction. The results showed freeze-drying lead to decrease in galacturonic acid (GalA) content (76.2%), molecular weight (M w 316 kDa), and crystallinity. The antioxidant activities of pectin were investigated utilizing the in-vitro DPPH and ABTS radical-scavenging systems. This study provided a novel and efficient extraction method of sunflower pectin, and confirmed that different drying processes had an effect on the structure and properties of pectin.

Abstract In the basin of western China, four different kinds of lithological reservoirs are developed, including low-permeability sandstone, sedimentary tuff, shale and volcanic rock. There is generally a large difference in the micropore structure characteristics and distribution laws due to different reservoirs. The reserving capacity as well as the porous flowability, mechanism and laws are determined by the micropore structure characteristics and distribution laws of hydrocarbon reservoirs. Low-temperature nitrogen adsorption and desorption technology, high-pressure mercury injection experiment and nuclear magnetic resonance (NMR) testing technology are applied to study the micropore size, quantity, structure and distribution laws of four different kinds of lithological reservoirs as well as their similarities and differences of corresponding relation with macroporosity–permeability physical parameters. This paper also studies the movable fluid and nonlinear seepage flow characteristics of four different kinds of lithological reservoirs.

This study aimed to explore the effects of the incremental injection of lipopolysaccharide (LPS) on liver histopathology, inflammation, oxidative status, and mitochondrial function in piglets. Forty healthy Duroc × Landrace × Yorkshire castrated boars (21 ± 2 days old, weight 6.84 ± 0.11 kg) were randomly assigned to five groups (n = 8) and then slaughtered on days 0 (group 0, without LPS injection), 1 (group 1), 5 (group 5), 9 (group 9), and 15 (group 15) of LPS injection, respectively. The results showed that, compared to the piglets without LPS injection, LPS injection caused liver injury in the early phase, as manifested by the increased activities of serum liver injury-related parameters (aspartate amino transferase, alanine aminotransferase, alkaline phosphatase, cholinesterase, and total bile acid) on day 1, and impaired liver morphology (disordered hepatic cell cord arrangement, dissolved and vacuolized hepatocytes, karyopycnosis, and inflammatory cell infiltration and congestion) on days 1 and 5. Meanwhile, LPS injection caused liver inflammation, oxidative stress, and mitochondrial dysfunction on days 1 and 5, as reflected by the upregulated mRNA expression of TNF-α, IL-6, IL-1β, TLR4, MyD88, and NF-κB; increased MPO and MDA content; and impaired mitochondrial morphology. However, these parameters were ameliorated in the later phase (days 9~15). Taken together, our data indicate that the incremental injection of the LPS-induced liver injury of piglets could be self-repaired.

In this paper, we study the propagation properties of twisted Hermite–Gaussian Schell- model (THGSM) beams propagating in a uniaxial crystal orthogonal to the optical axis. We derive the concrete analytical expression of the cross-spectral density (CSD) function in the crystal and simulate the evolution characteristics of such beams, including normalized spectral intensity, the spectral degree of coherence (DOC), and effective beam width. We find that the spectral intensity distribution exhibits a non-circular symmetric self-splitting while rotating, and the distribution of the spectral DOC is non-circular symmetric rotationally distorted, which is quite different from that in an isotropic medium. The initial beam parameters and crystal parameters both affect the distribution of spectral intensity and DOC. Furthermore, increasing the twist factor and adjusting the ratio of the extraordinary light refractive index and the ordinary light refractive index ne/no of the uniaxial crystal can suppress the beam expansion as propagating in the crystal. Our results show that the uniaxial crystal can be used to determine whether light beams carry a twist phase or not, and to modulate the characteristics of light beams.

Free-space optical communication is restricted by random media-stimulated beam degradation. However, partially coherent structured beams modulated by the coherence structure can potentially mitigate this negative effect. By employing the extended Huygens–Fresnel integral, we provide an examination of the second-order statistical features of a common type of partly coherent structured beams, self-splitting structured beams, in a turbulent ocean. The implications of turbulence parameters relating to the ocean and beginning beam parameters corresponding to the progression of such beam propagation attributes are fully investigated. Our numerical outcomes show that, for turbulence with a low-dissipation kinetic energy rate per unit mass of fluid, small Kolmogorov inner scale, large relative strength of temperature to salinity undulations, and large dissipation rate of mean-square temperature has a greater negative effect on the structured beams. In addition, we suggest an effective approach, enhancing the order of the beam and reducing the coherence length of the beams, to lower the oceanic turbulence-induced negative effects, and thus have future extensive possibilities in free-space optical communication.

The creation of biomaterials which are resorbable and have biomimetic mechanical properties is key to successful tissue engineering. Here the authors report on the creation of a new biopolymer where the mechanical properties can be tuned by changing the ratios of cis:trans double bonds in the backbone.

PurposesThe purpose of this study was to explore the diagnostic performance of Cho peak area (Cho Are), Cho peak amplitude (Cho Amp), and the combined approach (Cho Are_Amp) in detecting rabbit VX2 liver cancer at the early stage via hydrogen-1 proton magnetic resonance spectroscopy (1H-MRS), as well as the correlations between Cho Are, Cho Amp, and tumor parameters like diameter and volume.MethodsConventional magnetic resonance imaging (MRI) and MRS were performed to scan the VX2 liver cancer in rabbit. The tumor diameter was measured on T2-weighted imaging (T2WI), and the tumor volume was accordingly calculated. Cho Are and Cho Amp were obtained from MRS. The diagnostic performance of Cho Are, Cho Amp, and Cho Are_Amp was assessed by a receiver operating characteristic (ROC) curve and area under ROC curve (AUC), whereas specificity and sensitivity were calculated by the maximum Youden’s index. Spearman’s correlation analysis was performed to evaluate the relevance between tumor parameters (diameter, volume) and radiological indexes (Cho Are, Cho Amp).ResultsROC curve analysis showed that Cho Amp, Cho Are, and Cho Are_Amp were effective in diagnosing VX2 liver cancer. The AUC of Cho Amp was 0.883, and the specificity and sensitivity were 0.944 and 0.722, respectively (p < 0.001). The AUC of Cho Are was 0.807, and the specificity and sensitivity were 0.778 and 0.833, respectively (p < 0.05). The AUC of Cho Are_Amp was 0.892, and the specificity and sensitivity were 0.833 and 0.833, respectively (p < 0.001). Cho Are and Cho Amp exhibited a high positive correlation with tumor diameter and tumor volume, among which Cho Amp demonstrated better correlations to tumor diameter and tumor volume (r = 0.956 and 0.946) than that of Cho Are (r = 0.787 and 0.794). A high positive correlation was detected between Cho Are and Cho Amp (r = 0.787), as well as tumor diameter and tumor volume (r = 0.965).ConclusionCho Are_Amp can be used as an effective tool in diagnosing early-stage VX2 liver cancer with satisfied diagnostic accuracy. Cho Are and Cho Amp were positively correlated with tumor volume and tumor diameter. The results of this study provide further evidence that Cho Amp and Cho Are_Amp of MRS could aid in the early diagnosis of liver cancer.

Few biomaterials are suitable for long-term tissue engineering applications and these examples usually possess limited property scope, can be difficult to process, and are non-responsive to external stimuli. Here, the authors overcome these issues by developing a class of easily processable polyamides with stereo-controlled mechanical properties and high-fidelity shape memory behaviour.

Abstract Background Our study aims to develop and validate diagnostic models of the common parotid tumors based on whole-volume CT textural image biomarkers (IBMs) in combination with clinical parameters at a single institution. Methods The study cohort was composed of 51 pleomorphic adenoma (PA) patients and 42 Warthin tumor (WT) patients. Clinical parameters and conventional image features were scored retrospectively and textural IBMs were extracted from CT images of arterial phase. Independent-samples t test or Chi-square test was used for evaluating the significance of the difference among clinical parameters, conventional CT image features, and textural IBMs. The diagnostic performance of univariate model and multivariate model was evaluated via receiver operating characteristic (ROC) curve and area under ROC curve (AUC). Results Significant differences were found in clinical parameters (age, gender, disease duration, smoking), conventional image features (site, maximum diameter, time-density curve, peripheral vessels sign) and textural IBMs (mean, uniformity, energy, entropy) between PA group and WT group (P

The durable responses and favorable long-term outcomes are limited to a proportion of advanced melanoma patients treated with immune checkpoint inhibitors (ICI). Considering the critical role of antitumor immunity status in the regulation of ICI therapy responsiveness, we focused on the immune-related gene profiles and aimed to develop an individualized immune signature for predicting the benefit of ICI therapy. During the discovery phase, we integrated three published datasets of metastatic melanoma treated with anti-PD-1 (n = 120) and established an immune-related gene pair index (IRGPI) for patient classification. The IRGPI was constructed based on 31 immune-related gene pairs (IRGPs) consisting of 51 immune-related genes (IRGs). The ROC curve analysis was performed to evaluate the predictive accuracy of IRGPI with AUC = 0.854. Then, we retrospectively collected one anti-PD-1 therapy dataset of metastatic melanoma (n = 55) from Peking University Cancer Hospital (PUCH) and performed the whole-transcriptome RNA sequencing. Combined with another published dataset of metastatic melanoma received anti-CTLA-4 (VanAllen15; n = 42), we further validated the prediction accuracy of IRGPI for ICI therapy in two datasets (PUCH and VanAllen15) with AUCs of 0.737 and 0.767, respectively. Notably, the survival analyses revealed that higher IRGPI conferred poor survival outcomes in both the discovery and validation datasets. Moreover, correlation analyses of IRGPI with the immune cell infiltration and biological functions indicated that IRGPI may be an indicator of the immune status of the tumor microenvironment (TME). These findings demonstrated that IRGPI might serve as a novel marker for treating of melanoma with ICI, which needs to be validated in prospective clinical trials.

Coherence in a light beam has the potential to serve as a degree of freedom for manipulating the beam. In this work, the self-focusing property of a partially coherent beam with a non-uniform correlation structure propagating in a non-linear medium is investigated. The analysis of the evolution of beam width reveals that the coherence structure plays a vital role in the self-focusing formation. A threshold condition for the coherence radius is proposed for the first time, and the relation of self-focusing length and initial coherence radius is studied numerically and analytically. It is shown that a feasible approach for manipulating the self-focusing length by adjusting the initial coherence radius is achieved.

We study the propagation characteristics (spectral intensity and degree of coherence) of a new type of Lorentz non-uniformly correlated (LNUC) beam based on the extended Huygens–Fresnel principle and the spatial power spectrum of oceanic turbulence. The effects of the oceanic turbulence parameters and initial beam parameters on the evolution propagation characteristics of LNUC beams are studied in detail by numerical simulation. The results indicate that such beams exhibit self-focusing propagation features in both free space and oceanic turbulence. Decreasing the dissipation rate of kinetic energy per unit mass of fluid and the Kolmogorov inner scale, or increasing the relative strength of temperature to salinity undulations and the dissipation rate of mean-square temperature of the turbulent ocean tends to increase the negative effects on the beams. Furthermore, we propose a strategy of increasing the beam width and decreasing the coherence length, to reduce the negative effects of the turbulence.

Iron is a trace element necessary for cell growth, development, and cellular homeostasis, but insufficient or excessive level of iron is toxic. Intracellularly, sufficient amounts of iron are required for mitochondria (the center of iron utilization) to maintain their normal physiologic function. Iron deficiency impairs mitochondrial metabolism and respiratory activity, while mitochondrial iron overload promotes ROS production during mitochondrial electron transport, thus promoting potential disease development. This review provides an overview of iron homeostasis, mitochondrial iron metabolism, and how mitochondrial iron imbalances-induced mitochondrial dysfunction contribute to diseases.

This study aimed to investigate the effects of lipopolysaccharide (LPS)-induced chronic immune stress on intestinal morphology and function, immune system, oxidative status, and mitochondrial function in piglets. Fifty healthy Duroc × Landrace × Yorkshire piglets (21 ± 2 days old, barrow, 6.98 ± 0.14 kg body weight) were selected and randomly allotted to five groups, which were slaughtered at 0 (0 group), 1, 5, 9, and 15 d of LPS injection. The results showed that compared with the piglets without LPS injection, LPS injection significantly impaired the intestinal morphology and permeability at 1, 5, and 9 d, as manifested by the increased serum lactic acid and decreased ratio of villus height to crypt depth (p < 0.05). Moreover, intestinal inflammation and oxidative and mitochondrial injury were caused at 1 d, as manifested by upregulated IL-6 mRNA expression, increased malondialdehyde content, and impaired mitochondrial morphology (p < 0.05). However, these parameters were restored to levels identical to 0 group at 9~15 d, accompanied by significantly increased antioxidant capacity, enhanced protein expression of CD3+ and CD68+, and upregulated mRNA abundance of genes related to mitochondrial biogenesis and functions (p < 0.05). Collectively, these results suggest that the intestinal injury of piglets caused by chronic immune stress could be self-repaired.

Obesity is a matter of concern to the public. Abundant evidence has been accumulated that nutritional intervention is a promising strategy to address this health issue. The objective of this study is to investigate alterations in the lipid metabolism in white adipose tissues and the gut microbiota of Shaziling pigs challenged by long-term protein restriction. Results showed that compared with the control group, reducing the protein level by 20% (−20%) increased the mRNA abundance of FABP4 in white adipose tissues (p < 0.05). This occurred in conjunction with increases in PPARγ protein expression. Conversely, the protein expression of C/EBPα was reduced in the −20% group (p < 0.05). Moreover, the −20% group had increased/decreased phosphorylation of AMPKα/mTOR, respectively (p < 0.05). As for the colonic gut microbiota, a 20% reduction in the protein level led to increased Lachnospiraceae XPB1014 group abundance at the genus level (p < 0.01). Collectively, these results indicated that a 20% protein reduction could modulate lipid metabolism and alter the colonic microbiota of Shaziling pigs, an approach which might be translated into a treatment for obesity.

Background: To investigate the diagnostic efficacy of choline (Cho) value of magnetic resonance spectroscopy (MRS) in rabbit with VX2 liver tumor via comparative and quantitative analysis with the choline compounds concentration measured by enzyme linked immunosorbent assay (ELISA). Methods: MRS was performed on normal liver and VX2 tumor. The Cho value of VX2 tumor was compared with that of normal liver. Tissues were harvested for ELISA to detect the concentrations of acetylcholine (ACh), glycophorophosphygholine (GPC) and phosphochorine (PC). The diagnostic performance of Cho value and concentrations of choline compounds were assessed by receiver operating characteristic (ROC) curve and area under ROC curve (AUC). The specificity and sensitivity were discussed by the maximum Youden’s index. Results: The concentration of ACh was obviously higher than that of GPC and PC both in VX2 tumor and normal liver ( P < 0.01). Furthermore, the concentration differences among ACh, GPC and PG were the third power of 10. Both the ACh concentration and Cho value of MRS in VX2 tumor were significantly higher than those in normal liver ( P < 0.01). The AUC of ACh in VX2 tumor was 0.883, when the cutoff value was 7259000, the sensitivity and specificity of the diagnosis of liver cancer were 94.4% and 77.8%, respectively. The AUC of Cho in VX2 tumor was 0.807, when the cutoff value was 28.35, the sensitivity and specificity of the diagnosis of liver cancer were 83.3% and 77.8%, respectively. Conclusion: The change of Cho value in MRS between liver cancer and normal liver was consistent with the changes of concentrations of choline compounds measured by ELISA, especially the change of ACh concentration. The diagnostic efficiency of Cho value and that of choline compounds concentration in liver cancer were extremely similar, with the AUC more than 0.8. We conclude that MRS may be applied as an important, non-invasive biomarker for the diagnosis of liver cancer.

Background The indoleamine 2,3-dioxygenase (IDO) pathway is a key counter-regulatory mechanism that, in cancer, is exploited by tumors to evade antitumor immunity. Indoximod is a small-molecule IDO pathway inhibitor that reverses the immunosuppressive effects of low tryptophan (Trp) and high kynurenine (Kyn) that result from IDO activity. In this study, indoximod was used in combination with a checkpoint inhibitor (CPI) pembrolizumab for the treatment for advanced melanoma.Methods Patients with advanced melanoma were enrolled in a single-arm phase II clinical trial evaluating the addition of indoximod to standard of care CPI approved for melanoma. Investigators administered their choice of CPI including pembrolizumab (P), nivolumab (N), or ipilimumab (I). Indoximod was administered continuously (1200 mg orally two times per day), with concurrent CPI dosed per US Food and Drug Administration (FDA)-approved label.Results Between July 2014 and July 2017, 131 patients were enrolled. (P) was used more frequently (n=114, 87%) per investigator’s choice. The efficacy evaluable population consisted of 89 patients from the phase II cohort with non-ocular melanoma who received indoximod combined with (P).The objective response rate (ORR) for the evaluable population was 51% with confirmed complete response of 20% and disease control rate of 70%. Median progression-free survival was 12.4 months (95% CI 6.4 to 24.9). The ORR for Programmed Death-Ligand 1 (PD-L1)-positive patients was 70% compared with 46% for PD-L1-negative patients. The combination was well tolerated, and side effects were similar to what was expected from single agent (P).Conclusion In this study, the combination of indoximod and (P) was well tolerated and showed antitumor efficacy that is worth further evaluation in selected patients with advanced melanoma.

With the development of the internet of things (IoT),5G and industrial technology,industrial IoT has become a new research field.Due to the specific requirements of delay,security and stability in industrial production,the traditional DNS has limitations to meet the needs of industrial IoT because of its single identity object,rigid resolution results,and weak security.In this context,how to provide efficient,flexible and secure resolution services for universal objects has become a hot area worldwide.Firstly,we discussed the design principles and key supporting technologies of the identity resolution system in industrial IoT.Then summarized and compared the existing identity resolution systems in detail.Next,the new identity resolution schemes in academic research were introduced.Finally,the core problems and the future research trend in this field were discussed.