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Neural network pruning is a popular approach to reducing the computational complexity of deep neural networks. In recent years, as growing evidence shows that conventional network pruning methods employ inappropriate proxy metrics, and as new types of hardware become increasingly available, hardware-aware network pruning that incorporates hardware characteristics in the loop of network pruning has gained growing attention. Both network accuracy and hardware efficiency (latency, memory consumption, etc.) are critical objectives to the success of network pruning, but the conflict between the multiple objectives makes it impossible to find a single optimal solution. Previous studies mostly convert the hardware-aware network pruning to optimization problems with a single objective. In this paper, we propose to solve the hardware-aware network pruning problem with Multi-Objective Evolutionary Algorithms (MOEAs). Specifically, we formulate the problem as a multi-objective optimization problem, and propose a novel memetic MOEA, namely HAMP, that combines an efficient portfolio-based selection and a surrogate-assisted local search, to solve it. Empirical studies demonstrate the potential of MOEAs in providing simultaneously a set of alternative solutions and the superiority of HAMP compared to the state-of-the-art hardware-aware network pruning method.

Abstract Background The aim of this study is to introduce a novel nanohydroxyapatite/polyamide 66(n-HA/PA66)n strut to improve biomechanical performance and reduce subsidence. Methods One validated intact and 2 ACCF-simulated C3–C7 cervical spine models were developed (old strut: Group A, new strut: Group B). In the ACCF models, C5 underwent corpectomy and was fixed by an anterior cervical plate. Screw angles were categorized as 1 (0 ) and 2 (45 ) and divided into 4 groups, A1, A2, B1 and B2, for each model. An axial force of 74 N and a moment couple of 1.0 Nm were imposed on the C3 vertebra. The range of motion (ROM) of each segment and the stress distribution on the screw–vertebra interface, strut, and strut–endplate interface were recorded and analysed. Results There was no significant difference in ROM between Group A and Group B during bending, extension and rotation under 74 N axial pressure. The stress concentration on the strut body in Group A was higher than that in Group B. The peak stress values at the screw–vertebral interface in Groups A1 and A2 were higher than those in Groups B1 and B2, except for during extension and lateral bending. Under axial pressure, the peak stress values at the strut body–endplate interface during bending, extension and rotation were lower in the A1 and A2 groups than in the B1 and B2 groups. The Group B model showed much higher graft stress than the Group A model. Conclusions Based on finite-element analysis, compared with the old strut, the novel strut showed better biomechanical performance at the screw–vertebra interface.

The essence of fluid phase transition is the jump of physical properties distinctly induced by shock waves in the hard-sphere model. Due to the strong impact of the wave, the internal freedoms of molecules are stimulated, releasing tremendous energy that commonly triggers the phase transition. Conversely, typical thermal and dynamic jumps can be described by the Rankine–Hugoniot conditions based on the Euler equation. In the theoretical simulation, the initial density and rotational freedoms of molecules are directly regarded as the primary factors to affect processes of phase transition. However, the influence of vibrational freedom in molecules has not been discussed yet. As the increasing temperature can gradually excite the affection of vibrational freedom, it is unwise to assume that the temperature element is constant in the theory. What would be a suitable model that accurately reflects the relationship between temperature and affection from vibrational freedom? The non-limited model has been courageously attempted with the temperature range from T0 to 6T0 (T0 is unperturbed temperature). We have found that the vibrational freedom can have a great effect on properties during phase transition processes.

Background: In order to lessen the burden of Alzheimer's disease (AD), timely and efficient management and intervention methods for mild cognitive impairment (MCI) are crucial. MCI is seen as a transitional stage between normal aging and dementia. Although sarcopenia is an important risk factor for MCI, it is unclear what factors mediates and regulates the brain-muscle communication. Our objective was to investigate the indirect moderating effects of sleep duration and leisure activity on depressive symptoms, sarcopenia and MCI. Method: Panel data from the 2015 China Health and Retirement Longitudinal Study (CHARLS) database was used in this investigation. we used Bootstrap sampling to determine the relationship between sleep duration, leisure activity, depressive symptoms, sarcopenia, and MCI in mediation and indirect moderation models. The outcome measurements were odds ratio (OR) and confidence interval (CI). Result: After adjusting for confounding variables, we discovered that sarcopenia and its traits, such as handgrip strength, gait speed, standing test, and muscle mass, were significantly correlated with MCI. Second, the results implied that depressive symptoms played a role in modulating the link between physical function, muscle strength, and MCI. This moderating effect was impacted by short sleep duration and moderate to high levels of leisure activities. Conclusion: We discovered that MCI was highly correlated not only with physical function and muscle strength but also with depressed symptoms, which acted as a partially mediating factor in this connection. Handgrip strength, gait speed, and standing test mediated the correction of MCI caused by depression symptoms. Importantly, leisure activities and sleep duration had indirect moderating effects on the above associations, and future management policies should take these factors into account.

Abstract This single-arm, multi-center clinical trial aimed to evaluate the safety, tolerability, DLT, recommended dose (RD), preliminary efficacy, and pharmacokinetics (PK) characteristics of lurbinectedin, a selective inhibitor of oncogenic transcription, in Chinese patients with advanced solid tumors, including relapsed SCLC. Patients with advanced solid tumors were recruited in the dose-escalation stage and received lurbinectedin in a 3 + 3 design (two cohorts: 2.5 mg/m2 and 3.2 mg/m2, IV, q3wk). The RD was expanded in the following dose-expansion stage, including relapsed SCLC patients after first-line platinum-based chemotherapy. The primary endpoints included safety profile, tolerability, DLT, RD, and preliminary efficacy profile, while the secondary endpoints included PK characteristics. In the dose-escalation stage, ten patients were included, while one patient had DLT in the 3.2 mg/m2 cohort, which was also the RD for the dose-expansion stage. At cutoff (May 31, 2022), 22 SCLC patients were treated in the ongoing dose-expansion stage, and the median follow-up was 8.1 months (range 3.0–11.7). The most common grade ≥ 3 treatment-related adverse events (TRAEs) included neutropenia (77.3%), leukopenia (63.6%), thrombocytopenia (40.9%), anemia (18.2%), and ALT increased (18.2%). The most common severe adverse events (SAEs) included neutropenia (27.3%), leukopenia (22.7%), thrombocytopenia (18.2%), and vomiting (9.1%). No treatment-related deaths occurred. The Independent Review Committee (IRC)-assessed ORR was 45.5% (95% CI 26.9–65.3). Lurbinectedin at the RD (3.2 mg/m2) showed manageable safety and acceptable tolerability in Chinese patients with advanced solid tumors, and demonstrates promising efficacy in Chinese patients with SCLC as second-line therapy. Trial registration: This study was registered with ClinicalTrials.gov NCT04638491, 20/11/2020.

Abstract Mechanical force contributes to perforin pore formation at immune synapses, thus facilitating the cytotoxic T lymphocytes (CTL)-mediated killing of tumor cells in a unidirectional fashion. How such mechanical cues affect CTL evasion of perforin-mediated autolysis remains unclear. Here we show that activated CTLs use their softness to evade perforin-mediated autolysis, which, however, is shared by T leukemic cells to evade CTL killing. Downregulation of filamin A is identified to induce softness via ZAP70-mediated YAP Y357 phosphorylation and activation. Despite the requirements of YAP in both cell types for softness induction, CTLs are more resistant to YAP inhibitors than malignant T cells, potentially due to the higher expression of the drug-resistant transporter, MDR1, in CTLs. As a result, moderate inhibition of YAP stiffens malignant T cells but spares CTLs, thus allowing CTLs to cytolyze malignant cells without autolysis. Our findings thus hint a mechanical force-based immunotherapeutic strategy against T cell leukemia.

Abstract Background Programmed cell death protein 1 (PD-1) monoclonal antibody, pembrolizumab, is a promising drug for platinum-pretreated, recurrent or metastatic nasopharyngeal cancer (NPC). We aimed to assess the cost-effectiveness of pembrolizumab compared with chemotherapy for Chinese patients in this NPC. Methods The cost-effectiveness of pembrolizumab versus chemotherapy was evaluated using a partitioned survival model with a 5-year boundary. Efficacy and toxicity data were derived from the KEYNOTE-122 trials. Economic indicators including life-years (LYs), quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), and lifetime cost were used. One-way analysis and probabilistic sensitivity analysis (PSA) were performed to explore the uncertainties. Additionally, various scenario analyses, including different pembrolizumab price calculations and discount rates were performed. Results Pembrolizumab or chemotherapy alone respectively yielded 2.82 QALYs (3.96 LYs) and 2.73 QALYs (3.93 LYs) with an ICER of $422,535 per QALYs ($1,232,547 per LYs). This model was primarily influenced by the price of pembrolizumab. Furthermore, PSA indicated that pembrolizumab had none probability of being cost-effective compared with chemotherapy at a willingness-to- pay (WTP) of $38223. Scenario analyses revealed that irrespective of any potential price reduction or adjustments in the discount rate, no discernible impact on the ultimate outcome was observed. Conclusion Pembrolizumab was less cost-effective for patients with platinum-pretreated, recurrent or metastatic NPC compared with chemotherapy in China.

Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas, and between the neocortex and other regions of the brain and spinal cord. Appropriate development of cortical projection neurons is regulated by certain essential events such as neural fate determination, proliferation, specification, differentiation, migration, survival, axonogenesis, and synaptogenesis. These processes are precisely regulated in a tempo-spatial manner by intrinsic factors, extrinsic signals, and neural activities. The generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions (such as sensory information integration, motor coordination, and cognition) but also to prevent the onset and progression of neurodevelopmental disorders (such as intellectual disability, autism spectrum disorders, anxiety, and depression). This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.

The properties of fluid phase transition can be distinctly induced by shock-waves in the hard-sphere model. Typical thermal and dynamic characteristics of the fluid have been described by conditions in the Rankine–Hugoniot (RH) theory based on Euler equations. Due to the strong impact from shock-waves, states of excitation or even phase transition can be detected. However, various factors can influence the jump in the fluid, such as degrees of freedom in molecules. The simple hard-sphere model typically assumes three degrees, neglecting internal freedoms of particles. However, the effect of molecular rotation often plays a significant role under general conditions, influencing fluid phase transition. So, the rotational freedom of molecules has been taken into the thermal equations in this work. The excited state or phase transition of the fluid has been substantiated by using the RH theory, and we have found that internal freedoms of the fluid can have a dramatic effect on the physical properties during phase transition processes.

ObjectiveTo assess the impact of automated algorithms on the trainees’ decision-making capacity and confidence for individualized surgical planning.MethodsAt Chinese PLA General Hospital, trainees were enrolled to undergo decision-making capacity and confidence training through three alternative visual tasks of the inferior clivus model formed from an automated algorithm and given consecutively in three exemplars. The rationale of automated decision-making was used to instruct each trainee.ResultsFollowing automated decision-making calculation in 50 skull base models, we screened out three optimal plans, infra-tubercle approach (ITA), trans-tubercle approach (TTA), and supra-tubercle approach (STA) for 41 (82.00%), 8 (16.00%), and 1 (2.00%) subject, respectively. From September 1, 2023, through November 17, 2023, 62 trainees (median age [range]: 27 [26–28]; 28 [45.16%] female; 25 [40.32%] neurosurgeons) made a decision among the three plans for the three typical models (ITA, TTA, and STA exemplars). The confidence ratings had fine test-retest reliability (Spearman's rho: 0.979; 95% CI: 0.970 to 0.988) and criterion validity with time spent (Spearman's rho: −0.954; 95%CI: −0.963 to −0.945). Following instruction of automated decision-making, time spent (initial test: 24.02 vs. 7.13 in ITA; 30.24 vs. 7.06 in TTA; 34.21 vs. 12.82 in STA) and total hits (initial test: 30 vs. 16 in ITA; 37 vs. 17 in TTA; 42 vs. 28 in STA) reduced significantly; confidence ratings (initial test: 2 vs. 4 in ITA; 2 vs. 4 in TTA; 1 vs. 3 in STA) increased correspondingly. Statistically significant differences (P

Epitaxial thin films of fully nonequilibrium hcp-Ru50Mo50(0001) nanoalloys were prepared as a chemically disordered alloy, in which the intrinsic spin Hall effect is expected to be negligible. Structural analyses confirmed the epitaxial growth and atomic scale alloying of the films. In contrast to a tiny torque efficiency (ξDL) of ∼0.4% for Ru50Mo50/CoFeB, the ξDL for the Ru50Mo50/Ni heterostructure reached ∼30% with a long-range relaxation length. The apparent dependence of ξDL on the ferromagnetic layer can be attributed to the orbital Hall effect (OHE). Interestingly, a smaller ξDL was observed for Ru/Ni, suggesting that the nonequilibrium Ru50Mo50 enhances its OHE. Furthermore, the enhanced ξDL is maintained by inserting a Ru layer between the Ru50Mo50 and Ni layers, showing orbital transport through Ru. This finding illustrates potential applications of nonequilibrium nanoalloy films in spin orbitronics and contributes to getting insights into the understanding of the interrelationships between nanostructures and orbital transport properties.

Abstract Background To develop a prediction model for in-hospital mortality of patients with heart failure (HF) and atrial fibrillation (AF). Methods This cohort study extracted the data of 10,236 patients with HF and AF upon intensive care unit (ICU) from the Medical Information Mart for Intensive Care (MIMIC). The subjects from MIMIC-IV were divided into the training set to construct the prediction model, and the testing set to verify the performance of the model. The samples from MIMIC-III database and eICU-CRD were included as the internal and external validation set to further validate the predictive value of the model, respectively. Univariate and multivariable Logistic regression analyses were used to explore predictors for in-hospital death in patients with HF and AF. The receiver operator characteristic (ROC), calibration curves and the decision curve analysis (DCA) curves were plotted to evaluate the predictive values of the model. Results The mean survival time of participants from MIMIC-III was 11.29 ± 10.05 days and the mean survival time of participants from MIMIC-IV was 10.56 ± 9.19 days. Simplified acute physiology score (SAPSII), red blood cell distribution width (RDW), beta-blocker, race, respiratory rate, urine output, coronary artery bypass grafting (CABG), Charlson comorbidity index, renal replacement therapies (RRT), antiarrhythmic, age, and anticoagulation were predictors finally included in the prediction model. The AUC of our prediction model was 0.810 (95%CI: 0.791–0.828) in the training set, 0.757 (95%CI: 0.729–0.786) in the testing set, 0.792 (95%CI: 0.774–0.810) in the internal validation set, and 0.724 (95%CI: 0.687–0.762) in the external validation set. The calibration curves of revealed that the predictive probabilities of our model for the in-hospital death in patients with HF and AF deviated slightly from the ideal model. The DCA curves revealed that the use of our prediction model increased the net benefit than use no model. Conclusion The prediction model had good discriminative ability, and might provide a tool to timely identify patients with HF complicated with AF who were at high risk of in-hospital mortality.

Background: Rezvilutamide, a novel androgen-receptor inhibitor with limited blood-brain barrier penetration, exhibits significant antitumour activity against highvolume, metastatic, hormone-sensitive prostate cancer (mHSPC). In this study, we aimed to compare the cost-effectiveness of rezvilutamide and bicalutamide as first-line treatments for untreated prostate cancer among Chinese patients, in order to evaluate the efficacy of rezvilutamide.Methods: In this study, we utilized partition survival model to assess the cost-effectiveness of rezvilutamide and bicalutamide treatments for highvolume mHSPC. The model was developed using TreeAge Pro 2022 software and relied on clinical data obtained from the CHART trial. Transition probabilities were estimated from the reported survival probabilities in trials using parametric survival modeling. From the perspective of the Chinese healthcare system, we calculated quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), and lifetime cost. A lifetime horizon and an annual discount rate of 5% were employed. To address modeling uncertainties, we conducted one-way sensitivity analysis and probabilistic sensitivity analysis.Results: The cost of rezvilutamide versus bicalutamide were $62700 and $13200. Rezvilutamide had an ICER of $41900 per additional QALYs gained compared with bicalutamide. Research indicated that rezvilutamide achieved at least an 28.20% probability of cost-effectiveness at the threshold of $38223.34/QALY. One-way sensitivity analysis revealed that the results were sensitive to utility of PD. Scenario analysis showed that rezvilutamide was cost-effectiveness if its price was reduced by more than 10%.Conclusion: Based on the analysis at the current price, rezvilutamide was found to be less cost-effective for patients with highvolume mHSPC compared to bicalutamide in China.

Copper-doped Zinc Tellurium (ZnTe:Cu) films were deposited on borosilicate glass using magnetron co-sputtering technique. The influence of the substrate temperature on the structural, morphological, optical and electrical properties of ZnTe:Cu films was investigated by X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), UV–Vis spectrophotometer and Hall effect measurement system. The results indicate that substrate temperature significantly affects the properties of the ZnTe:Cu films. When the substrate temperature increases from room temperature to 600 °C, the (111)-preferred orientation of ZnTe:Cu films is gradually replaced by the (220)-preferred orientation. At high substrate temperatures (≥500 °C), the CuxTe phase appears in the ZnTe:Cu films, resulting in higher carrier concentration (>1019 cm−3) and lower resistivity (

The dynamic phase transition of fluid has been specifically induced by the shockwave within the context of the hard-sphere model. Fundamental thermal and dynamic attributes of the fluid have been primarily examined, and the conditions following the Rankine–Hugoniot (RH) theory have been applied using the Euler equations. Due to the magnitude of the shockwave’s impact on the undisturbed equilibrium of the fluid, three archetypal states of excitation are manifested, encompassing liquid–liquid, liquid–solid, and liquid-coexistence states, categorized according to RH conditions subsequent to the influence of the shockwave. The characteristics of the fluid are portrayed employing the hard-sphere model, while the excited state of the fluid has been substantiated through an inquiry into the RH conditions and the generation of entropy. In consonance with the research, the excited state of the fluid exhibits a robust interrelation with its unperturbed equilibrium. The hard-sphere model stands as a suitable framework for examination of the shock-induced phase transition of the fluid.

The biological effect of irradiation is not solely determined by the physical dose. Gamma knife radiosurgery may be influenced by dose rate, beam-on-time, numbers of iso-centers, the gap between the individual iso-centers, and the dose‒response of various tissues. The biologically effective dose (BED) for radiosurgery considers these issues. Millions of patients treated with Models B and C provide a vast database to mine BED-related information. This research aims to develop MatBED_B&C, a 3-dimensional (3D) BED analytic approach, to generate a BED for individual voxels in the calculation matrix with related parameters extracted from Gammaplan. This approach calculates the distribution profiles of the BED in radiosurgical targets and organs at risk. A BED calculated on a voxel-by-voxel basis can be used to show the 3D morphology of the iso-BED surface and visualize the BED spatial distribution in the target. A 200 × 200 × 200 matrix can cover a greater range of the organ at risk. The BED calculated by MatBED_B&C can also be used to form BED-volume histograms to generate plan quality metrics, which will be studied in a retrospective study of gamma knife radiosurgery to guide future BED planning. • We develop MatBED_B&C to calculate the 3D BED in radiosurgical targets. • The BED of MatBED_B&C can visualize the BED spatial distribution profiles. • The BED of MatBED_B&C will generate plan quality metrics studied in a retrospective study.

Data trust is regarded as a new and credible data transaction model.Data trust is not only an organizational structure to guarantee information security, but also an innovative institutional design to enhance the trustworthiness of data factor market.A data trust operation mechanism was designed, and the organizational structure, characteristics, functions, and regulatory scheme of the data trust under this mechanism were discussed.That data trust contained two independent legal relationships were pointed out.Its most important feature was the risk segregation among participants, which was the basis of data trust as a credible data transaction model.Data trusts could play an important function in the data value chain, specifically in terms of data value addition, data escrow, and data commons.Finally, the unique advantages of data trust based on the institutional guidelines of “20 measures to build basic systems for data” were demonstrated, and that personal data trust and public data trust were feasible practical paths was pointd out.

BackgroundGlobally, type 2 diabetes mellitus (T2DM) accounts for approximately 90% of diabetes cases. Resistance training (RT) is frequently employed to diminish Glycated Hemoglobin (HbA1c) and Fast Blood Glucose (FBG) levels in T2DM patients. Yet, the specific dose-response relationships between RT variables such as training duration, frequency, and intensity for T2DM remain under-researched.ObjectivesThis meta-analysis aimed to elucidate the overarching effects of RT on HbA1c and FBG metrics and to provide dose-response relationships of RT variables. This was achieved by examining randomized controlled trials (RCTs) that reported reductions in HbA1c and FBG among T2DM patients.MethodsComprehensive literature searches were conducted up to 25th February 2023 across databases including EMBASE, Pubmed, Cochrane, CENTRAL, Web of Science, CNKI, Wanfang Data, VIP Database for Chinese Technical Periodicals, and the Chinese Biomedical Database. The Physical Therapy Evidence Database (PEDro) was leveraged to appraise the quality of selected studies based on predefined inclusion and exclusion criteria. The meta-analysis was conducted using Stata 16.Results26 studies that include 1336 participants met the criteria for inclusion. RT significantly reduced HbA1c and FBG levels in comparison to control groups (P

The hippocampus executes crucial functions from declarative memory to adaptive behaviors associated with cognition and emotion. However, the mechanisms of how morphogenesis and functions along the hippocampal dorsoventral axis are differentiated and integrated are still largely unclear. Here, we show that Nr2f1 and Nr2f2 genes are distinctively expressed in the dorsal and ventral hippocampus, respectively. The loss of Nr2f2 results in ectopic CA1/CA3 domains in the ventral hippocampus. The deficiency of Nr2f1 leads to the failed specification of dorsal CA1, among which there are place cells. The deletion of both Nr2f genes causes almost agenesis of the hippocampus with abnormalities of trisynaptic circuit and adult neurogenesis. Moreover, Nr2f1/2 may cooperate to guarantee appropriate morphogenesis and function of the hippocampus by regulating the Lhx5-Lhx2 axis. Our findings revealed a novel mechanism that Nr2f1 and Nr2f2 converge to govern the differentiation and integration of distinct characteristics of the hippocampus in mice.

The high-pressure rotary jet pile construction method has been widely used in airport projects, particularly in regions with soft soil foundations, such as coastal areas. The method’s primary aim is to establish a sound foundation bearing capacity. However, the conventional machinery used in constructing high-pressure rotary jet piles lacks automation. Therefore, it is necessary to find a method to achieve automatic monitoring of the construction quality of high-pressure rotary jet pile. To achieve real-time quality control in high-pressure rotary jet pile construction, the development of high-pressure rotary jet pile construction data acquisition and monitoring equipment is made possible by integrating key technologies such as the global navigation satellite system (GNSS), the Internet of Things and massive data processing. The acquisition and storage of crucial construction parameters, such as the drilling position, drill rod verticality, drilled hole depth, grouting pressure, grouting lifting speed and grouting volume for high-pressure rotary jet piles is successfully implemented in this paper. A large amount of actual construction data is collected through an on-site application, and the construction quality of the high-pressure rotary jet pile machine is monitored and analyzed using geographic information system (GIS) technology. Actual applications demonstrate that the proposed digital monitoring model and method for rotary jet pile construction quality control is viable, improves the on-site management level and efficiency and has significant future value.

The large-scale grid connection of renewable energy is an inevitable trend to realize the low-carbon development of the power system. Therefore, the impact of the uncertainty of high-energy enterprise load and renewable energy on the establishment of the maintenance strategy of power grid units cannot be ignored. Previous research methods usually only consider the grid side or the load side. Therefore, this paper proposes a method to determine the maintenance strategy of the unit through the information exchange between the grid side and the load side, while taking into account the impact of the uncertainty of renewable energy on the system. Introducing the tiered carbon transaction cost into the objective function can reduce the system’s carbon emissions and increase the consumption of renewable energy. When establishing the grid-side model, the relevant constraints of robust performance are added, and the influence of the uncertainty of the wind turbine is fully considered. The results of the calculation example show that the unit maintenance strategy established after considering the uncertainty of high-energy enterprises and renewable energy sources has good economic efficiency.

Abstract Macrophages in tumors (tumor-associated macrophages, TAMs), a major population within most tumors, play key homeostatic functions by stimulating angiogenesis, enhancing tumor cell growth, and suppressing antitumor immunity. Resetting TAMs by simple, efficacious and safe approach(s) is highly desirable to enhance antitumor immunity and attenuate tumor cell malignancy. Previously, we used tumor cell-derived microparticles to package chemotherapeutic drugs (drug-MPs), which resulted in a significant treatment outcome in human malignant pleural effusions via neutrophil recruitments, implicating that drug-MPs might reset TAMs, considering the inhibitory effects of M2 macrophages on neutrophil recruitment and activation. Here, we show that drug-MPs can function as an antitumor immunomodulator by resetting TAMs with M1 phenotype and IFN-β release. Mechanistically, drug molecules in tumor MPs activate macrophage lysosomal P450 monooxygenases, resulting in superoxide anion formation, which further amplifies lysosomal ROS production and pH value by activating lysosomal NOX2. Consequently, lysosomal Ca2+ signaling is activated, thus polarizing macrophages towards M1. Meanwhile, the drug molecules are delivered from lysosomes into the nucleus where they activate DNA sensor hnRNPA2B1 for IFN-β production. This lysosomal-nuclear machinery fully arouses the antitumor activity of macrophages by targeting both lysosomal pH and the nuclear innate immunity. These findings highlight that drug-MPs can act as a new immunotherapeutic approach by revitalizing antitumor activity of macrophages. This mechanistic elucidation can be translated to treat malignant ascites by drug-MPs combined with PD-1 blockade.

Abstract On 11th Jan 2020, the first COVID-19 related death was confirmed in Wuhan, Hubei. The Chinese government responded to the outbreak with a lockdown that impacted most residents of Hubei province and lasted for almost three months. At the time, the lockdown was the strictest both within China and worldwide. Using an interactive web-based experiment conducted half a year after the lockdown with participants from 11 Chinese provinces, we investigate the behavioral effects of this ‘shock’ event experienced by the population of Hubei. We find that both one’s place of residence and the strictness of lockdown measures in their province are robust predictors of individual social distancing behavior. Further, we observe that informational messages are effective at increasing compliance with social distancing throughout China, whereas fines for noncompliance work better within Hubei province relative to the rest of the country. We also report that residents of Hubei increase their propensity to social distance when exposed to social environments characterized by the presence of a superspreader, while the effect is not present outside of the province. Our results appear to be specific to the context of COVID-19 and are not explained by general differences in risk attitudes and social preferences.

Objective The type AO B2 thoracolumbar fracture is a kind of flexion‐distraction injury and the effect of disc injury on treatment results of patients with B2 fracture remains unclear. The objective of the current study was to compare and analyze the outcomes in AO Type B2 thoracolumbar fracture patients with and without disc injuries in terms of the Cobb angle of kyphosis, the incidence of complication, and the rate of implant failure. Methods This is a retrospective study. Of the 486 patients with thoracolumbar fractures who underwent posterior fixation, 38 patients with AO type B2 injuries were included. All the patients were divided into two groups according to changes in the adjoining discs. Disc injury group A included 17 patients and no disc injury group included 21 patients. Clinical and radiologic parameters were evaluated before surgery, after surgery, and at follow‐up. Clinical outcomes included visual analogue scale (VAS) scores, incidence of complications, and incidence of implant failure. Radiologic assessment was accomplished with the Cobb angle (CA), local kyphosis (LK), percentage of anterior vertebral height (AVBH%), intervertebral disc height, and intervertebral disc angle. Fisher's precision probability tests were employed and chi square test were used to compare categorical variables. Paired sample t tests and independent‐sample t tests were used to compare continuous data. Results Disc injury mainly involved the cranial disc (15/19, 78.9%). The mean follow‐up period for the patients was 30.2 ± 20.1 months. No neurologic deterioration was reported in the patients at the last follow‐up. Radiological outcomes at the last follow‐up showed significant differences in the CA (18.59° ± 13.74° vs 8.16° ± 9.99°, P = 0.008), LK (12.74° ± 8.00° vs 6.55° ± 4.89°, P = 0.006), and %AVBH (77.16% vs 90.83%, P = 0.01) between the two groups.Implant failure occurred after posterior fixation in five patients with disc injury who did not undergo interbody fusion during the initial surgery. Additionally, in the subgroup analysis, interbody fusion in the implant failure group were significantly different than in the no implant failure group (0% vs 75%, P = 0.009). Conclusions AO B2 fracture patients with disc injury have higher risk of complications, especially implant failure after posterior surgery. Interbody fusion should be considered in AO type B2 fracture patients with disc injury.

BackgroundThe incidence and mortality rates of stroke are escalating due to the growing aging population, which presents a significant hazard to human health. In the realm of stroke, brain-computer interface (BCI) technology has gained considerable attention as a means to enhance treatment efficacy and improve quality of life. Consequently, a bibliometric visualization analysis was performed to investigate the research hotspots and trends of BCI technology in stroke, with the objective of furnishing reference and guidance for future research.MethodsThis study utilized the Science Citation Index Expanded (SCI-Expanded) within the Web of Science Core Collection (WoSCC) database as the data source, selecting relevant literature published between 2013 and 2022 as research sample. Through the application of VOSviewer 1.6.19 and CiteSpace 6.2.R2 visualization analysis software, as well as the bibliometric online analysis platform, the scientific knowledge maps were constructed and subjected to visualization display, and statistical analysis.ResultsThis study encompasses a total of 693 relevant literature, which were published by 2,556 scholars from 975 institutions across 53 countries/regions and have been collected by 185 journals. In the past decade, BCI technology in stroke research has exhibited an upward trend in both annual publications and citations. China and the United States are high productivity countries, while the University of Tubingen stands out as the most contributing institution. Birbaumer N and Pfurtscheller G are the authors with the highest publication and citation frequency in this field, respectively. Frontiers in Neuroscience has published the most literature, while Journal of Neural Engineering has the highest citation frequency. The research hotspots in this field cover keywords such as stroke, BCI, rehabilitation, motor imagery (MI), motor recovery, electroencephalogram (EEG), neurorehabilitation, neural plasticity, task analysis, functional electrical stimulation (FES), motor impairment, feature extraction, and induced movement therapy, which to a certain extent reflect the development trend and frontier research direction of this field.ConclusionThis study comprehensively and visually presents the extensive and in-depth literature resources of BCI technology in stroke research in the form of knowledge maps, which facilitates scholars to gain a more convenient understanding of the development and prospects in this field, thereby promoting further research work.

BackgroundSelf-rated health (SRH), interviewer-rated health (IRH), and objective health reflect the overall health status from different aspects. This study aimed to investigate the associations of SRH, IRH, and objective health with mortality among Chinese older adults.MethodsThis study used data from the 2008 (baseline), 2011, 2014 and 2018 waves of the Chinese Longitudinal Healthy Longevity Survey. SRH and IRH were evaluated by questionnaire. Objective health was evaluated by the Chinese multimorbidity-weighted index (CMWI), which incorporated 14 diagnosed chronic diseases. SRH, IRH, and CMWI were assessed as: (1) baseline levels; (2) longitudinal changes by subtracting the values obtained in 2008 from the corresponding values in 2014; (3) trajectories by Group-Based Trajectory Modeling, respectively. The Cox proportional hazards model was used to explore the associations of baseline SRH, IRH, and CMWI, their changes, and trajectories with mortality.ResultsA total of 13,800 participants were included at baseline (2008). The baseline SRH ([hazard ratio] 0.93, [95% confidence interval] 0.91–0.96), IRH (0.84, 0.81–0.87), and CMWI (0.99, 0.98–1.00) in 2008 were significantly associated with 10-year mortality (2008 to 2018). Among 3,610 participants, the changes of SRH (0.93, 0.87–0.98), IRH (0.77, 0.71–0.83), and CMWI (0.97, 0.95–0.99) from 2008 to 2014 were significantly associated with 4-year mortality (2014–2018). The trajectories were divided into “high SRH/IRH/CMWI” and “low and declining SRH/IRH/CMWI.” Compared with “low and declining SRH/IRH/CMWI,” “high SRH” (0.58, 0.48–0.70), “high IRH” (0.66, 0.55–0.80), and “high CMWI” (0.74, 0.61–0.89) from 2008 to 2014 were significantly associated with 4-year mortality (2014–2018).ConclusionBaseline SRH, IRH, and CMWI, their changes and trajectories are all associated with mortality in Chinese older adults. It is possibly necessary to promote the use of cost-effective indicators in primary medical institutions to improve the health management of the older adults.

Rice-based Baijiu has gained popularity in the Chinese market. Qingya-flavored Baijiu, a variant of Xiaoqu-fermented Baijiu, employs rice as its primary raw material, with an improved production process compared to traditional rice-flavored Baijiu. We comprehensively characterized and compared the aroma profiles of these two rice-based Baijiu types using static sensory experiments (QDA, quantitative descriptive analysis) and dynamic sensory experiments (TDS, temporal dominance of sensations). Qingya-flavored Baijiu exhibited pronounced plant, oily, and roasted aromas, while traditional rice-flavored Baijiu displayed more prominent fruity, floral, and sour notes. Utilizing GC-O-MS (gas chromatography-olfactometry–mass spectrometry) and multi-method quantification, we qualitatively and quantitatively analyzed 61 key aroma compounds, identifying 22 compounds with significant aroma contributions based on odor activity values (OAVs). Statistical analyses, combining sensory and chemical results, were conducted to predict important aroma compounds responsible for the aroma differences between the two Baijiu types. Aroma Recombination and Omission experiments showed that seven compounds play key roles in the aroma of Qingya-flavored Baijiu, including (2E,4E)-Deca-2,4-dienal, linalool, apricolin, ethyl acetate, ethyl isobutyrate, ethyl caprylate, and ethyl isovalerate.

This work aimed to compare the aroma characteristics of representative brandies with different grades from Yantai (one of the Chinese core production areas) and Cognac and to establish relationships between sensory descriptors and chemical composition. Descriptive analysis was performed with a trained panel to obtain the sensory profiles. Forty-three aroma-active compounds were quantified by four different methodologies. A prediction model on the basis of partial least squares analysis was performed to identify candidate compounds that were unique to a certain group of brandies. The result showed that brandies from Yantai could be distinguished from Cognac brandies on the basis of spicy, dried fruit, floral, and fruity-like aromas, which were associated with an aromatic balance between concentrations of a set of compounds such as 5-methylfurfural, γ-nonalactone, and γ-dodecalactone. Meanwhile, brandy with different grades could be distinguished on the basis of compounds derived mostly during the aging process.

Abstract In the present study, two mitogenomes from the Filobasidium genus were assembled and compared with other Tremellomycetes mitogenomes. The mitogenomes of F. wieringae and F. globisporum both comprised circular DNA molecules, with sizes of 27,861 bp and 71,783 bp, respectively. Comparative mitogenomic analysis revealed that the genetic contents, tRNAs, and codon usages of the two Filobasidium species differed greatly. The sizes of the two Filobasidium mitogenomes varied greatly with the introns being the main factor contributing to mitogenome expansion in F. globisporum. Positive selection was observed in several protein-coding genes (PCGs) in the Agaricomycotina, Pucciniomycotina, and Ustilaginomycotina species, including cob, cox2, nad2, and rps3 genes. Frequent intron loss/gain events were detected to have occurred during the evolution of the Tremellomycetes mitogenomes, and the mitogenomes of 17 species from Agaricomycotina, Pucciniomycotina, and Ustilaginomycotina have undergone large-scale gene rearrangements. Phylogenetic analyses based on Bayesian inference and the maximum likelihood methods using a combined mitochondrial gene set generated identical and well-supported phylogenetic trees, wherein Filobasidium species had close relationships with Trichosporonales species. This study, which is the first report on mitogenomes from the order Filobasidiales, provides a basis for understanding the genomics, evolution, and taxonomy of this important fungal group.

Abstract Background A retrospective study compared the results of a lamina with spinous process (LSP) and an iliac graft (IG) as bone grafts in single-segment lumbar pyogenic spondylodiscitis (LPS) through one-stage-posterior-only approach with radical debridement and instrumentation. Methods A LSP was placed in 17 patients (group A), and an IG was implemented in 20 patients (group B). The surgery time, surgery hemorrhage, hospital stay, drainage, and follow-up (FU) were recorded and compared. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, visual analogue scale (VAS), Oswestry Disability Index (ODI), segmental angle, intervertebral height and bony fusion time were compared preoperatively and at the final FU. Results All patients were followed-up for a mean of 27.94 ± 2.35 months in group A and 30.29 ± 1.89 months in group B, without a difference. The mean age was younger in group A than in group B (P

Real-time monitoring and accurate prediction of toxic gas concentration in the future are of great significance for emergency capability assessment and rescue work. At present, the method of gas concentration prediction based on artificial intelligence still has problems of low accuracy, slow convergence speed and equal feature importance. This paper proposes a feature-aware LSTM model to predict pollutant gas concentration. First of all, we design a set of multi-component toxic gas monitoring equipment that applies in pollution environment, which can at the same time monitor CO, NO2, NH3, HCN, H2S and SO2, six common pollutants; To accurate estimate the toxic gas concentration, we combine the collected the gas data and the environmental parameters and regard them as the input features, and then we obtain toxic gas data based on the sampling policy and the environmental data as our data-set. Finally, we train a FA-LSTM gas concentration prediction model on these data-set. We test the proposed model and compared with ARIMA, ETS and BP network on the same test set. Experimental results show that the proposed model outperforms traditional concentration prediction model. Also, it is better than other state-of-the-art models in predicting accuracy.

Abstract Background The three-dimensional (3D) visualization model has ability to quantify the surgical anatomy of far-lateral approach. This study was designed to disclose the relationship between surgical space and exposed tissues in the far-lateral approach by the volumetric analysis of 3D model. Methods The 3D skull base models were constructed using MRI and CT data of 15 patients (30 sides) with trigeminal neuralgia. Surgical corridors of the far-lateral approach were simulated by triangular pyramids to represent two surgical spaces exposing bony and neurovascular tissues. Volumetric comparison of surgical anatomy was performed using pair t test. Results The morphometric results were almost the same in the two surgical spaces except the vagus nerve (CN X) exposed only in one corridor, whereas the volumetric comparison represented the statistical significant differences of surgical space and bony and neurovascular tissues involved in the two corridors (P

Fiber optic sensors are often used as acoustic sensors to detect sound waves because of their apparent advantages, such as anti-electromagnetic interference and strong adaptation to the environment. The transverse vibration mode of the fiber caused by the acoustic wave can be obtained, and the principle of the optical fiber sensor to detect the acoustic wave signal was explored by using a simple model. It is found that the acoustic wave can effectively cause the change in birefringence of the fiber only when the number of azimuthal modes is 2, and the acoustic wave was detected by using a fiber sensor. It is found, by analyzing the detection mechanism, that the spectral width is proportional to the acoustic impedance of the surrounding medium, and the acoustic interaction between the TR22 mode and the surrounding medium is much weaker than that of the TR21 mode. This provides a theoretical basis for the detection of acoustic signals by fiber optic sensors.

Abstract Background A retrospective study investigated the degeneration trend of uncovertebral joints in a healthy population based on CT assessment. Methods A total of 200 males and 160 females, aged 21–79 years old (50.82 ± 17.06), who underwent CT examination in our hospital from September 2020 to March 2021 were enrolled. Sixty patients were included in each age group. According to the Kellgren and Lawrence classification and CT was used to evaluate the uncovertebral joints degeneration in different groups. Results With the increase of age, the degeneration of each segment was gradually aggravated. The uncovertebral joints started degenerating in the 20 s, and the C5–6 is the most degenerative segment, followed by the C4–5 and C6–7. Significant degeneration occurred in each segment between the 40 s and 60 s and became more severe after the 70 s. Conclusions The modified Kellgren and Lawrence classification based on CT scan could provide a quantitative assessment of uncovertebral joints degeneration in a healthy population and could provide more details for artificial cervical arthroplasty.

Abstract This work reports on Ni and Fe doping and interface effects on spin–orbit torques (SOTs) generated from a topological semimetal CoSi. CoSi thin films grown on Al2O3(0001) substrates by magnetron co‐sputtering show the B20 structure with a texture in the [210] orientation even after Ni or Fe doping. The SOTs from the films exerted on the magnetization of a CoFeB layer are evaluated by harmonic Hall and spin‐torque ferromagnetic resonance measurements. The spin Hall efficiency ξSH of the textured B20‐CoSi at room temperature is determined to be 9.6%, which decreases to 1.8% for Ni0.15Co0.85Si and to 5.5% for Fe0.26Co0.74Si. The electrical conductivity dependence of the spin Hall conductivity is assigned to the regime of intrinsic mechanism of spin Hall effect, suggesting that the reduction of ξSH with the element doping can be due to the degradation in topological electronic structures of CoSi. Furthermore, inserting a Cu layer at the Co(Ni, Fe)Si/CoFeB interface results in an increase of the ξSH up to 10.9% for CoSi, 4.0% for Ni0.15Co0.85Si, and 8.3% for Fe0.26Co0.74Si. These enhancements of the ξSH can be attributed to the improvement in the interfacial spin transparency between the Co(Ni, Fe)Si and CoFeB layers.

Activity distance, which is commonly used to describe the transformation from a bound state to a transition state in the potential energy landscape model, is the key factor in the bio-molecular system to study dynamic properties. Adopted both in phenomenological theory and the statistical model, activity distance is the fundamental parameter to describe the kinetic characteristics of bio-molecules and is usually connected with the change in the pulling force F. The effects of activity distance Δx‡ are easy to be detected in a single dimensional landscape model because the force only expresses the mechanical work −Fx, which mainly overlaps with the fluctuation of the configuration of bio-molecules. However, as the force cannot affect the transformation directly in the multidimensional landscape model, the deflection angle φ is introduced in our work to discuss the pulling force, which has partial effects on the Q dimension. By comparing the mean waiting time ⟨t⟩ under the conditions of normal kinetics and dynamic disorder, in this study, we show the typical results from the effects of activity distance on the multidimensional potential energy model.

Genome-wide association study (GWAS) has identified thousands of single nucleotide polymorphisms (SNPs) associated with complex diseases and traits. However, deciphering the functions of these SNPs still faces challenges. Recent studies have shown that SNPs could alter chromatin accessibility and result in differences in tumor susceptibility between individuals. Therefore, systematically analyzing the effects of SNPs on chromatin accessibility could help decipher the functions of SNPs, especially those in non-coding regions. Using data from The Cancer Genome Atlas (TCGA), chromatin accessibility quantitative trait locus (caQTL) analysis was conducted to estimate the associations between genetic variants and chromatin accessibility. We analyzed caQTLs in 23 human cancer types and identified 9,478 caQTLs in breast carcinoma (BRCA). In BRCA, these caQTLs tend to alter the binding affinity of transcription factors, and open chromatin regions regulated by these caQTLs are enriched in regulatory elements. By integrating with eQTL data, we identified 141 caQTLs showing a strong signal for colocalization with eQTLs. We also identified 173 caQTLs in genome-wide association studies (GWAS) loci and inferred several possible target genes of these caQTLs. By performing survival analysis, we found that ~10% caQTLs potentially influence the prognosis of patients. To facilitate access to relevant data, we developed a user-friendly data portal, BCaQTL (http://gong_lab.hzau.edu.cn/caqtl_database), for data searching and downloading. Our work may facilitate fine-map regulatory mechanisms underlying risk loci of cancer and discover the biomarkers or therapeutic targets for cancer prognosis. The BCaQTL database will be an important resource for genetic and epigenetic studies.

Background: The cure rates of Helicobacter pylori (H. pylori) treatment using a proton pump inhibitor (PPI) are gradually decreasing due to antibiotic resistance, poor compliance, high gastric acidity, and cytochrome P450 2C19 (CYP2C19) polymorphism, and the effects of PPI depend on metabolic enzymes, cytochrome P450 enzymes. The aim of this meta-analysis was to determine whether CYP2C19 polymorphisms affect H. pylori cure rates in patients treated with different proton pump inhibitors (PPIs) according to stratified analysis.Materials and methods: The literature was searched with the key words “H. pylori” and “CYP2C19” in PubMed, CNKI, and Wanfang up to 31 May 2022, and the studies were limited to clinical observational or randomized controlled trials (RCTs). Finally, seven RCTs and 29 clinical observational studies met the inclusion criteria and were used for the meta-analysis via STATA version 16.Results: The cure rates were significantly different between genotypes of homozygous extensive metabolizers (EM) and poor metabolizers (PM) (OR = 0.58, 95% CI: 0.47–0.71) and between EM and heterozygous extensive metabolizers (IM) (OR = 0.71, 95% CI: 0.59–0.86), but not between IM and PM. Moreover, there was a significantly lower H. pylori cure rate in EM subjects than that in IM subjects when treated with omeprazole (66.4% vs. 84.1%), lansoprazole (76.1% vs. 85.6%), but not rabeprazole, esomeprazole, or pantoprazole. In addition, there was a significantly lower H. pylori cure rate in EM subjects than that in IM subjects when treated with a PPIs for 7 days (77.4% vs. 82.1%), but not 14 days (85.4% vs. 90.0%).Conclusion: Carriers of CYP2C19 loss-of-function variant alleles (IM and PM) exhibit a significantly greater cure rate of H. pylori than noncarriers (EM) regardless of other factors (84.7% vs. 79.2%). In addition, pantoprazole- and rabeprazole-based quadruple therapy for H. pylori treatment is less dependent on the CYP2C19 genotype and should be prioritized in Asian populations with H. pylori.

Because of affections from fluctuation, the migration or reaction rate of bio-molecules is mainly related to the time-memory effect. This kinetic phenomenon is primarily dominated by dynamic ductility and molecular crowding in the solvent. These two important elements directly connect with the affections of the random force and systematic friction (ζ) in a real solvent. They can affect fluctuation characteristics of bio-molecules. Properties of bio-molecular kinetics are mainly submitted to the configuration quality and random collision. The multidimensional landscape must be needed in typical research processes for kinetics of bio-molecules. The random collision affection in the x dimension and the typical ductility for the free-energy surface in the Q dimension have been abstracted in our work. The two-dimensional generalized Langevin equation including fractional Gaussian noise or white noise is used to study the migration rate or the mean waiting time. The essential quality of the bio-molecules’ kinetic properties can be revealed by the comparative study between dynamic disorder (DD) and common diffusion. We have found that there are sharp dynamic differences between DD and normal kinetics. Moreover, dynamic ductility and solvent friction can lead to great affections to the bio-molecular dynamics.

Abstract Background Spatial variation of land cover can result in the changes of community similarities and biotic homogenization, whereby the increasing similarity would reduce the adaptive capacity of biotic assemblages to further disturbance, and degenerate ecosystem services they offer. However, it remains scarce to integrate multidimensional diversity for unveiling how variations in land cover may influence the patterns and processes of biotic homogenization in the Anthropocene. In this study, we examined how spatial variation of land cover could alter taxonomic, phylogenetic and functional homogenization of bird communities simultaneously in a compound ecosystem of Zoige Marsh on the eastern Qinghai-Tibetan Plateau. Acting as the largest alpine marsh and peatland in the world, Zoige Marsh has undergone great changes in the land cover pattern due to climate change and anthropogenic activities. Methods We conducted transect surveys for bird communities over six years (2014‒2019) during breeding seasons in four main land cover types (meadow, woodland, village and marsh), representing the spatial variation of land covers in the study area. We compared multidimensional diversity (taxonomic, phylogenetic and functional diversity) among land covers to assess the effects of spatial variation in land cover type on bird communities, particularly whether this variation has homogenized biotic communities. Results Bird communities during breeding seasons were different and complementary in the four land covers. Taxonomic, phylogenetic and functional similarities were significantly lower in meadow than in the other three types, i.e. woodland, village and marsh. However, when we controlled for the effects of taxonomic similarities, the pattern of phylogenetic similarities almost reversed, with the highest standardized effect size (SES) phylogenetic similarity in meadow; and we found no significant difference in SES functional similarity among land covers. Conclusions Our results suggest that spatial variation of land cover can play a crucial role in regulating multiple dimensions of bird diversity in Zoige Marsh. The findings indicate that taxonomic, phylogenetic and functional homogenization of bird communities may differently response to the variation of land covers. It thus highlights not only the relative roles of different land covers in maintaining biodiversity and community structures of birds, but also the urgency of retarding ecosystem degradations on the eastern Qinghai-Tibetan Plateau.

With the rapid advance of industrialization and urbanization and the intensified impact of global climate change, the contradiction between the global water shortage and economic growth has become prominent. This paper, taking Henan province as an example, analyzed the influence of water resource policy on regional economic growth through a calculable general equilibrium model and further discussed the relevant policy recommendations. The results showed that the improvement of water supply, water efficiency and water technology could promote the growth of the regional economy and result in a positive effect on regional GDP, employment and resident income. However, the rise of water price has a negative impact on regional economic development, mainly reflected in regional GDP, employment and household income. The improvement of water price, water efficiency and water conservancy technology would lead to a decrease in regional water consumption, while only the increase of the water supply would lead to an increase in water consumption. Accordingly, the paper puts forward policy suggestions, such as accelerating the improvement of water conservancy facilities, establishing a reasonable water price mechanism and actively exploring experience in water conservation and emission reduction. Highlights The quantitative analysis method is used to simulate the impact of four policy changes of water supply, water price, water-use efficiency and water conservancy technology on the main regional economic indicators.; The aim of this move is to reflect the effect and potential impact of future policy changes and put forward policy suggestions for appropriate adjustment of relevant policy programs.;

Abstract Objective To explore the clinical efficacy of posterior LFF for cervical OPLL with radicular pain of upper limbs Methods Between January 2014 and January 2018, 48 OPLL patients with radicular pain symptoms of upper limbs who underwent a one-stage posterior laminectomy and instrumented fusion with/without foraminotomy were reviewed retrospectively and divided into two groups: LF group (laminectomy with instrumented fusion without foraminotomy) and LFF group (laminectomy with instrumented fusion and foraminotomy). Clinical data were assessed and compared between the two groups. The radicular pain of upper limbs and neck was measured using the visual analog scale (VAS). The neurological function was evaluated with the American Spinal Injury Association (ASIA) scale. Changes of sagittal alignment were investigated by postoperative plain x-ray or computed tomography (CT). Moreover, the decompression of the spinal cord was evaluated based on postoperative MRI. Results All the 48 patients were followed up for 24–42 months with an average follow-up time of 31.1±5.3 months. A total of 56 cervical intervertebral foramens were enlarged in 48 patients, including 40 cases (83.3%) with 1 intervertebral foramen enlargement and 8 cases (16.7%) with 2 intervertebral foramen enlargements. There were no significant differences in intraoperative blood loss, postoperative drainage amount, Japanese Orthopaedic Association (JOA) scores, JOA recovery rates, VAS scores for neck pain, and ASIA grade between two groups. The mean operative time was shorter in the LF group compared with the LFF group. The VAS score for arm pain was significantly lower while the surgical duration was longer in group B. No statistical difference was observed between the two groups in terms of C2–C7 SVA, cervical lordosis, focal angulation at the foraminotomy segment, and local spinal cord angle. Compared with the LF group, there was no segmental kyphosis or instability where the additional posterior foraminotomy was performed in the LFF group. Conclusions One-stage posterior LFF can achieve satisfied clinical efficacy in improving neurological function and relieving the radicular pain of the upper limbs for OPLL patients with radiculopathy symptoms.

This study comprehensively characterized and compared the aroma differences between four different grades of Fenjiu (FJ, the most representative light-flavor Baijiu). Aroma-active compounds were analyzed by liquid-liquid extraction (LLE) coupled with gas chromatography-olfactometry-mass spectrometry (GC-O-MS). A total of 88 aroma-active compounds were identified, and 70 of them were quantified. The results showed that a majority of aroma compounds in high-grade FJ had higher aroma intensities and concentrations. Among these compounds, there were 28 compounds with odor activity values (OAVs) greater than one in all four wines, which indicated that they might contribute to the characteristic aroma of FJ. Temporal dominance of sensation (TDS) and quantitative descriptive analysis (QDA) were used to characterize the sensory differences. The results suggested that high-grade FJ had a rich, pleasant and lasting retronasal aroma perception and exhibited pleasant orthonasal aroma of floral, fruity, sweet and grassy. Partial least squares regression (PLSR) analysis effectively distinguished four kinds of FJ and revealed associations between the orthonasal aroma attributes and the aroma compounds with OAVs >1. There were 15 compounds with variable importance in projection (VIP) values >1, and they were considered potential aroma markers for quality prediction.

Extracellular vesicles (EVs) are membrane-bound vesicles that can be released by all cell types. They may have different biogenesis, physical features, and cargo. EVs are important biomarkers for the diagnosis and prediction of many diseases due to their essential role in intercellular communication, their highly variable cargoes, and their accumulation in various body fluids. These natural particles have been investigated as potential therapeutic materials for many diseases. In our previous studies, the clinical usage of tumor-cell-derived microparticles (T-MPs) as a novel medication delivery system was examined. This review summarizes the clinical translation of EVs and related clinical trials, aiming to provide suggestions for safer and more effective oncology therapeutic systems, particularly in biotherapeutic and immunotherapeutic systems.

Abstract To compare the surgical outcomes of autogenous spinous process with iliac bone graft in managing single segment lumbar pyogenic spondylitis (PS) after posterior debridement and instrumentation. We performed a retrospective study for adult patients with single level lumbar PS. 60 patients with single segment lumbar PS underwent one-stage posterior debridement, autogenous bone graft and instrumentations. The patients were divided into Group A (autogenous iliac bone) and Group B (autogenous spinous process). Preoperative Charlson comorbidity index (CCI) was analyzed to assess the comorbidity. Low back pain was evaluated using the visual analog scale (VAS). Neurological status was assessed with the American Spinal Injury Association (ASIA) scale. Clinical infection index including the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) was also reviewed. Moreover, fusion and changes of sagittal alignment were investigated radiologically. There was a significantly longer operative time, hospital stay and greater blood loss in group A. The VAS scores improved significantly at each follow-up interval and post-operative VAS score was significantly lower in group B. At the last follow-up, ESR and CRP returned to normal for all patients. There was at least one grade level improvement in ASIA score. No statistical difference in corrected rate, loss of sagittal angle and lumbar lordosis was found between the two groups. There was no significant difference in fusion rate, mean fusion time and complications between the two groups. Compared with iliac bone graft, the autogenous spinous process bone graft can be less invasive and painful for the single segment lumbar PS. One-stage posterior debridement, autogenous spinous process bone graft and instrumentation can provide satisfactory results for appropriate cases.

Abstract A retrospective study investigated the results of the lamina with spinous process (LSP) as a bone graft in one-level thoracic or lumbar spinal tuberculosis with the one-stage posterior approach of debridement, fusion and internal instrumentation. Data from 35 patients from January 2013 to December 2015 were analysed. Surgery time, blood loss, hospitalization time, drainage volume, and follow-up (FU) duration were recorded. The visual analogue scale (VAS), Oswestry Disability Index (ODI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), American Spinal Injury Association (ASIA) grade, segmental angle, and bone fusion were compared between preoperative and final FU. All of the patients were followed up for a mean 43.90 ± 10.39 months. The mean age, surgery time, blood loss, hospitalization time, hospital cost and drainage volume were 33.65 ± 11.06 years, 182.40 ± 23.82 min, 280.80 ± 76.82 mL, 14.05 ± 3.58 days, 74,382.00 ± 11,938.00 yuan, and 340.00 ± 167.20 mL, respectively. VAS and ODI were significantly improved at the final FU. The ESR and CRP recovered to normal. The mean angle of 24.35 ± 5.74°preoperatively showed a significant difference between 1 week, postoperatively and final FU. Although there were the loss of angle at final FU comparing with the 1 week postoperatively, it still maintain the good alignment and the segmental stability. All patients achieved bony fusion with a mean time of 12.90 ± 3.91 months. In conclusion, the LSP as a structural bone graft is reliable, safe and effective for segmental stability reconstruction, which could be one choice for surgical management of thoracic or lumbar spinal TB.

Abstract Background Although serum albumin levels are increasingly used as an indicator of nutritional status in the clinic, the relationship between perioperative hypoalbuminemia and wound complications after posterior lumbar interbody fusion in the treatment of lumbar degenerative disease remains ambiguous. The aim of this study was to evaluate perioperative serum albumin in relation to postoperative wound complications after posterior lumbar interbody fusion in the treatment of single-segment lumbar degenerative disease. Material and methods We reviewed patients who underwent single-segment posterior lumbar interbody fusion surgery from December 2014 to April 2017 in the Department of Orthopedics at the First Affiliated Hospital of Chongqing Medical University. Perioperative (preoperative and early postoperative) serum albumin levels were assessed in all patients and were used to quantify nutritional status. We divided the patients into a surgical wound dehiscence (SWD) group and a normal wound healing group and into a surgical site infection (SSI) group and a non-SSI group. To evaluate the relationship between perioperative serum albumin level and postoperative wound complications, we conducted univariate and multiple logistic regression analyses. Results A total of 554 patients were enrolled in the study. The univariate and multiple logistic regression analysis of these differences showed that preoperative serum albumin < 3.5 g/dl (P = 0.001) and postoperative serum albumin < 3.0 g/dl (P = 0.001) were significantly correlated to SWD. There were also significant differences between the SSI groups in terms of preoperative serum albumin < 3.5 g/dl (P = 0.001) and chronic steroid use (P = 0.003). Additionally, the increased hospitalization costs (P < 0.001) and length of hospitalization (P < 0.001) were statistically significant for patients with perioperative hypoalbuminemia. Conclusions For patients who underwent single-segment posterior lumbar interbody fusion surgery, we need to pay more attention to perioperative hypoalbuminemia and chronic steroid use, which are more likely to be associated with increased wound complications, hospitalization costs, and length of hospitalization after surgery. Adequate assessment and management of these risk factors will help reduce wound complications and hospital stays for surgical patients and will save medical costs.

The limited treatment options for the increasing occurrence of Lassa hemorrhagic fever in West Africa poses an urgent need for the discovery and development of novel therapeutics. Dietary supplements, especially natural products that are edible and safe for human use, are a good source of drug discovery with potential for uncovering novel applications. In this study, we tested 40 natural products of dietary supplements and identified capsaicin, a common dietary supplement abundant in chili peppers, as an inhibitor of Lassa virus (LASV) entry with EC50 of 6.9–10.0 μmol/L using an HIV based pseudovirus platform. Capsaicin inhibits the entry of five LASV strains but not against the Old World arenavirus lymphocytic choriomeningitis virus (LCMV), showing a preferential activity against LASV. Capsaicin inhibits LASV entry by blocking the pH dependent viral fusion through affecting the stable signal peptide (SSP)-GP2 transmembrane (GP2TM) region of the LASV surface glycoprotein. Mutational study revealed the key residues Ala25, Val431, Phe434 and Val435 in SSP-GP2TM region in capsaicin's antiviral effect. This study for the first time reveals a direct acting antiviral effect of capsaicin against the hemorrhagic fever causing LASV, providing detailed interaction hot spots in the unique SSP-GP2TM interface of LASV glycoprotein that is crucial in fusion inhibition, and offering a new strategy in discovering and developing antivirals from natural products that are safe for human use.

Glycogen can be metabolized via glycogenolysis and the pentose phosphate pathway as well as into the production of UDP glucose, which when secreted can bind the P2Y14 receptor. Here the authors show how these glycogen metabolism pathways contribute to proinflammatory macrophage activation and susceptibility to sepsis.