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In the era of antiretroviral therapy (ART), mortality among people living with the human immunodeficiency virus (HIV) has significantly decreased, yet the population of people living with HIV remains substantial. Among people living with HIV (PLWH), HIV-associated lymphoma (HAL) has surpassed Kaposi’s sarcoma to become the most common tumor in this population in developed countries. However, there remains a dearth of comprehensive and systematic understanding regarding HIV-associated lymphomas. This review aims to shed light on the changes in the immune system among PLWH and the characteristics of the immune microenvironment in HIV-associated lymphoma, with a specific focus on the immune system’s role in these individuals. Additionally, it seeks to explore recent advancements in immunotherapy for the treatment of HIV-associated lymphoma, intending to enhance strategies for immunotherapy in this specific population.

Abstract Human immunodeficiency virus (HIV) infection is strongly associated with a heightened incidence of lymphomas. To mirror the natural course of human HIV infection, animal models have been developed. These models serve as valuable tools to investigate disease pathobiology, assess antiretroviral and immunomodulatory drugs, explore viral reservoirs, and develop eradication strategies. However, there are currently no validated in vivo models of HIV‐associated lymphoma (HAL), hampering progress in this crucial domain, and scant attention has been given to developing animal models dedicated to studying HAL, despite their pivotal role in advancing knowledge. This review provides a comprehensive overview of the existing animal models of HAL, which may enhance our understanding of the underlying pathogenesis and approaches for malignancies linked to HIV infection.

Abstract This paper sets out to develop an efficient probabilistic optimal power flow (POPF) algorithm to assess the influence of wind power on power grid. Given a set of wind data at multiple sites, their marginal distributions are fitted by a newly developed generalized Johnson system, whose parameters are specified by a percentile matching method. The correlation of wind speeds is characterized by a flexible Liouville copula, which allows to model the asymmetric dependence structure. In order to improve the efficiency for solving POPF problem, a lattice sampling method is developed to generate wind samples at multiple sites, and a logistic mixture model is proposed to fit distributions of POPF outputs. Finally, case studies are performed, the generalized Johnson system is compared with Weibull distribution and the original Johnson system for fitting wind samples, Liouville copula is compared against Archimedean copula for modelling correlated wind samples, and lattice sampling method is compared with Sobol sequence and Latin hypercube sampling for solving POPF problem on IEEE 118‐bus system, the results indicate the higher accuracy of the proposed methods for recovering the joint cumulative distribution function of correlated wind samples, as well as the higher efficiency for calculating statistical information of POPF outputs.

The discovery of a large number of ancient ivory and ivory artifacts in Sanxingdui site has elevated the importance of ancient ivory relics to the level of exploring the origins of Chinese civilization. To clarify the current preservation status of decayed ivory excavated from the Sanxingdui site, we have conducted an in-depth analysis of the structure-water state relationship of the ivory unearthed from the No. 4 sacrificial pit (K4) as an example. The research indicates that the ancient decayed ivory is composed of a mixed phase of hydroxyapatite [HA, Ca10(PO4)6(OH)2] and carbonated hydroxyapatite [CHA, Ca10(PO4)3(CO3)3(OH)2], which has a mixed structure of sheet-like and needle-like crystals. The organic fibrous protein within the ivory has basically disappeared, resulting in a porous structure with a porosity of approximately 39.2%. The pore size distribution is concentrated in the range of 2.5–100 nm, dominated by mesopores, with a handful of micropores. These pore structures are occupied by adsorbed water, free water and bound water, exhibiting a high water content (35%–40%). These water molecules play a filling and supporting role in the pore structure. During the dehydration and deterioration process of the ancient decayed ivory, the loss of water support results in internal stress within the microstructure of the ivory, leading to irreversible damage such as peeling, pulverization and cracking. The correlation study between the pore structure and water state of ancient decayed ivory provides clues for tracing the geological environment, sacrificial rituals, and ecological environments of ivories in ancient times, serving as a crucial window into Earth’s history and biological evolution.

PurposeWe aimed to investigate risk factors for COVID-19 pneumonia in patients with hematological malignancies (HM) after Omicron infection.MethodsData from a registered multi-center, prospective, observational study (ChiCTR2300071830) during the latest Omicron BA.5.2 wave in Chongqing, China was used for analysis.ResultsA total of 475 HM patients enrolled in this study. COVID-19 pneumonia was observed in 15.8% (75/475) of patients, with a median age of 58 years (interquartile range [IQR], 48-69 years) and males accounting for 61.3%. Risk factors associated with COVID-19 pneumonia included: 1) Active disease status of HM at infection, with an odds ratio (OR) of 3.42 (95% confidence interval [CI]: 1.59-7.37, P=0.002) compared to complete remission (CR); 2) Incomplete COVID-19 vaccination, 1-2 doses of the vaccine (OR=2.55, 95% CI: 1.28-5.10, P=0.008) or no vaccination (OR=4.81, 95% CI: 2.45-9.43, P

BackgroundIn cases of optic disc edema or a pale optic disc, distinguishing an episode of optic neuritis (ON) from that of non-arteritic anterior ischemic optic neuropathy (NAION) during a clinical examination is challenging. Optical coherence tomography angiography (OCTA) can reveal differences in peripapillary vascular network structures and provide biomarkers for differential diagnosis.MethodsA total of 23 eyes with NAION, 22 eyes with demyelinating ON (DON), and 27 eyes from healthy participants were imaged using OCTA to observe the radial peripapillary capillaries (RPCs). Optical coherence tomography was used to measure peripapillary retinal nerve fiber layer (RNFL) thickness and the macular ganglion cell complex (mGCC). Data for all patients were recorded at 2–3 weeks and more than 3 months after the symptom onset.ResultsA total of 23 affected eyes from 23 patients with NAION (average age 52.17 ± 7.92 years), 22 eyes from 22 patients with demyelinating optic neuritis (DON) (average age 47.88 ± 19.24 years), and 27 eyes from 27 healthy individuals (average age 46.43 ± 14.08 years) were included in the study. There were no significant differences in sex, age, and eye laterality between any two groups (F = 0.968, 0.475, 0.870; p > 0.05). Throughout the course of NAION and DON, the superior RPC, superior mGCC, and peripapillary RNFL decreased with time (p

BackgroundPsychiatric disorders, such as major depressive disorder (MDD), anxiety disorder (AD), bipolar disorder (BD), and schizophrenia (SCZ), are disturbances in brain activity that lead to disorders of cognition, behavior, and emotion regulation. Among Sjogren syndrome (SS) patients, psychiatric disorders are more prevalent than in the general population. Identifying associated risk factors can provide new evidence for clinical diagnosis and treatment.MethodsWe selected genetic instruments based on published genome-wide association studies (GWASs) to determine predisposition. Then, we conducted a 2-sample bidirectional Mendelian randomization (MR) analysis to explore the potential causal associations between SS and four major psychiatric disorders. The primary analysis was performed using MR with the inverse-variance weighted method. Confirmation was achieved through Steiger filtering and testing to determine the causal direction. Sensitivity analyses were conducted using MR-Egger, MR-PRESSO, and “leave-one-out” method methods.ResultsOur study showed that SS was linked to BD and SCZ, indicating that individuals with SS may have a reduced risk of developing BD (IVW: OR = 0.940, P=0.014) and SCZ (IVW: OR = 0.854, P=1.47*10-4), while there was no causal relationship between SS and MDD or AD. MR−Egger regression shows no evidence of pleiotropy (BD: intercept = 0.007, p = 0.774; SCZ: intercept = 0.051, p = 0.209). The same as the MR-PRESSO analysis (BD: global test p = 1.000; SCZ: global test p = 0.160). However, the results from the leave-one-out analysis demonstrated instability. Specifically, after excluding SNP rs3117581, the effects on BD and SCZ were found to be non-significant, suggesting the potential influence of unrecognized confounding factors. The results of the reverse MR show that four major psychiatric disorders had no causal effects on SS.ConclusionsOur research findings demonstrate a causal relationship between SS and SCZ, as well as between SS and BD. There are no causal effects between the four major psychiatric disorders and SS. These findings suggest that SS may have the potential to reduce the risk of both psychiatric disorders. This study provides new insight for their prevention and treatment.

Abstract The incidence, clinical characteristics, and prognostic factors of HIV-associated lymphoma remain poorly defined compared to HIV-negative lymphoma. Currently, there are no standard guidelines for treatment of these patients. We summarized several latest reports of HIV associated lymphoma from the 2023 ASH Annual Meeting (ASH2023).

ABSTRACTValidation of the TROPOspheric Monitoring Instrument (TROPOMI) SIF product is a necessity to evaluate its feasibility in various applications. A few validation works have been conducted through direct comparison with in-situ SIF retrievals or cross-comparison with similar satellite-based SIF or vegetation index (VI) products. Nevertheless, the influence of the geolocation mismatch between the validation pixel and reference data on validation results was never considered. This study, for the first time, quantifies the geolocation shift of the TROPOMI validation pixel based on a geometric location matching method and then the uncertainty caused by the geolocation mismatch. The results indicate that the geolocation shift of the TROPOMI pixel shows large temporal variations, with a standard deviation of 2.30 km and 1.91 km in the across- and along-track directions. The mean shifts are 0.17 km and 0.28 km in the across- and along-track directions respectively, indicating eastward shifts in the across-track direction and northward shifts in the along-track direction in general. More than half (42/54) of the time periods showed relative uncertainty larger than 5%, with the maximum even reaching 55.7%. Hence, the uncertainty caused by geolocation mismatch should be fully considered in the validation of satellite SIF products, especially over heterogeneous surfaces.

BackgroundCardiac stereotactic body radiotherapy (CSBRT) with photons efficaciously and safely treats cardiovascular arrhythmias. Proton therapy, with its unique physical and radiobiological properties, can offer advantages over traditional photon-based therapies in certain clinical scenarios, particularly pediatric tumors and those in anatomically challenging areas. However, dose uncertainties induced by cardiorespiratory motion are unknown.ObjectiveThis study investigated the effect of cardiorespiratory motion on intensity-modulated proton therapy (IMPT) and the effectiveness of motion-encompassing methods.MethodsWe retrospectively included 12 patients with refractory arrhythmia who underwent CSBRT with four-dimensional computed tomography (4DCT) and 4D cardiac CT (4DcCT). Proton plans were simulated using an IBA accelerator based on the 4D average CT. The prescription was 25 Gy in a single fraction, with all plans normalized to ensure that 95% of the target volume received the prescribed dose. 4D dose reconstruction was performed to generate 4D accumulated and dynamic doses. Furthermore, dose uncertainties due to the interplay effect of the substrate target and organs at risk (OARs) were assessed. The differences between internal organs at risk volume (IRV) and OARreal (manually contoured on average CT) were compared. In 4D dynamic dose, meeting prescription requirements entails V25 and D95 reaching 95% and 25 Gy, respectively.ResultsThe 4D dynamic dose significantly differed from the 3D static dose. The mean V25 and D95 were 89.23% and 24.69 Gy, respectively, in 4DCT and 94.35% and 24.99 Gy, respectively, in 4DcCT. Eleven patients in 4DCT and six in 4DcCT failed to meet the prescription requirements. Critical organs showed varying dose increases. All metrics, except for Dmean and D50, significantly changed in 4DCT; in 4DcCT, only D50 remained unchanged with regards to the target dose uncertainties induced by the interplay effect. The interplay effect was only significant for the Dmax values of several OARs. Generally, respiratory motion caused a more pronounced interplay effect than cardiac pulsation. Neither IRV nor OARreal effectively evaluated the dose discrepancies of the OARs.ConclusionsComplex cardiorespiratory motion can introduce dose uncertainties during IMPT. Motion-encompassing techniques may mitigate but cannot entirely compensate for the dose discrepancies. Individualized 4D dose assessments are recommended to verify the effectiveness and safety of CSBRT.

BackgroundAngiotensin II receptor blockers (ARBs) are utilized for the management of hypertension and diabetes. Previous meta-analyses suggested that azilsartan medoxomil (AZL-M) improved blood pressure (BP) reduction, but there were no safety findings or suggestions for patients with hypertension or diabetes.MethodsWe performed an efficacy and safety meta-analysis of randomized controlled trials (RCTs) evaluating AZL-M therapy for reducing BP in patients with hypertension. Patients with hypertension complicated by diabetes were analyzed. The relevant literature was searched in English and Chinese databases for RCTs involving AZL-M in hypertension. Efficacy variables included the change from baseline in the 24-h mean systolic/diastolic BP measured by ambulatory BP monitoring, the change from baseline in clinic systolic/diastolic BP, and responder rates. Safety variables included total adverse events (AEs), serious AEs, AEs leading to discontinuation, and AEs related to the study drug. The raw data from the included studies were utilized to calculate the odds ratio (OR) for dichotomous data and the mean difference (MD) for continuous data, accompanied by 95% confidence intervals (CIs). Statistical analysis was performed using R software.ResultsA total of 11 RCTs met the inclusion criteria, representing 7,608 patients, 5 of whom had diabetes. Pooled analysis suggested a reduction in BP among patients randomized to 40 mg of AZL-M vs. control therapy [24-h ambulatory blood pressure monitoring (ABPM) mean systolic blood pressure (SBP) (MD: −2.85 mmHg), clinic SBP (MD: −3.48 mmHg), and clinic diastolic blood pressure (DBP) (MD: −1.96 mmHg)] and for 80 mg of AZL-M vs. control therapy [24-h ABPM mean SBP (MD: −3.59 mmHg), 24-h ABPM mean DBP (MD: −2.62 mmHg), clinic SBP (MD: −4.42 mmHg), clinic DBP (MD: −3.09 mmHg), and responder rate (OR: 1.46)]. There was no difference in the reduction of risks, except for dizziness (OR: 1.56) in the 80-mg AZL-M group or urinary tract infection (OR: 1.82) in the 40-mg AZL-M group. Analysis of patients with diabetes revealed that AZL-M can provide superior management, while safety and tolerability were similar to those of control therapy.ConclusionsAZL-M appears to reduce BP to a greater extent than dose-control therapy and does not increase the risk of adverse events in patients with hypertension and diabetes compared with placebo.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=464284, identifier PROSPERO CRD42023464284.

Abstract Colorectal cancer (CRC) is one of the leading cancers worldwide, with metastasis being a major cause of high mortality rates among patients. In this study, dysregulated gene Tweety homolog 3 (TTYH3) was identified by Gene Expression Omnibus database. Public databases were used to predict potential competing endogenous RNAs (ceRNAs) for TTYH3. Quantitative real‐time polymerase chain reaction, western blot, and immunohistochemistry were utilized to analyze TTYH3 and histone deacetylase 7 (HDAC7) levels. Luciferase assays confirmed miR‐1271‐5p directly targeting the 3′ untranslated regions of TTYH3 and HDAC7. In vitro experiments such as transwell and human umbilical vein endothelial cell tube formation, as well as in vivo mouse models, were conducted to assess the biological functions of TTYH3 and HDAC7. We discovered that upregulation of TTYH3 in CRC promotes cell migration by affecting the Epithelial–mesenchymal transition pathway, which was independent of its ion channel activity. Mechanistically, TTYH3 and HDAC7 functioned as ceRNAs, reciprocally regulating each other's expression. TTYH3 competes for binding miR‐1271‐5p, increasing HDAC7 expression, facilitating CRC metastasis and angiogenesis. This study reveals the critical role of TTYH3 in promoting CRC metastasis through ceRNA crosstalk, offering new insights into potential therapeutic targets for clinical intervention.

To investigate the laser-based displays that can offer the light source with a high level of photobiological safety and are suitable for users of different ages, this research optimizes the light source of the three-primary laser-based displays from its peak wavelength and the fractions of radiant flux. The non-linear program based on genetic algorithm is used to set the color gamut coverage over 90% and the correlated color temperature at 6500K. Find suitable peak wavelength and fractions of radiant flux with the premise of less than the blue light hazard (BLH) caused by the D65 light source to the 1 year, and select the result with the maximum circadian action factor (CAF) as the optimization for each age. Meanwhile, this research explores the effect that a change in the peak wavelength and fractions of radiant flux near the optimal results on CAF and BLH in different age groups. It provides reference for the design of health consideration laser displays for different age users in the daily working environment.

Abstract Background Low-level viremia (LLV) has been identified as a potential precursor to virologic failure (VF), yet its clinical implications, particularly within the context of Integrase Strand Transfer Inhibitors (INSTIs)-based regimens, remain insufficiently explored. The study aimed to investigate the relationship between LLV and VF within ART-naïve patients on INSTIs-based regimens in China. Methods A longitudinal cohort study was conducted with ART-naïve patients aged ≥ 18 years at Beijing Ditan Hospital, under the Chinese National Free Antiretroviral Treatment Program (NFATP). The LLV was defined as a viral load (VL) ranging from 50 to 199 copies/mL after six months of ART initiation, and VF as a VL ≥ 200 copies/mL. Sensitive analyses were also performed, defining LLV as 50–999 copies/mL and VF as exceeding 1000 copies/mL. Multivariate logistic regression, Kaplan-Meier (KM) curve, and Generalized Estimating Equation (GEE) models were used to evaluate the risk factors associated with LLV and VF events. Results The study involved 830 ART-naïve patients, comprising 600 in the INSTIs group and 230 in the protease inhibitors (PIs) group. LLV events were observed in 10.4% of patients on PIs-based regimens and and 3.2% on INSTIs-based regimens (P

Purposes Traffic flow prediction is crucial for the effective management and operation of urban transportation systems. The flows of different road sections or intersections in a traffic network change dynamically with time, meanwhile the flows of spatially neighboring road sections or intersections affect each other. In order to better learn the spatial and temporal correlation of the traffic flow of different road sections or intersections from the traffic flow sequences, and to improve the performance of short-term prediction of traffic flow, in this paper we propose a traffic flow prediction method based on Dynamic Graph Convolution Network with Multi-head Attention (DGCNMA). Methods The DGCNMA model first introduces graph convolution networks into the Transformer framework to learn the spatial embedding of traffic flow sequences and incorporate them into the traffic flow sequences, and then adopts the mechanism of Multi-head Attention to capture the temporal and spatial correlation of the traffic flow sequences from multiple perspectives at the same time; second, the Interactive Dynamic Graph Convolution Network is introduced to simultaneously learn the local and global spatial-temporal correlations of traffic flow sequences through the interactive learning of convolutional network and dynamic graph convolutional network, and the interactive fusion of parity subsequence features. Findings Experiments on highway traffic flow datasets (PEMS03, PEMS04, PEMS08) and subway crowd flow datasets (HZME inflow and HZME outflow) show that the proposed DGCNMA model has better traffic flow prediction performance than the baseline models.

Stripe noise is a general phenomenon in original remote sensing images that both degrades image quality and severely limits its quantitative application. While the classical statistical method is effective in correcting common stripes caused by inaccurately calibrating relative gains and offsets between detectors, it falls short in correcting other nonlinear stripe noises originating from subtle nonlinear changes or random contamination within the same detector. Therefore, this paper proposes a novel trend repair method based on two normal columns directly adjacent to a defective column to rectify the trend by considering the geospatial structure of contaminated pixels, eliminating residual stripe noise evident in level 0 (L0) remote sensing images after histogram matching. GF5-02 VIMI (Gaofen5-02, visual and infrared multispectral imager) images and simulated Landsat 8 thermal infrared sensor (TIRS) images deliberately infused with stripe noise are selected to test the new method and two other existing methods, the piece-wise method and the iterated weighted least squares (WLS) method. The effectiveness of these three methods is reflected by streaking metrics (Streaking), structural similarity (SSIM), peak signal-to-noise ratio (PSNR), and improvement factor (IF) on the uniformity, structure, and information content of the corrected GF5-02 VIMI images and by the accuracy of the corrected simulated Landsat 8 TIRS images. The experimental results indicate that the trend repair method proposed in this paper removes nonlinear stripe noise effectively, making the results of IF > 20. The remaining indicators also show satisfactory results; in particular, the mean accuracy derived from the simulated image remains below a digital number (DN) of 15, which is far superior to the other two methods.

ObjectiveThis research investigates the role of human factors of all hierarchical levels in radiotherapy safety incidents and examines their interconnections.MethodsUtilizing the human factor analysis and classification system (HFACS) and Bayesian network (BN) methodologies, we created a BN-HFACS model to comprehensively analyze human factors, integrating the hierarchical structure. We examined 81 radiotherapy incidents from the radiation oncology incident learning system (RO-ILS), conducting a qualitative analysis using HFACS. Subsequently, parametric learning was applied to the derived data, and the prior probabilities of human factors were calculated at each BN-HFACS model level. Finally, a sensitivity analysis was conducted to identify the human factors with the greatest influence on unsafe acts.ResultsThe majority of safety incidents reported on RO-ILS were traced back to the treatment planning phase, with skill errors and habitual violations being the primary unsafe acts causing these incidents. The sensitivity analysis highlighted that the condition of the operators, personnel factors, and environmental factors significantly influenced the occurrence of incidents. Additionally, it underscored the importance of organizational climate and organizational process in triggering unsafe acts.ConclusionOur findings suggest a strong association between upper-level human factors and unsafe acts among radiotherapy incidents in RO-ILS. To enhance radiation therapy safety and reduce incidents, interventions targeting these key factors are recommended.

Background Although several studies have addressed plasma proteomics in heart failure with preserved ejection fraction, limited data are available on the prognostic value of urinary proteomics. The objective of our study was to identify urinary proteins/peptides associated with death and heart failure admission in patients with heart failure with preserved ejection fraction. Methods and Results The study population included participants enrolled in TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial). The relationship between urine protein levels and the risk of death or heart failure admission was assessed using Cox regression, in both nonadjusted analyses and adjusting for urine creatinine levels, and the MAGGIC (Meta‐Analysis Global Group in Chronic Heart Failure) score. A total of 426 (12.4%) TOPCAT participants had urinary protein data and were included. There were 40 urinary proteins/peptides significantly associated with death or heart failure admission in nonadjusted analyses, 21 of which were also significant adjusted analyses. Top proteins in the adjusted analysis included ANGPTL2 (angiopoietin‐like protein 2) (hazard ratio [HR], 0.5731 [95% CI, 0.47–0.7]; P=3.13E‐05), AMY2A (α amylase 2A) (HR, 0.5496 [95% CI, 0.44–0.69]; P=0.0001), and DNASE1 (deoxyribonuclease‐1) (HR, 0.5704 [95% CI, 0.46–0.71]; P=0.0002). Higher urinary levels of proteins involved in fibrosis (collagen VI α‐1, collagen XV α‐1), metabolism (pancreatic α‐amylase 2A/B, mannosidase α class 1A member 1), and inflammation (heat shock protein family D member 1, inducible T cell costimulatory ligand) were associated with a lower risk of death or heart failure admission. Conclusions Our study identifies several novel associations between urinary proteins/peptides and outcomes in heart failure with preserved ejection fraction. Many of these associations are independent of clinical risk scores and may aid in risk stratification in this patient population.

The growing interest in renewable energy solutions for sustainable development has significantly advanced the design and analysis of floating offshore wind turbines (FOWTs). Modeling FOWTs presents challenges due to the considerable coupling between the turbine’s aerodynamics and the floating platform’s hydrodynamics. This review paper highlights the critical role of computational fluid dynamics (CFD) in enhancing the design and performance evaluation of FOWTs. It thoroughly evaluates various CFD approaches, including uncoupled, partially coupled, and fully coupled models, to address the intricate interactions between aerodynamics, hydrodynamics, and structural dynamics within FOWTs. Additionally, this paper reviews a range of software tools for FOWT numerical analysis. The research emphasizes the need to focus on the coupled aero-hydro-elastic models of FOWTs, especially in response to expanding rotor diameters. Further research should focus on developing nonlinear eddy viscosity models, refining grid techniques, and enhancing simulations for realistic sea states and wake interactions in floating wind farms. The research aims to familiarize new researchers with essential aspects of CFD simulations for FOWTs and to provide recommendations for addressing challenges.

Sarcopenia is an age-related syndrome characterized by the loss of skeletal muscle mass and function. Community screening, commonly used in early diagnosis, usually lacks features such as real-time monitoring, low cost, and convenience. This study introduces a promising approach to sarcopenia screening by dynamic plantar pressure monitoring. We propose a wearable flexible-printed piezoelectric sensing array incorporating barium titanate thin films. Utilizing a flexible printer, we fabricate the array with enhanced compressive strength and measurement range. Signal conversion circuits convert charge signals of the sensors into voltage signals, which are transmitted to a mobile phone via Bluetooth after processing. Through cyclic loading, we obtain the average voltage sensitivity (4.844 mV/kPa) of the sensing array. During a 6 m walk, the dynamic plantar pressure features of 51 recruited participants are extracted, including peak pressures for both sarcopenic and control participants before and after weight calibration. Statistical analysis discerns feature significance between groups, and five machine learning models are employed to screen for sarcopenia with the collected features. The results show that the features of dynamic plantar pressure have great potential in early screening of sarcopenia, and the Support Vector Machine model after feature selection achieves a high accuracy of 93.65%. By combining wearable sensors with machine learning techniques, this study aims to provide more convenient and effective sarcopenia screening methods for the elderly.

Clematis Florida (CF) is a folk medicinal herb in the southeast of China, which is traditionally used for treating osteoarticular diseases. However, the mechanism of its action remains unclear. The present study used network pharmacology and experimental validation to explore the mechanism of CF in the treatment of rheumatoid arthritis (RA). Liquid chromatography–mass spectrometry (LC-MS/MS) identified 50 main compounds of CF; then, their targets were obtained from TCMSP, ETCM, ITCM, and SwissTargetPrediction databases. RA disease-related targets were obtained from DisGeNET, OMIM, and GeneCards databases, and 99 overlapped targets were obtained using a Venn diagram. The protein–protein interaction network (PPI), the compound–target network (CT), and the compound–potential target genes–signaling pathways network (CPS) were constructed and analyzed. The results showed that the core compounds were screened as oleanolic acid, oleic acid, ferulic acid, caffeic acid, and syringic acid. The core therapeutic targets were predicted via network pharmacology analysis as PTGS2 (COX-2), MAPK1, NF-κB1, TNF, and RELA, which belong to the MAPK signaling pathway and NF-κB signaling pathway. The animal experiments indicated that topical application of CF showed significant anti-inflammatory activity in a mouse model of xylene-induced ear edema and had strong analgesic effect on acetic acid-induced writhing. Furthermore, in the rat model of adjuvant arthritis (AA), topical administration of CF was able to alleviate toe swelling and ameliorate joint damage. The elevated serum content levels of IL-6, COX-2, TNF-α, IL-1β, and RF caused by adjuvant arthritis were reduced by CF treatment. Western blotting tests showed that CF may regulate the ERK and NF-κB pathway. The results provide a new perspective for the topical application of CF for treatment of RA.

As an important way to realize the circular economy, remanufacturing faces the problem of low consumer recognition of remanufactured products. Given that factor, this study formulates a model that integrates offline direct sales with online distribution led by remanufacturers, assuming that consumers perceive differences between channels. We develop a Stackelberg game model to represent cases of remanufactured channel promotion and generic promotion and analyze the optimization of pricing and the level of promotion effort decisions for remanufactured products. Furthermore, considering the market conditions, such as the difference coefficient of consumer channel perception and the spillover effect in generic promotion, we investigate the selection of the optimal promotion strategy for remanufacturers. The research findings reveal the following: (i) Under channel promotion, the level of promotion effort and the prices of online and offline products are positively correlated with the difference coefficient of consumer value perception. Conversely, under generic promotion, the level of promotion effort and the prices of online and offline products initially decrease and then increase with the difference coefficient of consumer value perception. (ii) Under the generic promotion, the differences in prices between online and offline products are significantly smaller compared to channel promotion. (iii) The remanufacturer’s profit from channel promotion is higher when the difference in consumer channel perception is either small or large. Conversely, when the difference in consumer channel perception is moderate, the optimal strategy for remanufacturers is generic promotion, thereby achieving a mutually beneficial outcome with retailers. This study provides a theoretical foundation for remanufacturers to formulate effective pricing and promotion strategies in dual-channel marketing, thereby enhancing the market recognition and sales of remanufactured products.

In this paper, it aims to model wind speed time series at multiple sites. The five-parameter Johnson distribution is deployed to relate the wind speed at each site to a Gaussian time series, and the resultant m-dimensional Gaussian stochastic vector process Z(t) is employed to model the temporal-spatial correlation of wind speeds at m different sites. In general, it is computationally tedious to obtain the autocorrelation functions (ACFs) and cross-correlation functions (CCFs) of Z(t), which are different to those of wind speed times series. In order to circumvent this correlation distortion problem, the rank ACF and rank CCF are introduced to characterize the temporal-spatial correlation of wind speeds, whereby the ACFs and CCFs of Z(t) can be analytically obtained. Then, Fourier transformation is implemented to establish the cross-spectral density matrix of Z(t), and an analytical approach is proposed to generate samples of wind speeds at m different sites. Finally, simulation experiments are performed to check the proposed methods, and the results verify that the five-parameter Johnson distribution can accurately match distribution functions of wind speeds, and the spectral representation method can well reproduce the temporal-spatial correlation of wind speeds.

Abstract Field-measured spectra are critical for remote sensing physical modelling, retrieval of structural, biophysical, and biochemical parameters, and other practical applications. We present a library of field spectra, which includes (1) portable field spectroradiometer measurements of vegetation, soil, and snow in the full-wave band, (2) multi-angle spectra measurements of desert vegetation, chernozems, and snow with consideration of the anisotropic reflectance of land surface, (3) multi-scale spectra measurements of leaf and canopy of different vegetation cover surfaces, and (4) continuous reflectance spectra time-series data revealing vegetation growth dynamics of maize, rice, wheat, rape, grassland, and so on. To the best of our knowledge, this library is unique in simultaneously providing full-band, multi-angle, multi-scale spectral measurements of the main surface elements of China covering a large spatial extent over a 10-year period. Furthermore, the 101 by 101 satellite pixels of Landsat ETM/OLI and MODIS surface reflectance centered around the field site were extracted, providing a vital linkage between ground measurements and satellite observations. The code language used for this work is Matlab 2016a.

Objective: To systematically review the efficacy and safety of nonsteroidal mineralocorticoid receptor antagonists (MRAs) in chronic kidney disease (CKD).Methods: We systematically searched six databases to identify randomized controlled trials (RCTs) about nonsteroidal MRAs for CKD, from inception to 22 August 2023. Two reviewers independently screened the retrieved articles, extracted data, and assessed the risk of bias of included RCTs using the Cochrane risk of bias tool. We then conducted meta-analysis of the data using Stata 17.0 software.Results: 11 RCTs (n = 15,817) were included in this meta-analysis. Compared with placebo, nonsteroidal MRAs significantly reduced the proportion of patients with ≥40% decline in estimated glomerular filtration rate (eGFR) from baseline [RR = 0.85, 95% CI (0.78, 0.92), p < 0.001], although the magnitude of eGFR reduction was greater [WMD = −2.83, 95% CI (−3.95, −1.72), p < 0.001]. The experimental group also had lower incidence of composite renal outcome [RR = 0.86, 95% CI (0.79, 0.93), p < 0.001] and greater reduction in urine albumin-to-creatinine ratio (UACR) from baseline [WMD = −0.41, 95% CI (−0.49, −0.32), p < 0.001], as well as reduced cardiovascular events [RR = 0.88, 95% CI (0.80, 0.95), p = 0.003]. MRAs did not increase any adverse events compared to placebo [RR = 1.00, 95% CI (0.99, 1.01), p = 0.909], but had higher incidence of hyperkalemia [RR = 2.05, 95% CI (1.85, 2.280), p < 0.001]. Compared with eplerenone, there was no significant difference in the proportion of patients with ≥40% decline in eGFR [RR = 0.57, 95% CI (0.18, 1.79), p = 0.335] or hyperkalemia [RR = 0.95, 95%CI (0.48, 1.88), p = 0.875].Conclusion: Nonsteroidal MRAs can reduce the incidence of end-stage renal disease and cardiovascular adverse events in patients. Although there was still a risk of hyperkalemia compared to placebo, there was no significant difference in any adverse events compared to either placebo or eplerenone. It has become a new option for drug treatment of CKD patients, but more clinical trials are still needed to verify its efficacy and safety. Especially further direct comparison of the nonsteroidal MRAs to eplerenone in view of the relatively small number of patients reviewed are needed.

In mountainous surfaces, land surface temperature (LST) plays a vital role in surface energy budget and vegetation–soil ecosystems. Despite advancements in retrieving LST from thermal infrared measurements at various spatial and temporal scales, accurately estimating LST for complex terrain remains challenging. This challenge arises from the conflict between the topographic effect and the assumption of flatten surface in many existing studies. In the absence of a simple and practical model for the topographic effect on the directional anisotropies of LST (LSTDA) over mountainous areas, the equivalent slope method is introduced to bridge the gap between studies conducted on flat surfaces and complex terrain. The proposed thermal equivalent slope kernel-driven (TESKD) model is validated using measurements and simulations from an unmanned aerial vehicle (UAV) system and a 3-dimensional raytracing model, respectively. Results indicate the following: (a) Under varying topographic conditions, vegetation cover, and solar zenith angles, there is a significant impact of topography on LSTDA. The average effect is greater than 0.5 K and can reach up to 1.5 K at the higher solar zenith angle (50°). (b) Based on UAV data, TESKD provides a better explanation and fitting effect for LSTDA in 3 typical mountainous surfaces including valley, peak, and solo-slope, with an average root mean square error (RMSE) of 0.27 K and an average coefficient of determinations of 0.628 of the 3 conditions, compared to a flat model (0.35 K and 0.335). (c) Based on simulations, TESKD exhibits more than a 30% improvement in accuracy, and for sparsely vegetated surfaces, the difference in RMSE can be up to 0.8 K when considering the topographic effect compared to not considering it. The new model can help to understand the radiative transfer process in heterogeneous mountainous surfaces and serves as a valuable tool for studies associated with water and carbon cycles.

BackgroundAntiretroviral Therapy (ART) in children remains challenging due to resource-constrained settings. We conducted a 13-year, prospective, multicenter cohort study on the effectiveness and safety of LPV/r-based regimens in ART-naive and ART-experienced children.MethodsFrom January 2008 to May 2021, children living with HIV-1 were recruited with LPV/r-based regimens from 8 clinical research sites in 6 provinces in China. Effectiveness outcomes were virologic failure (defined as at least two consecutive measurements of VL > 200 copies/mL after 6 months of ART) and immune response (defined as CD4% recovered to more than 25% after 12 months of treatment). The safety outcomes were treatment-related grade 2–4 adverse events and abnormal laboratory test results.ResultsA total of 345 ART-naïve children and 113 ART-experienced children were included in this cohort study. The median follow-up time was 7.3 (IQR 5.5–10.5) years. The incidence density of virologic failure was 4.1 (95% CI 3.3–4.9) per 100 person-years in ART-naïve children and 5.0 (95% CI 3.5–6.5) per 100 person-years in ART-experienced children. Kaplan Meyer (KM) curve analysis showed children with ART experience were at a higher risk of virologic failure (p 5 days of LPV intake (aHR = 1.889, 1.004–3.554); The risk factor of virologic failure in ART-experienced children was missed dose times >5 days (aHR = 2.689, 1.299–5.604) and mother as caregivers for ART administration (aHR = 0.475, 0.238–0.948). However, during long-term treatment, viral suppression rates between ART-naïve and ART-experienced children remained similar. No significant differences were observed in the immune response, treatment-related grade 2–4 events, and abnormal laboratory test results between ART-naïve children and ART-experienced children.ConclusionOur research underscores that with consistent, long-term treatment of LPV/r-based regimens, ART-experienced children can achieve therapeutic outcomes comparable to ART-naïve children. It provides crucial insights on LPV/r-based regimens in pediatric HIV treatment, especially in resource-limited settings where high-cost Integrase Strand Transfer Inhibitors (INSTs) are inaccessible. This evidence-based understanding provides an essential addition to the global therapeutic strategies for pediatric HIV treatment.

Abstract Background Myeloid neoplasms (MN) tend to relapse and deteriorate. Exploring the genomic mutation landscape of MN using next‐generation sequencing (NGS) is a great measure to clarify the mechanism of oncogenesis and progression of MN. Methods This multicenter retrospective study investigated 303 patients with MN using NGS from 2019 to 2021. The characteristics of the mutation landscape in the MN subgroups and the clinical value of gene variants were analyzed. Results At least one mutation was detected in 88.11% of the patients (267/303). TET2 was the most common mutation in the cohort, followed by GATA2, ASXL1, FLT3, DNMT3A, and TP53. Among patients with myeloid leukemia (ML), multivariate analysis showed that patients aged ≥60 years had lower overall survival (OS, p = 0.004). Further analysis showed TET2, NPM1, SRSF2, and IDH1 gene mutations, and epigenetic genes (p

Abstract As one of the common physical materials in Chinese archaeological excavations, ancient bronzes are an essential basis for studying the development of Chinese bronze culture, which is of great significance for exploring the development law of ancient human civilization and reconstructing ancient human society. As China’s infrastructure advances, the number of bronzes unearthed by archaeological excavations continues to increase. However, environmental damage to artefacts is very complex, whether the buried environment of the artefacts or the above-ground environment when the artefacts are unearthed, leading to different health problems for the excavated bronzes. A scientific assessment of these bronzes needs to be carried out prior to extraction to inform staff how they should be extracted, moved, and transported and how they should be restored afterwards. In response to the above problems, this paper takes excavated bronzes from archaeological sites as the research object and, by analysing and studying the relevant industry standards and the disease characteristics of bronzes, establishes a three-tier indicator framework for assessing the health of bronzes in a layer-by-layer refinement and proposes quantitative indicators with typical correlations. Through extensive research and testing, we screened out efficient, non-destructive, convenient and reliable assessment and testing methods and assessment models that combine subjective and objective aspects suitable for archaeological sites. On this basis, the paper achieves a scientific and practical assessment of the health status of bronzes excavated from archaeological sites. After repeated experiments, a set of comprehensive methods for quickly and conveniently assessing the health status of excavated bronzes was proposed for the first time and successfully applied to the archaeological excavation site of Sanxingdui site in Guanghan City, Sichuan Province, China.

Land surface temperature (LST) is a fundamental parameter in global climate, environmental, and geophysical studies. Remote sensing is an essential approach for obtaining large-scale and frequently updated LST data. However, due to the wide field of view of remote sensing sensors, the observed LST with diverse view geometries suffers from inconsistency caused by the thermal radiation directionality (TRD) effect, which results in LST products being incomparable, especially during daytime. To address this issue and correct current off-nadir LSTs to nadir LSTs, a semi-physical time-evolved kernel-driven model (TEKDM) is proposed, which depicts multitemporal TRD patterns during the daytime. In addition, we employ a Bayesian optimization method to calibrate seven unknown parameters in the TEKDM. Validation results using the U.S. Climate Reference Network (USCRN) sites show that the RMSE (MBE) for GOES-16 and MODIS off-nadir LST products is reduced from 3.29 K (−2.0 K) to 2.34 K (−0.02 K), with an RMSE reduction of 0.95 K (29%) and a significant reduction in systematic bias. Moreover, the proposed method successfully eliminates the angular and temporal dependence of the LST difference between the satellite off-nadir LST and in situ nadir LST. In summary, this study presents a feasible approach for estimating the high-accuracy nadir LST, which can enhance the applicability of LST products in various domains.

Surface upward longwave radiation (SULR) is one of the four components of surface net radiation. Geostationary satellites can provide high temporal but coarse spatial resolution SULR products. Downscaling coarse SULR to a higher resolution is important for fine-scale thermal condition monitoring. Statistical regression downscaling is widely used due to its simplicity and is built on the assumption that the thermal parameter like land surface temperature (LST) or SULR has a relationship with the related surface factors like the normalized difference vegetation index (NDVI), and the relationship remains unchanged in any scales. In this study, to establish the relationship between SULR and the related surface factors, we chose the multiple linear regression (MLR) model and five surface factors (i.e., the modified normalized difference water index (MNDWI), normalized difference built-up and soil index (NDBSI), NDVI, normalized moisture difference index (NMDI), and urban index (UI)) to drive the downscaling process. Additionally, a step-by-step downscaling strategy was applied to reach the 100-fold increase in spatial resolution, transitioning the estimated SULR from 4 km of the advanced geostationary radiation imager (AGRI) onboard FengYun-4B (FY-4B) satellite to 40 m of the visual and infrared multispectral imager (VIMI) in infrared spectrum onboard GaoFen5-02 (GF5-02). Finally, we evaluated the downscaling results by comparing the downscaled SULR values with the in situ measured SULR and GF5-02-calculated SULR, and the root mean square errors (RMSEs) were 19.70 W/m2 and 24.86 W/m2, respectively. Throughout this MLR-based step-by-step downscaling method (high-frequency data from FY-4B and high spatial resolution data from GF5-02), high spatiotemporal SULR (15 min temporal resolution, 40 m spatial resolution) were successfully generated instead of coarse spatial resolution ones from the FY-4B satellite or a coarse temporal resolution one from the GF5-02 satellite, relieving the above-mentioned conflict to some extent.

Persistent human papillomavirus (HPV) infections is necessary for the development of cervical cancers. An increasing number of retrospective studies have found the depletion of Lactobacillus microbiota in the cervico-vagina facilitate HPV infection and might be involved in viral persistence and cancer development. However, there have been no reports confirming the immunomodulatory effects of Lactobacillus microbiota isolated from cervico-vaginal samples of HPV clearance in women. Using cervico-vaginal samples from HPV persistent infection and clearance in women, this study investigated the local immune properties in cervical mucosa. As expected, type I interferons, such as IFN-α and IFN-β, and TLR3 globally downregulated in HPV+ persistence group. Luminex cytokine/chemokine panel analysis revealed that L. jannaschii LJV03, L. vaginalis LVV03, L. reuteri LRV03, and L. gasseri LGV03 isolated from cervicovaginal samples of HPV clearance in women altered the host's epithelial immune response, particularly L. gasseri LGV03. Furthermore, L. gasseri LGV03 enhanced the poly (I:C)-induced production of IFN by modulating the IRF3 pathway and attenuating poly (I:C)-induced production of proinflammatory mediators by regulating the NF-κB pathway in Ect1/E6E7 cells, indicating that L. gasseri LGV03 keeps the innate system alert to potential pathogens and reduces the inflammatory effects during persistent pathogen infection. L. gasseri LGV03 also markedly inhibited the proliferation of Ect1/E6E7 cells in a zebrafish xenograft model, which may be attributed to an increased immune response mediated by L. gasseri LGV03.

Abstract Background To explore the dosimetric difference between IMRT-VB plan based on the establishment of external expansion structure and virtual bolus (VB) and IMRT-SF based on the skin flash (SF) tool of the Eclipse treatment planning system in postoperative chest wall target intensity modulation radiotherapy plan of breast cancer. Methods Twenty patients with breast cancer were randomly selected as subjects to develop IMRT-VB plan based on virtual bolus and IMRT-SF plan based on skin flash tool of Eclipse treatment planning system. The planning target volume, monitor unit (MU) of every single treatment and the dosimetric parameters of organ at risk (OARs) were recorded. Paired t-test was used for normal distribution data while nonparametric paired Wilcoxon rank sum test was used for non-normal distribution data. Results Both IMRT-VB and IMRT-SF plan can expand outward to the chest wall skin and meet the dose requirements of clinical prescription. The conformal index, the homogeneity index, D2%, D98% and D50% were significantly better in IMRT-SF plan than those in IMRT-VB plan (P

Abstract Candida albicans is an important human fungal pathogen. Our previous study disclosed that aryloxy‐phenylpiperazine skeleton was a promising molecule to suppress C. albicans virulence by inhibiting hypha formation and biofilm formation. In order to deeply understand the efficacy and mechanism of action of phenylpiperazine compounds, and obtain new derivatives with excellent activity against C. albicans, hence, we synthesized three series of (1‐heteroaryloxy‐2‐hydroxypropyl)‐phenylpiperazines and evaluated their inhibitory activity against C. albicans both in vitro and in vivo in this study. Compared with previously reported aryloxy‐phenylpiperazines, part of these heteroaryloxy derivatives improved their activities by strongly suppressing hypha formation and biofilm formation in C. albicans SC5314. Especially, (9H‐carbazol‐4‐yl)oxy derivatives 25, 26, 27 and 28 exhibited strong activity in reducing C. albicans virulence in both human cell lines in vitro and mouse infection models in vivo. The compound 27 attenuated the virulence of various clinical C. albicans strains, including clinical drug‐resistant C. albicans strains. Moreover, additive effects of the compound 27 with antifungal drugs against drug‐resistant C. albicans strains were also discussed. Furthermore, the compound 27 significantly improved the composition and richness of the faecal microbiota in mice infected by C. albicans. These findings indicate that these piperazine compounds have great potential to be developed as new therapeutic drugs against C. albicans infection.

Abstract Background Highly active anti-retroviral therapy (HAART) can successfully suppress human immunodeficiency virus (HIV) viral replication and reconstruct immune function reconstruction in HIV-1-infected patients. However, about 15–30% of HIV-1-infected patients still fail to recover their CD4+ T cell counts after HAART treatment, which means immune reconstruction failure. Pyroptosis plays an important role in the death of CD4+ T cells in HIV-1- infected patients. The study aims to explore the association between the expression of pyroptosis in peripheral blood and immune function reconstruction in HIV-1- infected patients. Methods One hundred thirty-five HIV-1-infected patients including immunological non-responders (INR) group, immunological responders (IR) group and normal immune function control (NC) group were analyzed. The expression of GSDMD and Caspase-1 in peripheral blood of HIV-1-infected patients were measured by qPCR. The concentrations of GSDMD, Caspase-1, IL-1β and IL-18 in the peripheral serum were quantified by ELISA. The associations between the expression of pyroptosis in peripheral blood and immune function reconstruction were analyzed using multivariate logistic models. Results The relative expression of GSDMD mRNA and caspase-1 mRNA in peripheral blood, as well as the expression of IL-18 cytokine in the INR, were significantly higher than those in the IR and NC (P 0.05). Multivariate logistic analysis showed that the patients with baseline CD4+ T cell counts less than 100 cells/μL (aOR 7.051, 95% CI 1.115–44.592, P = 0.038), high level of expression of Caspase-1mRNA (aOR 2.803, 95% CI 1.065–7.377, P = 0.037) and IL-18 cytokine (aOR 10.131, 95% CI 1.616–63.505, P = 0.013) had significant poor CD4+ T cell recovery. Conclusions The baseline CD4+ T cell counts less than 100 cells/μL, high relative expression of Caspase-1 mRNA, and high expression of IL-18 cytokine are associated factors that affect the reconstruction of immune function.

Abstract Pseudostellaria heterophylla, also called Tai-zi-shen (TZS) in Traditional Chinese Medicine (TCM), is always used clinically to treat spleen deficiency symptoms. Polysaccharides in TZS have various pharmacological activities, including anti-diabetic, immune regulation, and myocardial protection. However, the relationship between the spleen-invigorating effects of TZS or its polysaccharides and intestinal flora are not clear. This study investigated the effects of TZS decoction (PHD) and polysaccharide (PHP) on immune function and intestinal flora in a rat model of spleen deficiency syndrome (SDS) induced by a decoction of raw rhubarb (RRD). PHD and PHP increased immune organ index, alleviated inflammatory cell filtration, and reduced the levels of pro-inflammatory cytokines in rats with spleen deficiency syndrome. In addition, the production of butyric acid was promoted in PHD and PHP groups. Moreover, 16S rRNA gene sequencing showed that PHD and PHP reduced the relative abundance of Firmicutes while increasing the one of Bacteroidetes; significantly increased the abundance of Lactobacillus and decreased the abundance of Rombutsia; and PHP significantly increased the abundance of Alloprevotella. And there was a significant positive correlation between the alleviation of SDS and short-chain fatty acids (SCFAs)-producing bacteria. These findings suggested PHD and PHP, especially PHP, has a potential to relieve spleen deficiency by reducing intestinal inflammation, modulating structure and composition of gut microbiota, and promoting the production of butyric acid.

Abstract Background The incidence of colorectal cancer (CRC) is considered to be the third-highest malignant tumor among all carcinomas. The alterations in cellular bioenergetics (metabolic reprogramming) are associated with several malignant phenotypes in CRC, such as tumor cell proliferation, invasion, metastasis, chemotherapy resistance, as well as promotes its immune escape. However, the expression pattern of metabolism-associated genes that mediate metabolic reprogramming in CRC remains unknown. Methods In this study, we screened out CPT2 by investigating the function of a series of metabolism-related genes in CRC progression by integrating the data from the TCGA and GEO databases. Next, we collected CRC tissues (n = 24) and adjacent non-tumor tissues (n = 8) and analyzed mRNA levels by qRT-PCR, and proteins levels of CPT2 in CRC cell lines by western blotting. CCK-8 assay, colony formation assay, Edu assay and flow cytometry assay were performed to assess the effects of CPT2 on proliferation in vitro. Results We identified 236 metabolism-related genes that are differentially expressed in colorectal cancer, of which 49 up-regulated and 187 down-regulated, and found CPT2 as the most significant gene associated with favorable prognosis in CRC. It was revealed that CPT2 expression was consistently down-regulated in CRC cell lines and tissues. Moreover, knockdown of CPT2 could promote the proliferative ability of CRC cells, whereas over-expression of CPT2 significantly suppressed the cell growth. Conclusion In summary, CPT2 can provide new insights about the progression and occurrence of the tumor as it acts as an independent prognostic factor in CRC sufferers.

Abstract Background Dexmedetomidine was found to be protective against traumatic brain injury (TBI) in animal studies and safe for use in previous clinical studies, but whether it improves TBI patient survival remains to be determined. We sought to answer this question by analyzing data from the MIMIC clinical database. Methods Data for TBI patients from the MIMIC III and MIMIC IV databases were extracted and divided into a dexmedetomidine group and a control group. In the former group, dexmedetomidine was used for sedation, while in the latter, it was not used. Parameters including patient age, the Acute Physiology score III, the Glasgow Coma Scale, other sedatives used, and pupillary response within 24 h were employed in propensity score matching to achieve a balance between groups for further analysis. In-hospital survival and 6-month survival were analyzed by Kaplan–Meier survival analysis and compared by log-rank test. Cox regression was used repeatedly for the univariate analysis, the multivariate analysis, the propensity score-matched analysis, and the inverse probability of treatment weighted analysis of survival data. Meanwhile, the influences of hypotension, bradycardia, infection, and seizure on outcome were also analyzed. Results Different types of survival analyses demonstrated the same trend. Dexmedetomidine significantly improved TBI patient survival. It caused no more incidents of hypotension, infection, and seizure. Hypotension was not correlated with in-hospital mortality, but was significantly correlated with 6-month mortality. Conclusions Dexmedetomidine may improve the survival of TBI patients. It should be used with careful avoidance of hypotension.

To investigate the manoeuvring performance of a body-caudal fin robot fish, a numerical framework combining computational fluid dynamics and multi-body dynamics with a closed-loop control algorithm was established in this study. Within this framework, we modelled a body-caudal fin swimmer as a multi-body system with the shape of a NACA0012 hydrofoil. The manoeuvring performance was investigated by using different curvature magnitudes and distributions along the centre line (the curvature is defined by means of a curvature envelop function as part of the general body undulation equation). To characterize the turning performance, a new parameter named cost of manoeuvring (CoM) is proposed. This parameter provides a combined assessment of the turning radius, linear and angular velocity components, and power. It is found that when the body curvature is introduced, the swimmer switches from straight-line swimming to quasi-steady turning at a constant speed. Further investigations were conducted to study contributions of head and tail deformations on the turning performance by comparing predominantly head and tail curved envelopes. Results reveal that a tail-dominated envelope improves performance, whereas a head-dominated envelope has a negative effect.

Highly active antiretroviral therapy (ART) can effectively inhibit virus replication and restore immune function in most people living with human immunodeficiency virus (HIV). However, an important proportion of patients fail to achieve a satisfactory increase in CD4+ T cell counts. This state is called incomplete immune reconstitution or immunological nonresponse (INR). Patients with INR have an increased risk of clinical progression and higher rates of mortality. Despite widespread attention to INR, the precise mechanisms remain unclear. In this review, we will discuss the alterations in the quantity and quality of CD4+ T as well as multiple immunocytes, changes in soluble molecules and cytokines, and their relationship with INR, aimed to provide cellular and molecular insights into incomplete immune reconstitution.

PurposeThis study aimed to evaluate the changes in the blood flow of the optic disk in patients with nonarteritic anterior ischemic optic neuropathy (NAION) using optical coherence tomography–angiography (OCTA) and to investigate the relationship among the changes in the blood flow of the optic disk, visual field defect, peripapillary retinal nerve fiber layer (RNFL), and macular ganglion cell complex (mGCC).MethodsThis was a prospective observational case series study. A total of 89 patients (89 eyes) with NAION were included in this study. All patients underwent best corrected visual acuity (BCVA), slit-lamp and direct ophthalmoscopic examinations, color fundus photography, visual field test, and blood flow indicators of the radial peripapillary capillaries (RPC) including whole en face image vessel density (VD), peripapillary VD by OCTA, the peripapillary RNFL, and mGCC by spectral-domain optic coherence tomography (OCT). The changes of blood flow in the optic disk at ≤3, 4–8, 9–12, 13–24, and >24 weeks of the natural course of NAION were measured, and the relationship among the changes in the blood flow of the optic disk, visual field defect, peripapillary RNFL, and mGCC was also analyzed.ResultsThe mean age of 89 patients with NAION was 56.42 ± 6.81 years (ranging from 39 to 79). The initial RPC whole en face image VD was significantly reduced after acute NAION (≤3 weeks) (F = 45.598, P < 0.001) and stabilized from the eighth week onward. Over the course of NAION, the superonasal RPC, superior mGCC, and superotemporal RNFL decreased mostly with time (F = 95.658, 109.787, 263.872, respectively; P < 0.001). Maximal correlations were found between superior mGCC and temporosuperior RPC in the NAION phase (R = 0.683, P < 0.01) and between superonasal RPC and superonasal RNFL (R = 0.740, P < 0.01). The mean defect was correlated with temporosuperior RPC (R = −0.281, P < 0.01) and superior mGCC (R = −0.160, P = 0.012).ConclusionOver the course of NAION, OCTA shows a tendency toward change in the retinal capillary plexus of the optic disk. OCTA is proved to be a practical and useful tool for observing papillary perfusion in NAION.

Abstract The probabilistic power flow (PPF) computation involves quantifying and propagating uncertainty over hundreds of variables. Zhao's point estimate method (PEM) has been widely used for PPF computation, and the computational burden increases linearly with respect to the number of PPF inputs. In this paper, Zhao's PEM is reformulated as the Kronecker product of Gauss‐Hermite quadrature and an identity matrix. Following this formulation, a new PEM termed Nested PEM is developed based on Hadamard matrix, which can reduce the computational burden nearly by half relative to Zhao's PEM. In order to consider the dependence among PPF inputs, the extended generalized lambda distribution (EGLD) is employed to model marginal distributions of correlated PPF inputs, and the t$t$‐copula is introduced to map PPF problem to the independent standard normal space. Finally, case studies are conducted on a modified IEEE 118‐bus system to illustrate the proposed PEM.

Abstract Multiple evidence shows that metformin serves as a potential agent for Colorectal Cancer (CRC) treatment, while its molecular mechanisms still require detailed investigation. Here, we revealed that metformin specifically suppressed the proliferation of CRC cells by causing G1/S arrest, and INHBA is a potential target for metformin to play an anti-proliferation effect in CRC. We verified the oncogene role of INHBA by knocking down and overexpressing INHBA in CRC cells. Silencing INHBA abrogated the cell growth, while overexpression INHBA promotes the proliferation of CRC cells. As an oncogene, INHBA was aberrant overexpression in CRC tissues and closely related to the poor prognosis of CRC patients. In mechanism, INHBA is an important ligand of TGF-β signaling and metformin blocked the activation of TGF-β signaling by targeting INHBA, and then down-regulated the activity of PI3K/Akt pathway, leading to the reduction of cyclinD1 and cell cycle arrest. Together, these findings indicate that metformin down-regulates the expression of INHBA, then attenuating TGF-β/PI3K/Akt signaling transduction, thus inhibiting the proliferation of CRC. Our study elucidated a novel molecular mechanism for the anti-proliferation effect of metformin, providing a theoretical basis for the application of metformin in CRC therapy.

Abstract Oxaliplatin is widely used in the frontline treatment of colorectal cancer (CRC), but an estimated 50% of patients will eventually stop responding to treatment due to acquired resistance. This study revealed that diminished MEIS1 expression was detected in CRC and harmed the survival of CRC patients. MEIS1 impaired CRC cell viabilities and tumor growth in mice and enhanced CRC cell sensitivity to oxaliplatin by preventing DNA damage repair. Mechanistically, oxaliplatin resistance following MEIS1 suppression was critically dependent on enhanced FEN1 expression. Subsequently, we confirmed that EZH2-DNMT3a was assisted by lncRNA ELFN1-AS1 in locating the promoter of MEIS1 to suppress MEIS1 transcription epigenetically. Based on the above, therapeutics targeting the role of MEIS1 in oxaliplatin resistance were developed and our results suggested that the combination of oxaliplatin with either ELFN1-AS1 ASO or EZH2 inhibitor GSK126 could largely suppress tumor growth and reverse oxaliplatin resistance. This study highlights the potential of therapeutics targeting ELFN1-AS1 and EZH2 in cell survival and oxaliplatin resistance, based on their controlling of MEIS1 expression, which deserve further verification as a prospective therapeutic strategy.

Validation merely provides the “impression of accuracy” of satellite products but does not deal with their errors. There have been several error correction/adjustment models. Nevertheless, their performances have not been evaluated and compared. In this study, three typical models, namely random forests (RF), cumulative distribution function (CDF), and Kalman filter (KF) were comprehensively evaluated based on the pixel scale ground “truth” regarding their ability to correct errors of coarse-resolution satellite albedo products. Moderate-resolution imaging spectroradiometer albedo product (i.e., MCD43A3 V006) was utilized as an example due to its widespread use and application. These three models all show significant improvements regarding the accuracy of the corrected MCD43A3. Root-mean-square error (RMSEs) decreased from 0.037–0.020, 0.021, and 0.025 for RF, CDF, and KF, respectively. Biases were reduced from -0.018–0.004, -0.001, and -0.001 for these three models, respectively. And R2 was increased from 0.585–0.849, 0.823, and 0.764 for RF, CDF, and KF, respectively. Generally, RF shows the best overall performance, followed by CDF and KF. These three models are more adept at handling the bias of MCD43A3 than their consistency with respect to the pixel scale ground “truth”, and the improvement is the most significant at the sites with large errors. Nevertheless, the performance of RF shows dependence on both the number and representativeness of training samples. When these conditions were not satisfied, CDF performs best in this situation. Regarding the stability of their performance, RF performs better in reducing RMSE while CDF performs better in reducing Bias and improving consistency.

Abstract The Wnt/β-catenin pathway comprises a family of proteins that play critical roles in embryonic development and adult tissue homeostasis. The deregulation of Wnt/β-catenin signalling often leads to various serious diseases, including cancer and non-cancer diseases. Although many articles have reviewed Wnt/β-catenin from various aspects, a systematic review encompassing the origin, composition, function, and clinical trials of the Wnt/β-catenin signalling pathway in tumour and diseases is lacking. In this article, we comprehensively review the Wnt/β-catenin pathway from the above five aspects in combination with the latest research. Finally, we propose challenges and opportunities for the development of small-molecular compounds targeting the Wnt signalling pathway in disease treatment.

A surface soil moisture (SM) condition at high spatiotemportal resolutions is required by regional Earth system applications. Here, we mapped daily 1-km SM in the Babao River Basin in the northwest of China during the summers from 2013 to 2015 using a random forest (RF) method by merging SM information retrieved from in situ measurements, optical/thermal remote sensing, and topographical indices. Relative importance analysis was used to determine the optimal predictors for estimating high-resolution SM. A specific RF model (RFVI+sup) was constructed using the optimal predictors including remote sensing albedo, apparent thermal inertia (ATI), normalized difference vegetation index, normalized difference infrared index 5, soil adjusted vegetation index, and topographical indices (aspect and elevation). The RFVI+sup also accounted for missing observations of the thermal index (e.g., ATI) over the mountainous regions. In the comparison between the SM estimates using the new RFVI+sup model and other RF models, the spatial coverage of available estimates increased from 14% to 64% over the study region, the correlation coefficient values were improved to 0.75, the unbiased root-mean-squared difference values decreased to 0.032 m3/m3. Thus, the proposed RF method provided accurate SM estimates with high spatiotemporal resolution over the mountainous regions, by merging multiresource datasets from in situ measurements, remotely-sensed, and topographical indices.

Over the past 2 to 3 decades, Chinese forests are estimated to act as a large carbon sink, yet the magnitude and spatial patterns of this sink differ considerably among studies. Using 3 microwave (L- and X-band vegetation optical depth [VOD]) and 3 optical (normalized difference vegetation index, leaf area index, and tree cover) remote-sensing vegetation products, this study compared the estimated live woody aboveground biomass carbon (AGC) dynamics over China between 2013 and 2019. Our results showed that tree cover has the highest spatial consistency with 3 published AGC maps (mean correlation value R = 0.84), followed by L-VOD (R = 0.83), which outperform the other VODs. An AGC estimation model was proposed to combine all indices to estimate the annual AGC dynamics in China during 2013 to 2019. The performance of the AGC estimation model was good (root mean square error = 0.05 Pg C and R2 = 0.90 with a mean relative uncertainty of 9.8% at pixel scale [0.25°]). Results of the AGC estimation model showed that carbon uptake by the forests in China was about +0.17 Pg C year−1 from 2013 to 2019. At the regional level, provinces in southwest China including Guizhou (+22.35 Tg C year−1), Sichuan (+14.49 Tg C year−1), and Hunan (+11.42 Tg C year−1) provinces had the highest carbon sink rates during 2013 to 2019. Most of the carbon-sink regions have been afforested recently, implying that afforestation and ecological engineering projects have been effective means for carbon sequestration in these regions.