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Proactive hedging European option is an exotic option for hedgers in the options market proposed recently by Wang et al. It extends the classical European option by requiring option holders to continuously trade in underlying assets according to a predesigned trading strategy, to proactively hedge part of the potential risk from underlying asset price changes. To generalize this option design for practical application, in this study, a proactive hedging option with discrete trading strategy is developed and its pricing formula is deducted assuming the underlying asset price follows Geometric Fractional Brownian Motion. Simulation studies show that proactive hedging option with discrete trading strategy still enjoys strong price advantage compared to the classical European option for majority of parameter space. The observed price advantage is stronger when the underlying asset has more volatility or when the asset price follows closer to Geometric Brownian Motion. Additionally, we found that a higher frequency trading strategy has stronger price advantage if there is no trading cost. The findings in this research strongly facilitate the practical application of the proactive hedging option, making this lower-cost trading tool more feasible. [ABSTRACT FROM AUTHOR]

Atherosclerosis, which is a vascular pathology characterized by inflammation and plaque build-up within arterial vessel walls, acts as the important cause of most cardiovascular diseases. Except for a lipid-depository and chronic inflammatory, increasing evidences propose that epigenetic modifications are increasingly associated with atherosclerosis and are of interest from both therapeutic and biomarker perspectives. The chronic progressive nature of atherosclerosis has highlighted atherosclerosis heterogeneity and the fact that specific cell types in the complex milieu of the plaque are, by far, not the only initiators and drivers of atherosclerosis. Instead, the ubiquitous effects of cell type are tightly controlled and directed by the epigenetic signature, which, in turn, is affected by many proatherogenic stimuli, including low-density lipoprotein, proinflammatory, and physical forces of blood circulation. In this review, we summarize the role of DNA methylation and histone post-translational modifications in atherosclerosis. The future research directions and potential therapy for the management of atherosclerosis are also discussed. 3_oGVuwH1TkeHfgUq_GtC4 Video Abstract [ABSTRACT FROM AUTHOR]

Background: Individuals with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs) are at risk of developing venous thromboembolism (VTE), a serious complication. There is no established clinical model for predicting VTE in the Chinese population. We develop a new risk assessment model (RAM) for IMiD-associated VTE in Chinese MM patients. Methods: We retrospectively selected 1334 consecutive MM patients receiving IMiDs from 16 medical centers in China and classified them randomly into the derivation and validation cohorts. A multivariate Cox regression model was used for analysis. Results: The overall incidence of IMiD-related VTE in Chinese MM patients was 6.1%. Independent predictive factors of VTE (diabetes, ECOG performance status, erythropoietin-stimulating agent use, dexamethasone use, and VTE history or family history of thrombosis) were identified and merged to develop the RAM. The model identified approximately 30% of the patients in each cohort at high risk for VTE. The hazard ratios (HRs) were 6.08 (P < 0.001) and 6.23 (P < 0.001) for the high-risk subcohort and the low-risk subcohort, respectively, within both the derivation and validation cohorts. The RAM achieved satisfactory discrimination with a C statistic of 0.64. The stratification approach of the IMWG guidelines yielded respective HRs of 1.77 (P = 0.053) and 1.81 (P = 0.063). The stratification approach of the SAVED score resulted in HRs of 3.23 (P = 0.248) and 1.65 (P = 0.622), respectively. The IMWG guideline and the SAVED score-based method yielded C statistics of 0.58 and 0.51, respectively. Conclusions: The new RAM outperformed the IMWG guidelines and the SAVED score and could potentially guide the VTE prophylaxis strategy for Chinese MM patients. [ABSTRACT FROM AUTHOR]

Proactive hedging option is an exotic European stock option designed for hedgers. Such option requires option holders to buy in (or sell out) the underlying asset (stock) and allows them to adjust the holdings of the underlying asset per its price changes within an option period. The proactive hedging option is an attractive choice for hedgers because its price is lower than that of classical options and because it completely hedges the risk of exposure for option holders. In this study, the underlying asset price movement is assumed to follow geometric fractional Brownian motion. The pricing formula for proactive hedging call options is derived with a linear position strategy by applying the risk-neutral evaluation principle. We use simulations to confirm that the price of this exotic option is always no more than that of the classical European option under the same parameters. [ABSTRACT FROM AUTHOR]

Gamma interferon (IFN-γ) is known to negatively regulate murine gammaherpesvirus-68 (MHV-68 or γHV-68) replication. This process involves the suppression of the viral gene replication and transcription activator (RTA) promoter, as well as activation of signal transducers and activators of transcription (STAT1). Notably, this effect is gradually attenuated during MHV-68 infection of bone marrow-derived macrophages (BMMs), which raised the possibility that the virus may utilize a mechanism that counteracts the antiviral effect of IFN-γ. By identifying the cellular factors that negatively regulate JAK-STAT1 signaling, we revealed that the infection of BMMs by MHV-68 induces the expression of suppressor of cytokine signaling 1 (SOCS1) and that depletion of SOCS1 restores the inhibitory effect of IFN-γ on virus replication. Moreover, we demonstrated that the expression of SOCS1 was induced as a result of the Toll-like receptor 3 (TLR3) mediated activation of the NF-κB signaling cascade. In conclusion, we report that TLR3-TRAF-NF-κB signaling pathway play a role in the induction of SOCS1 that counteracts the antiviral effect of IFN-γ during MHV-68 infection. This process is cell type-specific: it is functional in macrophages, but not in epithelial cells or fibroblasts. Our study reveals a mechanism that balances the immune responses and the escape of a gamma-herpesvirus in some antigen-presenting cells. [ABSTRACT FROM AUTHOR]

To get strong, stiff and light cylindrical shell, carbon fiber reinforced hierarchical orthogrid stiffened cylinders are designed and fabricated. The cylinder is stiffened by two-scale orthogrid. The primary orthogrid has thick and high ribs and contains several sub-orthogrid cells whose rib is much thinner and lower. The primary orthogrid stiffens the bending rigidity of the cylinder to resist the global instability while the sub-orthogrid stiffens the bending rigidity of the skin enclosed by the primary orthogrid to resist local buckling. The cylinder is fabricated by filament winding method based on a silicone rubber mandrel with hierarchical grooves. Axial compression tests are performed to reveal the failure modes. With hierarchical stiffeners, the cylinder fails at skin fracture and has high specific strength. The cylinder will fail at end crushing if the end of the cylinder is not thickened. Global instability and local buckling are well restricted by the hierarchical stiffeners. [ABSTRACT FROM AUTHOR]

[Display omitted] Martynoside (MAR), a bioactive component in several well-known tonic traditional Chinese herbs, exhibits pro-hematopoietic activity during 5-fluorouracil (5-FU) treatment. However, the molecular target and the mechanism of MAR are poorly understood. Here, by adopting the mRNA display with a library of even-distribution (md-LED) method, we systematically examined MAR-protein interactions in vitro and identified the ribosomal protein L27a (RPL27A) as a key cellular target of MAR. Structural and mutational analysis confirmed the specific interaction between MAR and the exon 4,5-encoded region of RPL27A. MAR attenuated 5-FU-induced cytotoxicity in bone marrow nucleated cells, increased RPL27A protein stability, and reduced the ubiquitination of RPL27A at lys92 (K92) and lys94 (K94). Disruption of MAR binding at key residues of RPL27A completely abolished the MAR-induced stabilization. Furthermore, by integrating label-free quantitative ubiquitination proteomics, transcriptomics, and ribosome function assays, we revealed that MAR restored RPL27A protein levels and thus rescued ribosome biogenesis impaired by 5-FU. Specifically, MAR increased mature ribosomal RNA (rRNA) abundance, prevented ribosomal protein degradation, facilitated ribosome assembly, and maintained nucleolar integrity. Collectively, our findings characterize the target of a component of Chinese medicine, reveal the importance of ribosome biogenesis in hematopoiesis, and open up a new direction for improving hematopoiesis by targeting RPL27A. [ABSTRACT FROM AUTHOR]

Eu 2+ and Eu 3+ codoping phosphor have attracted much attention due to their tunable luminescence color and potential application in lighting and display. In this work, Eu 3+ ions are controllably reduced to Eu 2+ ions in Ba 1- x Sr x Gd 1- y Y y B 9 O 16 to synthesize Eu 2+ and Eu 3+ codoping phosphors by using a high-temperature solid-state method. In the obtained phosphors, the Eu 2+ shows a blue emission of ∼460 nm, and Eu 3+ shows a characteristic red emission with a maximum at ∼617 nm. The relative emission intensity of Eu 2+ and Eu 3+ can be tuned by the incorporation of Sr 2+ or Y 3+ , which results in a tunable luminescence color in the range of purplish blue to purplish red. The results indicate that BaGd 0.2 Y 0.76 B 9 O 16 :0.04Eu simultaneously show bright red and blue emission, and its chromatic coordinate is the closest to the white-light region. The tunable luminescence color is explained on the basis of the crystal structure of BaGdB 9 O 16 . [ABSTRACT FROM AUTHOR]

Purpose: Biogas slurry is increasingly used as crop fertilizer. Previous researches focused on the relationships between aboveground and root growth under biogas slurry application, with little attention to root exudates. The aims of this study were to investigate the influences of biogas slurry application on the quantity and composition of root exudates and their correlations with plant growth. Methods: Four application levels of biogas slurry were performed according to total N of 0, 120, 240, and 480 kg ha−1 (N0, N120, N240, and N480). The labile organic carbon (C), nitrogen (N), sugar and organic acids in root exudates were quantified at four growth stages (seedling, bolting, flowering, and ripening) of oilseed rape. Results: Biogas slurry at N480 significantly increased plant height, branch height, branch number, pod number, pod length, and yield, but it had little influence on root morphology. Biogas slurry significantly decreased root C and N exudation at bolting. Organic acid exudation at bolting and flowering stages in N480 decreased by 44% and 81% compared to control, respectively. C, N exudation at bolting, organic acids at bolting and flowering stages were negatively linearly correlated with the application rate of biogas slurry. C, N, and organic acid exudation at bolting and flowering showed negatively correlations with inflorescence length, pod number and length. Conclusion: Biogas slurry reduced root exudation rates and retained more C and N to improve reproductive growth, promoting the increase in yield. The results improve our understanding of the role of root exudates in plant development. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to depict the clinical features, including myositis specific or associated antibody (MSA/MAA) profile of systemic lupus erythematosus (SLE) patients with muscle involvement in a Chinese cohort. Methods: We retrospectively studied a cohort of 1696 SLE inpatients and screened for concurrent myositis features from January 2013 to June 2021. Propensity score matching was applied to enroll controls without myositis features from our cohort. Demographic, clinical and laboratory variables were collected. MSA/MAA panels containing 16 autoantibodies (TIF1‐γ, MDA5, NXP2, Mi‐2α/β, SAE1, Jo‐1, PL‐7, PL‐12, EJ, OJ, SRP, HMGCR, cN‐1A, PM‐Scl75/100, Ku and Ro52) were tested by line‐blotting assay. Binary logistic regression and K‐means clustering were applied. Results: Forty‐one of 1696 (2.42%) SLE patients in our SLE inpatient cohort showed features of myositis. Binary logistic regression revealed that new‐onset SLE (odds ratio [OR] = 4.77, 95% CI = 1.10–20.57), interstitial lung disease (ILD) (OR = 10.07, 95% CI = 1.65–61.51), positive anti‐U1RNP antibody (OR = 4.38, 95% CI = 1.08–17.75), and Raynaud's phenomenon (OR = 7.94, 95% CI = 1.41–44.69) were associated with muscle involvement. Except for anti‐Ro52 (50%), anti‐Ku antibody (38.2%) was the next frequently detected MSA/MAA in the panel, followed by anti‐NXP2 antibody (11.8%). It was noteworthy that multiple MSA/MAAs (≥2, excluding anti‐Ro52) coexisted in 9 patients. Patients with myositis features were clustered into 2 subgroups. Cluster 1 was characterized by anti‐Ku or anti‐Ro52 with high SLE Disease Activity Index, whereas cluster 2 presented with anti‐U1RNP, Raynaud's phenomenon and pulmonary arterial hypertension resembling mixed connective tissue disease. Conclusion: In our Chinese SLE inpatient cohort, muscle involvement was infrequent. Nevertheless, distinct features in these SLE patients deserve further study. [ABSTRACT FROM AUTHOR]

This document is a retraction notice for an article titled "Targeting of KDM5A by miR-421 in Human Ovarian Cancer Suppresses the Progression of Ovarian Cancer Cells." The retraction was requested by the authors due to concerns about image duplication from another article authored by the first author. The authors were unable to provide a satisfactory explanation for the duplicated images or satisfactory data for the study. The retracted article will remain online but will be digitally watermarked as "Retracted." [Extracted from the article]

SUMMARY: Occupation of living space is one of the main driving forces of adaptive evolution, especially for aquatic plants whose leaves float on the water surface and thus have limited living space. Euryale ferox, from the angiosperm basal family Nymphaeaceae, develops large, rapidly expanding leaves to compete for space on the water surface. Microscopic observation found that the cell proliferation of leaves is almost completed underwater, while the cell expansion occurs rapidly after they grow above water. To explore the mechanism underlying the specific development of leaves, we performed sequences assembly and analyzed the genome and transcriptome dynamics of E. ferox. Through reconstruction of the three sub‐genomes generated from the paleo‐hexaploidization event in E. ferox, we revealed that one sub‐genome was phylogenetically closer to Victoria cruziana, which also exhibits gigantic floating leaves. Further analysis revealed that while all three sub‐genomes promoted the evolution of the specific leaf development in E. ferox, the genes from the sub‐genome closer to V. cruziana contributed more to this adaptive evolution. Moreover, we found that genes involved in cell proliferation and expansion, photosynthesis, and energy transportation were over‐retained and showed strong expression association with the leaf development stages, such as the expression divergence of SWEET orthologs as energy uploaders and unloaders in the sink and source leaf organs of E. ferox. These findings provide novel insights into the genome evolution through polyploidization, as well as the adaptive evolution regarding the leaf development accomplished through biased gene retention and expression sub‐functionalization of multi‐copy genes in E. ferox. Significance Statement: Through the separation, reconstruction and evolutionary dissection of the three sub‐genomes of Euryale ferox, we reveal that the three sub‐genomes have different origins, with one sub‐genome showing a closer phylogenetic relationship to Victoria cruziana, which shows a similar adult leaf development process as that in E. ferox. Further analysis revealed that while all three sub‐genomes promoted the evolution of the specific leaf development process in E. ferox, the genes from the sub‐genome closer to V. cruziana contributed more to this adaptive evolution. Moreover, we found that genes involved in cell proliferation and expansion, photosynthesis, and energy transportation were over‐retained in multi‐copies and showed strong expression association with the different leaf development stages in E. ferox. [ABSTRACT FROM AUTHOR]

Abstract: Filament winding and twice co-curing processes were applied to make advanced carbon fiber reinforced composite (CFRC) sandwich cylinder with lattice cores. Split metallic moulds were designed and adopted for easy demoulding after winding the lattice core. The cylinders were designed with a small tapering to assure tight contact between the lattice core and the inner skin. To avoid local failure at the end of the cylinder, flange structures were placed continuously from the fibers of skins and lattices. Axial compression was carried out to reveal the mechanical behaviors of the fabricated sandwich cylinder. The experiment shows that the advanced making technology shows the promise of lattice sandwich cylinder (LSC) avoiding instability, local buckling, local cracking and debonding. [Copyright &y& Elsevier]

We prospectively investigated the neurological development in infants born from mothers treated with telbivudine (LdT) in the third trimester for prevention of hepatitis B virus (HBV) mother-to-infant transmission. Mothers with high HBV load were assigned to either the LdT group (n = 81, 600 mg of LdT each day from gestational week 28 to delivery) or the Control group (n = 39, untreated). Their infants were followed for 36 months to assess physical and neurological developments with Gesell Developmental Schedule tools. At 12 months after birth, the mean scores in the LdT group for gross motor, fine motor, adaptive, linguistic, and personal social domains were similar to those in the Control group. At 36 months, infants in the LdT group had higher mean scores for gross motor than the Control group (98.42 ± 9.69 vs. 94.54 ± 7.48, P = 0.03). In the LdT group, the rates of normal development were higher for gross motor (96.30% vs. 82.05% P = 0.01) and lower for adaptive (74.07% vs. 92.31% P = 0.02). Multivariate regression analyses showed that exposure to LdT during pregnancy was independently associated with infant's development in gross motor (OR 6.49, 95% CI 1.37–30.20, P = 0.02) and adaptive (OR 0.18, 95% CI 0.05–0.71, P = 0.01) at 36 months. These results suggest that prenatal LdT exposure might affect neurological development in long-term observation. Abbreviations: LdT: telbivudine; HBV: hepatitis B virus; HBsAg: hepatitis B surface antigen; HBeAg: hepatitis Be antigen; HbsAb: hepatitis B surface antibody; ALT: alanine aminotransferase; NA: nucleoside/nucleotide analog; LAM: lamivudine; MTCT: mother-to-child transmission; GDS: Gesell Developmental Schedule; OR: odds ratio; CI: confidence interval; DQ: developmental quotient; RMB: renminbi; BMI: body mass Index; HBIG: hepatitis B immunoglobulin. [ABSTRACT FROM AUTHOR]

Discrete choice experiments have proven useful in areas such as marketing, government planning, medical studies and psychological research, to help understand consumer preferences. To aid in these experiments, several groups of authors have contributed to the theoretical development of D-optimal and A-optimal discrete choice designs under the multinomial logit (MNL) model. In the setting in which the class of feasible designs is too large for complete search, Sun and Dean (J Stat Plann Inference 170:144–157, 2016) proposed a construction method for A-optimal designs for estimating a set of orthonormal contrasts in the option utilities via a linearization of the MNL model. In this paper, we show that the set of A-optimal designs that result from this linearization may or may not include the optimal design under the MNL model itself. We provide an alternative linearization that leads to an information matrix which coincides with that under the MNL model and, consequently, selects the same set of designs as being A-optimal. We obtain a bound for the average variance of a set of contrasts of interest under the MNL model, and show that the construction method of Sun and Dean (2016) can be used to identify A-optimal and A-efficient designs under the MNL model for both equal and unequal utilities. [ABSTRACT FROM AUTHOR]

Purpose: The retinoblastoma binding protein RBP2 (KDM5A) is a histone demethylase that promotes cell growth in many human cancers. A series of functional experiments were conducted to explore the role of miR-421/KDM5A in ovarian cancer cells and their underlying molecular mechanisms. Materials and Methods: Public microarray databases were analyzed to assess KDM5A and miR-421 expression in ovarian cancer. KDM5A was predicted to be a target of miR-421 using software analysis. The expression of the miR-421/KDM5A regulatory axis in ovarian cancer and the mechanisms of its effects on proliferation, migration, and invasion of ovarian cancer cell lines were investigated. Results: Compared with normal ovarian tissues, the expression of KDM5A mRNA and protein was elevated (P< 0.05), and miR-421 expression was reduced in ovarian cancer tissue (P< 0.05). miR-421 was found to bind specifically to the KDM5A gene. Silencing KDM5A or overexpressing miR-421 significantly inhibited proliferation, migration, and invasion of OVCAR-8 and SKOV-3 cells. Similarly, compared with nude mice injected with cells transfected with empty capsids, the in vivo proliferation rate of OVCAR-8 cells after miR-421 overexpression was reduced significantly. Conclusion: The miR-421/KDM5A regulatory axis plays an important role in the development and progression of ovarian cancer cells. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) gastrointestinal (GI) complication is characterized by multi-segment and multi-compartment involvement. The aim of this study is to develop a computed tomography (CT) image-based system for disease evaluation. SLE patients with GI involvement from two independent cohorts were retrospectively included. Baseline abdominal CT scan with intravenous and oral contrast was obtained from each individual. A CT scoring system incorporating the extent of GI tract involvement and intestinal wall thickness, along with extra-GI compartment involvement, was developed and validated. The outcome measurement was the time to GI functional recovery, defined as the time to tolerable per os (PO) intake ≥50% of ideal calories (PO50). A total of 54 and 37 patients with SLE GI involvement were enrolled in the derivation and validation cohorts, respectively. The CT scores for SLE GI involvement were positively correlated with patients' time to PO50 (r = 0.57, p < 0.0001, derivation cohort; r = 0.42, p = 0.0093, validation cohort). Patients with a CT score ≤ 3 had a shorter time to PO50 (median time of 0 day) in pooled cohort, whereas those with a CT score > 3 incurred a significantly prolonged recovery with a median time to PO50 of 13 days (p < 0.0001). The CT-based scoring system may facilitate more accurate assessment and individualized management of SLE patients with GI involvement. [ABSTRACT FROM AUTHOR]

Cryptosporidium spp., Giardia duodenalis , Cyclospora cayetanensis , and Enterocytozoon bieneusi are known etiological agents of self-limiting diarrhea, chronic disorders, and severe debilitating illnesses in humans, particularly children and patients with immunodeficiency diseases. To assess the pathogen carriage status of raw vegetables and fruits and the potential transmission routes of the aforementioned parasites in Henan province, China, a total of 1099 vegetables and fruits samples (21 items) were purchased and collected from agricultural farms or open markets. Cryptosporidium spp., E. bieneusi , C. cayetanensis and G. duodenalis were screened by employing polymerase chain reaction (PCR) amplification of species-specific genes. Three kinds of human pathogenic agent (E. bieneusi , C. cayetanensis and C. parvum) were identified on the surfaces of the vegetables and fruits (3.7%, 41/1099). E. bieneusi was found in 3.5% (38/1099) of the samples, whereas C. cayetanensis and C. parvum were only identified in two (0.2%) and one (0.1%) of the vegetable and fruit samples, respectively. No G. duodenalis contamination was detected in the present study. In total, 12 different E. bieneusi ITS genotypes (eight known and four novel) were detected, of which the ten (EbpA, CM8, CHG19, EbpC, CTS3, Henan-IV, and CHV1 to CHV4) that occurred in 20 samples (20/38, 52.6%) clustered into the previously described high potential zoonotic group 1 in the phylogenetic analysis. The remaining two known genotypes (BEB8 and CD6) detected in 18 samples (18/38, 47.4%) belonged to group 2. That C. cayetanensis , C. parvum and some E. bieneusi genotypes have been reported in humans, highlights the possible risk of foodborne related disease outbreaks. • Three types of protozoan were identified on surface of vegetables and fruits. • These pathogens had previously been reported in human and animals stool. • A risk of parasitic illnesses associated with fresh fruits and vegetables consumption. [ABSTRACT FROM AUTHOR]

The slow onset of traditional antidepressants has become an urgent clinical issue, researchers are constantly exploring new antidepressants with prompt action. Previous studies have found that zinc levels were decreased in serum and brain of depressed patients or animal models. Zinc treatment can improve depressive symptoms and enhance the antidepressant effects of monoamine antidepressants. However, its mechanism of action is still unclear. This present study aims to investigate whether the zinc can enhance the rapid action of traditional antidepressant imipramine and to explore the potential mechanisms of action through the rapid antidepressant targets CREB (cAMP-response element binding protein) and mTOR (mammalian target of the rapamycin). Drug treatment included intraperitoneal injection of imipramine or zinc alone and imipramine plus zinc. Zinc had a rapid enhanced antidepressive effect on the imipramine and achieved a rapid antidepressant effect similar to ketamine. Combination of zinc with imipramine rapidly enhanced the phosphorylation of mTOR Ser2448 and CREB Ser133, and increased the expression of mTOR and CREB, which were dependent on the activation of PKA. In conclusion, combination therapy with zinc and monoamine antidepressants may overcome the problem of slow-onset action of traditional antidepressants in clinical uses. • The slow onset of traditional antidepressants has become an urgent clinical issue. • Zinc can improve depressive symptoms and enhance monoamine antidepressants' efficacy. • PKA, mTOR, CREB are the targets in the mechanisms of rapid antidepressant ketamine. • Zinc rapidly enhanced the efficacy of imipramine through the activation of PKA. • Traditional antidepressants' actions can be fast potentiated by zinc supplementation. [ABSTRACT FROM AUTHOR]

Abstract GPS radio occultation (RO) ionospheric products obtained by Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) mission during the year of 2014 and the observations from 3 digisonde stations which are located at different latitudes are used to study the influence of different time and space collocation windows on the comparisons of the ionospheric characteristic parameters (ICPs), including the peak density and peak height, derived from the two techniques. The results show that the correlation coefficients (CC) and the standard deviation of the absolute biases (SDAB) between the ICPs derived from the two techniques vary distinctly under different spatial and time collocation windows. Generally, the CC (SDAB) of the ICPs decrease (increase) as the size of the collocation window increases in time dimension or in space dimension. The rate of change of the statistic parameters with the increase in the size of the collocation window in time dimension and space dimension is analyzed for each digisonde station. It is found that within the collocation window of 60 m i n , 20 ° , 20 ° , the influence of the increase of 1 ° in the space window on the statistical comparison is much more significant than that of the increase of 1 min in the time window, and it is suggested that there can be appropriate relaxation on the time window within the threshold of 60 min to get a balance between the quality of the comparison results and the number of the matched pairs. In addition, it is found that the same variations in the longitude window and in the latitude window may have different influences on the comparison results when the horizontal gradients in electron density are distinctly different along different directions at the digisonde station, and strict space collocation window is preferred when comparing the observations from COSMIC RO with those from the digisonde station in such cases. [ABSTRACT FROM AUTHOR]

Biogas slurry has ammonia (NH 4 +-N) abundance and is applied in a major production region, Southwest China. This study compared the consequent environmental risk of nitrogen (N) leaching in two major soils, yellow soil and calcareous soil, in Southwest China, and investigated underlying microbial mechanisms. Biogas slurry was applied to soil columns packed with yellow soil and calcareous soil at the rates of 0 to 240 kg N/hm2. Soil N leaching, N contents, and N-related bacteria gene abundances were measured, with their responses to slurry application analyzed through partial least squares-structural equation modeling (PLS-SEM). Nitrate (NO 3 −-N) dominated in N leaching as a result of soil NO 3 −-N accumulation and microbial regulation. Nitrification increased yellow soil NO 3 −-N contents and leaching, however, both were inhibited by dissimilatory nitrate reduction to ammonium (DNRA) and assimilatory nitrate reduction to ammonium (ANRA) in the two soils. Further, NO 3 −-N leaching was enhanced by biogas slurry in yellow soil by promoting nitrification and preventing DNRA and ANRA; but it was not affected in calcareous soil. Accordingly, yellow soil has higher NO 3 −-N leaching than calcareous soil. The leaching can be regulated by the DNRA and ANRA in both soils, which were overlooked relative to nitrification but probably reactive to slurry, warranting further exploration. [Display omitted] • Yellow soil has higher nitrate leaching than calcareous soil with slurry application. • Slurry raises yellow soil nitrate leaching via nitrification and nitrate reduction. • Slurry increases calcareous soil nitrate but not the leaching via nitrate reduction. • Nitrification controls yellow soil nitrate leaching but not that in calcareous soil. • Nitrate reduction as DNRA and ANRA regulate both soils' nitrate leaching. [ABSTRACT FROM AUTHOR]

Hierarchical metallic thin-walled tubes are more weight-efficient than single-cell tubes (STs) in energy absorption. Tubes with regular hexagonal single-cell section and hierarchical section are designed, tested and analyzed. Crushing mechanisms of these structures are revealed through finite element analyses (FEAs) and axial compression experiments. It is found that for hierarchical tubes (HTs) there are three folding styles, including sub-cell folding, mixed folding and global folding. Sub-cell folding greatly increases the mean crushing force (MCF) of the tube and the MCF reaches to the apex when appears the mixed folding, which is the transition from sub-cell folding to global bending. Plastic models for these three folding styles are built and consistently predict the MCF. The research indicates that the HT is a more weight-efficient energy absorber. [ABSTRACT FROM AUTHOR]

Background: Clinical reports have shown that scopolamine produces a rapid (3-4 d) and potent anti-depressive response without severe adverse effects. Animal experiments have proven that scopolamine induces mTOR pathway activation in an AMPAR dependent manner. The present study aimed to determine the role of PKA in scopolamine-induced potentiation of AMPAR, as well as in mTOR pathway activation and rapid antidepressant effects.Methods: We utilized electrophysiological recording, Western blotting, and behavior tests to examine the effects of scopolamine, the selective M2 cholinergic receptor antagonist methoctramine, and H89, a PKA specific inhibitor on AMPAR potentiation, mTOR pathway activation, and behavioral responses in a rat depression model of learned helplessness.Results: Scopolamine (1μM) rapidly increased AMPAR-fEPSP amplitudes and membrane GluA1 expression in CA1 region of hippocampal slices, both of which were abolished by H89. Moreover, scopolamine promoted AMPAR phosphorylation on GluA1 ser845, a PKA site involved in GluA1 membrane insertion. H89 disrupted both GluA1 ser845 phosphorylation and mTOR activation, as well as the antidepressant effects of scopolamine as determined via forced swim test. Additionally, methoctramine mimicked the effects of scopolamine on phosphorylation and counter-depressive action in a PKA-dependent manner.Limitations: Only one test was used to evaluate depressive behavior, and gene knock-out rats were not yet utilized to refine our hypotheses.Conclusion: Our findings revealed that PKA pathway is necessary for scopolamine-induced synaptic plasticity and mTOR pathway activation, and indicated that a potential M2-PKA mechanism underlies scopolamine's antidepressant effects. Such findings suggest that GluA1 ser845 phosphorylation may be a trigger event for scopolamine's actions, and that PKA may represent a novel target for the treatment of depressive symptoms. [ABSTRACT FROM AUTHOR]

This paper studies the plastic collapse mechanisms of uniaxially-loaded cylindrical shell-plate periodic honeycombs with identical mass (or relative density) but varying geometric parameters, by series of in-plane and out-of-plane experiments and finite element numerical simulations. The coupled experimental-numerical results show that mechanical properties of the honeycomb can be optimized in all three loading cases, thanks to the complementary changes of the mechanical properties of cylindrical shell and plate as the geometric parameters vary. The work presents a concept to optimize lattice structures by combining different substructures, and can be used in designing new low-density honeycomb structures with desired mechanical requirements but less base materials and weight. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Although individuals with posttraumatic stress disorder (PTSD) are at heightened risk for several serious health conditions, research has not examined how having PTSD impacts receipt of invasive procedures that may alleviate these problems. We examined whether PTSD, after controlling for major depression, was associated with odds of receiving common types of major invasive procedures, and whether race, ethnicity, and gender was associated with odds of procedures. Methods: Veterans Health Administration patients with PTSD and/or depression were age-matched with patients without these disorders. The odds of invasive hip/knee, digestive system, coronary artery bypass graft/percutaneous coronary intervention (CABG/PCI), and vascular procedures during FY2006–2009 were modeled for the full sample of 501,489 patients and for at-risk subsamples with medical conditions alleviated by the procedures examined. Results: Adjusting for demographic covariates and medical comorbidity, PTSD without depression was associated with decreased odds of all types of procedures (odds ratios [OR] range 0.74–0.82), as was depression without PTSD (OR range 0.59–0.77). In analyses of at-risk patients, those with PTSD only were less likely to undergo hip/knee (OR=0.78) and vascular procedures (OR=0.73) but not CABG/PCI. African-Americans and women at-risk patients were less likely to undergo hip/knee, vascular, and CABG/PCI procedures (OR range 0.31–0.82). Conclusion: With the exception of CABG/PCI among at-risk patients, Veterans with PTSD and/or depression were less likely to undergo all types of procedures examined. Future studies should examine the reasons for this disparity and whether it is associated with subsequent adverse outcomes. [Copyright &y& Elsevier]

Rationale, aims and objectives Acute fever is the most common early clinical symptom of many critical illnesses with a high mortality rate. It is necessary to identify patients with severe acute fever early and accurately. The aim of this study is to identify risk factors for critically ill outpatients with acute fever and formulate activation criteria of adult fever state score (AFSS) to alert outpatient clinic doctors. Methods Retrospectively, 357 adult patients with acute fever were divided into two groups: 180 patients with a severe state and 177 patients with a mild state. Logistic regression was used to determine risk factors for the severe state. Risk factors were weighted and an AFSS was formulated. A receiver operating characteristic (ROC) analysis of weighted cumulative scores was performed to evaluate the diagnostic accuracy of AFSS, and the kappa test was used to confirm diagnostic reliability. A χ2-test for trend was applied to determine the relevance between AFSS and admission rate and in-hospital mortality. A Kruskal-Wallis test was used to examine the relationship between AFSS and length of stay. Results Risk factors for state included: old age, long fever course, past medical history, abnormal temperature, abnormal respiratory rate, abnormal heart rate, abnormal mean arterial pressure and abnormal peripheral white blood cell count. The area under the ROC curve of AFSS was 0.964 and ≥8 points predicted severe state; the Kappa value was 0.801. With an increase in score, there was an increase in admission rate, mortality rate and length of stay. The forecast performance of AFSS was superior to the modified early warning score. Conclusions The AFSS has high diagnostic accuracy and reliability for the early identification of patients with severe acute fever. [ABSTRACT FROM AUTHOR]

Acute fever is the most common clinical symptom for infectious diseases. It is necessary to identify risk factors for infectious patients with acute fever and formulate activation criteria of early warning infectiosity score system (EWIS) to alert outpatient clinic doctors. Logistic regression analysis was used to determine risk factors for infectious diseases from the clinical data of 758 patients with acute fever. Risk factors were weighted and an EWIS was formulated. A receiver operator characteristic (ROC) analysis of weighted cumulative scores was performed to evaluate the diagnostic accuracy of EWIS, and the Kappa test used to confirm diagnostic reliability. A χ-test for trend was applied to determine the relevance between EWIS and incidence of infectious diseases. Risk factors for infections included conjunctival hyperaemia, rash, diarrhoea, increased alanine aminotransferase, splenomegaly and abnormal percentage of peripheral neutrophils (NE%). Risk factors were weighted and tabulated. The areas under the ROC curves of the EWIS was 0.929 and ≥4 points predicted infectious diseases, and the Kappa values were 0.750. As the score increased, the incidence of infectious diseases increased. The areas under the ROC curves of the EWIS predicting on single viral and bacterial infectious diseases were 0.961 and 0.896, and the Kappa values were 0.807 and 0.701, respectively. Risk factors for infections have been identified, quantified and formulated into a table of EWIS that have high diagnostic accuracy and reliability for the early identification of contagious diseases. [ABSTRACT FROM AUTHOR]

Increased de novo lipogenesis is a hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD) in obesity, but the macronutrient carbon source for over half of hepatic fatty acid synthesis remains undetermined. Here, we discover that dietary protein, rather than carbohydrates or fat, is the primary nutritional risk factor for MASLD in humans. Consistently, ex vivo tracing studies identify amino acids as a major carbon supplier for the tricarboxylic acid (TCA) cycle and lipogenesis in isolated mouse hepatocytes. In vivo, dietary amino acids are twice as efficient as glucose in fueling hepatic fatty acid synthesis. The onset of obesity further drives amino acids into fatty acid synthesis through reductive carboxylation, while genetic and chemical interventions that divert amino acid carbon away from lipogenesis alleviate hepatic steatosis. Finally, low-protein diets (LPDs) not only prevent body weight gain in obese mice but also reduce hepatic lipid accumulation and liver damage. Together, this study uncovers the significant role of amino acids in hepatic lipogenesis and suggests a previously unappreciated nutritional intervention target for MASLD., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Myocardial mitochondrial dysfunction underpins the pathogenesis of heart failure (HF), yet therapeutic options to restore myocardial mitochondrial function are scarce. Epigenetic modifications of mitochondrial DNA (mtDNA), such as methylation, play a pivotal role in modulating mitochondrial homeostasis. However, their involvement in HF remains unclear., Methods: Experimental HF models were established through continuous angiotensin II and phenylephrine (AngII/PE) infusion or prolonged myocardial ischemia/reperfusion injury. The landscape of N 6 -methyladenine (6mA) methylation within failing cardiomyocyte mtDNA was characterized using high-resolution mass spectrometry and methylated DNA immunoprecipitation sequencing. A tamoxifen-inducible cardiomyocyte-specific Mettl4 knockout mouse model and adeno-associated virus vectors designed for cardiomyocyte-targeted manipulation of METTL4 (methyltransferase-like protein 4) expression were used to ascertain the role of mtDNA 6mA and its methyltransferase METTL4 in HF., Results: METTL4 was predominantly localized within adult cardiomyocyte mitochondria. 6mA modifications were significantly more abundant in mtDNA than in nuclear DNA. Postnatal cardiomyocyte maturation presented with a reduction in 6mA levels within mtDNA, coinciding with a decrease in METTL4 expression. However, an increase in both mtDNA 6mA level and METTL4 expression was observed in failing adult cardiomyocytes, suggesting a shift toward a neonatal-like state. METTL4 preferentially targeted mtDNA promoter regions, which resulted in interference with transcription initiation complex assembly, mtDNA transcriptional stalling, and ultimately mitochondrial dysfunction. Amplifying cardiomyocyte mtDNA 6mA through METTL4 overexpression led to spontaneous mitochondrial dysfunction and HF phenotypes. The transcription factor p53 was identified as a direct regulator of METTL4 transcription in response to HF-provoking stress, thereby revealing a stress-responsive mechanism that controls METTL4 expression and mtDNA 6mA. Cardiomyocyte-specific deletion of the Mettl4 gene eliminated mtDNA 6mA excess, preserved mitochondrial function, and mitigated the development of HF upon continuous infusion of AngII/PE. In addition, specific silencing of METTL4 in cardiomyocytes restored mitochondrial function and offered therapeutic relief in mice with preexisting HF, irrespective of whether the condition was induced by AngII/PE infusion or myocardial ischemia/reperfusion injury., Conclusions: Our findings identify a pivotal role of cardiomyocyte mtDNA 6mA and the corresponding methyltransferase, METTL4, in the pathogenesis of mitochondrial dysfunction and HF. Targeted suppression of METTL4 to rectify mtDNA 6mA excess emerges as a promising strategy for developing mitochondria-focused HF interventions., Competing Interests: None.

Glucose oxidase (GOx) is often used to starvation therapy. However, only consuming glucose cannot completely block the energy metabolism of tumor cells. Lactate can support tumor cell survival in the absence of glucose. Here, we constructed a nanoplatform (Met@HMnO 2 -GOx/HA) that can deplete glucose while inhibiting the compensatory use of lactate by cells to enhance the effect of tumor starvation therapy. GOx can catalyze glucose into gluconic acid and H 2 O 2 , and then HMnO 2 catalyzes H 2 O 2 into O 2 to compensate for the oxygen consumed by GOx, allowing the reaction to proceed sustainably. Furthermore, metformin (Met) can inhibit the conversion of lactate to pyruvate in a redox-dependent manner and reduce the utilization of lactate by tumor cells. Met@HMnO 2 -GOx/HA nanoparticles maximize the efficacy of tumor starvation therapy by simultaneously inhibiting cellular utilization of two carbon sources. Therefore, this platform is expected to provide new strategies for tumor treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Acute kidney injury (AKI) is a critical medical condition characterized by high morbidity and mortality rates. The pathogenesis of AKI potentially involves bursts of reactive oxygen species (ROS) bursts and elevated levels of inflammatory mediators. Developing nanoparticles (NPs) that downregulate ROS and inflammatory mediators is a promising approach to treat AKI. However, such NPs would be affected by the glomerular filtration barrier (GFB). Typically, NPs are too large to penetrate the glomerular system and reach the renal tubules─the primary site of AKI injury. Herein, we report the development of ultrasmall carbon dots-gallic acid (CDs-GA) NPs (∼5 nm). These NPs exhibited outstanding biocompatibility and were shown not only to efficiently eliminate ROS and alleviate oxidative stress but also to suppress the activation of the NF-κB signaling pathway, leading to a reduction in the release of inflammatory factors. Importantly, CDs-GA NPs were shown to be able to rapidly accumulate rapidly in the renal tissues without the need for intricate targeting strategies. In vivo studies demonstrated that CDs-GA NPs significantly reduced the incidence of cisplatin (CDDP)-induced AKI in mice, surpassing the efficacy of the small molecular drug, N -acetylcysteine. This research provides an innovative strategy for the treatment of AKI.

Objectives: To investigate the effectiveness of belimumab on active lupus nephritis (LN) and explore the predictors, including serological biomarkers, of renal response to belimumab in a real-world setting., Methods: This multicentre, real-world observational study enrolled patients with active LN receiving intravenous belimumab as an add-on therapy with 24-hour urine protein≥1 g and estimated glomerular filtration rate≥30 mL/min/1.73 m 2 at baseline. Complete renal response (CRR), partial renal response (PRR), no renal response (NRR) and primary efficacy renal response (PERR) were evaluated. Multivariable logistic regression was used to identify risk factors for NRR to belimumab at 6 months., Results: Among the 122 patients enrolled, the proportions of patients achieving CRR, PRR, NRR and PERR were 35.9%, 17.1%, 47.0% and 44.4% at 6 months (n=117) and 55.6%, 19.4%, 26.4% and 58.3% at 12 months (n=72), respectively. Proteinuria, daily prednisone dosage and Systemic Lupus Erythematosus Disease Activity Index 2000 scores significantly decreased at 6 and 12 months (p<0.0001). NRR at 6 months (NRR6) was the strongest negative predictor of CRR at 12 months. Baseline anti-dsDNA positivity inversely predicted NRR6 (OR=0.32,95% CI=0.10 to 0.98, p=0.049), while anti-SSA/Ro60 positively predicted NRR6 (OR=3.16, 95% CI=1.14 to 8.74, p=0.027). The combination of anti-SSA/Ro60 and anti-dsDNA serotype quantitatively predicted belimumab renal response., Conclusion: The effectiveness of belimumab was reproducible in Chinese patients with active LN. The simple yet interesting serotype predictive model needs further validation and its possible underlying mechanistic relevance deserves further exploration., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cadmium ion (Cd 2+ ) stress is a major abiotic stressor affecting plant photosynthesis. However, the impact of sustained high-concentration Cd stress on the photosynthetic electron transport chain of aquatic plants is currently unclear. Here, prompt fluorescence (PF), delayed fluorescence (DF), and P700 signals were simultaneously measured to investigate the effect of Cd stress on photosynthesis in water dropwort [ Oenanthe javanica (Blume) DC.]. We aimed to elucidate how Cd stress continuously affects the electron transport chain in this species. The PF analysis showed that with prolonged Cd stress, the F J , F I and F P steadily decreased, accompanied by a positive shift in the K-band and L-band. Moreover, JIP-test parameters, including TR O /ABS, ABS/CS O , TR O /CS O and PI ABS , were significantly reduced. The P700 signals showed that exposure to Cd stress hindered both the fast decrease and slow increase phases of the MR transient, ultimately resulting in a gradual reduction in both V PSI and V PSII-PSI . The DF analysis showed a gradual decrease in the I 1 and I 2 values as the duration of stress from Cd increased. The above results suggested that Cd stress affected the photosynthetic electron transport in water dropwort by influencing the amount of active PSII and PSI, primarily affecting PSII RCs in the early to mid-stages and PSI reductive activity in the later stage., Competing Interests: The authors declare no conflicts of interest.

Aqueous supercapacitors have occupied a significant position among various types of stationary energy storage equipment, while their widespread application is hindered by the relatively low energy density. Herein, N/F co-doped carbon materials activated by manganese clusters (NCM) are constructed by the straightforward experimental routine. Benefiting from the elevated conductivity structure at the microscopic level, the optimized NCM-0.5 electrodes exhibited a remarkable specific capacitance of 653 F g -1 at 0.4 A g -1 and exceptional cycling stability (97.39% capacity retention even after 40,000 cycles at the scanning rate of 100 mV s -1 ) in a neutral 5 M LiCl electrolyte. Moreover, we assembled an asymmetric device pairing with a VO x anode (NCM-0.5//VO x ), which delivered a durable life span of 95% capacity retention over 30,000 cycles and an impressive energy density of 77.9 Wh kg -1 . This study provides inspiration for transition metal element doping engineering in high-energy storage equipment.

Background: Indeterminate readout of the quantitative interferon-γ release test (QFT) for Mycobacterium tuberculosis screening is a specific laboratory finding for systemic lupus erythematosus (SLE), which may be due to T-cell exhaustion and abnormal programmed death receptor 1 (PD-1)/programmed death-ligand 1 (PD-L1) signalling., Methods: We enrolled 104 patients with SLE and 225 with other rheumatic musculoskeletal diseases (RMDs) who presented to the outpatient clinic between 2020 and 2023. Twenty healthy donors served as the controls. The QFT was performed in all participants, and those with indeterminate results were compared among the groups. Immunophenotyping and functional assays were performed using blood mononuclear cells. Interferon (IFN)-γ was detected in vitro and ex vivo in patients with SLE with indeterminate or negative QFT results, before or after rituximab therapy., Results: 104 patients with SLE had a significantly higher rate of indeterminate QFT results was significantly higher (17.31%) than that of 225 patients with RMD (3.56%). Patients with SLE with indeterminate QFT had more active disease (SLEDAI-2K, mean 10.94 vs 4.02, p<0.0001), including a higher incidence of active nephritis (55.56% vs 29.07%). Indeterminate QFT in SLE is mainly caused by an insufficient IFN-γ response in CD8+T cells with exhausted immunophenotypes. The abnormal interaction between exhausted PD-1 high CD8 + T cells and activated PD-L1 low memory B cells in SLE can be reversed with a PD-1 agonist or increased PD-L1 expression. Rituximab treatment indirectly reversed this IFN-γ response., Conclusion: The PD-1/PD-L1 signalling pathway, which governs the crosstalk between exhausted CD8 + T cells and activated memory B cells, is a mechanistic explanation for insufficient interferon-γ response in patients with SLE., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To characterize the in vivo corneal epithelial thickness (CET) remodeling profile in a population of eyes after small incision lenticule intrastromal keratoplasty (SMI-LIKE) for hyperopia., Methods: The CET profile was measured by RTVue-100 Fourier-domain OCT system across the central 6-mm diameter of the cornea of 17 eyes from 12 subjects (five males and seven females) who accepted corneal stromal lens implantation surgery for correcting hyperopia. The CET were measured at positions with a radius of 0-1.0 mm, 1.0-2.5 mm (divided into eight quadrants) and 2.5-3.0 mm (divided into eight quadrants) from the corneal center. Corneal maximum simulated keratometry (Km) was measured by Pentacam HR anterior segment analyzer to analyze CET changes. The examination data of subjects were collected in four time periods, which were preoperative, short-term postoperative (one week after surgery), mid-term postoperative (the last review within 3-6 months after surgery), and long-term postoperative (the last review over 1-2.5 years after surgery). The changes of CET were compared and analyzed in the four time periods., Results: Mean CET in 0-1.0 mm, 1.0-2.5 mm and 2.5-3.0 mm of the cornea decreased in one week after surgery, respectively, as compared to CET in the preoperative period, which turned from 55.06 ± 0.82 μm、54.42 ± 0.75 μm、53.46 ± 0.60 μm to 51.18 ± 1.05 μm (P = 0.005), 49.38 ± 0.70 μm (P = 0.000), 51.29 ± 0.59 μm (P = 0.025). In the mid-term postoperative period, mean CET in 0-1.0 mm and 1.0-2.5 mm areas kept thinner than mean CET in the preoperative period, CET in 0-1.0 mm is 50.59 ± 0.76 μm (P = 0.000),CET in 1.0-2.5 mm is 50.23 ± 0.57 μm (P = 0.000), while mean CET in 2.5-3.0 mm area recovered to the same thickness as the preoperative level, which is 54.36 ± 0.66 μm (P = 1.000), until the long-term period, CET stabilized in the above doughnut pattern., Conclusions: After stromal lenticule implantation for hyperopia, CET showed a remodeled form of thinning in the 0-2.5 mm area and thickening in the 2.5-3.0 mm area, and remained stable within one year after surgery., (© 2024. The Author(s).)

Background: MicroFlow imaging (MFI) is a novel noninvasive ultrasound (US) technique that depicts microcirculatory blood vessels in the kidney while filtering out tissue motion and enhancing blood flow signals. We aimed to investigate the value of MFI for the detection of renal microvascular perfusion in chronic kidney disease caused by stage I-II membranous nephropathy (MN)., Methods: Seventy-six participants including biopsy-proven MN (n=38) and healthy volunteers (n=38) were prospectively examined using MFI from March 2020 to December 2020. In addition, patients with MN were subdivided into a mild group, a moderate group, and a severe group based on the results of vascular pathology evaluation. All MFI images were analyzed by Image Pro Plus to obtain a cortical vascular index (VI). Basic patient information, relative US parameters and laboratory results were then acquired for each participant. Finally, after the univariate analysis among multiple groups, binary logistic regression (forward LR) and ordered logistic regression were used for multivariate analysis. Significance was set at P<0.05., Results: VI was significantly lower in MN patients compared with that of healthy controls (0.65±0.09 vs. 0.35±0.18, P<0.001). After multivariate analysis, we found that the exploratory diagnostic performance of VI [area under the curve (AUC): 0.94; 95% confidence interval (CI): 0.89-0.99] outperformed that of serum creatinine (Scr) (AUC: 0.87; 95% CI: 0.79-0.95) in identifying MN. We also observed considerable differences among MN groups in parameters including VI (P=0.006), estimated glomerular filtration rate (eGFR) (P=0.037), shape (P=0.013), and impression (P=0.007). In addition, in the group with mild vascular damage, the exploratory diagnostic performance of VI (AUC: 0.79; 95% CI: 0.64-0.94) was better than other parameters, such as eGFR (AUC: 0.63; 95% CI: 0.43-0.84)., Conclusions: MFI detected abnormal renal microvascular perfusion in patients with MN (particularly in those with early vascular damage or preserved renal function) without the use of a contrast agent. Combining MFI with B-mode US can improve the predictive performance of traditional kidney US., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1010/coif). The authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Aims: To analyse spatial and temporal changes in the global burden of diabetes mellitus (DM) attributable to dietary factors from 1990 to 2019., Materials and Methods: The burden of DM was analysed in terms of age-standardized disability-adjusted life-year (DALY) rates and age-standardized death rates (ASDRs), which were obtained from the Global Burden of Disease Study 2019, and their corresponding estimated annual percentage changes (EAPCs)., Results: The ASDR exhibited a decreasing trend (EAPC = -0.02), while the age-standardized DALY rate exhibited an increasing trend (EAPC = 0.65). Forty-four percent of the burden of DM was attributable to dietary factors, with the three largest contributors being high intake of red meat, high intake of processed meat, and low intake of fruit. Residence in a region with a high sociodemographic index (SDI) was associated with a diet low in whole grains and high in red meat and processed meat, while residence in a low-SDI region was associated with a diet low in whole grains and fruits, and high in red meat., Conclusions: The age-standardized DALYs of DM attributable to dietary factors increased between 1990 and 2019 but differed among areas. The three largest dietary contributors to the burden of DM were high intake of red meat, high intake of processed meat, and low intake of fruit., (© 2023 John Wiley & Sons Ltd.)

Objectives: To explore the differences in clinical characteristics, prognosis, and risk factors between type I and type II endometrial cancer (EC)., Materials and Methods: We retrospectively collected EC patients diagnosed with type I or type II EC from 2009 to 2021 in the First Affiliated Hospital of Zhengzhou University., Results: In total, 606 eligible EC patients (396 type I, and 210 type II) were included. Baseline analyses revealed that type II patients were older, had more advanced clinical stage, were more likely to receive chemoradiotherapy, and had higher incidence of myometrial infiltration, cervix involvement, lymph node metastasis and positive ascites cytology. Type II significantly favored poorer overall survival (OS) (HR = 9.10, 95%CI 4.79-17.28, P < 0.001) and progression-free survival (PFS) (HR = 6.07, 95%CI 2.75-13.37, P < 0.001) compared to type I. For all included EC, univariate and multivariate COX analyses revealed age, myometrial infiltration and pathological type were independent risk factors for OS and PFS. Subgroup analyses identified age, menopause, clinical stage, and lymph node metastasis as independent risk factors for type I regarding OS. While age, myometrial infiltration and chemoradiotherapy were identified as risk and protective factors for type II regrading OS. Age and cervix involvement were identified as independent risk factors for type I regarding PFS. Myometrial infiltration was identified as independent risk factor for type II regarding PFS., Conclusion: Type II patients shared different clinical characteristics and worse prognosis compared to type I, and their independent risk and protective factors also varied., (© 2023. The Author(s).)

Abstract: Heart failure with preserved ejection fraction (HFpEF) is highly prevalent, accounting for 50% of all heart failure patients, and is associated with significant mortality. Sodium-glucose cotransporter subtype inhibitor (SGLT2i) is recommended in the AHA and ESC guidelines for the treatment of HFpEF, but the mechanism of SGLT2i to prevent and treat cardiac remodeling and dysfunction is currently unknown, hindering the understanding of the pathophysiology of HFpEF and the development of novel therapeutics. HFpEF model was induced by a high-fat diet (60% calories from lard) + N [w] -nitro- l -arginine methyl ester ( l -NAME-0.5 g/L) (2 Hit) in male Sprague Dawley rats to effectively recapture the myriad phenotype of HFpEF. This study's results showed that administration of dapagliflozin (DAPA, SGLT2 inhibitor) significantly limited the 2-Hit-induced cardiomyocyte hypertrophy, apoptosis, inflammation, oxidative stress, and fibrosis. It also improved cardiac diastolic and systolic dysfunction in a late-stage progression of HFpEF. Mechanistically, DAPA influences energy metabolism associated with fatty acid intake and mitochondrial dysfunction in HFpEF by increasing β-hydroxybutyric acid (β-OHB) levels, directing the activation of citrate synthase, reducing acetyl coenzyme A (acetyl-CoA) pools, modulating adenosine 5'-triphosphate production, and increasing the expression of mitochondrial oxidative phosphorylation system complexes I-V. In addition, following clinical DAPA therapy, the blood levels of β-OHB and citrate synthase increased and the levels of acetyl-CoA in the blood of HFpEF patients decreased. SGLT2i plays a beneficial role in the prevention and treatment of cardiac remodeling and dysfunction in HFpEF model by attenuating cardiometabolic dysregulation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Epidemiological studies emphasize the link between metabolic factors and thyroid cancer. Using Mendelian randomization (MR), we assessed the possible causal impact of metabolic factors on thyroid cancer for the first time., Methods: Summary statistics for metabolic factors and thyroid cancer were obtained from published Genome-wide association studies. The causal relationships were assessed using the inverse-variance weighted (IVW) method as the primary method through a two-sample Mendelian Randomization (MR) analysis. To account for the potential existence of horizontal pleiotropy, four additional methods were employed, including Mendelian Randomization-Egger (MR-Egger), weighted median method (WM), simple mode, and weighted mode method. Given the presence of interactions between metabolic factors, a multivariable MR analysis was subsequently conducted., Results: The results showed there was a genetic link between HDL level and protection effect of thyroid cancer using IVW (OR= 0.75, 95% confidence intervals [CIs] 0.60-0.93, p=0.01) and MR-Egger method (OR= 0.70, 95% confidence intervals [CIs] 0.50- 0.97, p=0.03). The results remained robust in multivariable MR analysis for the genetic link between HDL level and protection effect of thyroid cancer (OR= 0.74, 95% confidence intervals [CIs] 0.55-0.99, p=0.04)., Conclusions: This study suggests a protection role for HDL on thyroid cancer. The study findings provide evidence for the public health suggestion for thyroid cancer prevention. HDL's potential as a pharmacological target needs further validation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liang and Sun.)

Accurate evaluation of patients with disorders of consciousness (DoC) is crucial for personalized treatment. However, misdiagnosis remains a serious issue. Neuroimaging methods could observe the conscious activity in patients who have no evidence of consciousness in behavior, and provide objective and quantitative indexes to assist doctors in their diagnosis. In the review, we discussed the current research based on the evaluation of consciousness rehabilitation after DoC using EEG, fMRI, PET, and fNIRS, as well as the advantages and limitations of each method. Nowadays single-modal neuroimaging can no longer meet the researchers` demand. Considering both spatial and temporal resolution, recent studies have attempted to focus on the multi-modal method which can enhance the capability of neuroimaging methods in the evaluation of DoC. As neuroimaging devices become wireless, integrated, and portable, multi-modal neuroimaging methods will drive new advancements in brain science research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Gao, Xiang, Sun and Yang.)

Objectives: A 24-hour urine protein (24hUP) is a key measurement in the management of lupus nephritis (LN); however, trajectories of 24hUP in LN is poorly defined., Methods: Two LN cohorts that underwent renal biopsies at Renji Hospital were included. Patients received standard of care in a real-world setting and 24hUP data were collected over time. Trajectory patterns of 24hUP were determined using the latent class mixed modelling (LCMM). Baseline characters were compared among trajectories and multinomial logistic regression was used to determine independent risk factors. Optimal combinations of variables were identified for model construction and user-friendly nomograms were developed., Results: The derivation cohort composed of 194 patients with LN with 1479 study visits and a median follow-up of 17.5 (12.2-21.7) months. Four trajectories of 24hUP were identified, that is, Rapid Responders, Good Responders, Suboptimal Responders and Non-Responders, with the KDIGO renal complete remission rates (time to complete remission, months) of 84.2% (4.19), 79.6% (7.94), 40.4% (not applicable) and 9.8% (not applicable), respectively (p<0.001). The 'Rapid Responders' distinguish itself from other trajectories and a nomogram, composed of age, systemic lupus erythematosus duration, albumin and 24hUP yielded C-indices >0.85. Another nomogram to predict 'Good Responders' yielded C-indices of 0.73~0.78, which composed of gender, new-onset LN, glomerulosclerosis and partial remission within 6 months. When applied to the validation cohort with 117 patients and 500 study visits, nomograms effectively sorted out 'Rapid Responders' and 'Good Responders'., Conclusion: Four trajectories of LN shed some light to guide the management of LN and further clinical trials design., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

During the pathogenesis of heart failure with preserved ejection fraction (HFpEF), fibroblasts are activated and express the fibroblast activation protein (FAP). Targeted imaging of FAP can qualitatively and quantitatively assess the fibroblast activity. This study aimed to use [ 18 F]AlF-NOTA-FAPI-04 (AlF = aluminum fluoride; NOTA = 1,4,7-triazacyclononane-1,4,7-triacetic acid; FAPI = FAP inhibitor) positron emission tomography/computed tomography (PET/CT) imaging to detect activated fibroblasts in a rat HFpEF model. The rat HfpEF model was established by feeding a high-fat diet plus l-NAME ( N ω -nitro-l-arginine methyl ester) for 10 weeks. Blood pressure, echocardiography, and [ 18 F]AlF-NOTA-FAPI-04 PET/CT were used to assess the progression of HfpEF. The biodistribution of [ 18 F]AlF-NOTA-FAPI-04 in healthy rats was obtained. Cardiac tissue sections were also analyzed using Masson's, hematoxylin and eosin (H&E), and FAP immunohistochemistry (IHC) staining. The echocardiography and blood pressure data indicated that the rat HfpEF model was successfully established. [ 18 F]AlF-NOTA-FAPI-04 PET/CT imaging showed obvious radiotracer accumulation in the left ventricular wall of the HfpEF rats from the seventh week. A biodistribution test showed that the tracer was cleared mainly via renal and intestinal excretion. Percentage of injected dose per gram tissue (% ID) of the heart and its surrounding organs was lower in normal rats, which was conducive to image analysis. Masson's and H&E stainings showed large areas of vascular and interstitial fibrosis in the HfpEF rat hearts. IHC staining also confirmed the presence of FAP-positive cardiac fibroblasts of the HfpEF rat hearts, with a good correlation with FAPI PET. Thus, [ 18 F]AlF-NOTA-FAPI-04 PET/CT is a promising and non-invasive method to assess the progression of fibrosis in HfpEF to facilitate the clinical management.

Objective : The effectiveness and safety of belimumab in Chinese lupus patients with different disease activities were investigated in a real-world setting. Method : Patients who received 10 mg/kg belimumab intravenously on weeks 0, 2, and 4, and then every 4 weeks on a background of standard-of-care (SoC) therapy and had a follow-up of more than 6 months were enrolled from four centers in China. They were stratified according to the Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score at baseline as the moderate/severe (SELENA-SLEDAI > 6) or mild subgroups (SELENA-SLEDAI ≤ 6). Attainment of the Lupus Low Disease Activity State (LLDAS) or remission on treatment was analyzed in all patients. The SLE Responder Index 4 (SRI-4) and SELENA-SLEDAI Flare Index (SFI) were evaluated for patients with moderate/severe disease and mild disease, respectively. Patients in the control arm with SoC alone from previous metformin lupus trials were selected by propensity score matching (PSM) as the reference group. Results : 224 SLE patients with a mean follow-up of 11.7 months receiving belimumab were enrolled in this observational study, of which 126 and 98 were in the moderate/severe and mild subgroup, respectively. At 12 months, 54.76% of the patients attained LLDAS and 28.57% attained remission. Lower daily prednisone at baseline were independently associated with 12-month LLDAS. Further, 87% of the subgroup with moderate/severe disease achieved SRI-4 at 12 months and a high SLEDAI at baseline was its predictive factor. For the mild subgroup, a reduced flare rate was observed compared with PSM reference (17.5%, vs. 38.6%, p = 0.021). Infection events, particularly viral infections and pneumonia were recorded in 7 and 6 patients, respectively. Conclusion : Our real-world data supported the effectiveness and safety of belimumab in Chinese lupus patients.

One of the most common routes of chronic hepatitis B virus (HBV) infection is mother-to-child transmission (MTCT). Approximately 6.4 million children under the age of five have chronic HBV infections worldwide. HBV DNA high level, HBeAg positivity, placental barrier failure, and immaturity of the fetal immune are the possible causes of chronic HBV infection. The passive-active immune program for children, which consists of the hepatitis B vaccine and hepatitis B immunoglobulin, and antiviral therapy for pregnant women who have a high HBV DNA load (greater than 2 × 10 5 IU/ml), are currently two of the most important ways to prevent the transmission of HBV from mother to child. Unfortunately, some infants still have chronic HBV infections. Some studies have also found that some supplementation during pregnancy can increase cytokine levels and then affect the level of HBsAb in infants. For example, IL-4 can mediate the beneficial effect on infants' HBsAb levels when maternal folic acid supplementation. In addition, new research has indicated that HBV infection in the mother may also be linked to unfavorable outcomes such as gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, and premature rupture of membranes. The changes in the immune environment during pregnancy and the hepatotropic nature of HBV may be the main reasons for the adverse maternal outcomes. It is interesting to note that after delivery, the women who had a chronic HBV infection may spontaneously achieve HBeAg seroconversion and HBsAg seroclearance. The maternal and fetal T-cell immunity in HBV infection is important because adaptive immune responses, especially virus-specific CD8 T-cell responses, are largely responsible for viral clearance and disease pathogenesis during HBV infection. Meanwhile, HBV humoral and T-cell responses are important for the durability of protection after fetal vaccination. This article reviews the literature on immunological characteristics of chronic HBV-infected patients during pregnancy and postpartum, blocking mother-to-child transmissions and related immune mechanisms, hoping to provide new insights for the prevention of HBV MTCT and antiviral intervention during pregnancy and postpartum., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor SY declared a shared affiliation with the authors at the time of review., (Copyright © 2023 Lu, Cao, Zhang, Yang, Bi, Lin, Deng, Jiang, Sun, Zeng, Lu, Zhang, Liu, Gao, Wu, Hao, Chen, Hu, Xu, Xiong, Dong, Song, Li and Xie.)