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ABSTRACT Importance Emicizumab (EMI) is efficacious and safe for hemophilia A (HA) prophylaxis. However, its high cost poses a challenge in China. Objective To explore the possibility of using reduced‐dosage EMI in Chinese HA children. Methods We conducted a retrospective study for HA children in our Comprehensive Care Center. Data were collected pre‐ and post‐EMI treatment to evaluate bleeding rates. Laboratory analyses included factor VIII (FVIII)‐like activity and EMI concentration measurements. Results Thirty‐four HA children receiving EMI prophylaxis for a median (range) 24.5 (2.5–47.9) months by June 2023. Of these, 25 (73.5%) were under 3 years of age, 26 (76.5%) had severe hemophilia and 12 (35.3%) were minimally treated or previously untreated patients. Thirty‐one (91.2%) of the 34 patients received reduced‐dosage EMI for economic reasons. EMI concentration and FVIII‐like activity measured showed a strong correlation. Overall, while on EMI, their annual treated bleeding rate (ATBR) and annual bleeding rate (ABR) decreased significantly (2–0) while their zero‐bleeding rate (ZBR) increased significantly (11.5%–65.4%). After 6 months of EMI, there was no significant difference in ATBR and ABR among various maintenance dosages. However, ZBR was significantly lower in dosages under 4 mg/kg (P = 0.0156). Receiver operator characteristic curves suggested the following cutoff values for zero bleeding: EMI 4‐weekly maintenance dosage 3.8 mg/kg, EMI concentration 48.1 μg/mL, and FVIII‐like activity 15.4 IU/dL. Interpretation We showed EMI effectively prevented bleeding even at reduced dosages. However, the bleeding risk may be higher with EMI 4‐weekly maintenance dosage

Abstract The capture of radioactive iodine species from nuclear waste is crucial for environmental protection and human health. Porous organic cages (POCs), an emerging porous material, have showed potential in iodine adsorption due to the advantages of tunable pores and processibility. However, integrating multiple desirable characteristics into a single POC through bottom‐up assembly of pre‐designed building blocks remains challenging. Post‐synthetic modification (PSM) offers an alternative approach, enabling the introduction of various functions into a single POC. Herein, a viable and highly efficient three‐step PSM strategy to modify a representative POC (CC3), is presented. The modified POC, OFT‐RCC36+6Br−, features a charged confined space, electron‐rich heteroatom, and halide ions, exhibiting significantly enhanced iodine vapor uptake compared to the parental cage. The universality of the PSM strategy has been verified by successfully modifying two other POCs. The iodine adsorption behaviors of three modified cage adsorbents in organic solvent and aqueous solution have also been investigated, all of which exhibited improved performance, especially in comparison to ionic cages modified through direct protonation. This work provides an effective PSM strategy for POCs to facilitate iodine adsorption. More importantly, the introduction of a new PSM strategy enriches the functional diversity of POCs, potentially broadening their future applications.

Previous studies on commodity price bubbles mainly focused on futures markets and ignored the performance of spot markets. Using the price data for corn and soybeans in China, this study identifies the exact bubble dates for the futures and spot markets, and finds asynchronous price bubbles between these two markets. Bubbles are more frequent for commodity spot prices, while the corresponding futures prices still dominate the process of price discovery. Further analysis reveals that, the lack of (immediate) linear transmission between the cointegrated prices may have inhibited bubble synchronization, and caused more spot price bubbles. The nonlinear transmission effects between the futures and spot prices suggest the existence of speculative storage and market power. This may further explain why spot price bubbles cannot be arbitraged away.

IntroductionThe primary objective was to investigate the value of the fluid attenuated inversion recovery (FLAIR) signal intensity ratio (SIR) in identifying stroke within 4.5 h. The secondary objective was to ascertain whether large vessel occlusion (LVO) mediated the relationship between the SIR and stroke within 4.5 h.MethodsWe analyzed 633 acute stroke patients within 24 h of clear symptom onset. The SIR and DWI-FLAIR mismatch were evaluated. First, we determined whether demographic variables, vascular risk factors and LVO were related to stroke within 4.5 h with multivariate logistic regression analyses and stratified regression analysis. Next, we used mediation analysis to determine whether LVO explained the association between SIR and stroke within 4.5 h. Finally, we used receiver operating characteristic (ROC) analysis to assess the value of SIR, independent variable, and multiparameter models in identifying stroke within 4.5 h and compared with DWI-FLAIR mismatch.ResultsHyperlipemia, LVO and SIR were associated with stroke within 4.5 h. Mediation analysis revealed that LVO partially mediated the relationship between SIR and stroke within 4.5 h (p

ABSTRACT Importance It remained unclear that the efficacy comparison between low‐dose immune tolerance induction (LD‐ITI) incorporating immunosuppressants (IS) when severe hemophilia A (SHA) patients had inhibitor‐titer ≥200 Bethesda Units (BU)/mL (LD‐ITI‐IS200 regimen) and LD‐ITI combining with IS when SHA patients had inhibitor‐titer ≥40 BU/mL (LD‐ITI‐IS40 regimen). Objective To compare the efficacy of the LD‐ITI‐IS200 regimen with that of the LD‐ITI‐IS40 regimen for SHA patients with high‐titer inhibitors. Methods A prospective cohort study on patients receiving LD‐ITI‐IS200 compared to those receiving LD‐ITI‐IS40 from January 2021 to December 2023. Both received LD‐ITI [FVIII 50 IU/kg every other day]. IS (rituximab + prednisone) was added when peak inhibitor tier ≥200 BU/mL in the LD‐ITI‐IS200 regimen and ≥40 BU/mL in the LD‐ITI‐IS40 regimen. Success is defined as a negative inhibitor plus FVIII recovery ≥66% of the expected. Results We enrolled 30 patients on LD‐ITI‐IS200 and 64 patients on LD‐ITI‐IS40, with similar baseline clinical characteristics. A lower IS‐use rate was discovered in the LD‐ITI‐IS200 regimen compared to the LD‐ITI‐IS40 regimen (30.0% vs. 62.5%). The two regimens (LD‐ITI‐IS200 vs. LD‐ITI‐IS40) had similar success rate (70.0% vs. 79.7%), median time to success (9.4 vs. 10.6 months), and annualized bleeding rate during ITI (3.7 vs. 2.8). The cost to success was lower for LD‐ITI‐IS200 than for LD‐ITI‐IS40 (2107 vs. 3256 US Dollar/kg). Among patients with peak inhibitor‐titer 40–199 BU/mL, 10 non‐IS‐using (on LD‐ITI‐IS200 regimen) and 28 IS‐using (on LD‐ITI‐IS40 regimen) had similar success rates (70.0% vs. 78.6%) and time to success (9.0 vs. 8.8 months). Interpretation In LD‐ITI, IS are not necessary for inhibitor titer

Abstract Objective To evaluate the benefit of bevacizumab under the comprehensive treatment strategy and its advantages over other drugs, so as to provide reference for the formulation of clinical plans. Methods As of October 1, 2022, the randomized controlled clinical trials of bevacizumab in combination with metastatic colorectal cancer published in PubMed, Cochrane Library and Medline databases were searched. The odds ratio (OR) and its 95% confidence interval (CI) were used to evaluate the short-term disease control effect and long-term survival of the treatment strategy. Results 21 RCTs (6665 patients; 3356 patients in the experimental group and 3309 patients in the control group; average age, 55–75 years) were treated with bevacizumab as the experimental group for metastatic colorectal cancer. BEV has stronger anti-tumor activity than the single treatment scheme (OR = 1.30, 95% CI: 1.11–1.52). And Benefits of the BEV group were 0.73 (0.55, 0.96), 1.26 (0.71, 2.24), 1.63 (0.92, 2.87) and 0.07 (0.02, 0.25) compared with CET, VAN, CED and PAN respectively. The disease control of BEV combined therapy was better (OR = 1.36, 95% CI: 1.04–1.78). The same as compared with cediranib (OR = 1.94, 95% CI: 1.06–3.55). However, the long-term prognosis of BEV, including the overall survival (HRs = 0.98, 95% CI: 0.84–1.15) and progression-free survival (HRs = 1.05,95% CI: 0.97–1.13) were not prolonged. The survival benefits of cetuximab and panitumumab were not reflected. Conclusion The addition of BEV can enhance the anti-tumor ability and disease control, while cetuximab and panitumumab may have stronger ability. However, it did not effectively improve the survival of patients. A more reasonable and effective treatment plan needs more clinical experimental support.

Abstract Purpose Cytokines regulate the interaction between the immune system and malignant tumors. Among them, interleukin-10 (IL-10) is a multifunctional anti-inflammatory cytokine mainly produced by immune cells. The correlation between gastric cancer and T/C single nucleotide polymorphism (SNP) of interleukin-10 (IL-10) promoter−819(rs1800871)was opaque and remained to be determined. We aim to explore the pertinence of gastric cancer and SNP of interleukin 10–819 by meta-analysis via five statistical models. Methods Databases including PubMed, Cochrane Library, Embase, the Scopus, and Google Scholars were comprehensively retrieved for the eligible studies on the related topic from inception to March 2022. Odds ratios (ORs) were generated for dichotomous variants by meta-analysis in each model via STATA 17.0 MP. The statistical models comprised recessive model, over-dominant model, allele model, co-dominant model and dominant model. Subgroup analysis was performed to investigate the difference across races as well as the source of heterogeneity if necessary. Results Eventually a total of 15 articles reporting 7779 patients were enrolled in our study. There were 2383 patients and 5396 controls, collectively. There was no correlation between gastric cancer and IL-10 819 in recessive model, co-dominant model or dominant model, and subgroup analysis showed that Asian, Latin American and Caucasian had no correlation with the risk of gastric cancer. In the allelic model, there was significant correlation between gastric cancer and IL-10 819 (OR = 3.96%, 95%CI: 3.28 to 3.78). In the over-dominant model, there is no correlation between gastric cancer and IL-10 819, but subgroup analysis uncovered significant vulnerability of Asian people with regard to gastric cancer. Conclusions In our study, both Asians, Latin Americans, and Europeans showed an increased risk of gastric cancer in the allelic model, whereas only Asians showed significant susceptibility in the super dominant model. Of course, more large cohort studies are needed to confirm our results.

Automatic ship target detection technique is a typical and meaningful application for synthetic aperture radar (SAR) image interpretation. Nevertheless, the detection of ship targets within SAR imagery is encumbered by several detracting elements, including obscured outlines, varying dimensions, and elaborate backgrounds, which collectively render the identification process challenging. Existing methodologies for discerning ship targets prove inadequate in effectively navigating these complications. Therefore, we propose a new deep neural network to automatically detect ship target from SAR images, which is named as hierarchical feature fusion and attention network (HFFANet). HFFANet is based on CSPDarknet, the backbone network of YOLOX, and adaptive feature fusion and attention (AFFA) module is innovated to enhance feature extraction. In AFFA, adaptive multilevel feature fusion module is proposed to achieve effective multilevel feature adaptive fusion to better extract target contours and suppress background clutter to reduce false alarms, and enhanced residual coordinate attention module is also proposed to enhance spatial location information and embed it into channel features in the channel layer. The experiments on SAR ship dataset have been conducted, and the mean average precision of HFFANet is 98.53%. Compared with the classical networks, the experimental results show that our model not only achieves the optimal balance in precision and recall, but also achieves the optimal calculation cost.

Emerging economies often establish commodity futures markets to discover price signals, manage price risks and improve market integration, but establishing a futures market may not be feasible for agricultural perishables. In this study, we evaluated the function of the world's first fresh fruit futures contract for apples. Combining partial cointegration with state-space modelling, we derived time-varying price discovery metrics for the apple futures market. Our findings revealed a limited and time-varying dominance of price discovery by the futures market, while a substantial share of price discovery occurred in the spot market. Moreover, poor convergence of disaggregated spot prices to the futures price suggests that commercial traders in the apple supply chain tended to focus more on the spot market than on the futures market. Thus, emerging economies should be cautious about the new establishment of futures markets for agricultural perishables. Future research using more specific data on the spot market may provide a better insight on the limited function of the futures market.

Abstract Indochina is one of the regions with the most severe biomass burning (BB) in the world, which produces enormous amounts of atmospheric aerosols, mostly in spring. Moreover, the spring soil moisture anomalies in Indochina have been found to have a significant influence on the summer rainfall in the Yangtze River Valley (YRV). It is still partially unclear how spring BB in Indochina influences the local and regional climate and land–atmosphere interactions. Here, we use regional model experiments and observational data to show that the radiative effect of BB aerosols in Indochina stabilizes the atmosphere and reduces local precipitation and soil moisture. The dry soil in Indochina persists from spring to summer, which warms the land surface and the atmosphere. As a result, the western Pacific subtropical high (WPSH) is stronger and extends westward from spring to summer. This leads to stronger moisture transport to and more precipitation in the YRV (increases of approximately 5% in July and 10% in August). Thus, the effect of BB aerosols on the YRV rainfall is similar to that of the Indochina dry soil anomaly. Additionally, the increase in the YRV summer rainfall caused by the Indochina spring dry soil anomaly is almost doubled when there are BB aerosols compared to that without BB aerosols, suggesting the importance of BB aerosols in regulating the regional land–atmosphere interactions.

ABSTRACT: We use the ARIMA-GARCH model to estimate the shocks of COVID-19 on Chinese agricultural markets and utilize the ARDL-ECM model to estimate the integration relationships between Chinese and international agricultural markets which are based on the effective market hypothesis theory and daily trading data of US, UK, China and India. The main study findings showed that COVID-19 has a significant negative impact on agricultural product market, specifically, India suffered with the greatest negative impact, followed by the UK, the US and China. Further, this study results revealed that Chinese grain markets that are considered strategic places have not been separated from international markets, but there still exist segmentation phenomena among non-strategic agricultural markets.

Abstract Neoantigens are emerging as attractive targets to develop personalized cancer vaccines, but their immunization efficacy is severely hampered by their restricted accessibility to lymphoid tissues where immune responses are initiated. Leveraging the capability of red blood cells (RBCs) to capture and present pathogens in peripheral blood to the antigen‐presenting cells (APCs) in spleen, we developed a RBC‐driven spleen targeting strategy to deliver DNA vaccine encoding hepatocellular carcinoma (HCC) neoantigen. The DNA vaccine‐encapsulating polymeric nanoparticles that were intentionally hitchhiked on the preisolated RBCs could preferentially accumulate in the spleen to promote the neoantigen expression by APCs, resulting in the burst of neoantigen‐specific T‐cell immunity to prevent tumorigenesis in a personalized manner, and slow down tumor growth in the established aggressively growing HCC. Remarkably, when combined with anti‐PD‐1, the vaccine achieved complete tumor regression and generated a robust systemic immune response with long‐term tumor‐specific immunological memory, which thoroughly prevented tumor recurrence and spontaneous lung metastasis. This study offers a prospective strategy to develop personalized neoantigen vaccines for augmenting cancer immunotherapy efficiency in immune “cold” HCC.

This study aims to investigate alterations in effective connectivity (EC) within the fronto-thalamic circuit and their associations with motor and cognitive declines in pontine infarction (PI). A total of 33 right PI patients (RPIs), 38 left PI patients (LPIs), and 67 healthy controls (HCs) were recruited. The spectral dynamic causal modeling (spDCM) approach was used for EC analysis within the fronto-thalamic circuit, including the thalamus, caudate, supplementary motor area (SMA), medial prefrontal cortex (mPFC), and anterior cingulate cortex (ACC). The EC differences between different sides of the patients and HCs were assessed, and their correlations with motor and cognitive dysfunctions were analyzed. The LPIs showed increased EC from the mPFC to the R-SMA and decreased EC from the L-thalamus to the ACC, the L-SMA to the R-SMA, the R-caudate to the R-thalamus, and the R-thalamus to the ACC. For RPIs, the EC of the R-caudate to the mPFC, the L-thalamus and L-caudate to the L-SMA, and the L-caudate to the ACC increased obviously, while a lower EC strength was shown from the L-thalamus to the mPFC, the LSMA to the R-caudate, and the R-SMA to the L-thalamus. The EC from the R-caudate to the mPFC was negatively correlated with the MoCA score for RPIs, and the EC from the R-caudate to the R-thalamus was negatively correlated with the FMA score for LPIs. The results demonstrated EC within the fronto-thalamic circuit in PI-related functional impairments and reveal its potential as a novel imaging marker.

Objective:To evaluate the inhibitory effect and mechanism of Pien Tze Huang (PZH) on long non-coding RNA-ANRIL(LncRNA-ANRIL) mediated lymphangiogenesis in colorectal cancer (CRC) in vitro.Methods:HCT-116 cells were cultured in vitro, and divided into control group and PZH group (treated with 0.25, 0.50, 0.75 mg/mL). CCK-8 assay was used to evaluate cell ability. The expression of LncRNA-ANRIL was detected by RT-qPCR, and the expression of VEGF-C was examined by Western blot. HCT-116 cells were transfected with Lipofectamine RNAiMAX and divided into Si-NC and Si-ANRIL groups. RT-qPCR was used to detect the expression of LncRNA-ANRIL. Phase-contrast microscope was used to observe the cell morphology. CCK-8 assay was used to detect cell viability. Western blot was used to detect the expression of VEGF-C protein. Treat HCT-116 cells with Si-NC, Si-ANRIL and Si-NC+PZH(0.25 mg/mL) respectively and collect cell culture supernatants (Tumor culture supernatants, TSNs) for theculture of human lymphatic endothelium cell (HLEC). CCK-8 assay was used to detect cell proliferation, cell migration and invasion were evaluated by Transwell assay. Tube Formation assay was used to observe lymphatic vessel formation ability.Results:Treatment of HCT-116 cells with different doses of PZH significantly inhibited the viability (P< 0.01). At the same time, PZH treatment in HCT-116 cells also reduced the expression of LncRNA-ANRIL(P< 0.01) and the expression of VEGF-C protein in a dose-dependent. Silencing LncRNA-ANRIL in HCT-116 cells, compared with Si-NC group, the expression of LncRNA-ANRIL in Si-ANRIL group was significantly reduced (P< 0.05), and the expression of cell density, cell viability (P< 0.01) and VEGF-C protein was also decreased. After the collected TSNssupernatant was used to treat HLEC cells, compared with the Si-NC group, Si-ANRIL and Si-NC+PZH(0.25 mg/mL) groups could remarkably decrease HLEC cell viability, migration and invasion ability and tube formation ability (P< 0.01).Conclusion:PZH can inhibit the expression of LncRNA-ANRIL in colorectal cancer cells and its mediated lymphangiogenesis in colorectal cancer. LncRNA-ANRIL is one of the targets of PZH in inhibiting lymphangiogenesis in colorectal cancer.

Soil moisture is a crucial component of the water cycle and plays an important role in regional weather and climate. However, owing to the lack of In Situ observations, an accurate understanding of the spatiotemporal variations of soil moisture (SM) on the Tibetan Plateau (TP) is still lacking. In this study, we used three gridded SM products to characterize the spatiotemporal features of SM on the TP during the warm season (May to August). We analyzed the fifth-generation European Centre for Medium-Range Weather Forecasts atmospheric reanalysis (ERA5), Global Land Data Assimilation System (GLDAS), and Soil Moisture Active Passive (SMAP) datasets and used station observation data and triple collocation to quantify product accuracy and consistency. Results of the evaluation based on observation data show that both ERA5 and GLDAS overestimate SM, while the accuracy of SMAP is high. In terms of capturing the temporal variations of SM measured at stations, the performance of ERA5 and that of SMAP are superior to that of GLDAS. According to the evaluation based on triple collocation, SMAP exhibits the smallest random error over the TP and the highest temporal correlation with the unknown true SM in eastern TP. For SMAP, SM variability is the largest in the southern TP. For ERA5 and GLDAS, variability in the western TP is substantially larger than that for SMAP. Low-frequency (30–90 days) variations are the largest contributor to TP SM intraseasonal variability. Relative to SMAP, the contribution of high-frequency variations is low in ERA5 and GLDAS. Land-atmosphere coupling is stronger (weaker) in the western (southeastern) TP, which is relatively dry (wet). Our evaluation of SM product performance over the TP may facilitate the use of these products for disaster monitoring and climate and hydrological studies.

Non-alcoholic fatty liver disease (NAFLD) has emerged as a leading public health challenge and is closely associated with metabolic syndromes, such as obesity. Intestinal microbiota dysbiosis could play a vital role in the pathogenesis and progression of NAFLD. Tea is the second most popular health drink in the world behind water, and exhibits many health-promoting effects. In this study, the protective effects of different black and dark teas on NAFLD induced by long-term high-fat diet (HFD) exposure and their regulation of gut microbiota were evaluated and explored. The results indicated that supplementation with different black and dark tea extracts could significantly suppress the energy intake, alleviate abnormal accumulation of visceral fat, and prevent obesity, hepatic abnormal lipid deposition and liver steatosis in HFD-fed mice at varying degrees. In addition, Dianhong tea and Liupao tea interventions could significantly decrease the ratio of Firmicutes to Bacteroidetes, and selenium-enriched black tea and selenium-enriched dark rea supplementation could remarkably reduce the relative abundance of Actinobacteria compared to the model group. Moreover, these teas could partly shift the relative abundances of Allobaculum, Roseburia and Dubosiella. Taken together, black teas and dark teas could prevent HFD-induced features of obesity and NAFLD, which might partly be due to the modulation of gut microbiota.

Gut microbiota dysbiosis has been a crucial contributor to the pathogenesis of alcoholic fatty liver disease (AFLD). Tea is a popular beverage worldwide and exerts antioxidant and anti-inflammatory activities, as well as hepatoprotective effects. However, the potential role of gut microbiota regulated by tea in the prevention and management of AFLD remains unclear. Here, the protective effects of oolong tea, black tea, and dark tea on AFLD and its regulation of gut microbiota in chronic alcohol-exposed mice were explored and investigated. The results revealed that tea supplementation significantly prevented liver steatosis, decreased oxidative stress and inflammation, and modulated gut microbiota in chronic alcohol-exposed mice, especially oolong tea and dark tea. However, black tea showed less effectiveness against liver injury caused by alcohol. Moreover, the diversity, structure and composition of chronic alcohol-disrupted gut microbiota were restored by the supplementation of oolong tea and dark tea based on the analysis of gut microbiota. Furthermore, the relationship between liver injury biochemical indicators and gut microbiota indicated that some specific bacteria, such as Bacteroides, Alloprevotella, and Parabacteroides were closely associated with AFLD. In addition, the phytochemical components in tea extracts were measured by high-performance liquid chromatography, which could contribute to preventive effects on AFLD. In summary, oolong tea and dark tea could prevent chronic alcohol exposure-induced AFLD by modulating gut microbiota.

Glypican-2 (GPC2) has been reported to promote tumor progression through metabolic pathways. However, the role of GPC2 in colon adenocarcinoma (COAD) remains to be further investigated. This study was designed to evaluate the role of GPC2 in COAD. Based on patients with complete clinical information and GPC2 expression from the Cancer Genome AtlasCOAD database, we found that GPC2 mRNA was highly expressed in COAD tissues, which was associated with poor prognosis and tumornode-metastasis (TNM) stage. The predicted survival probability based on GPC2 mRNA expression and TNM stage was in good agreement with the observed survival probability. Furthermore, the genes coexpressed with GPC2 in COAD tissues were significantly enriched in basal cell carcinoma, Notch signaling pathway, and Hedgehog signaling pathway. After GPC2 was decreased through transfecting short hairpin RNA of GPC2 into HCT-8 and SW620 cells, cell cycle was arrested in G0/G1 phase, proliferation was decreased, apoptosis was increased, and migration and invasion were repressed. In conclusion, decreasing GPC2 significantly inhibited proliferation, migration, and invasion, and enhanced apoptosis, which implied that GPC2 can be considered a promising therapeutic target of COAD in the future. [ABSTRACT FROM AUTHOR]