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The “23.7” event, an extreme rainstorm that affected North China from July 29 to 2 August 2023, was simulated using the Weather Research and Forecasting (WRF) model, version 4.2. We focus on dynamically diagnosing and analyzing the mass and latent heat budgets of rainwater during the extreme precipitation event on July 31 in the Beijing area, where the hourly rainfall reached an extraordinary 111.8 mm. Generally, the model effectively simulated the rainstorm, enabling further assessment of the extreme precipitation. Results indicated that under the combined influence of three major weather systems—the residual circulation of Typhoon Doksuri (a low-pressure system after typhoon landfall), the embryonic stage of Typhoon Khanun, and the North China high-pressure dam—a continuous influx of moisture and energy was transported to the North China region, promoting heavy precipitation. Application of vorticity equation diagnostics indicates that the horizontal transport term is the primary source term. Mass balance analysis reveals that the primary source of rainwater is the accretion of cloud droplets by rain, and the condensation of water vapor into cloud droplets is the main contributor to the latent heat.

Background The authors aimed to elucidate the relationship between latest ischemic event and the incidence of subsequent ischemic stroke in patients with symptomatic artery occlusion. Methods and Results We analyzed the association between qualifying event—the latest ischemic event (transient ischemic attack [TIA] or stroke)—and the incidence of ipsilateral ischemic stroke in patients with symptomatic artery occlusion treated with medical therapy alone in CMOSS (Carotid or Middle Cerebral Artery Occlusion Surgery Study). The incidence of CMOSS primary outcomes, including any stroke or death within 30 days after randomization or ipsilateral ischemic stroke between 30 days and 2 years, between the bypass surgical and medical groups, stratified by qualifying events, was also compared. Of the 165 patients treated with medical therapy alone, 75 had a TIA and 90 had a stroke as their qualifying event. The incidence of ipsilateral ischemic stroke did not significantly differ between patients with a TIA and those with a stroke as their qualifying event (13.3% versus 6.7%, P=0.17). In multivariate analysis, the qualifying event was not associated with the incidence of ipsilateral ischemic stroke. There were no significant differences in the CMOSS primary outcomes between the surgical and medical groups, regardless of the qualifying event being TIA (10.1% versus 12.2%, P=0.86) or stroke (6.7% versus 8.9%, P=0.55). Conclusions Among patients with symptomatic artery occlusion and hemodynamic insufficiency, the risk of subsequent ipsilateral ischemic stroke does not appear to be lower in patients presenting with a TIA compared with those with a stroke. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01758614.

Objectives Diabetes is a metabolic disease and early detection is crucial to ensuring a healthy life for people with prediabetes. Community care plays an important role in public health, but the association between community follow-up of key life characteristics and diabetes risk remains unclear. Based on the method of optimal feature selection and risk scorecard, follow-up data of diabetes patients are modeled to assess diabetes risk. Methods We conducted a study on the diabetes risk assessment model and risk scorecard using follow-up data from diabetes patients in Haizhu District, Guangzhou, from 2016 to 2023. The raw data underwent preprocessing and imbalance handling. Subsequently, features relevant to diabetes were selected and optimized to determine the optimal subset of features associated with community follow-up and diabetes risk. We established the diabetes risk assessment model. Furthermore, for a comprehensible and interpretable risk expression, the Weight of Evidence transformation method was applied to features. The transformed features were discretized using the quantile binning method to design the risk scorecard, mapping the model's output to five risk levels. Results In constructing the diabetes risk assessment model, the Random Forest classifier achieved the highest accuracy. The risk scorecard obtained an accuracy of 85.16%, precision of 87.30%, recall of 80.26%, and an F1 score of 83.27% on the unbalanced research dataset. The performance loss compared to the diabetes risk assessment model was minimal, suggesting that the binning method used for constructing the diabetes risk scorecard is reasonable, with very low feature information loss. Conclusion The methods provided in this article demonstrate effectiveness and reliability in the assessment of diabetes risk. The assessment model and scorecard can be directly applied to community doctors for large-scale risk identification and early warning and can also be used for individual self-examination to reduce risk factor levels.

Currently, petrochemical plastics dominate the food service industry due to their good mechanical properties and barrier against heat, water vapor, carbon dioxide, and oxygen. This widespread use is not only harmful to humans but also to the ecosystem as synthetic plastics disrupt ecological balance and deplete petroleum-based oil resources. Researchers and manufacturers are continuously addressing this problem by developing bio-based alternatives that provide numerous advantages including structural flexibility, biodegradability, and effective barrier properties. However, the high cost of production and unavailability of equipment for batch processing impede the potential for widespread manufacturing. Natural fibers mixed with bio-based adhesives derived from plants provide one of the biggest potential sources of bio-based materials for the food container industry. Not only does this address the issue of high raw material cost but it also has the potential to become sustainable once processing steps have been optimized. In this review, the current findings of several research related to the production of bio-based disposable food containers, packaging, and composites made from bio-based materials and bio-based adhesives are critically discussed. Several properties and characteristics important to the production of food service containers and primary packaging, as well as the existing challenges and future perspectives, are also highlighted.

Summary: DHX15 has been implicated in RNA splicing and ribosome biogenesis, primarily functioning as an RNA helicase. To systematically assess the cellular role of DHX15, we conducted proteomic analysis to investigate the landscape of DHX15 interactome, and identified MYC as a binding partner. DHX15 co-localizes with MYC in cells and directly interacts with MYC in vitro. Importantly, DHX15 contributes to MYC protein stability at the post-translational level and independent of its RNA binding capacity. Mechanistic investigation reveals that DHX15 interferes the interaction between MYC and FBXW7, thereby preventing MYC polyubiquitylation and proteasomal degradation. Consequently, the abrogation of DHX15 drastically inhibits MYC-mediated transcriptional output. While DHX15 depletion blocks T cell development and leukemia cell survival as we recently reported, overexpression of MYC significantly rescues the phenotypic defects. These findings shed light on the essential role of DHX15 in mammalian cells and suggest that maintaining sufficient MYC expression is a significant contributor to DHX15-mediated cellular functions.

Abstract The effect of double filtration plasma apheresis (DFPP) on improving the outcomes of patients with hypertriglyceridaemia-induced acute pancreatitis (HTG-AP) remains unclear. The aim of this study was to evaluate the relationship between the initiation time of DFPP and the risk of persistent organ failure (POF) in an HTG-AP cohort in China. We retrospectively evaluated data from HTG-AP patients treated with DFPP 48 h after diagnosis between January 2017 and January 2022. Comparisons across tertiles of the interval from diagnosis to completion of one DFPP session (DTD) were analysed. Logistic regression models and restricted cubic splines (RCS) were used to determine the correlation between the DTD time and risk of POF. Of the 89 patients enrolled, 46 patients (51.69%) suffered POF in the first week of HTG-AP. DFPP was initiated at a median of 17 h after the diagnosis was confirmed. The patients in the highest tertile of DTD time had a significantly increased prevalence of POF. After multivariate adjustment, the logistic regression models found a significant decrease in the odds ratios (OR) of POF from the highest to the lowest DTD tertile (P for trend = 0.006). Moreover, the RCS curves showed a nonlinear relationship in the adjusted OR of POF and DTD time, which remained relatively low and flat during the early DTD time but increased sharply afterwards. Early initiation of DFPP treatment correlates with a reduced risk of POF in HTG-AP patients.

Approaching precipitation forecast refers to the prediction of precipitation within a short time scale, which is usually regarded as a spatiotemporal sequence prediction problem based on radar echo maps. However, due to its reliance on single-image prediction, it lacks good capture of sudden severe convective events and physical constraints, which may lead to prediction ambiguities and issues such as false alarms and missed alarms. Therefore, this study dynamically combines meteorological elements from surface observations with upper-air reanalysis data to establish complex nonlinear relationships among meteorological variables based on multisource data. We design a Residual Spatiotemporal Convolutional Network (ResSTConvNet) specifically for this purpose. In this model, data fusion is achieved through the channel attention mechanism, which assigns weights to different channels. Feature extraction is conducted through simultaneous three-dimensional and two-dimensional convolution operations using a pure convolutional structure, allowing the learning of spatiotemporal feature information. Finally, feature fitting is accomplished through residual connections, enhancing the model’s predictive capability. Furthermore, we evaluate the performance of our model in 0–3 h forecasting. The results show that compared with baseline methods, this network exhibits significantly better performance in predicting heavy rainfall. Moreover, as the forecast lead time increases, the spatial features of the forecast results from our network are richer than those of other baseline models, leading to more accurate predictions of precipitation intensity and coverage area.

Tomato brown rugose fruit virus (ToBRFV) is a newly-emerging tobamovirus which was first reported on tomatoes in Israel and Jordan, and which has now spread rapidly in Asia, Europe, North America, and Africa. ToBRFV can overcome the resistance to other tobamoviruses conferred by tomato Tm-1, Tm-2, and Tm-22 genes, and it has seriously affected global crop production. The rapid and comprehensive transcription reprogramming of host plant cells is the key to resisting virus attack, but there have been no studies of the transcriptome changes induced by ToBRFV in tomatoes. Here, we made a comparative transcriptome analysis between tomato leaves infected with ToBRFV for 21 days and those mock-inoculated as controls. A total of 522 differentially expressed genes were identified after ToBRFV infection, of which 270 were up-regulated and 252 were down-regulated. Functional analysis showed that DEGs were involved in biological processes such as response to wounding, response to stress, protein folding, and defense response. Ten DEGs were selected and verified by qRT-PCR, confirming the reliability of the high-throughput sequencing data. These results provide candidate genes or signal pathways for the response of tomato leaves to ToBRFV infection.

Sulfur utilization in high-mass-loading positive electrodes is crucial for developing practical all-solid-state lithium-sulfur batteries. Here, authors propose a low-density inorganic solid-state electrolyte to improve the sulfur utilization in lab-scale Li-In||S all-solid-state cells.

The objectives of this research were to explore the potential of blue, red and white maize as sustainable resource for production of distilled spirits and to study the effect and interaction of yeast strains and maize variety on alcohol yield and formation of volatile compounds that are related to the flavor quality. Four maize varieties (yellow, white, blue, and red maize) and four yeast strains (GR-2, DADY, HG-1, and USW-6) were used for distilled spirit production. Blue maize had the highest average alcohol yield (∼90%) and alcohol concentration (12.6%) among the four maize verities. The fermentation efficiency of red maize (89%) was similar to yellow maize (89.3%), while white maize (85.9) was lower than yellow maize. The average alcohol concentration of white maize (11.9%) was similar to yellow maize (12.0%), while red maize (11.5%) was lower that yellow maize. These results show that blue, red and white maize, especially blue maize, are also sustainable resource for spirit production. The type of yeast strains also had significant effect on alcohol yield and concentration. GR-2 achieved consistently the highest average alcohol concentration (12.12%, v/v) and highest alcohol yield (90.16%) regardless of maize variety. HG-1 and USW-6 yielded the similar average alcohol concentration (∼11.94%) and yield (∼88.35%). DADY had the lowest average alcohol concentration (11.84%) and yield (87.62%) among the four yeast strains. Alcohol fermentation also produces other metabolites such as glycerol and lactic acid as the two major byproducts. For all conditions, the lactic acid level was less than 0.1% (v/v) and glycerol level was less than 1.5% (v/v). 1-Butanol, 3-methyl, ethyl octanoate, and ethyl tridecanoate are the indicators of volatile flavor compounds identified in maize raw spirit distillates. These flavors produce maize spirits’ distinctive alcohol, fruity, sweet, and floral flavor profile.

Background and purposeDiabetes mellitus (DM) is a well-established cardiovascular risk factor for atherosclerotic disease; however, its effect on the risk of rupture of intracranial aneurysms remains controversial. Herein, we aimed to perform a case–control study to investigate the relationship between DM and aneurysmal subarachnoid hemorrhage (aSAH).MethodsWe retrospectively reviewed the data of patients with ruptured or unruptured aneurysms who were treated between 2013 and 2023. Univariate and multivariate analyses were performed. Propensity score matching (PSM) analysis was conducted to evaluate the relationship between DM and risk of aSAH.ResultsA total of 4,787 patients with 5,768 intracranial aneurysms were included. Among them, 2,957 (61.8%) were females, 1765 (36.9%) had ruptured aneurysms, and 531 (11.1%) presented with DM. Female sex, current drinking, and hypercholesterolemia were associated with a higher risk of aSAH, whereas old age, former smoking, and DM were associated with a lower risk of aSAH in multivariate analysis (p

Abstract Background Measurement of knee laxity after anterior cruciate ligament (ACL) injury is crucial for appropriate treatment and rehabilitation decision-making. This study examined the potential of a new digital arthrometer (Ligs, Innomotion, Shanghai, China) to quantify anterior tibial translation (ATT) in patients with ACL injuries and in healthy subjects. Methods A total of 60 participants included 30 subjects with single-leg ACL injuries and 30 healthy subjects included as controls. The lower leg was immobilized. The thruster is positioned posterior to the lower leg and parallel to the tibial tuberosity in the sagittal plane. The load is applied vertically to the tibia under a dynamic load of 0–150 N, with continuous displacement recorded. The intrarater and interrater reliability will be examined. ATT and side-to-side differences (SSD) between the control and ACL injury groups were compared. Receiver operating characteristic (ROC) curves were analyzed, and the area under the curve (AUC) was calculated to determine the diagnostic accuracy of the Ligs. Results The interrater ICC was 0.909 and the intrarater ICC was 0.943. Significant differences in the SSD were observed between the control and ACL injury groups (for all P

IntroductionSafranal is an active component of the traditional Tibetan medicine (TTM) saffron, which has potential anticancer activity.Methods and resultsHere, we studied the therapeutic effect and mechanism of safranal on GBM. CCK-8, GBM-brain organoid coculture experiments and 3D tumour spheroid invasion assays showed that safranal inhibited GBM cell proliferation and invasion in vitro. Network pharmacology, RNA-seq, molecular docking analysis, western blotting, apoptosis, and cell cycle assays predicted and verified that safranal could promote GBM cell apoptosis and G2/M phase arrest and inhibit the PI3K/AKT/mTOR axis. In vivo experiments showed that safranal could inhibit GBM cell growth alone and in combination with TMZ.ConclusionThis study revealed that safranal inhibits GBM cell growth in vivo and in vitro, promotes GBM cell apoptosis and G2/M phase arrest, inhibits the PI3K/AKT/mTOR axis and cooperate with TMZ.

BackgroundVertebral artery stenosis and occlusion (VASO) is a high-risk factor for posterior circulation stroke. Post-stent restenosis and drug tolerance have facilitated the exploration of microsurgical vascular reconstruction. This study aims to evaluate the safety and efficacy of microsurgical reconstruction of the proximal VA.MethodsTwenty-nine patients (25 men, aged 63.2 years) who had symptoms of posterior circulation ischemia underwent microsurgical revascularization for proximal VASO were retrospectively included in this study. Procedural complications and clinical and angiographic outcomes were reviewed.ResultsTwelve, three, and five patients underwent VA endarterectomy, artery transposition, or both, respectively; seven patients underwent vertebral endarterectomy plus stent implantation; and two patients failed surgery because of the difficult exposure of the VA and the occurrence of vascular dissection. The perioperative period-related complications included seven cases of Horner’s syndrome, five cases of hoarseness, and one case of chylothorax. No cases of perioperative stroke or death were reported. The mean follow-up period was 28.4 (8–62 months). Most patients improved clinically; however, the vertebrobasilar ischemia symptoms did not decrease significantly in two patients during the follow-up. Moreover, follow-up imaging was performed in all the patients, and no signs of anastomotic stenosis were reported.ConclusionMicrosurgical reconstruction is an alternative option that can effectively treat refractory proximal VASO disease and in-stent stenosis, with a high rate of postoperative vascular recirculation. Prospective cohort studies with larger sample sizes must be conducted to validate the above conclusions.

Abstract Background Childhood asthma has substantial effects on children's health. It is important to identify factors in early life that influence childhood asthma. Accumulating evidence indicates that Helicobacter pylori may protect against allergic diseases. This study aimed to evaluate the relationship between H. pylori infection and pediatric asthma in Chongqing, China. Materials and methods This cross-sectional study included healthy children aged 4–18 years who underwent a 13C urea breath test during medical checkups in 2021. All medical information was extracted from electronic medical records and a big data system. Logistic regression was used to evaluate the association between H. pylori infection and pediatric asthma, and multivariate regression models were adjusted for covariates. Results In our study, 2241 participants, including 1240 boys (55.33%) and 1001 girls (44.67%), underwent urea breath testing (average age: 8.67 ± 2.70 years). Among them, 292 (13.03%) were positive for H. pylori and 152 (6.78%) had asthma. The rates of asthma diagnosis in H. pylori-negative and -positive children were 7.23% and 3.77%, respectively (odds ratio = 1.995; 95% confidence interval: 1.003–3.968; P

Abstract Background After traumatic brain injury (TBI), peripheral monocytes infiltrate into the central nervous system due to disruption of the blood–brain barrier, and play an important role in neuroinflammation. However, the mechanisms regulating the movement and function of peripheral monocytes after TBI have not been fully investigated. Methods TBI patients who underwent surgery at our hospital were recruited. CXCR2 expression in CD14+ monocytes from peripheral blood and cerebrospinal fluid (CSF) of TBI patients around surgery was analyzed by flow cytometry and compared with that of patients who suffered TBI 2–24 months prior and underwent cranioplasty. In vitro, serum or CSF from TBI/non-TBI patients were used to treat peripheral monocytes isolated from healthy volunteers to evaluate their effect on CXCR2 expression. Transwell experiments were performed to analyze the role of CXCR2 in monocyte chemotaxis toward the CSF. The role of CXCR2 in monocyte-mediated immunogenic cell death (ICD) of nerve cells was explored in an indirect co-culture system. Results Transient CXCR2 upregulation in monocytes from the peripheral blood and CSF of TBI patients was detected soon after surgery and was associated with unfavorable outcomes. TBI serum and CSF promoted CXCR2 expression in monocytes, and dexamethasone reversed this effect. Peripheral monocytes from TBI patients showed enhanced chemotaxis toward the CSF and increased inflammatory cytokine secretion. The CXCR2 antagonist SB225002 decreased monocyte chemotaxis toward TBI CSF, and lowered pro-inflammatory cytokine secretion in monocytes treated with TBI serum. SB225002 also relieved ICD in nerve cells co-cultured with TBI serum-treated monocytes. Conclusions CXCR2 is transiently overexpressed in the peripheral monocytes of TBI patients post-surgery, and drives peripheral monocyte chemotaxis toward CSF and monocyte-mediated ICD of nerve cells. Therefore, CXCR2 may be a target for monocyte-based therapies for TBI.

3D electrodes have shown extraordinary promise for electrochemical energy storage devices in wearable electronics. However, it is still a significant challenge to rationally design 3D electrode that has the characteristics of lightweight, flexibility, low cost, high performance and miniaturization. In this work, we present a novel design of 3D electrode by directly growing the nanocrystalline TiO2 film on carbonized eggshell membrane. The unique architecture can supply not only a continuous electron transport pathway through an interconnected carbon fibrous network but also an efficient electrolyte flux via an interpenetrating porous network. Besides, nanocrystalline TiO2 film on carbonized eggshell membrane offers a short ion diffusion path in the solid-phase, leading to a rapid kinetic of electrochemical reaction. When tested as an anode for Li-ion battery, TiO2 film in 3D electrode demonstrated excellent electrochemical performance with a large reversible capacity, excellent rate capacity and long life cycling property.

RNA-binding proteins (RBP) have emerged as essential regulators that control gene expression and modulate multiple cancer traits. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy derived from transformation of T-cell progenitors that normally undergo discrete steps of differentiation in the thymus. The implications of essential RBP during T-cell neoplastic transformation remain largely unclear. Systematic evaluation of RBP identifies RNA helicase DHX15, which facilitates the disassembly of the spliceosome and release of lariat introns, as a T-ALL dependency factor. Functional analysis using multiple murine T-ALL models demonstrates the essential importance of DHX15 in tumor cell survival and leukemogenesis. Moreover, single-cell transcriptomics reveals that DHX15 depletion in T-cell progenitors hinders burst proliferation during the transition from doublenegative to double-positive cells (CD4-CD8- to CD4+CD8+). Mechanistically, abrogation of DHX15 perturbs RNA splicing and leads to diminished levels of SLC7A6 and SLC38A5 transcripts due to intron retention, thereby suppressing glutamine import and mTORC1 activity. We further propose a DHX15 signature modulator drug ciclopirox and demonstrate that it has prominent anti-T-ALL efficacy. Collectively, our data highlight the functional contribution of DHX15 to leukemogenesis through regulation of established oncogenic pathways. These findings also suggest a promising therapeutic approach, i.e., splicing perturbation by targeting spliceosome disassembly, may achieve considerable anti-tumor efficacy.

It is important to assess the nutritional concentrations of forage before it can be used for tremendous improvements in the dairy industry. This improvement requires a rapid, accurate, and portable method for detecting nutrient values, instead of traditional laboratory analysis. Fourier-transform infrared (ATR-FTIR) spectroscopy technology was applied, and partial least squares regression (PLSR) and backpropagation artificial neural network (BP-ANN) algorithms were used in the current study. The objective of this study was to estimate the discrepancy in nutritional content and rumen degradation in WPCS grown in various regions and to propose a novel analytical method for predicting the nutrient content of whole plant corn silage (WPCS). The Zhengdan 958 cultivar of WPCS was selected from eight different sites to compare the discrepancies in nutrients and rumen degradation. A total of 974 WPCS samples from 235 dairy farms scattered across five Chinese regions were collected, and nutritional indicators were modeled. As a result, substantial discrepancies in nutritional concentrations and rumen degradation of WPCS were found when they were cultivated in different growing regions. The WPCS in Wuxi showed 1.14% higher dry matter (DM) content than that in Jinan. Lanzhou had 11.57% and 8.25% lower neutral detergent fiber (NDF) and acid detergent fiber (ADF) concentrations than Jinan, respectively. The DM degradability of WPCS planted in Bayannur was considerably higher than that in Jinan (6 h degradability: Bayannur vs. Jinan = 49.85% vs. 33.96%), and the starch of WPCS from Bayannur (71.79%) was also the highest after 6 h in the rumen. The results indicated that the contents of NDF, ADF, and starch were estimated precisely based on ATR-FTIR combined with PLSR or the BP-ANN algorithm (R2 ≥ 0.91). This was followed by crude protein (CP), DM (0.82 ≤ R2 ≤ 0.90), ether extract (EE), and ash (0.66 ≤ R2 ≤ 0.81). The BP-ANN algorithm had a higher prediction performance than PLSR (R2PLSR ≤ R2BP-ANN; RMSEPLSR ≥ RMSEBP-ANN). The same WPCS cultivar grown in different regions had various nutrient concentrations and rumen degradation. ATR-FTIR technology combined with the BP-ANN algorithm could effectively evaluate the CP, NDF, ADF, and starch contents of WPCS.

While inhibition of the EZH2 methyltransferase activity has been used for targeting EZH2, its role in cancer progression remains unclear. Here, the authors use neuroblastoma and small cell lung carcinoma model systems and reveal the crosstalk between EZH2 and MYC(N) in the regulation of tumour formation.

Severe acute pancreatitis (SAP) is a critical illness characterized by a severe systemic inflammatory response resulting in persistent multiple organ failure and sepsis. The intestinal microbiome is increasingly appreciated to play a crucial role in modulation of AP disease outcome, but limited information is available about the identity and mechanism of action for specific commensal bacteria involved in AP-associated inflammation. Here we show that Bifidobacteria, particularly B. animalis, can protect against AP by regulating pancreatic and systemic inflammation in germ-free (GF) and oral antibiotic-treated (Abx) mouse models. Colonization by B. animalis and administration of its metabolite lactate protected Abx and GF mice from AP by reducing serum amylase concentration, ameliorating pancreatic lesions and improving survival rate after retrograde injection of sodium taurocholate. B. animalis relieved macrophage-associated local and systemic inflammation of AP in a TLR4/MyD88- and NLRP3/Caspase1-dependent manner through its metabolite lactate. Supporting our findings from the mouse study, clinical AP patients exhibited a decreased fecal abundance of Bifidobacteria that was inversely correlated with the severity of systemic inflammatory responses. These results may shed light on the heterogeneity of clinical outcomes and drive the development of more efficacious therapeutic interventions for AP, and potentially for other inflammatory disorders.

Abstract Background Willis covered stent is the first stent designed exclusively for intracranial vasculature, and its application in carotid-cavernous fistula is limited. The aim is to evaluate the feasibility and efficacy of this device in treating direct carotid-cavernous fistula. Methods Ten consecutive patients with direct carotid-cavernous fistula were treated in our institution with Willis covered stents from September 2013 to December 2015. The characteristics of these patients and the immediate and follow-up results were retrospectively reviewed. Results Of the 10 patients, 8 were treated for the first time, and 2 had been treated elsewhere. Willis covered stents were successfully released in 9 patients. Abnormal arteriovenous shunt disappeared in 6 cases immediately after stent deployment and endoleak occurred in 3 cases. Endoleak disappeared at 6-month angiography follow-up in one case and was sealed with coils through a pre-set microcatheter in another case. Parent artery was sacrificed as endoleak remained despite repeated balloon dilation and a second stent deployment in the third case. All patients got clinical follow-ups for at least 24 months and 7 patients received angiographic follow-up. Symptoms were relieved gradually in all cases except for slight oculomotor paralysis and visual acuity in one case, respectively. In-stent stenosis was found in 1 case, and no recurrence was observed. Conclusions Willis covered stent is feasible for direct carotid-cavernous fistula.

The treatment of complex cerebrovascular diseases (CCVDs) at the skull base, such as complex intracranial aneurysms, carotid-cavernous sinus fistulas, and intracranial artery traumatic injuries, is a difficult clinical problem despite advances in endovascular and surgical therapies. Covered stents or stent graft insertion is a new concept for endovascular treatment that focuses on arterial wall defect reconstruction, differing from endovascular lesion embolization or flow diverter therapies. In recent years, covered stents specifically designed for cerebrovascular treatment have been applied in the clinical setting, allowing thousands of patients with CCVDs to undergo intraluminal reconstruction treatment and achieving positive results, even in the era of flow diverters. Since there is no unified reference standard for the application of covered stents for treating CCVDs, it is necessary to further standardize and guide the clinical application of this technique. Thus, we organized authoritative experts in the field of neurointervention in China to write an expert consensus, which aims to summarize the results of covered stent insertion in the treatment of CCVDs and propose suitable standards for its application in the clinical setting. Based on the contents of this consensus, clinicians can use individualized intraluminal reconstruction treatment techniques for patients with CCVDs.

The objectives of this research were to investigate the fermentation performance of US sorghum varieties for the production of distilled spirits as well as their associated coproducts and to study the formation of volatile compounds that are related to the flavor quality of the spirits. Three US sorghum varieties (red, white, and waxy sorghums) and four yeast strains (DADY, Ethanol Red, GR-2, and 71B) were used for distilled spirit production. Both sorghum variety and type of yeast strains had effects on alcohol concentration and alcohol yield. The alcohol concentration varied from 10.26 to 11.34% (v/v) while alcohol yield varied from 80.93 to 90.33%. Using Ethanol Red yeast achieved consistently the highest average alcohol concentration (11.10%, v/v) and yield (87.33%) regardless of variation in sorghum variety. Waxy sorghum demonstrated significantly higher average alcohol concentration (11.20%, v/v) and yield (89.65%) than white sorghum (10.74% for concentration and 84.7% for yield) and red sorghum (10.28% for concentration and 82.27% for yield). Alcohol fermentation also produces other metabolites as byproducts. Glycerol and lactic acid are the two major byproducts found from sorghum spirit fermentation. DADY produced the highest level of glycerol (∼1.4–1.5%, v/v) during fermentation, while GR-2 produced the lowest level of glycerol (0.9–1.1%, v/v). For all conditions, the lactic acid level was less than 1.2% (v/v). Eight volatile compounds were identified in sorghum spirits which mainly relate to fruity, sour, sweet, floral, buttery, and creamy flavors of the spirits.

ObjectiveChronic internal carotid artery occlusion (CICAO) can cause transient ischemic attack (TIA) and ischemic stroke. Carotid artery stenting (CAS) with embolic protection devices and hybrid surgery combining carotid endarterectomy and endovascular treatment are effective methods for carotid revascularization. The objective of this study was to evaluate and compare the effect and safety of the two surgical procedures.MethodsThis was a single-center retrospective study. In this study, 44 patients who underwent hybrid surgery and 35 who underwent endovascular intervention (EI) at our center were enrolled consecutively between May 2016 and March 2022. All patients were classified into four groups (A-D), as described by Hasan et al. We recorded and analyzed clinical data, angiographic characteristics, technical success rate, perioperative complications, and follow-up data.ResultsThere was no significant difference in baseline characteristics between hybrid surgery group and EI group, except for plasma high density lipoproteins (HDL) levels (median [interquartile range]: hybrid surgery, 0.99 [0.88–1.18] vs. EI, 0.85 [0.78–0.98] mmol/L, P = 0.001). The technical success rate of hybrid surgery was higher than that of EI (37/44 [84.1%] vs. 18/35 [51.4%], P = 0.002; type A: 15/16 [93.8%] vs. 10/11 [90.9%], P = 1.000; type B: 9/10 [90.0%] vs. 5/7 [71.4%], P = 0.537; type C: 12/15 [80.0%] vs. 3/12 [25.0%], P = 0.004; type D: 1/3 [33.3%] vs. 0/5 [0%], P = 0.375). No significant difference was observed in the incidence of perioperative complications between the two procedures (hybrid surgery: 7/44 [15.9%] vs. EI: 6/35 [17.1%], P = 0.883). In addition, there were no significant differences in the rates of stroke and restenosis during follow-up.ConclusionsFor patients with symptomatic CICAO, hybrid surgery may have an advantage over EI in successfully recanalizing occluded segments. There was no significant difference in safety and restenosis between hybrid surgery and EI.

Atherosclerosis is a chronic inflammatory disease closely associated with immunological activity. Lymph nodes (LNs) are essential secondary lymphoid organs, in which complex immune responses occur. Enlarged LNs are commonly observed around inflamed tissues or tumors; however, their role in atherosclerosis is not well understood. We hypothesized that enlarged pericarotid LNs would be present in symptomatic patients with carotid atherosclerosis. Therefore, we recorded the size of LNs around the carotid artery during surgery in patients undergoing carotid endarterectomy (CEA) for carotid atherosclerotic stenosis. Patients were stratified by enlarged LNs, defined as a diameter ≥ 10mm in the transverse diameters. Demographic and clinical data of participants were measured and analyzed. Hematoxylin and eosin (H&E), Sirius red, DAB-enhanced Perls’ Prussian blue, alizarin red, and immunohistochemistry (IHC) staining were performed for composition identification of plaques or LNs. Symptomatic patients were defined as those presenting with an ipsilateral cerebral ischemic event. Compared with patients with non-enlarged LNs, patients with enlarged LNs were more likely to be symptomatic (22/32, 68.8% versus 9/40, 22.5%, P < 0.001) and use calcium channel blocker drugs (17/32, 53.1% versus 10/40, 25%, P=0.014). In addition, they showed lower body mass index (mean ± SD: 24.00 ± 2.66 versus 25.34 ± 2.56 kg/m2, P=0.034), lower weight (median [interquartile range]: 64 [60.00-76.00] versus 72.5 [65.00-77.50] Kg, P = 0.046) and higher diastolic blood pressure (mean ± SD: 78.94 ± 9.30 versus 73.93 ± 8.84 mmHg, P = 0.022). The plague from patients with enlarged LNs exhibited a lower relative percentage of fibrous tissue (29.49 ± 10.73% versus 34.62 ± 10.33%, P = 0.041). The enlarged LNs remained oval-shaped by visual inspection. Compared to non-enlarged LNs, the predominant changes in enlarged LNs were atrophic lymphatic sinuses and dilated LNs parenchyma. Enlarged LNs contained more germinal centers and lymphocytes. In conclusion, symptomatic patients with carotid atherosclerosis have enlarged pericarotid LNs. The current study supports the conclusion that enlarged LNs with an activated and enhanced adaptive immune response may indicate plaque instability. Pericarotid LNs will be a promising marker of plaque stability and may be a potential therapeutic target in patients with carotid atherosclerosis.

Lithium-sulfur batteries suffer from the shuttle effect of lithium polysulfides and interfacial instability of the lithium metal anode. Here, the authors use 1,3,5-benzenetrithiol as an electrolyte additive to protect sulfur cathode and lithium metal anode.

Background and PurposeAneurysm wall enhancement (AWE) on vessel wall magnetic resonance imaging has been suggested as a marker of the unstable status of intracranial aneurysm (IA) and may predict IA rupture risk. However, the role of abnormal hemodynamics in unruptured IAs with AWE remains poorly understood. This study aimed to determine the association between abnormal hemodynamics and AWE in unruptured middle cerebral artery (MCA) aneurysms.MethodsA total of 28 patients with 32 bifurcation aneurysms of the middle cerebral artery>3mm in size were retrospectively selected for this study. Vessel wall magnetic resonance images were reviewed, and the AWE pattern of each aneurysm was classified as no AWE, partial AWE, and circumferential AWE. Computational fluid dynamics were used to calculate the hemodynamic variables of each aneurysm. Univariate and multivariate analyses investigated the association between AWE and hemodynamic variables.ResultsAWE was present in 13 aneurysms (40.6%), with 7 (21.9%) showing partial AWE and 6 (18.7%) showing circumferential AWE. Kruskal–Wallis H analysis revealed that hemodynamic variables including wall shear stress (WSS), oscillatory shear index, aneurysm pressure (AP), relative residence time, and low shear area (LSA) were significantly associated with AWE (p < 0.05). Further ordinal logistic regression analysis found that WSS was the only factor with a significant association with AWE (p = 0.048); similar trends were identified for LSA (p = 0.055) and AP (p = 0.058). Spearman's correlation analysis showed that AWE was negatively correlated with WSS (rs = −0.622, p < 0.001) and AP (rs = −0.535, p = 0.002) but positively correlated with LSA (rs = 0.774, p < 0.001).ConclusionLow wall shear stress, low aneurysm pressure, and increased low shear area were associated with aneurysm wall enhancement on vessel wall magnetic resonance imaging in unruptured cerebral aneurysms. These abnormal hemodynamic parameters may induce inflammation and cause aneurysm wall enhancement. However, the association between these parameters and their underlying pathological mechanisms requires further investigation.

Background: Both patency maintenance and neoangiogenesis contribute to cerebrovascular bypass efficacy. However, the combined impact of the aforementioned two indicators on postoperative revascularization following superficial temporal artery-to-middle cerebral artery (STA-MCA) bypass has been less well elucidated. Meanwhile, there is a paucity of evidence with conflicting results about postoperative aspirin therapy.Objective: The objective of the study was to investigate the correlation between aspirin use and STA-MCA bypass efficacy, including patency, postoperative neoangiogenesis, and follow-up outcomes.Methods: A total of 181 MMD patients (201 procedures) undergoing STA-MCA bypass at our institution (2017–2019) were retrospectively reviewed. The bypass efficacy level and postoperative complications were compared between aspirin and non-aspirin groups.Results: Among 95 PS-matched pairs, the aspirin group presented a significantly more favorable bypass efficacy than the non-aspirin group [odds ratio (OR) 2.23, 95% confidence interval (CI) 1.11–4.61; p = 0.026]. Multivariate logistic regression analysis confirmed the profound impact of aspirin as an independent predictor of bypass efficacy [adjusted OR 2.91, 95% CI 1.34–6.68; p = 0.009]. A remarkable negative correlation was found between bypass efficacy and the rate of ischemic complications (Phi = −0.521). Postoperative aspirin therapy was associated with a non-significant trend toward a lower incidence of ischemic events [OR 0.73, 95% CI 0.23–2.19; p = 0.580]. No significant difference in bleeding rates was observed between aspirin and control groups [OR 1.00, 95% CI 0.12–8.48; p = 1.000].Conclusion: Among patients undergoing STA-MCA bypass procedures, bypass efficacy is a good predictor of follow-up outcomes. Postoperative aspirin therapy can improve patency, neoangiogenesis, and overall bypass efficacy, thereby protecting against postoperative ischemic complications.Clinical Trial Registration:http://www.chictr.org.cn/, identifier CTR2100046178.

Abstract Background African-Americans/Blacks have suffered higher morbidity and mortality from COVID-19 than all other racial groups. This study aims to identify the causes of this health disparity, determine prognostic indicators, and assess efficacy of treatment interventions. Methods We performed a retrospective cohort study of clinical features and laboratory data of COVID-19 patients admitted over a 52-day period at the height of the pandemic in the United States. This study was performed at an urban academic medical center in New York City, declared a COVID-only facility, serving a majority Black population. Results Of the 1103 consecutive patients who tested positive for COVID-19, 529 required hospitalization and were included in the study. 88% of patients were Black; and a majority (52%) were 61–80 years old with a mean body mass index in the “obese” range. 98% had one or more comorbidities. Hypertension was the most common (79%) pre-existing condition followed by diabetes mellitus (56%) and chronic kidney disease (17%). Patients with chronic kidney disease who received hemodialysis were found to have lower mortality, than those who did not receive it, suggesting benefit from hemodialysis Age > 60 years and coronary artery disease were independent predictors of mortality in multivariate analysis. Cox proportional hazards modeling for time to death demonstrated a significantly high ratio for COPD/Asthma, and favorable effects on outcomes for pre-admission ACE inhibitors and ARBs. CRP (180, 283 mg/L), LDH (551, 638 U/L), glucose (182, 163 mg/dL), procalcitonin (1.03, 1.68 ng/mL), and neutrophil:lymphocyte ratio (8.3:10.0) were predictive of mortality on admission and at 48–96 h. Of the 529 inpatients 48% died, and one third of them died within the first 3 days of admission. 159/529patients received invasive mechanical ventilation, of which 86% died and of the remaining 370 patients, 30% died. Conclusions COVID-19 patients in our predominantly Black neighborhood had higher in-hospital mortality, likely due to higher prevalence of comorbidities. Early dialysis and pre-admission intake of ACE inhibitors/ARBs improved patient outcomes. Early escalation of care based on comorbidities and key laboratory indicators is critical for improving outcomes in African-American patients.

Because of the excellent thermal conduction, corrosion resistance, and tribological properties, copper-based friction materials (CBFMs) were widely used in airplanes, high-speed trains, and wind power generation. With operating speed continuously increasing, CBFMs are suffering more complicated and extreme working conditions, which would cause abnormal abrasion. This paper presents an experiment to investigate how the tribological behaviors of CBFMs are regulated by granulation technology. Samples were prepared by the method of granulation and cool-pressed sinter. The tribological properties of specimens with different granule sizes were studied. The results showed that granulation could improve the tribological properties of CBFMs. The friction coefficient (COF) increased first and then decreased with increasing granule size. Specimen fabricated with 5–8 mm granules obtained the lowest COF, which was reduced by 22.49% than that made of powders. Moreover, the wear rate decreased first and then increased as granule size increased. The wear rate of samples prepared by granules 3–5 mm was lower than that of all of the other samples. This is because the structured samples prepared by wet granulation can promote the formation of secondary plateaus, which are beneficial for enhancing tribological properties. This makes granulation a promising method for enhancing the tribological performances of CBFMs.

The southwest vortex (SWV), a low-pressure system bringing severe rainfall in southwest China, is one of the most important synoptic systems in China. Using both the National Centers for Environmental Prediction Final (NCEP-FNL) operational global analysis dataset and the Weather Research and Forecasting (WRF) model simulation, a sophisticated SWV with dual-core structure (DCSWV) over the Sichuan Basin in 2010 was studied. The DCSWV system consisted of two cores, one near Leshan City (named “C1”) and another near Langzhong City (named “C2”). The high-resolution WRF model reproduced the life cycle of the DCSWV well. The diagnostic analysis of the vorticity budget indicated that the stretching and tilting terms played important roles in the development stage of “C1”, while the stretching and vertical advection of vorticity were the major contributors to the formation and development stage of “C2”, which implied the importance of moisture convergence and ascending motion. Sensitivity experiments showed that the DCSWV was closely associated with the release in latent heat as well as the effect of topography. The great release in latent heat provided significantly positive feedback to the DCSWV system, which was decisive to the formation and development stages of “C2”. The topography of the Tibetan Plateau and the Yun-Gui Plateau affected the location and duration of the DCSWV.

Among all racial groups in the U.S., African Americans (AA) have the highest incidence of and mortality from colorectal cancer (CRC). Although socioeconomic factors, as the major contributors to racial disparity of CRC, have been widely investigated, there is a dearth of information germane to understanding its biological basis. To better elucidate the clinicopathologic features we extracted demographic, clinical, pathologic and molecular features of 500 consecutive cases of CRC diagnosed at our institution which has an AA-predominant patient population (75% of all patients). We compared data from our AA patients with those of white patients both from our institution and from SEER and the published literature for meaningful comparison. AA patients were more likely to be at an advanced disease stage (25.9% vs. 20.8%, p = 0.041), have low grade tumors (89.2% vs. 77.5%, p

Background. The neutrophil–lymphocyte ratio (NLR) has been proposed as a surrogate marker of inflammation with prognostic value in various diseases. Our objective was to investigate the predictive value of the NLR as an indicator of persistent organ failure (POF) in patients with hypertriglyceridemic pancreatitis (HTGP). Methods. We retrospectively reviewed the data from patients with HTGP between 2016 and 2019. The NLR was obtained at admission. The diagnostic performance of the NLR for POF was evaluated by the area under the receiver operator characteristics curve (AUROC). Multivariate logistic regression determined whether elevated NLR was independently associated with POF. Results. Of the 446 patients enrolled, 89 (20.0%) developed POF. Patients with POF showed a significantly higher NLR than those without POF (P6.56, the sensitivity and specificity were 73.0% and 55.7%, respectively. Multivariate analysis suggested that high NLR (>6.56) was independently associated with POF (odds ratio, 2.580; 95% confidence interval, 1.439-4.626; P=0.001). Patients with a high NLR (>6.56) had a worse overall clinical course in HTGP. Conclusion. Elevated NLR was significantly associated with an increased risk of developing POF and could be an early independent predictor of POF in patients with HTGP.

Abstract Background To investigate the dynamic change of lipid profile under double filtration plasmapheresis (DFPP) in severe hypertriglyceridemia-induced acute pancreatitis (sHTGP) patients and ascertain the association between these changes and the clinical prognosis. Methods sHTGP patients admitted within 72 h after disease onset were included, and all the patients received DFPP within 24 h after admission. Lipid profile were detected on admission, consecutive 4 days after DFPP and at discharge. Results There were 47 sHTGP patients enrolled in this study. At admission, all the parameters of lipid profile changed significantly except for low density lipoprotein. In the first day after DFPP, the serum level of TG, cholesterol and very low density lipoprotein declined significantly, while the high-density lipoprotein (HDL) as well as apoprotein A1 elevated obviously (P

Silicon-based anodes must maintain the electrode structure to fulfil their potential. Here the authors report the use of a supremely elastic gel polymer electrolyte to stabilize such anodes at electrode and particle levels, enabling superior battery performance with a commercial-level capacity.

Camelina (Camelina sativa L. Crantz) seeds, especially their bran, contain a significant amount of monosaccharides and polysaccharides (gums). A decortication procedure was used for improving gum isolation as well as increasing the efficiency of camelina protein isolation and protein quality. The effects of bran-to-water ratio (1:30, 1:40, and 1:50 g/mL), isolation temperature (25, 50, and 75 °C), isolation time (0.5, 1.5, and 2.5 h), and their interactions on gum yield, purity, and rheological properties were studied. Response surface methodology was used to determine the optimal condition for isolating gums from the bran of camelina seed. Gum yield, purity, and viscosity data fit the second-order model (R2 = 0.995, 0.877, and 0.804) better than the first-order model (R2 = 0.813, 0.568, and 0.636). Regression results from the second-order model showed that bran-to-water ratio, isolation temperature, and isolation time all had significant effect on gum yield, purity, and viscosity. The optimal gum isolation condition was found to be: bran-to-water ratio: 1:39 g/mL; isolation temperature: 35 °C; and isolation time: 1.5 h. Under these conditions, gum yield, purity, and viscosity were 19.08% (w/w), 56.24% (w/w), and 62.80 Pa·s, respectively. The maximum predicted value of all three responses was 0.839. The yield and quality of protein extracted from decorticated endosperm were significantly improved over those from whole seed meal.

This paper presents and parameterizes an equivalent circuit model of an all-solid-state lithium-sulfur battery cell, filling a gap in the literature associated with low computational intensity models suitable for embedded battery management applications. The paper addresses this gap by parameterizing a three-state equivalent circuit model using experimental pulse power characterization data from a laboratory-fabricated lithium-sulfur cell. The cell is mechanically loaded during electrical cycling to achieve maximum ionic conductivity and consistent capacity. A nested combination of linear and nonlinear least squares regression is used to estimate the model parameters. The model captures slow cycling and fast pulse charge/discharge dynamics within 34 mV RMS error. The series resistance changes significantly at high/low states of charge and low C-rates. A sensitivity analysis determines that accurately modeling the dependence of resistance on C-rate and state of charge is important for model fidelity.

As one of the oldest plants cultivated by humans, hemp used to be banned in the United States but returned as a legal crop in 2018. Since then, the United States has become the leading hemp producer in the world. Currently, hemp attracts increasing attention from consumers and scientists as hemp products provide a wide spectrum of potential functions. Particularly, bioactive peptides derived from hemp proteins have been proven to be strong antioxidants, which is an extremely hot research topic in recent years. However, some controversial disputes and unknown issues are still underway to be explored and verified in the aspects of technique, methodology, characteristic, mechanism, application, caution, etc. Therefore, this review focusing on the antioxidant properties of hemp proteins is necessary to discuss the multiple critical issues, including in vitro structure-modifying techniques and antioxidant assays, structure-activity relationships of antioxidant peptides, pre-clinical studies on hemp proteins and pathogenesis-related molecular mechanisms, usage and potential hazard, and novel advanced techniques involving bioinformatics methodology (QSAR, PPI, GO, KEGG), proteomic analysis, and genomics analysis, etc. Taken together, the antioxidant potential of hemp proteins may provide both functional food benefits and phytotherapy efficacy to human health.

The nutrition loss of silage is partly due to the heat production of silage. In this study, the amount of nutrition loss of silage was estimated by measuring the heat production of silage, and the concept of the accumulated temperature of fermentation was put forward. The laboratory measured the fermentation-accumulated temperature of whole-plant corn silage with different compaction densities. The samples were analyzed to establish a multiple linear regression model with nutrition loss. The results demonstrated a significant non-linear relationship between the whole-plant corn silage compaction density and fermentation-accumulated temperature. The multiple linear regression model between the accumulated-fermentation temperature and nutrition loss was significant under different densities. The amount of silage nutrition loss can be predicted by the fermentation-accumulated temperature.

Background and Purpose: The utilization of flow diversion for ruptured intracerebral aneurysms (IAs) is still limited. We aimed to demonstrate our multicenter experience using the pipeline embolization device (PED) for ruptured IAs that were difficult to treat by clipping and coiling.Methods: Thirty-eight patients with ruptured IAs who underwent PED treatment from 2015 to 2020 were retrospectively reviewed. Factors associated with procedure-related stroke (ischemic and hemorrhagic) and clinical and angiography outcomes were analyzed.Results: There were 14 (36.8%) saccular IAs, 12 (31.6%) blister-like IAs, and 12 (31.6%) dissecting IAs. Perforator involvement was noted in 10 (26.3%) IAs. Early PED placement ( ≤ 15 days) and adjunctive coiling treatment were performed in 27 (71.1%) and 22 (57.9%) cases, respectively. The overall rate of stroke-related complications was 31.6% (12/38) (including rates of 10.5% for procedure-related hemorrhagic complications and 15.8% for procedure-related infarction). The mortality rate was 13.2% (5/38), and 84.2% of patients (32/38) had favorable outcomes. Thirty-two (84.2%) patients underwent follow-up angiographic evaluations; of these, 84.4% (27 patients) had complete occlusion and 15.6% had incomplete obliteration. Multivariate analysis revealed that early PED placement was not associated with a high risk of procedure-related stroke or an unfavorable outcome. Adjunctive coiling exhibited an association with procedure-related stroke (p = 0.073). Procedure-related hemorrhagic complications were significantly associated with an unfavorable outcome (p = 0.003). Immediate contrast stasis in the venous phase was associated with complete occlusion during follow-up (p = 0.050).Conclusion: The PED is a feasible and effective treatment to prevent rebleeding and achieve aneurysm occlusion, but it is associated with a substantial risk of periprocedural hemorrhage and ischemic complications in acute ruptured IAs. Therefore, the PED should be used selectively for acutely ruptured IAs. Additionally, adjunctive coiling might increase procedure-related stroke; however, it may reduce aneurysm rebleeding in acutely ruptured IAs. Patients with immediate contrast stasis in the venous phase were more likely to achieve total occlusion. A prospective study with a larger sample size should be performed to verify our results.

Recombination activating genes 1 (Rag1) and Rag2 are expressed in immature lymphocytes and essential for generating the vast repertoire of antigen receptors. Yet, the mechanisms governing the transcription of Rag1 and Rag2 remain to be fully determined, particularly in thymocytes. Combining cDNA microarray and ChIP-seq analysis, we identify Rag1 and Rag2 as novel Notch1 transcriptional targets in acute T-cell lymphoblastic leukemia (T-ALL) cells. We further demonstrate that Notch1 transcriptional complexes directly bind the Rag1 and Rag2 locus in not only T-ALL but also primary double negative (DN) T-cell progenitors. Specifically, dimeric Notch1 transcriptional complexes activate Rag1 and Rag2 through a novel cis-element bearing a sequence-paired site (SPS). In T-ALL and DN cells, dimerization-defective Notch1 causes compromised Rag1 and Rag2 expression; conversely, dimerization-competent Notch1 achieves optimal upregulation of both. Collectively, these results reveal Notch1 dimerization-mediated transcription as one of the mechanisms for activating Rag1 and Rag2 expression in both primary and transformed thymocytes. Our data suggest a new role of Notch1 dimerization in compelling efficient TCRβ rearrangements in DN progenitors during T-cell development.

More than 3.5 million people have died globally from COVID-19, yet an effective therapy is not available. It is, therefore, important to understand the signaling pathways that mediate disease progression in order to identify new molecular targets for therapeutic development. Here, we report that the blood serum levels of ephrin-A1 and the sheddase ADAM12 were significantly elevated in COVID-19 patients treated at SUNY Downstate Hospital of Brooklyn, New York. Both ephrin-A1 and ADAM12 are known to be involved in inflammation and regulate endothelial cell permeability, thus providing a gateway to lung injury. The clinical outcome correlated with the ephrin-A1 and ADAM12 serum levels during the first week of hospitalization. In contrast, the serum levels of TNFα were elevated in only a small subset of the patients, and these same patients also had highly elevated levels of the sheddase ADAM17. These data indicate that ephrin-A1-mediated inflammatory signaling may contribute to COVID-19 disease progression more so than TNFα-mediated inflammatory signaling. They also support the notion that, in COVID-19 inflammation, ADAM12 sheds ephrin-A1, while ADAM17 sheds TNFα. Furthermore, the results suggest that elevated serum levels and activity of cytokines, such as TNFα, and other secreted inflammatory molecules, such as ephrin-A1, are not simply due to overexpression, but also to upregulation of sheddases that release them into the blood circulation. Our results identify ephrin-A1, ADAM12, and other molecules in the ephrin-A1 signaling pathway as potential pharmacological targets for treating COVID-19 inflammation.

Antioxidant dietary fiber (ADF) is the dietary fiber with natural phenolic compounds, which are beneficial for human health. The addition of ADF to bread increased nutrition and health benefits for consumers. Besides improving the dietary fiber content, polyphenol content, and antioxidant capacity, the addition of ADF increased dough development time due to fiber reduced rate of hydration and gluten development. Literatures showed that the addition of ADF increased hardness, reduced loaf volume, and affected color, texture, and sensory attributes of resultant bread. Therefore, this review covers the current research of the addition of ADF on dough rheological properties and bread qualities, as well as the current challenges of bread enriched with ADF. In addition, promising research topics are recommended for future study including the effect of particle size of ADF, pre-treatment of ADF (e.g., extrusion processing) and inclusion of hydrocolloids on wheat bread with the addition of ADF.

Chitosan-based hydrogel has been widely used in the field of tissue engineering due to its favorable biocompatibility and good biodegradability. However, this kind of hydrogel generally exhibits poor mechanical stability, which greatly limits its application in the field of 3D bioprinting. In this study, we provided a hybrid bioink created from photocurable chitosan and acrylamide (AM) for digital light processing (DLP) based 3D bioprinting in tissue engineering applications. This hybrid bioink was facilely prepared by combining AM and chitosan modified with methacryloyl groups (CHIMA). The gelling point of the hybrid pre-hydrogel bioink was greatly dependent on the photoinitiators. Both the mechanical properties and cytocompatibility of the hydrogel formed by the bioink can be modulated by varying the AM contents. The hybridization of natural CHIMA and synthetic AM enables the hybrid hydrogels with desirable biological activity and mechanical properties. Utilizing the DLP based 3D printing, this hybrid bioink can be processed into complex 3D hydrogel constructs with high-strength and good biocompatibility. Therefore, the photocurable hybrid bioink composed of CHIMA and AM in proper proportion is well suitable for use in DLP based 3D bioprinting, which would play a promising role in constructing tissues and organs in the future.

Intestinal immunity is coordinated by specialized mononuclear phagocyte populations, constituted by a diversity of cell subsets. Although the cell subsets constituting the mononuclear phagocyte network are thought to be similar in both small and large intestine, these organs have distinct anatomy, microbial composition, and immunological demands. Whether these distinctions demand organ-specific mononuclear phagocyte populations with dedicated organ-specific roles in immunity are unknown. Here we implement a new strategy to subset murine intestinal mononuclear phagocytes and identify two novel subsets which are colon-specific: a macrophage subset and a Th17-inducing dendritic cell (DC) subset. Colon-specific DCs and macrophages co-expressed CD24 and CD14, and surprisingly, both were dependent on the transcription factor IRF4. Novel IRF4-dependent CD14+CD24+ macrophages were markedly distinct from conventional macrophages and failed to express classical markers including CX3CR1, CD64 and CD88, and surprisingly expressed little IL-10, which was otherwise robustly expressed by all other intestinal macrophages. We further found that colon-specific CD14+CD24+ mononuclear phagocytes were essential for Th17 immunity in the colon, and provide definitive evidence that colon and small intestine have distinct antigen presenting cell requirements for Th17 immunity. Our findings reveal unappreciated organ-specific diversity of intestine-resident mononuclear phagocytes and organ-specific requirements for Th17 immunity.

Macrophage specific deletion of GGTase-I, a prenylation enzyme, in mice induces inflammatory response and rheumatoid arthritis. Here the authors show that GGTase-I deficiency and the resulting reduction of RAC1 prenylation increase RAC1 interaction with the adaptor protein IQGAP1, leading to GTP-loading of RAC1 and enhanced proinflammatory cytokine production.