TCMFP: a novel herbal formula prediction method based on network target's score integrated with semi-supervised learning genetic algorithms.

Traditional Chinese medicine (TCM) has accumulated thousands years of knowledge in herbal therapy, but the use of herbal formulas is still characterized by reliance on personal experience. Due to the complex mechanism of herbal actions, it is challenging to discover effective herbal formulas for diseases by integrating the traditional experiences and modern pharmacological mechanisms of multi-target interactions. In this study, we propose a herbal formula prediction approach (TCMFP) combined therapy experience of TCM, artificial intelligence and network science algorithms to screen optimal herbal formula for diseases efficiently, which integrates a herb score (Hscore) based on the importance of network targets, a pair score (Pscore) based on empirical learning and herbal formula predictive score (FmapScore) based on intelligent optimization and genetic algorithm. The validity of Hscore, Pscore and FmapScore was verified by functional similarity and network topological evaluation. Moreover, TCMFP was used successfully to generate herbal formulae for three diseases, i.e. the Alzheimer's disease, asthma and atherosclerosis. Functional enrichment and network analysis indicates the efficacy of targets for the predicted optimal herbal formula. The proposed TCMFP may provides a new strategy for the optimization of herbal formula, TCM herbs therapy and drug development.

Blenderized tube feeding in pediatrics - current evidence, guidelines, and considerations.

PURPOSE OF REVIEW: Recently, blenderized tube feeding (BTF) consisting of blended whole food components is emerging as a preferred approach to enteral nutrition in pediatric patients. Differences in the nutritional profile, viscosity, and other characteristics between BTF and conventional tube feeding formulas may impact clinical outcomes and practice considerations. RECENT FINDINGS: Increasing guidance and evidence are emerging for BTF in pediatric populations requiring tube feeding. The characteristics of each BTF formulation vary, which may affect patient tolerance and clinical outcome. SUMMARY: BTF is safe and generally well tolerated in children. It is shown to improve symptoms, clinical outcomes, and quality of life for many patients. A thorough risk assessment and nuanced approach may be required to optimize BTF administration.

From the kitchen to the medicine cabinet: Examples of food products and supplements used for therapeutic intent.

"Food as medicine" has existed for centuries as the foundation of health for many cultures around the globe. It is a practice built on the knowledge that food and diet play important roles in disease prevention and management. Foods that claim to have therapeutic properties are often referred to as functional foods. These foods contain a number of nutritional and nonnutritional compounds that can interact with pharmacologically relevant receptors, either directly or indirectly via their metabolites, to regulate cellular biochemical processes. Although opinions are changing, the concept of food as a therapeutic intervention goes against conventional Western medicine. To provide guidance to clinicians interested in using these products, members of the Food as Medicine working group of the Nutrition Committee for the North American Society For Pediatric Gastroenterology, Hepatology & Nutrition (NASPGHAN), as part of a two-part review series, have created summaries of several frequently used nutritional products for therapeutic intent (i.e., fermented foods, fiber, and long-chain omega-3 fatty acids) that includes indications, doses, and caveats. Gaps in their use in pediatric patients are discussed. Evidence supporting their use for management of GI conditions, especially in the pediatric population, is provided when available.

Whole Foods Introduction Associated With Symptomatic Anastomotic Ulceration in Children With Short Bowel Syndrome.

OBJECTIVES: Anastomotic ulceration (AU) is a rare but life-threatening complication of pediatric short bowel syndrome (SBS). AUs may be challenging to detect and refractory to treatment. This study aimed to identify features associated with symptomatic bleeding AUs in children with SBS and factors that may impact resolution of bleeding. The relationship between dietary changes and symptomatic anastomotic hemorrhage was also explored. METHODS: We conducted a retrospective chart review of 381 patients cared for in the Intestinal Rehabilitation Program at our center from 2013 to 2022. Patients with symptomatic AUs were identified based on at least 1 endoscopic procedure showing AUs and evidence of clinically significant gastrointestinal bleeding. We collected patient demographics, clinical characteristics, dietary history, radiologic imaging, and histopathology. We used descriptive statistics to identify patterns of presentation. RESULTS: AUs were identified in 22 patients who were followed for a median duration of 2.9 years after anastomotic ulcer identification. AUs uniformly evolved years after the initial anastomosis (median 3.2 years). Characteristics included bowel stricture (4/22), small bowel-colon anastomosis (19/22), partial colectomy (17/22), and an increase in whole foods fraction (12/18). Bleeding resolved with operative intervention in the majority with anastomotic stricture (3/4). Recurrent bleeding was common in those without stricture (13/18). In a subset of patients without stricture, whole food reduction was associated with improvement or resolution of bleeding (5/6). CONCLUSIONS: We observed a higher proportion of patients with AUs who responded to surgical intervention in the subset of children with definitive anastomotic strictures versus those without, suggesting that careful characterization of intestinal anatomy may be critical to predicting response to therapy. We also observed that bleeding from AU typically first manifested within 1 year of a shift from elemental or hydrolyzed enteral formula to a whole food-based diet (including commercial blenderized feeds), which may indicate that components of the enteral diet play a role in the pathogenesis of AU. Further studies are needed to validate these hypotheses.

Resveratrol regulates paracrine function of cardiac microvascular endothelial cells under hypoxia/reoxygenation condition.

The secreted factors from cardiac microvascular endothelial cells (CMECs) regulate the physiological activity of adjacent tissues and could be modulated by myocardial ischemia/reperfusion injury (MIRI). How this paracrine function of CMECs is regulated by MIRI and resveratrol remains to be elucidated. CMECs pretreated with/ without resveratrol were subjected to hypoxia/reoxygenation (H/R). Apoptosis was measured by flowcytometry. Protein antibody arrays were performed to find the alteration of cytokine secreted by CMECs. The Gene Ontology analysis was applied to interpret the function of modulated factors. We revealed resveratrol inhibited apoptosis of CMECs dose-dependently after H/R and reached its peak effect at the concentration of 100 µM. 29 factors were significantly changed by H/R, and resveratrol at 100 µM changed 98 types of factors compared with the H/R group. Among these factors, eight were increased by H/R and then were decreased by resveratrol. Eleven were attenuated by H/R and further decreased by resveratrol. Insulin-like growth factor binding protein-1 was upregulated by H/R and it was further increased by resveratrol. The altered factors were involved in cell proliferation, cell growth, cell motility, chemotaxis, angiogenesis and vasculogenesis. The study suggests that resveratrol inhibits the apoptosis and modulates the paracrine function of CMECs under ischemia/reperfusion condition.

Aucubin Alleviates Seizures Activity in Li-Pilocarpine-Induced Epileptic Mice: Involvement of Inhibition of Neuroinflammation and Regulation of Neurotransmission.

Neuroinflammation and imbalance of neurotransmitters play pivotal roles in seizures and epileptogenesis. Aucubin (AU) is an iridoid glycoside derived from Eucommia ulmoides that possesses anti-inflammatory and neuroprotective effects. However, the anti-seizure effects of AU have not been reported so far. The present study was designed to investigate the effects of AU on pilocarpine (PILO) induced seizures and its role in the regulation of neuroinflammation and neurotransmission. We found that AU reduced seizure intensity and prolonged the latency of seizures. AU significantly attenuated the activation of astrocytes and microglia and reduced the levels of interleukine-1 beta (IL-1ß), high mobility group box 1 (HMGB1), tumor necrosis factor-α (TNF-α). Furthermore, the contents of γ-aminobutyric acid (GABA) were increased while the levels of glutamate were decreased in the hippocampus with AU treatment. The expression of γ-aminobutyric acid type A receptor subunit α1 (GABAARα1) and glutamate transporter-1 (GLT-1) protein were up-regulated in AU treatment group. However, AU had no significant effect on N-methyl-d-aspartate receptor subunit 2B (NR2B) expression in status epilepticus (SE). In conclusion, our findings provide the first evidence that AU can exert anti-seizure effects by attenuating gliosis and regulating neurotransmission. The results suggest that AU may be developed as a drug candidate for the treatment of epilepsy.

Ginsenoside compound K attenuates cognitive deficits in vascular dementia rats by reducing the Aß deposition.

Ginsenoside compound K (CK) is the main metabolite of protopanaxadiol-type ginsenosides and has been demonstrated to exert neuroprotective and cognition-enhancing effects. The effects of CK on cognitive function in vascular dementia (VD) has not been elucidated. Therefore, the present study aims to elucidate the effects of CK on memory function as well as its potential mechanism in VD rats. Sprague-Dawley rats were subjected to Chronic Cerebral Hypoperfusion (CCH) by permanent bilateral common carotid artery occlusion (2VO). CCH induced neuronal damage and aggravated the aggregation of Amyloid-ß1-42 peptides (Aß1-42), which plays a critical role in the neurotoxicity and cognitive impairment. CK treatment attenuated CCH-induced Aß1-42 deposition and ameliorated cognition impairment. Furthermore, CK enhanced the activity of the pSer9-Glycogen synthase kinase 3ß (pSer9-GSK3ß) and the insulin degrading enzyme (IDE), which mainly involved the production and clearance of Aß1-42. Moreover, CK treatment enhanced the activity of protein kinase B (PKB/Akt), a key kinase in phosphatidylinositol 3 kinase (PI3K)/Akt pathway that can regulate the activity of GSK-3ß and IDE. In short, our findings provide the first evidence that CK might attenuate cognitive deficits and Aß1-42 deposition in the hippocampus via enhancing the expression of pSer9-GSK-3ß and IDE.

The Expression Alteration of BC1 RNA and its Interaction with Eukaryotic Translation Initiation Factor eIF4A Post-Status Epilepticus.

Abnormal dendritic sprouting and synaptic remodelling are important pathological features of temporal lobe epilepsy. BC1 RNA is a translation repressor involved in the regulation of the dendritic protein synthesis and mRNA transport, which is essential for dendritic development and plasticity. The expression alteration of BC1 RNA in the pilocarpine induced epilepsy model remains unknown. It is unclear if the interactions between BC1 RNA and eukaryotic initiation factor 4A (eIF4A) exists in this model. The purpose of this study was to investigate the expression changes of BC1 RNA and its interactions with eIF4A post-status epilepticus (SE). Chloride lithium and pilocarpine were used to induce the SE rat model. Either a whole brain or hippocampus tissues were collected at different time points after SE. The expression patterns of BC1 was detected by qPCR and in situ hybridization. The levels of eIF4AI/II protein expression were analyzed via western blotting and immunohistochemistry. The BC1 RNA-eIF4AI/II interaction was determined by electrophoretic mobility shift assay (EMSA). We found that the BC1 RNA levels decreased in hippocampus 3d, 1w and 2w post-SE before the levels recovered. The eIF4AI/II began to rise 3d post-SE and reached the maximum level 1w post-SE. After 1w post-SE the levels decreased in the hippocampal CA1, CA3 and DG subregions. EMSA analysis showed that BC1 RNA specifically interacted with the eIF4AI/II. The BC1 RNA-eIF4AI/II complex reduced to the lowest level 1w post-SE. Our results suggested that BC1 has a negative regulatory correlation with eIF4AI/II, where BC1 RNA could be involved in epileptogenesis by regulating dendritic protein synthesis.

Disruption of intestinal oxygen balance in acute colitis alters the gut microbiome.

The juxtaposition of well-oxygenated intestinal colonic tissue with an anerobic luminal environment supports a fundamentally important relationship that is altered in the setting of intestinal injury, a process likely to be relevant to diseases such as inflammatory bowel disease. Herein, using two-color phosphorometry to non-invasively quantify both intestinal tissue and luminal oxygenation in real time, we show that intestinal injury induced by DSS colitis reduces intestinal tissue oxygenation in a spatially defined manner and increases the flux of oxygen from the tissue into the gut lumen. By characterizing the composition of the microbiome in both DSS colitis-affected gut and in a bioreactor containing a stable human fecal community exposed to microaerobic conditions, we provide evidence that the increased flux of oxygen into the gut lumen augments glycan degrading bacterial taxa rich in glycoside hydrolases which are known to inhabit gut mucosal surface. Continued disruption of the intestinal mucus barrier through such a mechanism may play a role in the perpetuation of the intestinal inflammatory process.

Endotype-driven Co-module mechanisms of danhong injection in the Co-treatment of cardiovascular and cerebrovascular diseases: A modular-based drug and disease integrated analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiovascular and cerebrovascular diseases are the leading causes of death worldwide and interact closely with each other. Danhong Injection (DHI) is a widely used preparation for the co-treatment of brain and heart diseases (CTBH). However, the underlying molecular endotype mechanisms of DHI in the CTBH remain unclear. AIM OF THIS STUDY: To elucidate the underlying endotype mechanisms of DHI in the CTBH. MATERIALS AND METHODS: In this study, we proposed a modular-based disease and drug-integrated analysis (MDDIA) strategy for elucidating the systematic CTBH mechanisms of DHI using high-throughput transcriptome-wide sequencing datasets of DHI in the treatment of patients with stable angina pectoris (SAP) and cerebral infarction (CI). First, we identified drug-targeted modules of DHI and disease modules of SAP and CI based on the gene co-expression networks of DHI therapy and the protein-protein interaction networks of diseases. Moreover, module proximity-based topological analyses were applied to screen CTBH co-module pairs and driver genes of DHI. At the same time, the representative driver genes were validated via in vitro experiments on hypoxia/reoxygenation-related cardiomyocytes and neuronal cell lines of H9C2 and HT22. RESULTS: Seven drug-targeted modules of DHI and three disease modules of SAP and CI were identified by co-expression networks. Five modes of modular relationships between the drug and disease modules were distinguished by module proximity-based topological analyses. Moreover, 13 targeted module pairs and 17 driver genes associated with DHI in the CTBH were also screened. Finally, the representative driver genes AKT1, EDN1, and RHO were validated by in vitro experiments. CONCLUSIONS: This study, based on clinical sequencing data and modular topological analyses, integrated diseases and drug targets. The CTBH mechanism of DHI may involve the altered expression of certain driver genes (SRC, STAT3, EDN1, CYP1A1, RHO, RELA) through various enriched pathways, including the Wnt signaling pathway.

Neutrophil-mediated hypoxia drives pathogenic CD8+ T cell responses in cutaneous leishmaniasis.

Cutaneous leishmaniasis caused by Leishmania parasites exhibits a wide range of clinical manifestations. Although parasites influence disease severity, cytolytic CD8+ T cell responses mediate disease. Although these responses originate in the lymph node, we found that expression of the cytolytic effector molecule granzyme B was restricted to lesional CD8+ T cells in Leishmania-infected mice, suggesting that local cues within inflamed skin induced cytolytic function. Expression of Blimp-1 (Prdm1), a transcription factor necessary for cytolytic CD8+ T cell differentiation, was driven by hypoxia within the inflamed skin. Hypoxia was further enhanced by the recruitment of neutrophils that consumed oxygen to produce ROS and ultimately increased the hypoxic state and granzyme B expression in CD8+ T cells. Importantly, lesions from patients with cutaneous leishmaniasis exhibited hypoxia transcription signatures that correlated with the presence of neutrophils. Thus, targeting hypoxia-driven signals that support local differentiation of cytolytic CD8+ T cells may improve the prognosis for patients with cutaneous leishmaniasis, as well as for other inflammatory skin diseases in which cytolytic CD8+ T cells contribute to pathogenesis.

Comparable clinical advantages identification of three formulae on rheumatic disease using a modular-based network proximity approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbal formulae have been used in China for thousands of years but have unclear clinical positioning and unknown characteristic indications make it difficult to determine their specific application in various diseases, which seriously hamper their clinical value. Identifying the precise clinical positioning and clinical advantages of similar formulae for related diseases is a critical issue. AIM OF THIS STUDY: To develop a methodology based on modular pharmacology to determine the clinical advantages and precise clinical position of similar formulae. MATERIALS AND METHODS: In this study, we proposed a modular-based network proximity approach to explore drug repositioning and clinical advantages of three formulae, Shirebi tablets (SRB), Yuxuebi capsules (YXB), and Wangbifukang granules (WBFK), for rheumatic disease. First, we constructed a rheumatology target network, and modules were obtained using the cluster tool molecular complex detection (MCODE). Based on the modular interaction map established by a quantitative approach for inter-module coordination and its transition (IMCC), using a targeting rate (TR) matrix to identify targeted modules of three formulae. Moreover, the network proximity Z-score and Jaccard similarity coefficient were used to identify potential optimal symptomatic indications and related diseases using three formulae. At the same time, the driver genes for SRB and gouty arthritis were identified by flow centrality and shortest distance, and the epresentative driver genes were validated by in vivo experiments. RESULTS: 32 modules were obtained using the MCODE method. 4, 4, and 14 characteristic targeted modules of SRB, YXB, and WBFK, respectively, were identified using a targeting rate (TR) matrix. Module 2, 16, and 19 were targeted by both SRB and WBFK. The common effects of SRB and WBFK focused on inflammatory response and innate immune response, YXB was found to be involved in the collagen catabolic process, transmembrane receptor protein serine/threonine kinase signaling pathway. Moreover, potential optimal symptomatic indications and representative related diseases were identified for three formulae: SRB was significantly associated with GA (Z = -20.26); YXB was significantly associated with AS (Z = -4.532), MI (Z = -29.11), RhFv (Z = -6.945), OA (Z = -39.97), and GA (Z = -13.03); and WBFK was significantly associated with MI (Z = -205.5), SLE (Z = -37.65), RhFv (Z = -42.45), and GA (Z = -17.24). Finally, 8 driver genes for SRB and gouty arthritis were identified,the representative driver genes TRAF6 and NFE2L1 were validated by in vivo experiments. CONCLUSIONS: The modular-based network proximity approach proposed in this study may provide a new perspective for the precise drug repositioning and clinical advantages of similar formulae in disease treatment.

Tongxinluo attenuates atherosclerosis by inhibiting ROS/NLRP3/caspase-1-mediated endothelial cell pyroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Tongxinluo (TXL) is one of the most common traditional Chinese medicines and plays a vital role in treating atherosclerosis (AS). Endothelial cell (EC) pyroptosis plays a crucial role in the development of AS. Previous research revealed the inhibitory function of TXL in EC apoptosis and autophagy. However, whether TXL can inhibit the pyroptosis of ECs has not been determined. AIM OF THE STUDY: To explore the influence of TXL on EC pyroptosis and determine its underlying mechanism of action in AS. MATERIALS AND METHODS: The TXL components were determined by ultra-performance liquid chromatography coupled with a photodiode array detector. We used ApoE-/- mice to establish a disease model of AS. After treatment with TXL, we recorded pathological changes in the mice and performed immunofluorescence staining of mice aortas. We also measured protein and gene levels to explore the influence of TXL on pyroptosis in vivo. The model was established by stimulating mouse aortic endothelial cells (MAECs) with oxidized low-density lipoprotein (ox-LDL) and analyzing the effect of TXL on pyroptosis by Western blotting (WB), real-time PCR (RT-PCR), and flow cytometry (FCM). We also investigated the impact of TXL on reactive oxygen species (ROS) by FCM and WB. RESULTS: Ten major components of TXL were detected. The vivo results showed that TXL inhibited the development of AS and decreased EC pyroptosis, the activation of caspase-1, and the release of inflammatory cytokines. The vitro experiments showed that TXL significantly reduced the extent of injury to MAECs by oxidized LDL (ox-LDL). TXL reversed the high expression of gasdermin D and other proteins induced by ox-LDL and had a significant synergistic effect with the caspase-1 inhibitor VX-765. We also confirmed that TXL decreased the accumulation of ROS and the expression levels of its essential regulatory proteins Cox2 and iNOS. When ROS accumulation was reduced, EC pyroptotic damage was reduced accordingly. CONCLUSION: Our results indicated that TXL inhibited EC pyroptosis in AS. Reducing the accumulation of ROS may be the essential mechanism of AS inhibition by TXL.

Myeloidcells in the immunosuppressive microenvironment in glioblastoma: The characteristics and therapeutic strategies.

Glioblastoma (GBM) is the most common and lethal malignant tumor of the central nervous system in adults. Conventional therapies, including surgery, radiotherapy, and chemotherapy, have limited success in ameliorating patient survival. The immunosuppressive tumor microenvironment, which is infiltrated by a variety of myeloid cells, has been considered a crucial obstacle to current treatment. Recently, immunotherapy, which has achieved great success in hematological malignancies and some solid cancers, has garnered extensive attention for the treatment of GBM. In this review, we will present evidence on the features and functions of different populations of myeloid cells, and on current clinical advances in immunotherapies for glioblastoma.

Clinical and lifestyle patterns in Asian children with inflammatory bowel disease in the U.S.

BACKGROUND: While there are many epidemiologic studies of Asian immigrants to the West and risk of inflammatory bowel disease (IBD), the phenotype and lifestyle of Asian patients, particularly children, with IBD are not well described. In this study, we describe lifestyle practices, such as dietary pattern, as well as disease phenotype in Asian American children with IBD. METHODS: We reviewed the records of children with IBD, ages 0 to 21 years old, and race identified as Asian, Indian, or Pacific Islander. Patients who received outpatient IBD care at our center between January 2013 and January 2020 were included. We excluded patients who were international second opinions, who did not have a definitive diagnosis of IBD, and in whom a diagnosis of IBD was made after 18 years of age. A survey, including a food frequency questionnaire adapted from NHANES DSQ with modifications to include culturally appropriate food elements, was designed and conducted within this cohort to assess for dietary patterns. RESULTS: Asian patients in our cohort have similar phenotypes as non-Asians with few distinctive differences. There was a Crohn's disease and male predominance similar with non-Asians. However, there was a high rate of proctitis in ulcerative colitis in Asian patients. Asian patients reported a typical dietary pattern that reflects a Westernized pattern rather than a traditional pattern. Despite a similar dietary pattern, there was a high rate of 25-OH Vitamin D deficiency (44%) and insufficiency (40%). CONCLUSIONS: This single center study showed that the phenotype of Asian children with IBD in the U.S. is similar with that of non-Asian with a few distinct differences. The Asian children in our cohort reported following a Westernized dietary pattern and lifestyle. However, there was a high rate of Vitamin D deficiency surrounding diagnosis, suggesting a need for vigilant monitoring.

Comprehensive assessment of soil and dust heavy metal(loid)s exposure scenarios at residential playgrounds in Beijing, China.

Small playgrounds situated within residential communities are popular recreational areas. However, heavy metal(loid)s (HMs) in soil or equipment dust may pose a public health risk. This study provides a comprehensive assessment of the health risk associated with HMs exposure at residential playgrounds in cities, a field that has not been thoroughly investigated previously. 70 soil and 70 equipment dust samples were collected from 30 urban and 40 suburban playgrounds in Beijing. Results indicated significant enrichment of Cu, As, and Ni in the soil with Enrichment Factors (EFs) >5 from both anthropogenic and lithogenic sources. Correlation analyses showed that the levels of Be, Cr, Mn, Co, Ni in soil and Be, Mn, As, Cd in dust were positively correlated with the distance to the nearest highway, with p-values < 0.01. Enrichment and correlation analyses contributed to a better understanding of the sources and transport pathways of HMs in urban environment. Based on a site-specific Conceptual Site Model (CSM), the carcinogenic risks (CRs) and Hazard Quotients (HQs) were quantified for residents as the ratio of HMs exposure to reference doses. Risk assessment indicated the mean predicted CR for children and adults exposed to soil was 3.75 × 10-6 and 5.29 × 10-6, respectively, while that at dust exposure scenarios was lower, at 2.47 × 10-6 and 3.49 × 10-6, respectively, all of which were at the upper end of U.S. EPA's acceptable criteria of 1 × 10-6 to 1 × 10-4. Among the HMs, As and Ni were identified as the priority control contaminants due to significant contribution to CRs. Furthermore, the spatial distribution revealed an increasing trend in health risk from the urban center to the suburbs. This study emphasizes the need for effective measures to mitigate potential health risk and enhance the safety of recreational areas, particularly for susceptible individuals.

Unraveling the aging dynamics in the simultaneous immobilization of soil metal(loid)s using oxides.

Immobilization represents the most extensively utilized technique for the remediation of soils contaminated by heavy metals and metalloids. However, it is crucial to acknowledge that contaminants are not removed during this process, thereby leaving room for potential mobilization over time. Currently, our comprehension of the temporal variations in immobilization efficacy, specifically in relation to amendments suitable for industrial sites, remains very limited. To address this knowledge gap, our research delved into the aging characteristics of diverse oxides, hydroxides, and hydroxy-oxides (collectively referred to as oxides) for the simultaneous immobilization of arsenic (As), cadmium (Cd), and antimony (Sb) in soils procured from 16 contaminated industrial sites. Our findings unveiled that Ca-oxides initially showed excellent immobilization performance for As and Sb within 7 days but experienced substantial mobilization by up to 71 and 13 times within 1 year, respectively. In contrast, the efficacy of Cd immobilization by Ca-oxides was enhanced with the passage of time. Fe- and Mg-oxides, which primarily operate through encapsulation or surface complexation, exhibited steady immobilization performances over time. This reliable and commendable immobilization effect was observed across distinct soils characterized by varying physicochemical properties, including pH, texture, CEC, TOC, and EC, underscoring the suitability of such amendments for immobilizing metal(loid)s in diverse soil types. MgO, in particular, displayed even superior immobilization performance over time, owing primarily to gradual hydration and physical entrapment effects. Remarkably, Mg-Al LDHs emerged as the most effective candidate for the simultaneous immobilization of As, Cd, and Sb. The results obtained from this study furnish valuable data for future investigations on the immobilization of metals and metalloids in industrial soils. They enable the projection of immobilization performance and offer practical guidance in selecting suitable amendments for the immobilization of metal(loid)s.

Pathogenic CD8 T cell responses are driven by neutrophil-mediated hypoxia in cutaneous leishmaniasis.

Cutaneous leishmaniasis caused by Leishmania parasites exhibits a wide range of clinical manifestations. Although parasites influence disease severity, cytolytic CD8 T cell responses mediate disease. While these responses originate in the lymph node, we find that expression of the cytolytic effector molecule granzyme B is restricted to lesional CD8 T cells in Leishmania - infected mice, suggesting that local cues within inflamed skin induce cytolytic function. Expression of Blimp-1 ( Prdm1 ), a transcription factor necessary for cytolytic CD8 T cell differentiation, is driven by hypoxia within the inflamed skin. Hypoxia is further enhanced by the recruitment of neutrophils that consume oxygen to produce reactive oxygen species, ultimately increasing granzyme B expression in CD8 T cells. Importantly, lesions from cutaneous leishmaniasis patients exhibit hypoxia transcription signatures that correlate with the presence of neutrophils. Thus, targeting hypoxia-driven signals that support local differentiation of cytolytic CD8 T cells may improve the prognosis for patients with cutaneous leishmaniasis, as well as other inflammatory skin diseases where cytolytic CD8 T cells contribute to pathogenesis.

Blenderized enteral nutrition in pediatric short gut syndrome: Tolerance and clinical outcomes.

BACKGROUND: Blenderized feeds consisting of whole food components are emerging as a preferred approach to enteral nutrition. However, there is limited evidence-based guidance for this strategy in short bowel syndrome (SBS). We aimed to explore the tolerance and clinical outcome of blenderized feeds in patients with SBS. METHOD: We conducted a single-center, retrospective study of blenderized feeds in pediatric SBS. Of the 376 patients screened, 58 met inclusion criteria. Three patients were excluded because of a history of bowel transplant. Demographics, clinical history, and nutrition history were collected and analyzed. RESULT: Patients had improved diarrhea though worsening gas while receiving blenderized feeds. There was no significant difference in small bowel length in patients who discontinued blends compared with those who continued. However, patients with colonic resection were more likely to discontinue the blends. In a subgroup of patients who lost weight despite improved diarrhea (n = 19), most had a history of ileocecal valve (ICV) and colonic resection, but no difference in small bowel length compared with those who did not lose weight. CONCLUSION: Our cohort of patients with SBS experienced improved gastrointestinal symptoms and stool quality on blenderized feeds. Patients without an ICV and with colonic resection were more prone to weight loss. Stepwise titration of blenderized formula with previous formula regimen may be needed in a subset of patients to optimize tolerance and weight gain. Further study is warranted to understand factors contributing to variable tolerance and weight gain on blenderized formulas to guide their use in patients with SBS.

Manganese stabilization in mine tailings by MgO-loaded rice husk biochar: Performance and mechanisms.

Leachable metal in abandoned mine tailings may be toxic to vegetation, affecting effective ecological restoration. In this study, MRB was synthesized through MgCl2·6H2O wet impregnation followed by duplicate slow pyrolysis. Manganese tailings were mixed with MRB, rice husk biochar (RB), and MgO at a dosage of 0-5%, followed by 90-day incubation. Toxicity characteristic leaching procedure and sequential leaching were used to analyze the leachability and species of Mn in tailings, while a stabilization mechanism was proposed with the support of the characterization of the tailings before and after amendment. Results suggested MRB addition significantly decreased leachable Mn by 63.8%, reducing from 59.88 mg/L to 21.68 mg/L, while only a 14.39% reduction was achieved by rice husk biochar (RB). The sharp decline of leachable Mn after 90-day mixing was contributed by the transformation from labile to stable fractions. A microporous biochar matrix along with the uniform dispersion of MgO active component were both responsible for the better Mn stabilization. Only less than 10% of the variation in substrate pH was observed with the increase of MgO loading or incubation time. Linear correlation analyses indicated substrate pH's strongl negative relationship with leachable Mn and moderately positive relationship with residual fraction. Characterization results revealed that MRB exhibited different stabilization mechanisms in mine tailings, where Mn was likely to be stabilized by direct interaction with active MgO or indirect alkaline precipitation to form stable MgMn2O4, Mn(CH3COO)2, and MnO(OH)2. This work validated the promoting potential of recycling agricultural biomass waste for the amendment of manganese mine tailings.