TFTG: A comprehensive database for human transcription factors and their targets.

Transcription factors (TFs) are major contributors to gene transcription, especially in controlling cell-specific gene expression and disease occurrence and development. Uncovering the relationship between TFs and their target genes is critical to understanding the mechanism of action of TFs. With the development of high-throughput sequencing techniques, a large amount of TF-related data has accumulated, which can be used to identify their target genes. In this study, we developed TFTG (Transcription Factor and Target Genes) database (http://tf.liclab.net/TFTG), which aimed to provide a large number of available human TF-target gene resources by multiple strategies, besides performing a comprehensive functional and epigenetic annotations and regulatory analyses of TFs. We identified extensive available TF-target genes by collecting and processing TF-associated ChIP-seq datasets, perturbation RNA-seq datasets and motifs. We also obtained experimentally confirmed relationships between TF and target genes from available resources. Overall, the target genes of TFs were obtained through integrating the relevant data of various TFs as well as fourteen identification strategies. Meanwhile, TFTG was embedded with user-friendly search, analysis, browsing, downloading and visualization functions. TFTG is designed to be a convenient resource for exploring human TF-target gene regulations, which will be useful for most users in the TF and gene expression regulation research.

Sustained delivery of NT-3 and curcumin augments microenvironment modulation effects of decellularized spinal cord matrix hydrogel for spinal cord injury repair.

Decellularized extracellular matrix hydrogel, especially that derived from spinal cord (DSCM hydrogel), has been actively considered as a functional biomaterial for remodeling the extracellular matrix of the native tissue, due to its unique characteristics in constructing pro-regenerative microenvironment for neural stem cells (NSCs). Furthermore, DSCM hydrogel can provide multiple binding domains to growth factors and drugs. Therefore, both exogenous neurotrophic factors and anti-inflammatory drugs are highly desired to be incorporated into DSCM hydrogel, which may synergistically modulate the complex microenvironment at the lesion site after spinal cord injury (SCI). Herein, neurotrophin-3 (NT-3) and curcumin (Cur) were integrated into DSCM hydrogel for SCI therapy. Due to different affinities to the DSCM hydrogel, NT-3 underwent a controlled release manner, while curcumin released explosively within the first 24 h, followed by rather sustained but slower release. The integration of both NT-3 and curcumin significantly enhanced NSCs proliferation and their neuronal differentiation. Meanwhile, the release of curcumin promoted macrophages polarization into anti-inflammatory subtypes, which further facilitated NSCs differentiation into neurons. The in situ injected DSCM + NT3 + Cur hydrogel exerted superior capability in alleviating the inflammatory responses in rat contused spinal cord. Compared to DSCM hydrogel alone, DSCM + NT3 + Cur hydrogel more significantly promoted the recruitment of NSCs and their neuronal differentiation at the lesion site. These outcomes favored functional recovery, as evidenced by the improved hind limb movement. Overall, the bioactive DSCM hydrogel can serve as a multifunctional carrier for cooperatively release of growth factors and drugs, which significantly benefits microenvironment regulation and nerve regeneration after SCI.

Understanding the multi-functionality and tissue-specificity of decellularized dental pulp matrix hydrogels for endodontic regeneration.

Dental pulp is the only soft tissue in the tooth which plays a crucial role in maintaining intrinsic multi-functional behaviors of the dentin-pulp complex. Nevertheless, the restoration of fully functional pulps after pulpitis or pulp necrosis, termed endodontic regeneration, remained a major challenge for decades. Therefore, a bioactive and in-situ injectable biomaterial is highly desired for tissue-engineered pulp regeneration. Herein, a decellularized matrix hydrogel derived from porcine dental pulps (pDDPM-G) was prepared and characterized through systematic comparison against the porcine decellularized nerve matrix hydrogel (pDNM-G). The pDDPM-G not only exhibited superior capabilities in facilitating multi-directional differentiation of dental pulp stem cells (DPSCs) during 3D culture, but also promoted regeneration of pulp-like tissues after DPSCs encapsulation and transplantation. Further comparative proteomic and transcriptome analyses revealed the differential compositions and potential mechanisms that endow the pDDPM-G with highly tissue-specific properties. Finally, it was realized that the abundant tenascin C (TNC) in pDDPM served as key factor responsible for the activation of Notch signaling cascades and promoted DPSCs odontoblastic differentiation. Overall, it is believed that pDDPM-G is a sort of multi-functional and tissue-specific hydrogel-based material that holds great promise in endodontic regeneration and clinical translation. STATEMENT OF SIGNIFICANCE: Functional hydrogel-based biomaterials are highly desirable for endodontic regeneration treatments. Decellularized extracellular matrix (dECM) preserves most extracellular matrix components of its native tissue, exhibiting unique advantages in promoting tissue regeneration and functional restoration. In this study, we prepared a porcine dental pulp-derived dECM hydrogel (pDDPM-G), which exhibited superior performance in promoting odontogenesis, angiogenesis, and neurogenesis of the regenerating pulp-like tissue, further showed its tissue-specificity compared to the peripheral nerve-derived dECM hydrogel. In-depth proteomic and transcriptomic analyses revealed that the activation of tenascin C-Notch axis played an important role in facilitating odontogenic regeneration. This biomaterial-based study validated the great potential of the dental pulp-specific pDDPM-G for clinical applications, and provides a springboard for research strategies in ECM-related regenerative medicine.

The impact of ultrasonic-assisted extraction on the in vitro hypoglycemic activity of peach gum polysaccharide in relation to its conformational conversion.

BACKGROUND: Peach gum (PG) is an exudate of the peach tree (Prunus persica of the Rosaceae family), which consists primarily of polysaccharides with a large molecular weight and branching structure. Consequently, PG can only swell in water and does not dissolve easily, which severely limits its application. Current conventional extraction methods for PG polysaccharide (PGPS) are time consuming and inefficient. This study investigated the impact of ultrasonic-assisted extraction (UAE) on PGPS structure and conformation, and their relationship to hypoglycemic activity in vitro. RESULTS: In comparison with conventional aqueous extraction, UAE enhanced PGPS yielded from 28.07-32.83% to 80.37-84.90% (w/w) in 2 h. It drastically decreased the molecular size and conformational parameters of PGPS, including weight-average molecular weight (Mw), number-average molecular weight (Mn), z-average radius of gyration (Rg), hydrodynamic radius (Rh) and instrinsic viscosity ([η]) values. Peach gum polysaccharide conformation converted extended molecules to flexible random coil chains or compact spheres with no obvious primary structure alteration. Furthermore, UAE altered the flow behavior of PGPS solution from that of a non-Newtonian fluid to that of a Newtonian fluid. As a result, PGPS treated with UAE displayed weaker inhibitory activity than untreated PGPS, mostly because UAE weakens the binding strength of PGPS to α-glucosidase. However, this negative effect of UAE on PGPS activity was compensated by the increased solubility of polysaccharide. This enabled PGPS to achieve a wider range of doses. CONCLUSION: Ultrasonic-assisted extraction is capable of degrading PGPS efficiently while preserving its primary structure, resulting in a Newtonian fluid solution. The degraded PGPS conformations displayed a consistent correlation with their inhibitory effect on α-glucosidase activity. © 2024 Society of Chemical Industry.

Ginsenoside compound K induces ferroptosis via the FOXO pathway in liver cancer cells.

Liver cancer is a common malignant tumor worldwide, traditional Chinese medicine is one of the treatment measures for liver cancer because of its good anti-tumor effects and fewer toxic side effects. Ginsenoside CK (CK) is an active component of ginseng. This study explored the mechanism by which CK induced ferroptosis in liver cancer cells. We found that CK inhibited the proliferation of HepG2 and SK-Hep-1 cells, induced ferroptosis of cells. Ferrostatin-1, an ferroptosis inhibitor, was used to verify the role of CK in inducing ferroptosis of liver cancer cells. Network pharmacological analysis identified the FOXO pathway as a potential mechanism of CK, and western blot showed that CK inhibited p-FOXO1. In cells treated with the FOXO1 inhibitor AS1842856, further verify the involvement of the FOXO pathway in regulating CK-induced ferroptosis in HepG2 and SK-Hep-1 cells. A HepG2 cell-transplanted tumor model was established in nude mice, and CK inhibited the growth of transplanted tumors in nude mice, p-FOXO1 was decreased in tumor tissues, and SLC7A11 and GPX4 expressions were also down-regulated after CK treatment. These findings suggested that CK induces ferroptosis in liver cancer cells by inhibiting FOXO1 phosphorylation and activating the FOXO signaling pathway, thus playing an antitumor role.

EGCG suppresses PD-1 expression of T cells via inhibiting NF-κB phosphorylation and nuclear translocation.

Epigallocatechin-3-gallate (EGCG) is an important tea polyphenol with anti-tumor potential. Our previous studies revealed that EGCG was a promising immune checkpoint inhibitor (ICI) as it could downregulate expression of programmed cell death 1 ligand 1 (PD-L1) in tumor cells, thereby resulting tumor killing effect. In particular, EGCG can effectively avoid the inflammatory storm caused by anti-tumor therapy, which is a healthy green capacity absent from many ICIs. However, the relationship between EGCG and programmed cell death 1 (PD-1) of T cells remains unclear. In this work, we explored the effect of EGCG on T cells and found that EGCG suppressed PD-1 via inhibiting NF-κB phosphorylation and nuclear translocation. Furtherly, the capability of EGCG was confirmed in tumor-bearing mice to inhibit PD-1 expression in T cells and enhance apoptosis in tumor cells. These results implied that EGCG could inhibit the expression of PD-1 in T cells, thereby promoting anti-tumor effects of T cells. EGCG will be a promising candidate in anti-tumor therapy.

Therapeutic Plasma Exchange in AChR-Ab Positive Generalized Myasthenia Gravis: A Real World Study About Its Early Response.

Background: Since there is no clear priority or selection principle in the guidelines for myasthenia crisis, therapeutic plasma exchange (TPE) and intravenous immunoglobulin are often administered randomly. However, it should be more prudent in taking TPE due to its higher cost and risk. Studying its early response factors is crucial for managing myasthenia crisis and can improve medical and economic benefits. Methods: A prospective observational study was conducted, and patients classified as having "impending myasthenia crisis" or experiencing a myasthenia crisis and treated by TPE were included. The primary endpoint was the response after TPE. Univariate logistic regression analysis and repeated measurement were performed to analyze factors related to TPE efficacy. Results: A total of 30 patients who treated with TPE as their fast-acting treatments were enrolled. After TPE, those whose QMGs and/or MGCs decreased by ≥5 points or ≥30% of the baseline were judged as "response group", accounting for 66.67% (20/30). Respiratory symptoms had a response rate of 72.00% (18/25), showing the most remarkable improvement. Meanwhile, extraocular symptoms were the least sensitive, with only 8.00% (2/25) showing efficacy. Thymoma (100.00% vs 50.00%, P=0.002) and a high concentration of AChR-Ab (37.37 nmol/L vs 25.4 nmol/L, P=0.039) were common in the early response group. Repeated measures showed significant changes in AChR-Ab and CD19+ B cells before and after TPE (all with P < 0.05). After treatment, the CD19+ B cells tended to decrease in the response group. Discussion: These results indicated that, for AChR-Ab positive generalized MG, TPE can quickly improve respiratory symptoms. Thymoma and a high concentration of AChR-Ab before TPE predict an early better response. Additionally, TPE may work by decreasing AChR-Ab levels and inducing immune regulation. Future prospective and randomized controlled studies are needed.

A Knee Point Driven Evolutionary Algorithm for Multiobjective Bilevel Optimization.

Bilevel optimization is a special type of optimization in which one problem is embedded within another. The bilevel optimization problem (BLOP) of which both levels are multiobjective functions is usually called the multiobjective BLOP (MBLOP). The expensive computation and nested features make it challenging to solve. Most existing studies look for complete lower-level solutions for every upper-level variable. However, not every lower-level solution will participate in the bilevel Pareto-optimal front. Under a limited computational budget, instead of wasting resources to find complete lower-level solutions that may not be in the feasible region or inducible region of the MBLOP, it is better to concentrate on finding the solutions with better performance. Bearing these considerations in mind, we propose a multiobjective bilevel optimization solving routine combined with a knee point driven algorithm. Specifically, the proposed algorithm aims to quickly find feasible solutions considering the lower-level constraints in the first stage and then concentrates the computational resources on finding solutions with better performance. Besides, we develop several multiobjective bilevel test problems with different properties, such as scalable, deceptive, convexity, and (dis)continuous. Finally, the performance of the algorithm is validated on a practical petroleum refining bilevel problem, which involves a multiobjective environmental regulation problem and a petroleum refining operational problem. Comprehensive experiments fully demonstrate the effectiveness of our presented algorithm in solving MBLOPs.

Challenging anticoagulation therapy for multiple primary malignant tumors combined with thrombosis: A case report and review of literature.

BACKGROUND: Venous thromboembolism significantly contributes to patient deterioration and mortality. Management of its etiology and anticoagulation treatment is intricate, necessitating a comprehensive consideration of various factors, including the bleeding risk, dosage, specific anticoagulant medications, and duration of therapy. Herein, a case of lower extremity thrombosis with multiple primary malignant tumors and high risk of bleeding was reviewed to summarize the shortcomings of treatment and prudent anticoagulation experience. CASE SUMMARY: An 83-year-old female patient was admitted to the hospital due to a 2-wk history of left lower extremity edema that had worsened over 2 d. Considering her medical history and relevant post-admission investigations, it was determined that the development of left lower extremity venous thrombosis and pulmonary embolism in this case could be attributed to a combination of factors, including multiple primary malignant tumors, iliac venous compression syndrome, previous novel coronavirus infection, and inadequate treatment for prior thrombotic events. However, the selection of appropriate anticoagulant medications, determination of optimal drug dosages, and establishment of an appropriate duration of anticoagulation therapy were important because of concurrent thrombocytopenia, decreased quantitative fibrinogen levels, and renal insufficiency. CONCLUSION: Anticoagulant prophylaxis should be promptly initiated in cases of high-risk thrombosis. Individualized anticoagulation therapy is required for complex thrombosis.

Exogenous insulin autoimmune syndrome: A case report and review of literature.

BACKGROUND: Insulin autoimmune syndrome (IAS) is a severe manifestation of spontaneous hypoglycemia. It is characterized by elevated levels of immune-reactive insulin and highly potent insulin autoantibodies (IAAs), which are induced by endogenous insulin circulating in the bloodstream. It is distinguished by recurring instances of spontaneous hypoglycemia, the presence of IAA within the body, a substantial elevation in serum insulin levels, and an absence of prior exogenous insulin administration. Nevertheless, recent studies show that both conventional insulin and its analogs can induce IAS episodes, giving rise to the notion of non-classical IAS. Therefore, more attention should be paid to these diseases. CASE SUMMARY: In this case report, we present a rare case of non-classical IAS in an 83-year-old male patient who present with symptoms of a psychiatric disorder. Upon symptom onset, the patient exhibited Whipple's triad (including hypoglycemia, blood glucose level less than 2.8 mmol/L during onset, and rapid relief of hypoglycemic symptoms after glucose administration). Concurrently, his serum insulin level was significantly elevated, which contradicted his C-peptide levels. After a comprehensive examination, the patient was diagnosed with exogenous insulin autoimmune syndrome. Considering that the patient had type 2 diabetes mellitus and a history of exogenous insulin use before disease onset, it was presumed that non classical IAS was induced by this condition. The PubMed database was used to search for previous cases of IAS and non-classical IAS to analyze their characteristics and treatment approaches. CONCLUSION: The occurrence of non-classical IAS is associated with exogenous insulin or its analogs, as well as with sulfhydryl drugs. Symptoms can be effectively alleviated through the discontinuation of relevant medications, administration of hormones or immunosuppressants, plasma exchange, and lifestyle adjustments.

Natural products as potential drug treatments for acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL), which was once considered one of the deadliest types of leukemia, has become a curable malignancy since the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) as clinical treatments. ATO, which has become the first-line therapeutic agent for APL, is derived from the natural mineral product arsenic, exemplifying an important role of natural products in the treatment of APL. Many other natural products, ranging from small-molecule compounds to herbal extracts, have also demonstrated great potential for the treatment and adjuvant therapy of APL. In this review, we summarize the natural products and representative components that have demonstrated biological activity for the treatment of APL. We also discuss future directions in better exploring their medicinal value, which may provide a reference for subsequent new drug development and combination therapy programs.

Understanding the two-stage degradation process of peach gum polysaccharide within ultrasonic field.

This study investigated the dynamic degradation process of peach gum polysaccharide (PGPS) within ultrasonic field. The results show that the molecular weight, intrinsic viscosity, and polydispersity of PGPS were rapidly reduced within the initial 30 min and then gradually decreased. The solubility of PGPS was drastically improved from 3.0% to 40.0-42.0% (w/w) after 120 min. The conformation of PGPS changed from an extended chain to a flexible random coil within initial time of ultrasound, and gradually tended to be compact spheres. The apparent viscosity of PGPS significantly decreased after 30 min, and PGPS solution exhibited a near-Newtonian fluid behavior. It is possible that these above changes are a result of random cleavage of the decrosslinking and the backbone of PGPS, resulting in the preservation of its primary structure. The results will provide a fundamental basis for orientation design and process control of ultrasonic degradation of PGPS.

Effects of multiple metals exposure on abnormal liver function: The mediating role of low-density lipoprotein cholesterol.

Equilibration of metal metabolism is critical for normal liver function. Most epidemiological studies have only concentrated on the influence of limited metals. However, the single and synergistic impact of multiple-metal exposures on abnormal liver function (ALF) are still unknown. A cross-sectional study involving 1493 Chinese adults residing in Shenzhen was conducted. Plasma concentrations of 13 metals, including essential metals (calcium, copper, cobalt, iron, magnesium, manganese, molybdenum, zinc, and selenium) and toxic metals (aluminum, cadmium, arsenic, and thallium) were detected by the inductively coupled plasma spectrometry (ICP-MS). ALF was ascertained as any observed abnormality from albumin, alanine transaminase, aspartate transaminase, γ-glutamyl transpeptidase, and direct bilirubin. Diverse statistical methods were used to evaluate the single and mixture effect of metals, as well as the dose-response relationships with ALF risk, respectively. Mediation analysis was conducted to evaluate the role of blood lipids in the relation of metal exposure with ALF. The average age of subjects was 59.7 years, and 56.7 % were females. Logistic regression and the least absolute shrinkage and selection operator (LASSO) penalized regression model consistently suggested that increased levels of arsenic, aluminum, manganese, and cadmium were related to elevated risk of ALF; while magnesium and zinc showed protective effects on ALF (all p-trend < 0.05). The grouped weighted quantile sum (GWQS) regression revealed that the WQS index of essential metals and toxic metals showed significantly negative or positive relationship with ALF, respectively. Aluminum, arsenic, cadmium, and manganese showed linear whilst magnesium and zinc showed non-linear dose-response relationships with ALF risk. Mediation analysis showed that LDL-c mediated 4.41 % and 14.74 % of the relationship of plasma cadmium and manganese with ALF, respectively. In summary, plasma aluminum, arsenic, manganese, cadmium, magnesium, and zinc related with ALF, and LDL-c might underlie the pathogenesis of ALF associated with cadmium and manganese exposure. This study may provide critical public health significances in liver injury prevention and scientific evidence for the establishment of environmental standard.

Insights into the defensive roles of lncRNAs during Mycoplasma pneumoniae infection.

Mycoplasma pneumoniae causes respiratory tract infections, affecting both children and adults, with varying degrees of severity ranging from mild to life-threatening. In recent years, a new class of regulatory RNAs called long non-coding RNAs (lncRNAs) has been discovered to play crucial roles in regulating gene expression in the host. Research on lncRNAs has greatly expanded our understanding of cellular functions involving RNAs, and it has significantly increased the range of functions of lncRNAs. In lung cancer, transcripts associated with lncRNAs have been identified as regulators of airway and lung inflammation in a process involving protein complexes. An excessive immune response and antibacterial immunity are closely linked to the pathogenesis of M. pneumoniae. The relationship between lncRNAs and M. pneumoniae infection largely involves lncRNAs that participate in antibacterial immunity. This comprehensive review aimed to examine the dysregulation of lncRNAs during M. pneumoniae infection, highlighting the latest advancements in our understanding of the biological functions and molecular mechanisms of lncRNAs in the context of M. pneumoniae infection and indicating avenues for investigating lncRNAs-related therapeutic targets.

Antagonistic activity and mechanism of Bacillus subtilis CG-6 suppression of root rot and growth promotion in Alfalfa.

Root rot is a common disease, that severely affects the yield and quality of alfalfa. Biocontrol is widely used to control plant diseases caused by pathogenic fungi, however, biocontrol strains for alfalfa root rot are very limited. In this study, a Bacillus subtilis CG-6 strain with a significant biocontrol effect on alfalfa root rot was isolated. CG-6 secretes antibacterial enzymes and siderophore, phosphate solubilization and indoleacetic acid (IAA). The inhibition rate of strain CG-6 against Fusarium oxysporum was 87.33%, and it showed broad-spectrum antifungal activity. Inoculation with CG-6 significantly reduced the incidence of alfalfa root rot, the control effect of greenhouse cultivation reached 58.12%, and CG-6 treatment significantly increased alfalfa plant height, root length, fresh weight, and dry weight. The treatment with CG-6 significantly increased the levels of antioxidant enzymes (catalase, peroxidase, superoxide dismutase, and lipoxygenase) in alfalfa leaves by 15.52%-34.03%. Defensive enzymes (chitinase and ß-1,3-glucanase) increased by 24.37% and 28.08%, respectively. The expression levels of regulatory enzyme genes (MsCAT, MsPOD, MsCu, Zn-SOD1, MsCu, Zn-SOD2, MsCu, Zn-SOD3, and MsLOX2) and systemic resistance genes (MsPR1, MsPDF1.2, and MsVSP2) increased by 0.50-2.85 fold, which were higher than those in the pathogen treatment group. Therefore, CG-6 could be used as a potential strain to develop biopesticides against alfalfa root rot.

Hierarchically Biomimetic Scaffolds with Anisotropic Micropores and Nanotopological Patterns to Promote Bone Regeneration via Geometric Modulation.

Structural engineering is an appealing means to modulate osteogenesis without the intervention of exogenous cells or therapeutic agents. In this work, a novel 3D scaffold with anisotropic micropores and nanotopographical patterns is developed. Scaffolds with oriented pores are fabricated via the selective extraction of water-soluble polyethylene oxide from its poly(ε-caprolactone) co-continuous mixture and uniaxial stretching. The plate apatite-like lamellae are subsequently hatched on the pore walls through surface-induced epitaxial crystallization. Such a unique geometric architecture yields a synergistic effect on the osteogenic capability. The prepared scaffold leads to a 19.2% and 128.0% increase in the alkaline phosphatase activity of rat bone mesenchymal stem cells compared to that of the scaffolds with only oriented pores and only nanotopographical patterns, respectively. It also induces the greatest upregulation of osteogenic-related gene expression in vitro. The cranial defect repair results demonstrate that the prepared scaffold effectively promotes new bone regeneration, as indicated by a 350% increase in collagen I expression in vivo compared to the isotropic porous scaffold without surface nanotopology after implantation for 14 weeks. Overall, this work provides geometric motifs for the transduction of biophysical cues in 3D porous scaffolds, which is a promising option for tissue engineering applications.

Oxalic acid secretion alleviates saline-alkali stress in alfalfa by improving photosynthetic characteristics and antioxidant activity.

Saline-alkali stress significantly affects the growth and yield of alfalfa (Medicago sativa L.). Organic acid secretion is crucial in alleviating abiotic stress-induced damage in plants. In this study, we evaluated the contents of the major organic acids secreted by the roots of tolerant (ZD) and sensitive (LYL) varieties of alfalfa under saline-alkali stress and investigated the effects of these organic acids on the growth, and physiological functions of alfalfa. Our results indicated that the oxalic acid (OA) content was the highest among the organic acids secreted from alfalfa roots under saline-alkali stress, and oxalic acid content was the most significantly different between the two varieties, ZD and LYL, compared to the contents of the other organic acids. Oxalic acid alleviated the inhibition of alfalfa growth caused by saline-alkali stress, improved photosynthetic characteristics, reduced the accumulation of reactive oxygen species, and increased the activity of antioxidant enzymes and content of osmoregulatory substances. Furthermore, oxalic acid resulted in significantly increased expression of genes involved in photosynthesis and antioxidant system in alfalfa under saline-alkali stress. This study revealed the effects of oxalic acid secreted by the root system on stress-related physiological processes, providing valuable insights into the functions of root secretions in plant saline-alkali resistance.

Predicting particulate matter, nitrogen dioxide, and ozone across Great Britain with high spatiotemporal resolution based on random forest models.

In Great Britain, limited studies have employed machine learning methods to predict air pollution especially ozone (O3) with high spatiotemporal resolution. This study aimed to address this gap by developing random forest models for four key pollutants (fine and inhalable particulate matter [PM2.5 and PM10], nitrogen dioxide [NO2] and O3) by integrating multiple-source predictors at a daily level and 1-km resolution. The out-of-bag R2 (root mean squared error, RMSE) between predictions from models and measurements from monitoring stations in 2006-2013 was 0.85 (3.63 µg/m3) for PM2.5, 0.77 (6.00 µg/m3) for PM10, 0.85 (9.71 µg/m3) for NO2, and 0.85 (9.39 µg/m3) for maximum daily 8-h average (MDA8) O3 at daily level, and the predicting accuracy was higher at monthly and annual level. The high-resolution predictions captured characterized spatiotemporal patterns of the four pollutants. Higher concentrations of PM2.5, PM10, and NO2 were distributed in densely populated southern regions of Great Britain while O3 showed an inverse spatial pattern in general, which could not be fully depicted by monitoring stations. Therefore, predictions produced in this study could improve exposure assessment with less exposure misclassification and flexible exposure windows for future epidemiological studies to investigate the impact of air pollution across Great Britain.

Bupivacaine-fentanyl isobaric spinal anesthesia reduces the risk of ICU admission in elderly patients undergoing lower limb orthopedic surgery.

BACKGROUND: To evaluate if bupivacaine-fentanyl isobaric spinal anesthesia could reduce the risk of ICU admission compared with general anesthesia in elderly patients undergoing lower limb orthopedic surgery. METHODS: This study comprised a retrospective review of all lower limb orthopedic surgeries performed at our hospital between January 2013 and December 2019. According to anesthesia methods, patients were divided into the spinal anesthesia group (n = 1,728) and the general anesthesia group (n = 188). The primary outcome evaluated was the occurrence of ICU admission. Secondary outcomes included hemodynamic changes, postoperative complications, and mortality. RESULTS: Repeated measure analysis of variance indicated that the difference between the two groups in the systolic blood pressure (SBP) was not significant before anesthesia (T0), immediately after anesthesia (T1), and before leaving the operation room (T8) (P > 0.05), but significant (P < 0.01) from 5 min after anesthesia (T2) to after operation (T7). The proportions of ICU admission (6.4% vs. 23.8%, P < 0.01) and unplanned intubation (0.1% vs. 3.8%, P < 0.01) were significantly lower in the spinal anesthesia group compared with those in the general anesthesia group. Multivariate logistic regression revealed that after controlling for potential confounding factors, the odds of ICU admission for patients in the spinal anesthesia group was 0.240 times (95% CI 0.115-0.498; P < 0.01) than those in the general anesthesia group. CONCLUSIONS: Bupivacaine-fentanyl isobaric spinal anesthesia significantly reduced the risk of ICU admission and unplanned intubation, and provided better intraoperative hemodynamics in elderly patients undergoing lower limb orthopedic surgery. TRIAL REGISTRATION: This study has been registered in the Chinese Clinical Trial Registry (ChiCTR2000033411).