Estimation of irrigated crop artificial irrigation evapotranspiration in China.

Agriculture water use accounts for 70% of the total water withdrawal worldwide. The evapotranspiration during crop growth is one of the important hydrological processes in the agricultural water cycle. This study proposed the concept of artificial irrigation evapotranspiration of irrigated crops to describe that the evapotranspiration caused by irrigation water use. Irrigated crops rely on two kinds of water sources: precipitation and irrigation water. With the construction of irrigation schemes, the artificial irrigation evapotranspiration plays an increasingly important role in the dualistic water cycle system of irrigated cropland. To reveal the amount of artificial irrigation evapotranspiration of 17 categories of irrigated crops in China, this study proposed a new quantitative model system which was established based on traditional evapotranspiration models and soil water balance models. Based on the new model system, we calculated the annual artificial irrigation evapotranspiration of irrigated crops for the period 2013 to 2017 in China. The results showed that the proportion of artificial irrigation evapotranspiration to the total evapotranspiration of irrigated crops was 41.3%, whose value was 228.1 km3 a-1. The artificial irrigation evapotranspiration in different agricultural water management regions were 90.0 km3 a-1 in the northeast region, 86.0 km3 a-1 in the southeast region, and relatively low 52.2 km3a-1 in the west region. The results of this study can provide methods for water management and policy-making in agricultural irrigated areas, and it can also provide a preliminary understanding of the influence of human activities on the dualistic water cycle in cropland.

Associations of different combinations of moderate-vigorous physical activity and muscle-strengthening activity with mortality among US lung cancer survivors.

BACKGROUND: To investigate the associations of different combinations of moderate to vigorous physical activity (MVPA) and muscle strengthening activity (MSA) with all-cause and cancer mortality among lung cancer survivors. METHODS: This nationwide prospective cohort study used data from the US National Health Interview Survey 2009-2018. A total of 785 lung cancer survivors were included in the study. Participants were linked to the National Death Index through December 31, 2019. Self-reported MVPA and MSA frequency data were used to obtain 4 mutually exclusive exposure categories. Multivariate Cox proportional hazard models were applied to explore the association between exposure categories and outcomes. RESULTS: The mean (standard deviation [SD]) age of the study population was 69.1 (11.3) years and 429 (54.6%) were female. Among them, 641 (81.7%) were White and 102 (13.0%) were Black. The median follow-up time was 3 years (2526 person-years), and 349 (44.5%) all-cause deaths and 232 (29.6%) cancer deaths occurred. Compared to the MVPA < 60 min/week and MSA < 2 sessions/week group, individuals in the MVPA ≥ 60 min/week and MSA < 2 sessions/week group showed hazard ratios (HRs) of 0.50 (95% CI, 0.36-0.69) for all-cause mortality and 0.37 (95% CI, 0.20-0.67) for cancer mortality after the adjustment of covariates. Those in the MVPA ≥ 60 min/week and MSA ≥ 2 sessions/week group exhibited HRs of 0.52 (95% CI, 0.35-0.77) for all-cause mortality and 0.27 (95% CI, 0.12-0.62) for cancer mortality when compared to the MVPA < 60 min/week and MSA < 2 sessions/week group. We also identified distinct non-linear relationships between MVPA and outcomes risk among two MSA frequency subgroups. CONCLUSION: This cohort study demonstrated that higher levels of MVPA and MSA combined might be associated with optimal reductions of mortality risk in lung cancer survivors.

Association of copy number variation in X chromosome-linked PNPLA4 with heterotaxy and congenital heart disease.

BACKGROUND: Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD. METHODS: Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. RESULTS: Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. CONCLUSIONS: Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

PaMYB11 promotes suberin deposition in Norway spruce embryogenic tissue during cryopreservation: A novel resistance mechanism against osmosis.

The osmotic resistance mechanism has been extensively studied in whole plants or plant tissues. However, little is known about it in embryogenic tissue (ET) which is widely used in plant-based biotechnological systems. Suberin, a cell wall aliphatic and aromatic heteropolymer, plays a critical role in plant cells against osmosis stress. The suberin regulatory biosynthesis has rarely been studied in gymnosperms. Here, PaMYB11, a subgroup 11 R2R3-MYB transcription factor, plays a key role in the osmotic resistance of Norway spruce (Picea abies) ETs during cryoprotectant pretreatment. Thus, RNA-seq, histological, and analytical chemical analyses are performed on the stable transformations of PaMYB11-OE and PaMYB11-SRDX in Norway spruce ETs. DAP-seq, Y1H, and LUC are further combined to explore the PaMYB11 targets. Activation of PaMYB11 is necessary and sufficient for suberin lamellae deposition on Norway spruce embryogenic cell walls, which plays a decisive role in ET survival under osmotic stress. Transcriptome analysis shows that PaMYB11 enhances suberin lamellae monomer synthesis by promoting very long-chain fatty acid (VLCFA) synthesis. PaPOP, PaADH1, and PaTET8L, the first two (PaADH1 and PaPOP, included) involved in VLCFA synthesis, are proved to be the direct targets of PaMYB11. Our study identified a novel osmotic response directed by PaMYB11 in Norway spruce ET, which provides a new understanding of the resistance mechanism against osmosis in gymnosperms.

Identification of apoptosis-immune-related gene signature and construction of diagnostic model for sepsis based on single-cell sequencing and bulk transcriptome analysis.

Introduction: Sepsis leads to multi-organ dysfunction due to disorders of the host response to infections, which makes diagnosis and prognosis challenging. Apoptosis, a classic programmed cell death, contributes to the pathogenesis of various diseases. However, there is much uncertainty about its mechanism in sepsis. Methods: Three sepsis gene expression profiles (GSE65682, GSE13904, and GSE26378) were downloaded from the Gene Expression Omnibus database. Apoptosis-related genes were obtained from the Kyoto Encyclopedia of Genes and Genomes Pathway database. We utilized LASSO regression and SVM-RFE algorithms to identify characteristic genes associated with sepsis. CIBERSORT and single cell sequencing analysis were employed to explore the potential relationship between hub genes and immune cell infiltration. The diagnostic capability of hub genes was validated across multiple external datasets. Subsequently, the animal sepsis model was established to assess the expression levels of hub genes in distinct target organs through RT-qPCR and Immunohistochemistry analysis. Results: We identified 11 apoptosis-related genes as characteristic diagnostic markers for sepsis: CASP8, VDAC2, CHMP1A, CHMP5, FASLG, IFNAR1, JAK1, JAK3, STAT4, IRF9, and BCL2. Subsequently, a prognostic model was constructed using LASSO regression with BCL2, FASLG, IRF9 and JAK3 identified as hub genes. Apoptosis-related genes were closely associated with the immune response during the sepsis process. Furthermore, in the validation datasets, aside from IRF9, other hub genes demonstrated similar expression patterns and diagnostic abilities as observed in GSE65682 dataset. In the mouse model, the expression differences of hub genes between sepsis and control group revealed the potential impacts on sepsis-induced organ injury. Conclusion: The current findings indicated the participant of apoptosis in sepsis, and apoptosis-related differentially expressed genes could be used for diagnosis biomarkers. BCL2, FASLG, IRF9 and JAK3 might be key regulatory genes affecting apoptosis in sepsis. Our findings provided a novel aspect for further exploration of the pathological mechanisms in sepsis.

Time-programmed release of curcumin and Zn2+ from multi-layered RSF coating modified PET graft for improvement of graft-host integration.

Artificial graft serves as the primary grafts used in the clinical management of sports-related injuries. Until now, optimizing its graft-host integration remains a great challenge due to the excessive inflammatory response during the inflammatory phase, coupled with an absence of tissue-inductive capacity during the regeneration phase. Here, a multi-layered regenerated silk fibroin (RSF) coating loaded with curcumin (Cur) and Zn2+ on the surface of the PET grafts (Cur@Zn2+@PET) was designed and fabricated for providing time-matched regulation specifically tailored to address issues arising at both inflammatory and regeneration phases, respectively. The release of Cur and Zn2+ from the Cur@Zn2+@PET followed a time-programmed pattern in vitro. Specifically, cellular assays revealed that Cur@Zn2+@PET initially released Cur during the inflammatory phase, thereby markedly inhibit the expression of inflammatory cytokines TNF-a and IL-1ß. Meanwhile, a significant release of Zn2+ was major part during the regeneration phase, serving to induce the osteogenic differentiation of rBMSC. Furthermore, rat model of anterior cruciate ligament reconstruction (ACLR) showed that through time-programmed drug release, Cur@Zn2+@PET could suppress the formation of fibrous interface (FI) caused by inflammatory response, combined with significant new bone (NB) formation during regeneration phase. Consequently, the implementation of the Cur@Zn2+@PET characterized by its time-programmed release patterns hold considerable promise for improving graft-host integration for sports-related injuries.

Verapamil inhibits respiratory syncytial virus infection by regulating Ca2+ influx.

AIMS: The study evaluated the antiviral effect of Verapamil against respiratory syncytial virus (RSV) and investigated its underlying mechanism. MATERIALS AND METHODS: RSV-infected BALB/c mice were treated with Verapamil. Body weight, survival rates, viral load, lung damage, inflammatory factors, and the expression of RSV fusion (F) protein were analyzed. In cellular studies, intracellular Ca2+ and viral titers were measured in the presence of Verapamil, Calcium Chloride, and EGTA. A time-of-addition assay assessed the antiviral effect of Verapamil. KEY FINDINGS: Mice infected with RSV and treated with Verapamil exhibited a significant decrease in weight loss, an increase in survival rates, and reductions in viral titers, RSV F protein expression, inflammatory responses, and lung tissue injury. Verapamil reduced intracellular calcium levels, which correlated with reduced viral titers. The addition of calcium chloride reversed the anti-viral effects mediated by Verapamil, while EGTA potentiated them. The antiviral activity of Verapamil was observed during the early phase of RSV infection, likely by blocking Ca2+ channels and inhibiting virus replication. SIGNIFICANCE: Verapamil effectively inhibits RSV infection by blocking calcium channels and reducing intracellular calcium levels, thereby impeding viral replication. Thus, Verapamil shows promise as a treatment for RSV.

Short-Term Reproduction of Active Movement with Visual Feedback and Passive Movement with a Therapist's Hands.

Reproducing instructed movements is crucial for practice in motor learning. In this study, we compared the short-term reproduction of active pelvis movements with visual feedback and passive movement with the therapist's hands in an upright stance. Sixteen healthy males (M age = 34.1; SD = 10.2 years) participated in this study. In one condition, healthy males maintained an upright stance while a physical therapist moved the participant's pelvis (passive movement instruction), and in a second condition, the participant actively moved their pelvis with visual feedback of the target and the online trajectory of the center of pressure (active movement instruction). Reproduction errors (displacement of the center of pressure in the medial-lateral axis) 10 s after the passive movement instruction were significantly greater than after the active movement instruction (p < 0.001), but this difference disappeared 30 s after the instruction (p = 0.118). Error of movement reproduction in the anterior-posterior axis after the passive movement instruction was significantly greater than after the active movement instruction, no matter how long the retention interval was between the instruction and reproduction phases (p = 0.025). Taken together, active pelvis movements with visual feedback, rather than passive movement with the therapist's hand, is better to be used for instructing pelvis movements.

Design of Lidar Receiving Optical System with Large FoV and High Concentration of Light to Resist Background Light Interference.

Lidar has the advantages of high accuracy, high resolution, and is not affected by sunlight. It has been widely used in many fields, such as autonomous driving, remote sensing detection, and intelligent robots. However, the current lidar detection system belongs to weak signal detection and generally uses avalanche photoelectric detector units as detectors. Limited by the current technology, the photosensitive surface is small, the receiving field of view is limited, and it is easy to cause false alarms due to background light. This paper proposes a method based on a combination of image-side telecentric lenses, microlens arrays, and interference filters. The small-area element detector achieves the high-concentration reception of echo beams in a large field of view while overcoming the interference of ambient background light. The image-side telecentric lens realizes that the center lines of the echo beams at different angles are parallel to the central axis, and the focus points converge on the same focal plane. The microlens array collimates the converged light beams one by one into parallel light beams. Finally, a high-quality aspherical focusing lens is used to focus the light on the small-area element detector to achieve high-concentration light reception over a large field of view. The system achieves a receiving field of view greater than 40° for a photosensitive surface detector with a diameter of 75 µm and is resistant to background light interference.

Comparative optimization of polysaccharide-based nanoformulations for cardiac RNAi therapy.

Ionotropic gelation is widely used to fabricate targeting nanoparticles (NPs) with polysaccharides, leveraging their recognition by specific lectins. Despite the fabrication scheme simply involves self-assembly of differently charged components in a straightforward manner, the identification of a potent combinatory formulation is usually limited by structural diversity in compound collections and trivial screen process, imposing crucial challenges for efficient formulation design and optimization. Herein, we report a diversity-oriented combinatory formulation screen scheme to identify potent gene delivery cargo in the context of precision cardiac therapy. Distinct categories of cationic compounds are tested to construct RNA delivery system with an ionic polysaccharide framework, utilizing a high-throughput microfluidics workstation coupled with streamlined NPs characterization system in an automatic, step-wise manner. Sequential computational aided interpretation provides insights in formulation optimization in a broader scenario, highlighting the usefulness of compound library diversity. As a result, the out-of-bag NPs, termed as GluCARDIA NPs, are utilized for loading therapeutic RNA to ameliorate cardiac reperfusion damages and promote the long-term prognosis. Overall, this work presents a generalizable formulation design strategy for polysaccharides, offering design principles for combinatory formulation screen and insights for efficient formulation identification and optimization.

[Preparation of peptide-functionalized affinity materials for the highly specific capture and analysis of mitochondria].

Mitochondria perform various metabolic processes that significantly affect cell differentiation, proliferation, signal transduction, and programmed cell death. The disruption of mitochondrial bioenergetic and metabolic functions is closely related to many disorders. The specific isolation and purification of intact, high-purity, and functional mitochondria are central to the understanding of their mechanism of action but remain challenging tasks. In this study, a mitochondrial penetrating peptide (MPP) with the sequence FrFKFrFK(Ac) was used as a mitochondrial recognition motif to construct a peptide-guided affinity separation material. The multiple aromatic phenylalanine (F) residues in this amphiphilic peptide can confer lipophilicity to the mitochondrial membrane, whereas the basic residues (D-arginine and lysine) render the MPP surface positively charged, thereby promoting the binding of negatively charged mitochondria. After the derivatization of the N terminal of MPP with an oligoglycine spacer, the peptide ligands were conjugated to matrix beads (MB) with surface aldehyde functional groups. Peptide functionalization was performed via a condensation reaction between the amino group in the peptide ligand and the aldehyde group on the beads. The generated Schiff bases were reduced, affording stable covalent bonds. The dense and stable functionalization of the beads with the mitochondria-targeting peptides was demonstrated using high performance liquid chromatography (HPLC), zeta potential assay, and scanning electron microscopy (SEM). The immobilization efficiency of the peptide ligands was 1.47 µmol/g, and the surface potential of MB@MPP was 11 mV. MB@MPP was used for the direct isolation of mitochondria after cell homogenization. As observed by SEM, mitochondria with a cross-sectional diameter of 500 nm were efficiently captured on the MB@MPP surface. Because the mitochondrial membrane potential is an important marker of mitochondrial function and the driving force behind the staining of mitochondria with Mito Tracker dyes, the specific binding and separation of fluorescent mitochondria from the cell samples revealed that the proposed MB@MPP-based isolation approach can keep mitochondria intact and retain their functions. Western blot assays were employed to characterize the protein markers of the mitochondria (citrate synthase (CS) and voltage-dependent anion channel protein (VDAC)) and cytoplasmic protein (vinculin), and examine the integrity and purity of the captured mitochondria. The results showed that the lysates released from MB@MPP had high CS and VDAC contents. By contrast, vinculin, which is highly abundant in whole-cell lysates, was barely detected in the lysates from MB@MPP. These results suggest that MB@MPP isolates mitochondria with high affinity, specificity, and antifouling ability by using the targeting peptide as the capture handle. A comparison with a commercial mitochondrial isolation kit demonstrated that MB@MPP can separate mitochondria with higher CS and VDAC abundance and purity. Given the superior separation performance of MB@MPP, the molecular profiles of the isolated mitochondria under stress were subjected to further analysis of their molecular profiles under stress. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established to detect tryptophan (Trp) and riboflavin in the mitochondria. Quantification was performed in multiple-reaction monitoring (MRM) mode. Owing to the high purity of the mitochondria, the Trp and riboflavin contents were determined to be 265 and 0.67 nmol/mg, respectively. The metabolic response of mitochondria to external stimuli was further examined using acadesine, an adenosine 5'-monophosphate (AMP)-activated protein kinase activator with a wide range of metabolic effects, to treat cells. After cell homogenization, MB@MPP was used to separate the mitochondria from the cell samples with and without acadesine treatment, followed by LC-MS/MS analysis. The quantification results demonstrated that acadesine induced a 14% upregulation of Trp content in the mitochondria. By contrast, the riboflavin content decreased to 0.48 nmol/mg, which is 72% of that in untreated mitochondria. The changes in Trp and riboflavin contents could influence their metabolic pathways and, thus, the levels of their metabolites, such as nicotinamide adenine dinucleotide, flavin mononucleotide, and flavin adenine dinucleotide, which are essential coenzymes in mitochondria. Peptide-functionalized affinity microbeads with high affinity and specificity for mitochondria are promising for the efficient isolation of high-quality mitochondria, and offer a useful tool for understanding the complicated functions and dynamics of this unique organelle.

Solvent engineering for scalable fabrication of perovskite/silicon tandem solar cells in air.

Perovskite/silicon tandem solar cells hold great promise for realizing high power conversion efficiency at low cost. However, achieving scalable fabrication of wide-bandgap perovskite (~1.68 eV) in air, without the protective environment of an inert atmosphere, remains challenging due to moisture-induced degradation of perovskite films. Herein, this study reveals that the extent of moisture interference is significantly influenced by the properties of solvent. We further demonstrate that n-Butanol (nBA), with its low polarity and moderate volatilization rate, not only mitigates the detrimental effects of moisture in air during scalable fabrication but also enhances the uniformity of perovskite films. This approach enables us to achieve an impressive efficiency of 29.4% (certified 28.7%) for double-sided textured perovskite/silicon tandem cells featuring large-size pyramids (2-3 µm) and 26.3% over an aperture area of 16 cm2. This advance provides a route for large-scale production of perovskite/silicon tandem solar cells, marking a significant stride toward their commercial viability.

Anesthetic Management of One-Lung Ventilation in Patients With Tracheal Bronchus: A Narrative Review.

Tracheal bronchus is a rare congenital tracheal abnormality that generally refers to the right upper lobe bronchus of the lung that originates from the trachea. Tracheal bronchus is usually asymptomatic and is often accidentally detected by fiberoptic bronchoscopy or computed tomography for other conditions. Depending on the location of the tracheal bronchial opening and possible anatomical variations, the management of 1-lung ventilation in patients with tracheal bronchus is a significant challenge for anesthesiologists. To provide a reference for anesthesiologists to better manage anesthesia in such patients, we review the pathophysiology, definition, and Conacher classification of tracheal bronchus and then discuss the diagnosis of tracheal bronchus and management of 1-lung ventilation during anesthesia according to the Conacher classification.

Contribution of external reference frame to tactile localization.

The purpose of the present study was to elucidate whether an external reference frame contributes to tactile localization in blindfolded healthy humans. In a session, the right forearm was passively moved until the elbow finally reached to the target angle, and participants reached the left index finger to the right middle fingertip. The locus of the right middle fingertip indicated by the participants deviated in the direction of the elbow extension when vibration was provided to the biceps brachii muscle during the passive movement. This finding indicates that proprioception contributes to the identification of the spatial coordinate of the specific body part in an external reference frame. In another session, the tactile stimulus was provided to the dorsal of the right hand during the passive movement, and the participants reached the left index finger to the spatial locus at which the tactile stimulus was provided. Vibration to the biceps brachii muscle did not change the perceived locus of the tactile stimulus indicated by the left index finger. This finding indicates that an external reference frame does not contribute to tactile localization during the passive movement. Humans may estimate the spatial coordinate of the tactile stimulus based on the time between the movement onset and the time at which the tactile stimulus is provided.

Inflammation accelerating intestinal fibrosis: from mechanism to clinic.

Intestinal fibrosis is a prevalent complication of IBD that that can frequently be triggered by prolonged inflammation. Fibrosis in the gut can cause a number of issues, which continue as an ongoing challenge to healthcare systems worldwide. The primary causes of intestinal fibrosis are soluble molecules, G protein-coupled receptors, epithelial-to-mesenchymal or endothelial-to-mesenchymal transition, and the gut microbiota. Fresh perspectives coming from in vivo and in vitro experimental models demonstrate that fibrogenic pathways might be different, at least to some extent, independent of the ones that influence inflammation. Understanding the distinctive procedures of intestinal fibrogenesis should provide a realistic foundation for targeting and blocking specific fibrogenic pathways, estimating the risk of fibrotic consequences, detecting early fibrotic alterations, and eventually allowing therapy development. Here, we first summarize the inflammatory and non-inflammatory components of fibrosis, and then we elaborate on the underlying mechanism associated with multiple cytokines in fibrosis, providing the framework for future clinical practice. Following that, we discuss the relationship between modernization and disease, as well as the shortcomings of current studies. We outline fibrosis diagnosis and therapy, as well as our recommendations for the future treatment of intestinal fibrosis. We anticipate that the global review will provides a wealth of fresh knowledge and suggestions for future fibrosis clinical practice.

Accelerating the Discovery of Oxygen Reduction Electrocatalysts: High-Throughput Screening of Element Combinations in Pt-Based High-Entropy Alloys.

The vast number of element combinations and the explosive growth of composition space pose significant challenges to the development of high-entropy alloys (HEAs). Here, we propose a procedural research method aimed at accelerating the discovery of efficient electrocatalysts for oxygen reduction reaction (ORR) based on Pt-based quinary HEAs. The method begins with an element library provided by a large language model (LLM), combined with microscale precursor printing and pulse high-temperature synthesis techniques to prepare multi-element combination HEA array in one step. Through high-throughput measurement using scanning electrochemical cell microscopy (SECCM), precise identification of highly active HEA element combinations and exploration of composition space for a specific combination are achieved. Advantageous element combinations are further validated in practical electrocatalytic evaluations. The contributions of individual element sites and the synergistic effects among elements of such HEAs in enhancing reaction activity are elucidated via density functional theory (DFT) calculations. This method integrates high-throughput experiments, practical catalyst validation, and DFT calculations, providing a new pathway for accelerating the discovery of efficient multi-element materials in the field of energy catalysis.

An Analysis of Clinical Outcomes of Exploratory Pediatric Metformin Ingestions Reported to the Texas Poison Center Network From 2011 to 2021.

Background: Poison centers develop triage threshold guidelines for pediatric metformin ingestions. Our network uses 1700 mg, or 85 mg/kg. Objective: To describe the dose, clinical course, and outcomes for inadvertent metformin ingestions in children 5 years old and younger reported to our statewide poison center network. Methods: We searched the poison center database 2011 to 2021 for metformin ingestions in patients 5 years and younger. Variables included age, sex, weight, dose, symptoms, outcome, and more. We used descriptive statistics with medians and interquartile ranges (IQR) for continuous variables. Results: Of 669 cases, exposures by age were 208 (31.1%) 1 to 2 years, and 275 (41.1%) 2 years. Weight was recorded in 342 (51.1%) (median 13.5 kg; IQR: 3.7 kg), and dose in 149 (22.3%) (median 500 mg; IQR: 500 mg). Milligram/kilogram values were available for 103 (15.4%) with median 42.4 mg/kg, IQR: 39 mg/kg. Most (647, 98.5%) exposures were unintentional. Most (445/669, 66.5%) were managed at a non-healthcare facility, while 204 (30.7%) were already at or referred to a healthcare facility. Of these 204 patients, 169 (82.8%) were evaluated and treated at the emergency department and discharged. Four (2%) were admitted to critical care, and 7 (3.4%) to the ward. Medical outcomes by effect were 5 (0.7%) minor, 2 (0.3%) moderate, 253 (37.8%) none, 292 (43.6%) not followed (minimal effects possible), and no major effects or deaths. Of 20 clinical occurrences reported, vomiting was most common (8, 1.2%). Conclusion: Despite little recorded dosage information, pediatric metformin ingestions under 85 mg/kg had predominantly uneventful medical outcomes.

Development and validation of a novel criterion of histologic healing in ulcerative colitis defined by inflammatory cell enumeration in lamina propria mucosa: A multicenter retrospective cohort in China.

BACKGROUND: Histological healing is closely associated with improved long-term clinical outcomes and lowered relapses in patients with ulcerative colitis (UC). Here, we developed a novel diagnostic criterion for assessing histological healing in UC patients. METHODS: We conducted a retrospective cohort study in UC patients, whose treatment was iteratively optimized to achieve mucosal healing at Shanghai Tenth People's Hospital of Tongji University from January 2017 to May 2022. We identified an inflammatory cell enumeration index (ICEI) for assessing histological healing based on the proportions of eosinophils, CD177 + neutrophils, and CD40L + T cells in the colonic lamina propria under high power field (HPF), and the outcomes (risks of symptomatic relapses) of achieving histological remission vs . persistent histological inflammation using Kaplan-Meier curves. Intrareader reliability and inter-reader reliability were evaluated by each reader. The relationships to the changes in the Nancy index and the Geboes score were also assessed for responsiveness. The ICEI was further validated in a new cohort of UC patients from other nine university hospitals. RESULTS: We developed an ICEI for clinical diagnosis of histological healing, i.e., Y = 1.701X 1 + 0.758X 2 + 1.347X 3 - 7.745 (X 1 , X 2 , and X 3 represent the proportions of CD177 + neutrophils, eosinophils, and CD40L + T cells, respectively, in the colonic lamina propria under HPF). The receiver operating characteristics curve (ROC) analysis revealed that Y <-0.391 was the cutoff value for the diagnosis of histological healing and that an area under the curve (AUC) was 0.942 (95% confidence interval [CI]: 0.905-0.979) with a sensitivity of 92.5% and a specificity of 83.6% ( P  <0.001). The intraclass correlation coefficient (ICC) for the intrareader reliability was 0.855 (95% CI: 0.781-0.909), and ICEI had good inter-reader reliability of 0.832 (95% CI: 0.748-0.894). During an 18-month follow-up, patients with histological healing had a substantially better outcome compared with those with unachieved histological healing ( P  <0.001) using ICEI. During a 12-month follow-up from other nine hospitals, patients with histological healing also had a lower risk of relapse than patients with unachieved histological healing. CONCLUSIONS: ICEI can be used to predict histological healing and identify patients with a risk of relapse 12 months and 18 months after clinical therapy. Therefore, ICEI provides a promising, simplified approach to monitor histological healing and to predict the prognosis of UC. REGISTRATION: Chinese Clinical Trial Registry, No. ChiCTR2300077792.

Model predictive manipulation of compliant objects with multi-objective optimizer and adversarial network for occlusion compensation.

BACKGROUND: The manipulation of compliant objects by robotic systems remains a challenging task, largely due to their variable shapes and the complex, high-dimensional nature of their interaction dynamics. Traditional robotic manipulation strategies struggle with the accurate modeling and control necessary to handle such materials, especially in the presence of visual occlusions that frequently occur in dynamic environments. Meanwhile, for most unstructured environments, robots are required to have autonomous interactions with their surroundings. METHODS: To solve the shape manipulation of compliant objects in an unstructured environment, we begin by exploring the regression-based algorithm of representing the high-dimensional configuration space of deformable objects in a compressed form that enables efficient and effective manipulation. Simultaneously, we address the issue of visual occlusions by proposing the integration of an adversarial network, enabling guiding the shaping task even with partial observations of the object. Afterwards, we propose a receding-time estimator to coordinate the robot action with the computed shape features while satisfying various performance criteria. Finally, model predictive controller is utilized to compute the robot's shaping motions subject to safety constraints. Detailed experiments are presented to evaluate the proposed manipulation framework. SIGNIFICANT FINDINGS: Our MPC framework utilizes the compressed representation and occlusion-compensated information to predict the object's behavior, while the multi-objective optimizer ensures that the resulting control actions meet multiple performance criteria. Through rigorous experimental validation, our approach demonstrates superior manipulation capabilities in scenarios with visual obstructions, outperforming existing methods in terms of precision and operational reliability. The findings highlight the potential of our integrated approach to significantly enhance the manipulation of compliant objects in real-world robotic applications.

Advances in hyaluronic acid production: Biosynthesis and genetic engineering strategies based on Streptococcus - A review.

Hyaluronic acid (HA), which is a highly versatile glycosaminoglycan, is widely applied across the fields of food, cosmetics, and pharmaceuticals. It is primary produced through Streptococcus fermentation, but the product presents inherent challenges concerning consistency and potential pathogenicity. However, recent strides in molecular biology have paved the way for genetic engineering, which facilitates the creation of high-yield, nonpathogenic strains adept at synthesizing HA with specific molecular weights. This comprehensive review extensively explores the molecular biology underpinning pivotal HA synthase genes, which elucidates the intricate mechanisms governing HA synthesis. Moreover, it delineates various strategies employed in engineering HA-producing strains.