Search

Potassium (K) deficiency in plants can lead to metabolic disorders and growth retardation. Currently, nearly 50% of the arable land in China is experiencing a K resource deficit, significantly hindering the development of the apple industry. Resveratrol (Res), a phytoalexin, has been extensively reported to enhance plant resistance against various abiotic stresses. However, there have been no reports on the response of Res to K+ deficiency stress in apples. This study aims to investigate the effect of exogenous Res on the K+ deficiency tolerance of Malus hupehensis. The results demonstrated that applying 50 μM of exogenous Res could enhance the tolerance of M. hupehensis to K+ deficiency stress. Compared to non-Res treatments, external application of Res alleviated leaf chlorosis and improved root growth in apple seedlings. Additionally, it increased antioxidant enzyme activity, thereby reducing the production of reactive oxygen species induced by K+ deficiency stress. Res also regulated proline and soluble sugar content to maintain osmotic balance. Moreover, Res helped maintain the balance of mineral element contents in apple seedlings and the normal K+: Na+ ratio by enhancing the influx of K+. Furthermore, exogenous Res regulated the expression of related kinase genes, promoting Ca2+ signal transduction in response to K+ deficiency stress and inducing the expression of K+ transport genes to enhance K+ absorption, thus supporting normal plant growth. In conclusion, this study provides a theoretical basis for the application of exogenous Res to alleviate K+ deficiency stress in apples.

ObjectiveTo analyze the application value of wearable adhesive Patch ECG monitors combined with transesophageal electrophysiological study (TEPS) in the diagnosis of palpitations of unknown origin.MethodsThis was a retrospective study of patients with suspected arrhythmia who were admitted to Henan Provincial People's Hospital between October 2021 and July 2023 due to recurrent paroxysmal palpitations of unknown origin, with or without accompanying symptoms such as dizziness, amaurosis, and syncope. All patients underwent TEPS. Those who did not exhibit arrhythmia during the TEPS were selected for Patch ECG monitoring, which lasted several weeks (depending on the duration of symptom capture). The results of TEPS, Patch ECG monitors, and clinical diagnoses were observed and recorded. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value (NPV) for diagnosing palpitations of unknown origins was analyzed based on clinical diagnostic outcomes for (1) TEPS alone, (2) Patch ECG monitoring in patients with negative TEPS results, and (3) the combination of both methods.ResultsA total of 569 patients were included in this study. The TEPS results exhibited that 227 of the 569 patients did not detect arrhythmias and 342 detected arrhythmias. Of the 569 patients, 102 refused to undergo Patch ECG monitors, and 467 patients completed the entire study process. Among them, 379 cases (66.61%) were clinically diagnosed as arrhythmias. TEPS shows good performance in most evaluation indices except NPV (69.60%, 95% CI, 61.54%–77.66%). The combined diagnosis was strongly consistent with clinical diagnosis. The accuracy, sensitivity, and NPV of TEPS combined with Patch ECG monitors in the diagnosis of palpitations of unknown origin were significantly higher than those of TEPS alone.ConclusionWearable adhesive patch ECG monitors combined with TEPS can enhance the diagnostic efficiency of palpitations of unknown origin.

Spin-glass thin films exhibit many features different from the bulk. The freezing temperatures of spin-glass films are suppressed for reduced thickness and follow the Kenning relation. The dynamics are altered near the vacuum interface. These phenomena are closely related to the lower critical dimension of spin glasses, the spin-glass correlation length, and the dimensional crossover from d = 3 to d = 2. In this article, we review the experimental facts and theoretical perspectives for spin-glass thin films. We focus on canonical spin-glass systems with the Ruderman–Kittel–Kasuya–Yosida (RKKY) interaction between magnetic impurities in a nonmagnetic host. Open questions to be addressed are emphasized.

IntroductionThe aim of this study was to investigate effect of energy levels on liver oxidative state and gut microbiota of laying hens fed a low-protein diet.MethodsA total of 216 laying hens (57-week-old with similar body weight) were randomly divided into 3 groups: low-energy and low-protein diet (LL: 10.73 MJ/kg), middle-energy and low-protein diet (ML: 11.15 MJ/kg), and high-energy and low-protein diet (HL: 11.57 MJ/kg) groups. The experiment lasted for 10 weeks.ResultsResults showed that the liver MDA level was higher, while the liver T-AOC level was lower in the HL group compared with LL and ML groups. The dominant phyla in LL group, ML group, and HL group were Bacteroidetes (38.08%, 39.69%, and 40.93%) and Firmicutes (16.78%, 18.37%, and 17.44%). At the genus level, Alistipes (9.45%) was abundant in the LL group. Bacteroides (14.46%), Phocaeicola (4.48%) and Precotella (2.95%) were highest in the ML group. Parabacteroides (1.78%) and Desulfovibrio (1.02%) were highest in the HL group. At the species level, Bacteroides fragilis (0.42%) is lowest in LL group, Desulfovibrio piger increased with the increase of energy. MDA was significantly and positively correlated with Methanobrevibacter woesei between ML group and HL groups (p < 0.05). T-AOC was highly significantly and positively correlated with Phocaeicola sp. Sa1YUN3 (p < 0.01) .DiscussionThis study found that high-energy and low-protein diets might cause liver oxidative stress by gut microbes in the laying hens.

BackgroundOxidative stress plays a significant role in aging and cancer, yet there is currently a lack of research utilizing machine learning models to examine the relationship between oxidative stress and prognosis in elderly non-small cell lung cancer (NSCLC) patients.MethodsThis study included elderly NSCLC patients who underwent radical lung cancer resection from January 2012 to April 2018, exploring the relationship between Oxidative Stress Score (OSS) and prognosis. Machine learning techniques, including Decision Trees (DT), Random Forest (RF), and Support Vector Machine (SVM), were employed to develop predictive models for 5-year overall survival (OS).ResultsThe datasets consisted of 1647 patients in the training set, 705 in the internal validation set, and 516 in the external validation set. An OSS was formulated from six systemic oxidative stress biomarkers, such as albumin, total bilirubin, and blood urea nitrogen, among others. Boruta variable importance analysis identified low OSS as a key indicator of poor prognosis. The OSS was subsequently integrated into the DT, RF, and SVM models for training. These models, optimized through hyperparameter tuning on the training set, were then evaluated on the internal and external validation sets. The RF model demonstrated the highest predictive performance, with an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.794 in the internal validation set, compared to AUCs of 0.711 and 0.760 for the DT and SVM models, respectively. Similarly, in the external validation set, the RF model achieved an AUC of 0.784, outperforming the DT and SVM models, which had AUCs of 0.699 and 0.730, respectively. Calibration plots confirmed the RF model’s superior calibration, followed by the SVM model, with the DT model performing the poorest.ConclusionThe OSS-based clinical prediction model, constructed using machine learning methodologies, effectively predicts the prognosis of elderly NSCLC patients post-radical surgery.

ObjectiveThis study aims to evaluate the effects of pleural reconstruction during rib compartment tumor resection surgery on postoperative outcomes, including drainage volume, drainage duration, hospital stay, complications, and pain control.MethodsA retrospective analysis was conducted on 142 patients who underwent rib compartment tumor resection surgery at Beijing Jishuitan Hospital from January 2013 to October 2023. The patients were divided into two groups: those who received pleural reconstruction and those who did not. Data were collected from hospital medical records and outpatient care records, focusing on postoperative drainage volume, total drainage time, length of hospital stay, complications, and pain scores. Continuous variables were compared using t-tests or nonparametric tests, while categorical variables were analyzed using chi-square tests or Fisher's exact tests.ResultsThe analysis showed no significant differences between the two groups in terms of postoperative complications and pain thresholds. However, patients who underwent pleural reconstruction had significantly lower postoperative drainage volume (937.74 ± 855.97 vs. 1,595.26 ± 1,054.50 ml, p

Alfalfa (Medicago sativa L.) grassland is prone to degradation following multi-year maintenance. Yet, its mechanism regarding the stoichiometry of carbon (C) and nitrogen (N) across plant–soil system is still unclear. To address this issue, the method of space-for-time sampling was employed to investigate alfalfa grasslands with five planting years (5-, 8-, 10-, 15-, and 20-year periods) in the semiarid Loess Plateau. The results showed that the alfalfa above- and underground biomass decreased steadily decrease after the fifth to eighth years, showing a degradation tendency with the extension of planting duration. The mean weight diameter of aggregate registered an increase with planting years. However, the C and N stocks decreased with planting years in five soil aggregate fractions. Specifically, they were the highest in the fifth year and then started to gradually decrease along the 8th, 10th, 15th, and 20th year. Redundancy and correlation analysis confirmed that the C and N stocks of soil aggregates were closely positively associated with those of plant. Overall, the highest stability of soil physical structure was found during the period from the fifth to eighth year, and, afterward, the stability declined. In conclusion, alfalfa plantation improved soil structure stability but aggravated soil C and N stocks, and biomass and soil aggregate indicators accounted for alfalfa field degradation after a certain year of plantation.

Mixed gonadal dysgenesis is caused by a variety of chromosome abnormalities, most commonly Y chromosome mosaicism. An 8-year-old boy presented with short stature for possible treatment with recombinant growth hormone. He had a history of mixed gonadal dysgenesis (hypospadias, bilateral cryptorchidism, processus vaginalis, and dysplastic immature uterus) and a series of corrective surgeries. At 14 months of age, chromosomal karyotyping revealed 46,X,+mar. Upon presentation, lab testing was consistent with the male phenotype at prepuberty. Fluorescence in situ hybridization revealed 45,X[2]/46,X,der(Y).ish psu idic(Y)(q11.2)(SRY++,DYZ3++)[38] karyotype. A literature review identified eight case reports of mixed gonadal dysgenesis associated with 45,X/46,X,idic(Y)(q11.2). Neither sex phenotype nor short stature correlated with the 46,X,idic(Y)(q11.2) mosaic ratio.

The glycolytic enzyme cytoplasmic glyceraldehyde-3-phosphate dehydrogenase (GAPC3) is involved in multiple biological processes in plants, including transcriptional regulation, and material metabolism. However, the relationship between OsGAPC3 and the quality traits of rice is poorly understood. Here we identify OsGAPC3 mutations that enhance the protein content and grain nutritional quality of rice by regulating the OsAAP6 gene expression. The number and volume of type-II protein bodies in the endosperm of the OsGAPC3 mutants, and GPC increase significantly. We report significant increases in chalkiness area and degree, and decreases for starch content, gel consistency, and taste value. Results of proteomic detection and analysis reveal that OsGAPC3 affects the major storage substances (proteins and starch) metabolism in rice, and the accumulation of proteins and starch in the endosperm. Additionally, the OsGAPC3 mutation significantly decreases the rice-seedling salt tolerance. Therefore, OsGAPC3 affects multiple quality traits of rice, participates in regulating rice-seedling salt-stress response. These data can be used to design better-quality and stronger salt-resistant rice varieties.

Plant growth, crop yield, and pest and disease control are enhanced by PGPR (Plant growth promoting rhizobacteria), which are beneficial microorganisms found in a close symbiosis with plant roots. Phytohormones are secreted, nutrient uptake is improved, and soil properties along with the microbiological environment are regulated by these microorganisms, making them a significant focus in agricultural research. In this study, the efficient PGPR strain T1 was isolated and screened from tobacco inter-root soil, and identified and confirmed by ITS sequencing technology. Tobacco growth indicators and soil property changes were observed and recorded through potting experiments. The activities of key enzymes (e.g., sucrase, catalase, urease) in soil were further determined. High-throughput sequencing technology was utilized to sequence the soil microbial community, and combined with macro-genomics analysis, the effects of T1 strain on soil microbial diversity and metabolic pathways were explored. Following the application of T1, significant improvements were observed in the height, leaf length, and width of tobacco plants. Furthermore, the physical and chemical properties of the soil were notably enhanced, including a 26.26% increase in phosphorus availability. Additionally, the activities of key soil enzymes such as sucrase, catalase, and urease were significantly increased, indicating improved soil health and fertility. Comprehensive joint microbiomics and macrogenomics analyses revealed a substantial rise in the populations of beneficial soil microorganisms and an enhancement in metabolic pathways, including amino acid metabolism, synthesis, and production of secondary metabolites. These increase in beneficial microorganisms and the enhancement of their metabolic functions are crucial for plant growth and soil fertility. This study provides valuable references for the development of innovative microbial fertilizers and offers programs for the sustainable development of modern agriculture.

BackgroundThe approval of eslicarbazepine acetate (ESL) by the Food and Drug Administration (FDA) in 2013 marked an advancement in the treatment of adult patients with partial-onset seizures. However, there still remains a paucity of real-world studies regarding the adverse events (AEs) associated with this compound. The principal aim of the present study was to scrutinize ESL-related AEs by leveraging data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database.MethodsBy extracting all available data since the FDA approval of ESL (2013Q4-2024Q1), disproportionality analysis was performed using reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN) and multi-item gamma Poisson shrinker (MGPS) algorithms. AE signals that simultaneously met the requirements of all four algorithms were identified as significant positive signals. Demographic information, time of onset and gender-specific signal detection were also examined. In addition, a special screening process for designated medical events (DME) was implemented to focus on the evaluation and comparison of safety signals within DME and System Organ Classification (SOC) level, as well as SMQ (Standardised MedDRA Queries) level. Stratified analysis by logistic regression is employed to examine the variations across different gender (male and female) and age groups (65 years old).ResultsA total of 5,719 AE reports and 1,907 reported cases were obtained. ESL related AEs were identified in relation to 27 SOCs, among which the significant positive SOCs were nervous system disorders, injury poisoning and procedural complications, etc. There were 86 severely disproportional preferred terms that complied with the four algorithms. Most AEs occurred within the first month after treatment. According to the 86 valuable positive signals with DME screening results, 3 signals of dermatitis exfoliative, stevens-johnson syndrome, drug reaction with eosinophilia and systemic symptoms were consistent with PT signals on the DME-list, with the 3 PTs focusing on skin and subcutaneous tissue disorders and hypersensitivity. Males are more commonly affected by seizures than females. Seizures, hyponatremia, and confusional states were more frequently observed in the elderly population, while aggression, irritability, DRESS (drug reaction with eosinophilia and systemic symptoms), and abnormal behavior were found to be more common in the pediatric population. Both the children and elderly groups exhibited a higher proportion of agitation than the adult group.ConclusionOur research enhances the safety and tolerability profile of ESL, but the clinical use of ESL should be noticed and avoided in relation to AEs since it raises the risk of dermatitis exfoliative, stevens-johnson syndrome. Particular attention should be paid to DRESS in children and hyponatremia in the elderly.

IntroductionMutations in the protein WD repeat structural domain 26 (WDR26, MIM 617424) have been identified as the cause of autosomal dominant Skraban-Deardorff syndrome, a rare genetic disorder characterized by intellectual disability (ID), developmental delay (DD), hypotonia, epilepsy, infant feeding difficulties, gait abnormalities and distinctive facial features. The objective of this study is to investigate the genetic factors that may contribute to the development of Skraban-Deardorff syndrome in affected individuals.MethodsIn this study, we used whole-exome sequencing (WES) to analyze pathogenic and likely pathogenic variants in two unrelated Chinese patients with DD and ID. We confirmed the origin of the variants by conducting Sanger sequencing and classified them according to ACMG/AMP guidelines.ResultsHere, two novel de novo variants (c.1797delC(p.His599fs*11) and c.1414C>T(p.Gln472*)) in the WDR26 gene have been identified in two Chinese patients with Skraban-Deardorff syndrome. These patients exhibit a range of symptoms, including varying degrees of ID, DD, speech delay, an abnormal wide-foot and/or stiff-legged gait, facial dysmorphism, behavioural abnormalities, with or without seizures.ConclusionsIn this study, We report two unrelated Chinese patients with Skraban-Deardorff syndrome caused by novel de novo pathogenic variants of the WDR26 gene. These patients showed a clinical phenotype similar to that of patients with the WDR26 variant. Compared to reported cases with WDR26 pathogenic variants, patient 2 presented a novel complication of severe behavioural problems, including hyperactivity, social anxiety, self-mutilation, impulsivity and violent behaviour. This research broadens the range of genetic and clinical features of Skraban-Deardorff syndrome. In addition, the symptoms may become more pronounced as the patient ages. Furthermore, our report highlights the clinical diversity of Skraban-Deardorff syndrome. The findings may assist healthcare professionals in providing more accurate genetic testing and counselling to affected families and improving the overall management of the condition.

IntroductionThe present study explores the effect of ginseng stem leaf (GSL) extract on the production performance, meat quality, antioxidant status, immune function, and lipid metabolism of white feathered broilers.MethodsThere were 6 replicates in each group, with 10 broilers in each replicate. In the 42 day trial, 300 AA broilers were randomly divided into five groups: control group (CON), 1.25% GSL extract group (GSL-L), 2.5% GSL group (GSL-M), 5% GSL group (GSL-H), and 45 mg/kg chlortetracycline group (CTC).ResultsThe results showed that different doses of GSL extract could improve the body weight, feed to gain ratio (F/G), average daily feed intake (ADFI), average daily gain (ADG), and meat quality of broilers. Compared with the control group, the addition of different doses of GSL improved the antioxidant and immune abilities of broilers to varying degrees, and the effect of GSL extract was significant in the GSL-H group (p

BackgroundKindler Syndrome (KS, OMIM #173650), a rare autosomal recessive genetic disorder, is characterized by a spectrum of symptoms such as cutaneous fragility, blistering, photosensitivity, and mucosal involvement. These symptoms result from variations in the FERMT1 gene (Fermitin family member 1, OMIM: 607900), encoding kindlin-1, an essential component of focal adhesions.ObjectiveThis study aims to ascertain the potential pathogenicity of a FERMT1 variant identified in a Chinese patient and to explore the phenotypic and molecular genetic characteristics of all reported cases of Kindler Syndrome in the Chinese population.MethodsWhole-exome sequencing (WES) was performed on the patient to identify candidate variants associated with KS, and Sanger sequencing was utilized to authenticate their presence and origin. To further assess the potential impact of these genetic variants, we employed a variety of in silico prediction tools. Concurrently, a review of various databases was undertaken to ascertain and consolidate information regarding cases of KS in Chinese families.ResultsWe identified a novel likely pathogenic frameshift variant in the FERMT1 gene, specifically c.567_579delTATATATGACCCC (p.Ile190Serfs*10). The clinical presentation of this patient aligns with the diagnostic criteria for KS. The literature review reveals that the core clinical features of KS reported in the Chinese population include skin abnormalities (100%), as well as hyperkeratosis of the palms and soles (91.70%). Other clinical phenotypes encompass nail abnormalities (77.78%), abnormalities of the fingers/toes (75.00%), oral damage (70.00%), eye abnormalities (57.14%), and constipation (50.00%).ConclusionOur study enriches the genetic landscape of KS in the Chinese population and augments the understanding of phenotypic variability resulting from FERMT1 gene variants. The findings hold considerable significance for refining variant-based screening, genetic diagnosis, and comprehending the molecular pathogenesis underlying FERMT1-related disorders.

Submarine fan reservoirs are important accumulation zones for oil, gas, and natural gas hydrates, offering significant potential for hydrocarbon exploration. During the deposition period of the Sanya Formation in the southern part of the Changchang Sag of the Qiongdongnan Basin, a large submarine fan developed. However, the internal structure, source-sink system, and formation mechanism of this fan remain poorly understood, posing significant challenges to exploration in this area. This paper examines the source-to-sink sedimentary processes and deposition of submarine fans, using the Changchang Sag, in the Qiongdongnan Basin in the Northern South China Sea, as an example, which will provide valuable general guidance for deep water oil and gas exploration. Based on the theories of seismic stratigraphy and seismic sedimentology, this paper utilizes techniques such as seismic facies analysis, seismic attribute optimization, paleogeomorphology reconstruction, and source-to-sink sedimentary system analysis to analyze the 3D seismic data of the study area. Research indicates that the Sanya Formation in the Changchang Sag of the Qiongdongnan Basin comprises three depositional units: submarine fan, feeder channel, and Semi-deep marine to deep marine mudstone. The submarine fan is a fan formed by the coupling and convergence of submarine fans sourced from the southwest and southeast. Internally, it is divided into three sub-facies: the proximal fan of the sand-rich submarine fan, the main body of the sand-rich submarine fan lobes, and the distal lobes of the sand-rich submarine fan. The submarine fan sourced from the southwest extends nearly north-south and is primarily fed by sediment transported through three large, banded ancient valleys. The sedimentary filling is characterized by three-phase progradation. The submarine fan sourced from the southeast extends nearly east-west and is primarily fed by sediment transported through a single large, banded ancient valley. The sedimentary filling is characterized by two-phase lateral accumulation. During the deposition period of the Sanya Formation, certain areas of the southern uplift belt were exposed for extended periods and subjected to weathering and erosion. Sediments are transported to large ancient valleys through small supply channels. A large number of sediments were transported to the southern slope of the Changchang sag through the provenance channel system such as large ancient valleys and slope belts and deposited in the center of the sag. These make up a complete system of large ancient uplifts and submarine fan source-to-sink sedimentary systems.The sedimentary model is a lobed submarine fan controlled by semi-restricted ancient valleys and expansive basins.

IntroductionAthletes’ capability to perform activities with body rotation could be weakened by fatigue accumulation. Making pivot turning in unanticipated scenarios after fatigue may greatly challenge athletes’ ability to adapt rational motion strategies, elevating the risk of anterior cruciate ligament (ACL) injury. This study aimed to investigate the effects of fatigue and anticipation on biomechanical risk factors of ACL injury during 180° pivot turns in female soccer players.MethodsTwenty-one female soccer players were selected as participants. The participants performed anticipated turning maneuver before the fatigue intervention. The participants sprinted along the runway, decelerated and planted their foot on the force plate, and then executed a 180° pivot turn. For unanticipated tests, the pivot turn was mixed with side/cross-cuts, which were indicated to the participant using a custom-designed light system. The tests were repeated by the participant after receiving a fatigue intervention. Lower-limb joint angles and moments were characterized. Peak ground reaction forces (GRFs) and GRF loading rates were determined. Two-way repeated measures analysis of variance was applied to examine the effects of fatigue and anticipation on the variables of interest.ResultsCompared to the anticipated conditions, the approach speed was significantly lower in the unanticipated tests (P < 0.0001). Lower-limb kinematics showed varied angular patterns across conditions: greater hip joint variations in flexion, abduction, and internal rotation during unanticipated turns; consistent knee joint flexion and ankle plantarflexion with dorsiflexion observed mid-turn. Significant interactions (P = 0.023 to P = 0.035) between fatigue and anticipation influenced hip joint angles. Anticipation effects were notable at initial contact and peak ground reaction force, increasing hip, knee, and ankle joint angles (P < 0.0001 to P = 0.012). Participants showed consistent ground reaction force (GRF) patterns during pivot turns across fatigue and anticipation conditions, with the first peak occurring approximately 10% into the turn period. Significant interaction effects (P = 0.016) between fatigue and anticipation were observed for knee flex/extension moments at the first peak vertical GRF. Anticipation significantly increased first peak vertical (P < 0.0001), anteroposterior (P < 0.0001), and mediolateral (P < 0.0001) GRFs. Fatigue increased first peak vertical (P = 0.022), anteroposterior (P = 0.018), and mediolateral (P = 0.019) GRFs. Post-fatigue, participants exhibited reduced first peak GRFs and loading rates compared to pre-fatigue conditions, with higher rates observed in unanticipated turns (vertical GRF: P = 0.030; anteroposterior GRF: P < 0.0001).ConclusionFemale soccer players’ lower-limb Biomechanical characterization could be greatly affected by the change of anticipatory scenarios. With the associated increase of GRF, the risk of their ACL injury might be elevated. Fatigue affected female soccer players’ abilities on movement performances, but the interaction of these two factors could potentially weaken their knee’s functions during pivot turns. Cognitive training on unanticipated tasks may be important for rehabilitation training after ACL injury.

Drought, which is severe and recurring in Northern China, is the most significant meteorological disaster on a worldwide scale. However, a definitive conclusion has not yet been reached on the multi-scale drought features in Northern China under a warming context. Drought is affected by several circulation-related variables and a deeper scientific comprehension of their synergistic effects is required. This research addresses the spatiotemporal aspects of summer drought and its causes in the northern drought-prone belt of China (NDPB), based on meteorological observation and data reanalysis. The primary findings indicate that the NDPB is very vulnerable to drought, with the uniform mode being the region’s most significant spatial mode associated with summer droughts. Inter-annual variations are the primary cause of the summer drought in the NDPB when considering multi-scale changes. Regional drought has typically declined during this century because of the effect of multi-decadal scale changes, which cannot be disregarded. Considering the circulation background field, during summer drought years in the NDPB, the South Asian high is weaker and moves eastward, while the high-level westerly jet is weaker and more northerly. From Lake Baikal to Northern China, there is an anomalous anticyclonic circulation, and the mid-level subtropical high in the western Pacific is more southerly and easterly. As a result, the NDPB is governed by the unusual northerly circulation. The Mongolian and northeastern surface cyclone activity is decreasing, the low-level warm and humid airflow is feeble, and the NDPB is not experiencing anomalous water vapor transport. In the high-, middle-, and low-level arrangement, the NDPB circulations diverge at low levels and converge at high levels—unusual sinking in the vertical field results in regular droughts. Multiple circulation parameters on inter-annual, inter-decadal, and multi-decadal scales interact synergistically to impact summer droughts in NDPB. However, the synergistic elements that mainly impact various timescales differ. They are primarily influenced by northerly circulation, westerly winds, and the combined effect of the South Asian summer monsoon on inter-annual timescales. The combined impact of the upper westerly winds, northerly circulation, and East Asian, South Asian, and plateau summer monsoons significantly influences their inter-decadal timescales. The westerly winds, northerly circulation, and East Asian, plateau summer monsoons are the primary multi-decadal factors.

IntroductionThis study aims to examine brain activity during different swallowing actions in patients with dysphagia caused by medullary infarction (MI) before and after treatment using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging.MethodsFifteen patients were enrolled in this study. Brain activation during saliva swallowing and effortful saliva swallowing was observed using BOLD imaging in the acute phase of stroke and after 4 weeks of rehabilitation training. Differences in the activation of brain regions during saliva swallowing before and after treatment, during effortful saliva swallowing before and after treatment, and between the two swallowing actions before and after treatment were compared.ResultsIn the acute phase of stroke, only the bilateral precentral and left lingual gyrus were partially activated during saliva swallowing, and there was no obvious activation in the insula. Effortful saliva swallowing activated more brain regions than saliva swallowing before treatment, including the bilateral supplementary motor area (SMA), postcentral gyrus, and right insular cortex. The number of brain regions activated during saliva swallowing increased after treatment, including the bilateral precentral gyrus, postcentral gyrus, insula, thalamus, and SMA.DiscussionCortical activation increases after recovery from dysphagia, and the increased activation of the postcentral gyrus might play a functional compensatory role. Effortful saliva swallowing is a more effective rehabilitation training method for patients with dysphagia caused by MI.

Boehmeria is a taxonomically challenging group within the nettle family (Urticaceae). The polyphyly of the genus has been proposed by previous studies with respect to five genera (Debregeasia, Cypholophus, Sarcochlamys, Archiboehmeria, and Astrothalamus). Extensive homoplasy of morphological characters has made generic delimitation problematic. Previous studies in other plant groups suggest that plastome structural variations have the potential to provide characters useful in reconstructing evolutionary relationships. We aimed to test this across Boehmeria and its allied genera by mapping plastome structural variations onto a resolved strongly supported phylogeny. In doing so, we expanded the sampling of the plastome to include Cypholophus, Sarcochlamys, Archiboehmeria, and Astrothalamus for the first time. The results of our phylogenomic analyses provide strong support for Sarcochlamys as being more closely related to Leucosyke puya than to Boehmeria and for the clustering of Boehmeria s.l. into four subclades. The sizes of the plastomes in Boehmeria s.l. ranged from 142,627 bp to 170,958 bp. The plastomes recovered a typical quadripartite structure comprising 127~146 genes. We observe several obvious structural variations across the taxa such as gene loss and multiple gene duplication, inverted repeat (IR) contraction and wide expansions, and inversions. Moreover, we recover a trend for these variations that the early clades were relatively conserved in evolution, whereas the later diverging clades were variable. We propose that the structural variations documented may be linked to the adaptation of Boehmeria s.l. to a wide range of habitats, from moist broadleaf forests in Asia to xeric shrublands and deserts in Africa. This study confirms that variation in plastome gene loss/duplication, IR contraction/expansion, and inversions can provide evidence useful for the reconstruction of evolutionary relationships.

BackgroundAltitude illness has serious effects on individuals who are not adequately acclimatized to high-altitude areas and may even lead to death. However, the individualized mechanisms of onset and preventive measures are not fully elucidated at present, especially the relationship between altitude illness and elements, which requires further in-depth research.MethodsFresh serum samples were collected from individuals who underwent health examinations at the two hospitals in Xining and Sanya between November 2021 and December 2021. The blood zinc (Zn), iron (Fe), and calcium (Ca) concentrations, as well as hypoxia-inducible factor 1-alpha (HIF-1α) concentrations, were measured. This study conducted effective sample size estimation, repeated experiments, and used GraphPad Prism 9.0 and IBM SPSS version 19.0 software for comparative analysis of differences in the expression of elements and HIF-1α among different ethnic groups, altitudes, and concentration groups. Linear regression and multiple linear regression were employed to explore the relationships among elements and their correlation with HIF-1α.ResultsThis study included a total of 400 participants. The results from the repeated measurements indicated that the consistency of the laboratory test results was satisfactory. In terms of altitude differences, except for Fe (p = 0.767), which did not show significant variance between low and high altitude regions, Zn, Ca, and HIF-1α elements all exhibited notable differences between these areas (p

ObjectiveIn several randomized controlled trials (RCTs), sacrospinous hysteropexy and other forms of hysteropreservation have been compared. Nevertheless, there is no definitively best treatment. This study summarized RCT evidence for various uterine preservation surgical procedures.MethodsFrom each database inception to August 2023, we searched PubMed, Embase, Cochrane Library, and Web of Science for eligible RCTs. A comparison was made between sacrospinous hysteropexy and other hysteropreservation, including vaginal and abdominal surgery. For categorical and continuous variables, relative risks (RRs) and mean differences (MDs) were calculated using random-effects models.ResultsWe reviewed a total 1,398 studies and ultimately included five RCTs that met all inclusion criteria. These five studies included a total of 1,372 uterine POP cases all of whom received transvaginal surgery and had a follow-up period for assessment of recurrence from 12 months to 5 years. There were no significant differences between sacrospinous hysteropexy and other hysteropreservation for the incidences of recurrence (RR,1.24; 95% CI, 0.58 to 2.63; p = 0.58) or hematoma (RR,0.70; 95% CI, 0.17 to 2.92; p = 0.62). Moreover, neither sacrospinous hysteropexy nor hysteropreservation had any significant effect on the risk of mesh exposure (RR,0.34; 95% CI, 0.03 to 4.31; p = 0.41), dyspareunia (RR,0.45; 95% CI, 0.13 to1.6; p = 0.22), urinary tract infection (RR,0.66; 95% CI, 0.38 to 1.15; p = 0.15), bothersome bulge symptoms (RR,0.03; 95% CI, −0.02 to 0.08; p = 0.24), operative time (MD, −4.53; 95% CI, −12.08 to 3.01; p = 0.24), and blood loss (MD, −25.69; 95% CI, −62.28 to 10.91; p = 0.17). However, sacrospinous hysteropexy was associated with a lower probability of pain (RR,4.8; 95% CI, 0.79 to 29.26; p = 0.09) compared with other hysteropreservation.ConclusionThere was no difference between sacrospinous hysteropexy and hysteropreservation in terms of recurrence, hematoma, mesh exposure, dyspareunia, urinary tract infection, bothersome bulge symptoms, operative time, pain, and blood loss.Systematic Review RegistrationPROSPERO [CRD42023470025].

BackgroundAnxiety, depression, and sleep problems are prevalent comorbid mental disorders among university students. The World Health Organization (WHO) emphasized a mental health promotion objective, recommending the consideration of protective health-promoting factors in strategies aimed at preventing mental disorders. Integrating theoretically significant constructs (such as protective factors) enhances our comprehension of the intricate mechanisms that underpin mental disorders. This study employed network analysis to first identify core and bridge symptoms within comorbid mental disorders and then explore how health-promoting lifestyles (HPLs) were associated with these disorders. The ultimate goal is to offer health promotion recommendations to enhance students’ quality of life.MethodsA total of 3,896 qualified university students participated in this study. Anxiety, depression, sleep problems, and HPLs were assessed using the GAD-7, PHQ-9, PSQI, and HPLP-II scales. A Gaussian Graphical Model was used to construct the networks. The Network Comparison Test was applied to determine whether the associations between HPLs and comorbid symptoms vary by gender, educational level, family sibling, and mental health status.ResultsLow energy (PHQ4) had the highest strength centrality, followed by Daytime dysfunction (PSQI7) and Trouble relaxing (GAD4). Five bridge symptoms were identified: Daytime dysfunction (PSQI7), Self-harm even suicide (PHQ9), Sad mood (PHQ2), Low energy (PHQ4), and Feeling afraid (GAD7). Regarding protective HPLs, Physical activity, Spiritual growth, and Stress management generally emerged as the top three central mental health-promoting behaviors.ConclusionTargeting core and bridge symptoms with timely and appropriate interventions can alleviate anxiety, depression, and sleep problems in this population. Moreover, promoting physical activity, fostering spiritual growth, and managing stress are likely to significantly enhance the overall mental health of university students.

BackgroundFerroptosis has been proven to contribute to the progression of myocardial ischemia/reperfusion (I/R) injury and can be inhibited or promoted by ATF3. Short-chain fatty acids (SCFAs) have shown benefits in various cardiovascular diseases with anti-inflammatory and antioxidant effects. However, the impact of SCFAs on ferroptosis in ischemic-stimulated cardiomyocytes remains unknown. This study aimed to investigate the effect of SCFAs on cardiomyocyte ferroptosis, the expression of ATF3, and its potential upstream regulators.Methods and resultsThe expression of ATF3, ferroptosis pathway geneset (FPG), and geneset of potential regulators for ATF3 (GPRA, predicted by the PROMO database) was explored in the public human myocardial infarction single-cell RNA-seq (sma) dataset. Cardiomyocyte data was extracted from the dataset and re-clustered to explore the FPG, ATF3, and GPRA expression patterns in cardiomyocyte subclusters. A dose-dependent toxic experiment was run to detect the suitable dose for SCFA treatment. The erastin-induced ferroptosis model and hypoxia-reoxygenation (H/R) model (10 h of hypoxia followed by 6 h of reoxygenation) were adopted to assess the effect of SCFAs via the CCK8 assay. Gene expression was examined via RT-PCR and western blot. Ferroptosis markers, including lipid peroxides and Fe2+, were detected using the liperfluo and ferroOrange probes, respectively. In the sma dataset, upregulated ferroptosis pathway genes were mainly found in the infarction-stimulated cardiac cells (border zone and fibrotic zone), particularly the cardiomyocytes and adipocytes. The ATF3 and some of its potential transcription factors (VDR, EGR3, PAX5, and SP1) can be regulated by SCFA. SCFA can attenuate erastin-induced lipid peroxidation in cardiomyocytes. SCFA treatment can also reverse erastin-induced Fe2+ increase but may strengthen the Fe2+ in the H/R model. We also precisely defined a ferroptosis subcluster of cardiomyocytes (CM09) that highly expressed FPG, ATF3, and GPRA.ConclusionThe ATF3 and the ferroptosis pathway are elevated in cardiomyocytes of injury-related cardiac regions (border zone, ischemic zone, and fibrotic zone). SCFA can attenuate cardiomyocyte ferroptosis and regulate the expression of ATF3. Our study offers novel insights into the potential targets of SCFAs in the cardiovascular system.

Tobacco, a crop of significant economic importance, was greatly influenced in leaf quality by protein content. However, current processing parameters fail to adequately meet the requirements for protein degradation. Microorganisms possess potential advantages for degrading proteins and enhancing the quality of tobacco leaves, and hold substantial potential in the process of curing. To effectively reduce the protein content in tobacco leaves, thereby improving the quality and safety of the tobacco leaves. In this study, tobacco leaf were used as experimental material. From these, the BSP1 strain capable of effectively degrading proteins was isolated and identified as Bacillus subtilis by 16S rDNA analysis. Furthermore, the mechanisms were analyzed by integrating microbiome, transcriptome, and metabolome. Before curing, BSP1 was applied to the surface of tobacco leaves. The results indicated that BSP1 effectively improves the activity of key enzymes and the content of related substances, thereby enhancing protein degradation. Additionally, protein degradation was achieved by regulating the diversity of the microbial community on the surface of the tobacco leaves and the ubiquitin-proteasome pathway. This study provided new strategies for extracting and utilizing functional strains from tobacco leaves, opening new avenues for enhancing the quality of tobacco leaves.

BackgroundTo investigate the relationship between the Scottish inflammatory prognostic score (SIPS), treatment-related adverse events (TRAEs), and prognostication in patients with neoadjuvant immunochemotherapy (NICT) for esophageal squamous cell carcinoma (ESCC).MethodsA retrospective investigation was carried out on 208 ESCC patients treated with NICT. The relationships between the SIPS, TRAEs, and prognosis [disease-free survival (DFS) and overall survival (OS)] were analyzed.ResultsThe patients, comprising 62 (29.8%) cases of SIPS0, 103 (49.5%) cases of SIPS1, and 43 (20.7%) cases of SIPS2, were categorized into three groups based on SIPS. Among patients with SIPS2, the oldest age (P=0.006), lowest BMI (P=0.001), longest tumor length (P=0.001), most advanced ypT stage (P=0.014), and ypN stage (P

IntroductionRapid and accurate estimation of leaf area index (LAI) is of great significance for the precision agriculture because LAI is an important parameter to evaluate crop canopy structure and growth status.MethodsIn this study, 20 vegetation indices were constructed by using cotton canopy spectra. Then, cotton LAI estimation models were constructed based on multiple machine learning (ML) methods extreme learning machine (ELM), random forest (RF), back propagation (BP), multivariable linear regression (MLR), support vector machine (SVM)], and the optimal modeling strategy (RF) was selected. Finally, the vegetation indices with a high correlation with LAI were fused to construct the VI-fusion RF model, to explore the potential of multi-vegetation index fusion in the estimation of cotton LAI.ResultsThe RF model had the highest estimation accuracy among the LAI estimation models, and the estimation accuracy of models constructed by fusing multiple VIs was higher than that of models constructed based on single VIs. Among the multi-VI fusion models, the RF model constructed based on the fusion of seven vegetation indices (MNDSI, SRI, GRVI, REP, CIred-edge, MSR, and NVI) had the highest estimation accuracy, with coefficient of determination (R2), rootmean square error (RMSE), normalized rootmean square error (NRMSE), and mean absolute error (MAE) of 0.90, 0.50, 0.14, and 0.26, respectively. DiscussionAppropriate fusion of vegetation indices can include more spectral features in modeling and significantly improve the cotton LAI estimation accuracy. This study will provide a technical reference for improving the cotton LAI estimation accuracy, and the proposed method has great potential for crop growth monitoring applications.

Pentatricopeptide repeat (PPR) proteins constitute one of the largest protein families in land plants, with over 300 members in various species. Nearly all PPR proteins are nuclear-encoded and targeted to the chloroplast and mitochondria, modulating organellar gene expression by participating in RNA metabolism, including mRNA stability, RNA editing, RNA splicing, and translation initiation. Organelle RNA metabolism significantly influences chloroplast and mitochondria functions, impacting plant photosynthesis, respiration, and environmental responses. Over the past decades, PPR proteins have emerged as a research focus in molecular biology due to their diverse roles throughout plant life. This review summarizes recent progress in understanding the roles and molecular mechanisms of PPR proteins, emphasizing their functions in fertility, abiotic and biotic stress, grain quality, and chloroplast development in rice. Furthermore, we discuss prospects for PPR family research in rice, aiming to provide a theoretical foundation for future investigations and applications.

BackgroundSurgical site infection (SSI) is a common complication in HIV-positive fracture patients undergoing surgery, leading to increased morbidity, mortality, and healthcare costs. Accurate prediction of SSI risk can help guide clinical decision-making and improve patient outcomes. However, there is a lack of user-friendly, Web-based calculator for predicting SSI risk in this patient population.ObjectiveThis study aimed to develop and validate a novel web-based risk calculator for predicting SSI in HIV-positive fracture patients undergoing surgery in China.MethodA multicenter retrospective cohort study was conducted using data from HIV-positive fracture patients who underwent surgery in three tertiary hospitals in China between May 2011 and September 2023. We used patients from Beijing Ditan Hospital as the training cohort and patients from Chengdu Public Health and Changsha First Hospital as the external validation cohort. Univariate, multivariate logistic regression analyses and SVM-RFE were performed to identify independent risk factors for SSIs. A web-based calculator was developed using the identified risk factors and validated using an external validation cohort. The performance of the nomogram was evaluated using the area under the receiver operating characteristic (AUC) curves, calibration plots, and decision curve analysis (DCA).ResultsA total of 338 HIV-positive patients were included in the study, with 216 patients in the training cohort and 122 patients in the validation cohort. The overall SSI incidence was 10.7%. The web-based risk calculator (https://sydtliubo.shinyapps.io/DynNom_for_SSI/) incorporated six risk factors: HBV/HCV co-infection, HIV RNA load, CD4+ T-cell count, Neu and Lym level. The nomogram demonstrated good discrimination, with an AUC of 0.890 in the training cohort and 0.853 in the validation cohort. The calibration plot showed good agreement between predicted and observed SSI probabilities. The DCA indicated that the nomogram had clinical utility across a wide range of threshold probabilities.ConclusionOur study developed and validated a novel web-based risk calculator for predicting SSI risk in HIV-positive fracture patients undergoing surgery in China. The nomogram demonstrated good discrimination, calibration, and clinical utility, and can serve as a valuable tool for risk stratification and clinical decision-making in this patient population. Future studies should focus on integrating this nomogram into hospital information systems for real-time risk assessment and management.

BackgroundEmerging brain-computer interface (BCI) technology holds promising potential to enhance the quality of life for individuals with disabilities. Nevertheless, the constrained accuracy of electroencephalography (EEG) signal classification poses numerous hurdles in real-world applications.MethodsIn response to this predicament, we introduce a novel EEG signal classification model termed EEGGAN-Net, leveraging a data augmentation framework. By incorporating Conditional Generative Adversarial Network (CGAN) data augmentation, a cropped training strategy and a Squeeze-and-Excitation (SE) attention mechanism, EEGGAN-Net adeptly assimilates crucial features from the data, consequently enhancing classification efficacy across diverse BCI tasks.ResultsThe EEGGAN-Net model exhibits notable performance metrics on the BCI Competition IV-2a and IV-2b datasets. Specifically, it achieves a classification accuracy of 81.3% with a kappa value of 0.751 on the IV-2a dataset, and a classification accuracy of 90.3% with a kappa value of 0.79 on the IV-2b dataset. Remarkably, these results surpass those of four other CNN-based decoding models.ConclusionsIn conclusion, the amalgamation of data augmentation and attention mechanisms proves instrumental in acquiring generalized features from EEG signals, ultimately elevating the overall proficiency of EEG signal classification.

BackgroundDiabetic gastroparesis is a common complication in patient with diabetes. Dietary intervention has been widely used in the treatment of diabetic gastroparesis. The aim of this study is to evaluate the role of diet in the treatment of diabetic gastroparesis.MethodsThis systematic review was conducted a comprehensive search of randomized controlled trials using dietary interventions for the treatment of diabetic gastroparesis up to 9 November 2023. The primary outcomes were gastric emptying time and clinical effect, while fasting blood glucose, 2-hour postprandial blood glucose and glycosylated hemoglobin were secondary outcomes. Data analysis was performed using RevMan 5.4 software, and publication bias test was performed using Stata 15.1 software.ResultsA total of 15 randomized controlled trials involving 1106 participants were included in this review. The results showed that patients with diabetic gastroparesis benefit from dietary interventions (whether personalized dietary care alone or personalized dietary care+routine dietary care). Compared with routine dietary care, personalized dietary care and personalized dietary care+routine dietary care can shorten the gastric emptying time, improve clinical efficacy, and reduce the level of fasting blood glucose, 2-hour postprandial blood glucose and glycosylated hemoglobin.ConclusionsLimited evidence suggests that dietary intervention can promote gastric emptying and stabilize blood glucose control in patients with diabetic gastroparesis. Dietary intervention has unique potential in the treatment of diabetic gastroparesis, and more high-quality randomized controlled trials are needed to further validate our research results.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023481621.

BackgroundNeuroblastoma (NB), characterized by its marked heterogeneity, is the most common extracranial solid tumor in children. The status and functionality of mitochondria are crucial in regulating NB cell behavior. While the significance of mitochondria-related genes (MRGs) in NB is still missing in key knowledge.Materials and methodsThis study leverages consensus clustering and machine learning algorithms to construct and validate an MRGs-related signature in NB. Single-cell data analysis and experimental validation were employed to characterize the pivotal role of FEN1 within NB cells.ResultsMRGs facilitated the classification of NB patients into 2 distinct clusters with considerable differences. The constructed MRGs-related signature and its quantitative indicators, mtScore and mtRisk, effectively characterize the MRGs-related patient clusters. Notably, the MRGs-related signature outperformed MYCN in predicting NB patient prognosis and was adept at representing the tumor microenvironment (TME), tumor cell stemness, and sensitivity to the chemotherapeutic agents Cisplatin, Topotecan, and Irinotecan. FEN1, identified as the most contributory gene within the MRGs-related signature, was found to play a crucial role in the communication between NB cells and the TME, and in the developmental trajectory of NB cells. Experimental validations confirmed FEN1’s significant influence on NB cell proliferation, apoptosis, cell cycle, and invasiveness.ConclusionThe MRGs-related signature developed in this study offers a novel predictive tool for assessing NB patient prognosis, immune infiltration, stemness, and chemotherapeutic sensitivity. Our findings unveil the critical function of FEN1 in NB, suggesting its potential as a therapeutic target.

BackgroundThe Stenotrophomonas maltophilia complex (Smc) has emerged as a significant nosocomial pathogen contributing to increased mortality rates, particularly in case of bloodstream infections.MethodsThis study employed whole-genome sequencing (WGS) to assess the genetic diversity, antimicrobial resistance profiles, molecular epidemiology and frequencies of virulence genes among 55 S. maltophilia isolates obtained from bacteremic cases over a 9-year period.ResultsBased on the threshold of 95% average nucleotide identity (ANI) and 70% digital DNA–DNA hybridization (dDDH) for genospecies delineation, we classified 37 isolates into 6 known species, all belonging to the Smc. The remaining 18 isolates sequenced in this study were assigned to 6 new genomospecies. Among the 55 isolates, we identified 44 different sequence types (STs), comprising 22 known and 22 novel allele combinations. The resistance rate of Smc against trimethoprim-sulfamethoxazole (TMP/SMX) was found to be 3.6%, with the sul1 and class one integron integrase genes (intI) detected in these isolates. All Smc isolates were susceptible to minocycline. Furthermore, all Smc strains harbored the motA, pilU, smf-1 and Stmpr2 genes. Genomospecies 1 (100%, n = 9), Stenotrophomonas maltophilia (84.21%, n = 19) and Stenotrophomonas sepilia (71.43%, n = 7) demonstrated a higher percentage of the afaD gene, which was also associated with a higher separation rate. In addition to motA, pilU, smf-1, and Stmpr2 genes, all S. maltophilia strains (100%) contained entA, gspD, KatA, and stmPr1 genes, while all genomospecies 1 strains (100%) contained afaD, entA, gspD, and KatA genes.ConclusionOur study highlights the genetic diversity among Smc isolates from patients with bacteremia, revealing 22 novel ST types, 58 new alleles and 6 new genomospecies. S. maltophilia and S. pavanii were found to carry more virulence factors, emphasizing the importance of accurate strain identification. Minocycline emerged as a promising alternative antibiotic for patients who were resistant to TMP/SMX.

Objective: Inhaled corticosteroids (ICS) are widely used in chronic obstructive pulmonary disease (COPD) patients as a treatment option. However, ICS may also increase the risk of pneumonia and alter the composition of airway microbiota. In clinical application, the overuse of ICS exists pervasively and may potentially lead to adverse effects. Whether the long-term use of ICS confers enough benefit to COPD patients to justify its use so far remains unknown. Therefore, this study employed a single-center retrospective cohort study to compare alterations in airway function and the sputum microbial community structure between COPD patients who had undergone either long-term or short-term treatment with ICS.Methods: Sixty stable COPD patients who had used ICS were recruited and classified into the long-term use group (more than 3 months) and short-term use group (less than 3 months). The demographic features and clinical information of the subjects were investigated and their sputum samples were collected and subjected to metagenomic next-generation sequencing (mNGS).Results: The study found that compared with short-term ICS use, long-term ICS use did not further improve the clinical airway function, decrease the number of acute exacerbations, or decrease hospital readmission. In terms of sputum microbiota, the long-term use of ICS significantly altered the beta diversity of the microbial community structure (p < 0.05) and the top three phyla differed between the two groups. At the genus level, long-term ICS induced higher relative abundances of Abiotrophia, Schaalia, Granulicatella, Mogibacterium, Sphingobium, and Paraeggerthella compared to short-term ICS use. Additionally, alpha diversity was positively associated with clinical airway indicators (pre-bronchodilatory FEV1 and pre-bronchodilatory FVC) in the long-term ICS group. The relative abundances of Rothia, Granulicatella, Schaalia, and Mogibacterium genera had positive correlations with the eosinophil % (of all white blood cells). Conclusion: This study reveals the effect of long-term and short-term ICS use on sputum microbiota among COPD patients and provides a reference for the appropriate application of clinical ICS treatment in COPD patients.

Cu is an essential micronutrient for various physiological processes in almost all human cell types. Given the critical role of Cu in a wide range of cellular processes, the local concentrations of Cu and the cellular distribution of Cu transporter proteins in the lung are essential for maintaining a steady-state internal environment. Dysfunctional Cu metabolism or regulatory pathways can lead to an imbalance in Cu homeostasis in the lungs, affecting both acute and chronic pathological processes. Recent studies have identified a new form of Cu-dependent cell death called cuproptosis, which has generated renewed interest in the role of Cu homeostasis in diseases. Cuproptosis differs from other known cell death pathways. This occurs through the direct binding of Cu ions to lipoylated components of the tricarboxylic acid cycle during mitochondrial respiration, leading to the aggregation of lipoylated proteins and the subsequent downregulation of Fe-S cluster proteins, which causes toxic stress to the proteins and ultimately leads to cell death. Here, we discuss the impact of dysregulated Cu homeostasis on the pathogenesis of various respiratory diseases, including asthma, chronic obstructive pulmonary disease, idiopathic interstitial fibrosis, and lung cancer. We also discuss the therapeutic potential of targeting Cu. This study highlights the intricate interplay between copper, cellular processes, and respiratory health. Copper, while essential, must be carefully regulated to maintain the delicate balance between necessity and toxicity in living organisms. This review highlights the need to further investigate the precise mechanisms of copper interactions with infections and immune inflammation in the context of respiratory diseases and explore the potential of therapeutic strategies for copper, cuproptosis, and other related effects.

Plant growth regulators have been used in the cultivation of medicinal plants to increase yield, but the existing regulators decreased the content of active constituents which benefit human health. Therefore, it is necessary to find a new growth regulator to achieve the win-win goal of increasing yield and improving active constituents’ accumulation. The potential of replacing chlorocholine chloride with a new humic acid-based growth regulator was evaluated by measuring the yield and active constituents’ accumulation of Codonopsis pilosula. Three treatments including water (CK), chlorocholine chloride (T1) and humic acid regulator (T2) were applied by foliar spraying. Among them, both chlorocholine chloride and humic acid regulator belong to biostimulant. The result showed that the root yield in T1 and T2 were significantly increased by 59.1% and 54.9% compared with CK, respectively, and there was no significant difference between T1 and T2. Compared with CK, the yields of lobetyolin, syringin and atractylenolide III of Codonopsis pilosula were significantly decreased by 6.3%, 7.3% and 13.0% in T1, but were significantly increased by 22.8%, 14.8% and 32.0% in T2, respectively. Redundancy analyses showed that photosynthetic rate, sucrose phosphoric acid synthetase and phosphomannomutase had higher degree of explanation for yield and quality. Linear regression results indicated that photosynthetic rate and phosphomannomutase were the main factors to affect yield and active constituents yields, respectively. In addition, the output-input ratios based on the yields of polysaccharides, lobetyolin, syringin and atractylenolide III of Codonopsis pilosula in T2 was significantly increased by 6.5%, 15.2%, 8.7% and 31.2% respectively as compared with T1. Overall, compared with water treatment, both chlorocholine chloride and humic acid regulator treatments can increase the root yield of Codonopsis pilosula. Compared with chlorocholine chloride, humic acid regulator can improve the yield of active constituents and economic benefits of Codonopsis pilosula. This study indicated that reasonable selection of plant growth regulators is of great significance for achieving a win-win goal of increasing the root yield and active constituents of medicinal plants.

BackgroundAlthough social capital has been linked to dietary intake particularly in disadvantaged populations, little is known about the mechanisms. This study aimed to investigate whether social support (SS) and nutrition knowledge (NK) mediate the association between social capital and healthy eating habits.MethodsA probability sample of two ethnic minority groups in Yunnan Province, Southwest China were included (n = 1,033, mean age 47.5 ± 14.7 years). Bonding and bridging social capital (BOC and BRC) were assessed with the Personal Social Capital Scale (PSCS-16). Dietary data were evaluated with the Chinese Healthy Eating Index (CHEI), a measure of diet quality which reflects adherence to the Chinese Dietary Guidelines. NK and SS were measured with a validated questionnaire and scale, respectively. Structural Equation Modeling was used to calculate the direct, indirect and total effects of social capital on CHEI scores.ResultsThe mean score of CHEI was 57.4 ± 9.8, which was significantly lower in men and older people. Low adherence to dietary guidelines were to observed in the consumption of dairy, beans, nuts, animal-source food vegetables and fruits. BOC and BRC were positively associated with CHEI score (β = 0.37 and 0.38, all p

The germinal center response or reaction (GCR) is a hallmark event of adaptive humoral immunity. Unfolding in the B cell follicles of the secondary lymphoid organs, a GC culminates in the production of high-affinity antibody-secreting plasma cells along with memory B cells. By interacting with follicular dendritic cells (FDC) and T follicular helper (Tfh) cells, GC B cells exhibit complex spatiotemporal dynamics. Driving the B cell dynamics are the intracellular signal transduction and gene regulatory network that responds to cell surface signaling molecules, cytokines, and chemokines. As our knowledge of the GC continues to expand in depth and in scope, mathematical modeling has become an important tool to help disentangle the intricacy of the GCR and inform novel mechanistic and clinical insights. While the GC has been modeled at different granularities, a multiscale spatial simulation framework – integrating molecular, cellular, and tissue-level responses – is still rare. Here, we report our recent progress toward this end with a hybrid stochastic GC framework developed on the Cellular Potts Model-based CompuCell3D platform. Tellurium is used to simulate the B cell intracellular molecular network comprising NF-κB, FOXO1, MYC, AP4, CXCR4, and BLIMP1 that responds to B cell receptor (BCR) and CD40-mediated signaling. The molecular outputs of the network drive the spatiotemporal behaviors of B cells, including cyclic migration between the dark zone (DZ) and light zone (LZ) via chemotaxis; clonal proliferative bursts, somatic hypermutation, and DNA damage-induced apoptosis in the DZ; and positive selection, apoptosis via a death timer, and emergence of plasma cells in the LZ. Our simulations are able to recapitulate key molecular, cellular, and morphological GC events, including B cell population growth, affinity maturation, and clonal dominance. This novel modeling framework provides an open-source, customizable, and multiscale virtual GC simulation platform that enables qualitative and quantitative in silico investigations of a range of mechanistic and applied research questions on the adaptive humoral immune response in the future.

BackgroundSpondylitis caused by Brucella infection is a rare but challenging condition, and its successful management depends on timely diagnosis and appropriate treatment. This study reports two typical cases of thoracic and lumbar brucellosis spondylitis, highlighting the pivotal roles of real-time polymerase chain reaction (real-time PCR) detection and surgical intervention.Case presentationCase 1 involved a 49-year-old male shepherd who presented with a 6-month history of fever (40°C), severe chest and back pain, and 2-week limited lower limb movement with night-time exacerbation. Physical examination revealed tenderness and percussion pain over the T9 and T10 spinous processes, with grade 2 muscle strength in the lower limbs. CT showed bone destruction of the T9 and T10 vertebrae with narrowing of the intervertebral space, whereas MRI demonstrated abnormal signals in the T9–T10 vertebrae, a spinal canal abscess, and spinal cord compression. The Rose Bengal plate agglutination test was positive. Case 2 was a 59-year-old man who complained of severe thoracolumbar back pain with fever (39.0°C) and limited walking for 2 months. He had a 2.5 kg weight loss and a history of close contact with sheep. The Rose Bengal test was positive, and the MRI showed inflammatory changes in the L1 and L2 vertebrae. Diagnosis and treatment: real-time PCR confirmed Brucella infection in both cases. Preoperative antimicrobial therapy with doxycycline, rifampicin, and ceftazidime-sulbactam was administered for at least 2 weeks. Surgical management involved intervertebral foraminotomy-assisted debridement, decompression, internal fixation, and bone grafting under general anesthesia. Postoperative histopathological examination with HE and Gram staining further substantiated the diagnosis. Outcomes: both patients experienced significant pain relief and restored normal lower limb movement at the last follow-up (4–12 weeks) after the intervention.ConclusionReal-time PCR detection offers valuable diagnostic insights for suspected cases of brucellosis spondylitis. Surgical treatment helps in infection control, decompression of the spinal cord, and restoration of stability, constituting a necessary and effective therapeutic approach. Prompt diagnosis and comprehensive management are crucial for favorable outcomes in such cases.

ObjectiveTo describe the lipid metabolic profile of different patients with coronavirus disease 2019 (COVID-19) and contribute new evidence on the progression and severity prediction of COVID-19.MethodsThis case–control study was conducted in Peking University Third Hospital, China. The laboratory-confirmed COVID-19 patients aged ≥18 years old and diagnosed as pneumonia from December 2022 to January 2023 were included. Serum lipids were detected. The discrimination ability was calculated with the area under the curve (AUC). A random forest (RF) model was conducted to determine the significance of different lipids.ResultsTotally, 44 COVID-19 patients were enrolled with 16 mild and 28 severe patients. The top 5 super classes were triacylglycerols (TAG, 55.9%), phosphatidylethanolamines (PE, 10.9%), phosphatidylcholines (PC, 6.8%), diacylglycerols (DAG, 5.9%) and free fatty acids (FFA, 3.6%) among the 778 detected lipids from the serum of COVID-19 patients. Certain lipids, especially lysophosphatidylcholines (LPCs), turned to have significant correlations with certain immune/cytokine indexes. Reduced level of LPC 20:0 was observed in severe patients particularly in acute stage. The AUC of LPC 20:0 reached 0.940 in discriminating mild and severe patients and 0.807 in discriminating acute and recovery stages in the severe patients. The results of RF models also suggested the significance of LPCs in predicting the severity and progression of COVID-19.ConclusionLipids probably have the potential to differentiate and forecast the severity, progression, and clinical outcomes of COVID-19 patients, with implications for immune/inflammatory responses. LPC 20:0 might be a potential target in predicting the progression and outcome and the treatment of COVID-19.

BackgroundAttention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder of childhood, and pathogenesis is not fully understood. Observational studies suggest an association between fatty acids abnormalities and ADHD, but there are contradictions and differences between these findings. To address this uncertainty, we employed a two-sample bidirectional Mendelian Randomization (MR) analysis to investigate the causal relationship between fatty acids and ADHD.MethodsWe conducted a two-sample Mendelian Randomization (MR) study, selecting single nucleotide polymorphisms (SNPs) highly correlated with fatty acid levels from the CHARGE Consortium as our instruments. The outcome data were sourced from the Psychiatric Genomics Consortium (PGC) dataset on ADHD, comprising 225,534 individuals, with 162,384 cases and 65,693 controls. Inverse variance weighting, MR-Egger, and weighted median methods were employed to estimate the causal relationship between fatty acids and ADHD. Cochran’s Q-test was used to quantify heterogeneity of instrumental variables. Sensitivity analyses included MR-Egger intercept tests, leave-one-out analyses, and funnel plots.ResultsThe MR analysis revealed no significant associations between genetically predicted levels of various saturated, monounsaturated, and polyunsaturated fatty acids (including omega-3 and omega-6) and ADHD risk in the CHARGE and PGC cohorts. Notably, an initial association with Dihomo-gamma-linolenic acid (DGLA) (OR = 1.009, p = 0.032 by IVW) did not persist after correction for multiple testing (adjusted p-value = 0.286). Sensitivity analysis supported our findings, indicating robustness. Moreover, there was a lack of evidence supporting a causal link from ADHD to fatty acids.ConclusionWhile our study on the basis of genetic data does not provide evidence to support the causal role of fatty acids in ADHD, it does not preclude their potential involvement in reducing the risk of ADHD. Further research is needed to explore this possibility.

Lung cancer is one of the leading causes of cancer-related deaths worldwide that presents a substantial peril to human health. Non-Small Cell Lung Cancer (NSCLC) is a main subtype of lung cancer with heightened metastasis and invasion ability. The predominant treatment approaches currently comprise surgical interventions, chemotherapy regimens, and radiotherapeutic procedures. However, it poses significant clinical challenges due to its tumor heterogeneity and drug resistance, resulting in diminished patient survival rates. Therefore, the development of novel treatment strategies for NSCLC is necessary. Ferroptosis was characterized by iron-dependent lipid peroxidation and the accumulation of lipid reactive oxygen species (ROS), leading to oxidative damage of cells and eventually cell death. An increasing number of studies have found that exploiting the induction of ferroptosis may be a potential therapeutic approach in NSCLC. Recent investigations have underscored the remarkable potential of natural products in the cancer treatment, owing to their potent activity and high safety profiles. Notably, accumulating evidences have shown that targeting ferroptosis through natural compounds as a novel strategy for combating NSCLC holds considerable promise. Nevertheless, the existing literature on comprehensive reviews elucidating the role of natural products inducing the ferroptosis for NSCLC therapy remains relatively sparse. In order to furnish a valuable reference and support for the identification of natural products inducing ferroptosis in anti-NSCLC therapeutics, this article provided a comprehensive review explaining the mechanisms by which natural products selectively target ferroptosis and modulate the pathogenesis of NSCLC.

Tetraphenylethene-based ligands with lowered symmetry are promising building blocks for the construction of novel luminescent metal–organic frameworks (MOFs). However, few examples have been reported, and predicting the ligand conformation and the dimensionality of the resulting MOF remains challenging. In order to uncover how synthetic conditions and accessible ligand conformations may affect the resulting MOF structure, four new MOF structures were synthesized under solvothermal conditions using the meta-coordinated tetraphenylethene-based ligand m-ETTC and paddlewheel SBUs composed of Co(II), Cu(II), and Zn(II). WSU-10 (WSU = Washington State University) is formed with either Zn or Cu comprising stacked psuedo-2D layers. The dimensionality of WSU-10 can be intentionally increased through the addition of pyrazine as a pillar ligand into the synthesis, forming the 3D structure WSU-11. The third structure, WSU-20, is formed by the combination of Zn or Co with m-ETTC and is intrinsically 3D without the use of a pillar ligand; interestingly, this is the result of a distortion in the paddlewheel SBU. Finally, Cu was also found to form a new structure (WSU-12), which displays an m-ETTC conformation unique from that found in the other isolated MOFs. Structural features are compared across the series and a mechanistic relationship between WSU-10 and -20 is proposed, providing insight into the factors that can encourage the generation of frameworks with increased dimensionality.

BackgroundAn increasing number of studies suggest that environmental pollution may increase the risk of vitamin D deficiency (VDD). However, less is known about arsenic (As) exposure and VDD, particularly in Chinese pregnant women.ObjectivesThis study examines the correlations of different urinary As species with serum 25 (OH) D and VDD prevalence.MethodsWe measured urinary arsenite (As3+), arsenate (As5+), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) levels and serum 25(OH)D2, 25(OH)D3, 25(OH) D levels in 391 pregnant women in Tianjin, China. The diagnosis of VDD was based on 25(OH) D serum levels. Linear relationship, Logistic regression, and Bayesian kernel machine regression (BKMR) were used to examine the associations between urinary As species and VDD.ResultsOf the 391 pregnant women, 60 received a diagnosis of VDD. Baseline information showed significant differences in As3+, DMA, and tAs distribution between pregnant women with and without VDD. Logistic regression showed that As3+ was significantly and positively correlated with VDD (OR: 4.65, 95% CI: 1.79, 13.32). Meanwhile, there was a marginally significant positive correlation between tAs and VDD (OR: 4.27, 95% CI: 1.01, 19.59). BKMR revealed positive correlations between As3+, MMA and VDD. However, negative correlations were found between As5+, DMA and VDD.ConclusionAccording to our study, there were positive correlations between iAs, especially As3+, MMA and VDD, but negative correlations between other As species and VDD. Further studies are needed to determine the mechanisms that exist between different As species and VDD.

Super-sulfated cement (SSC) is known for its low-carbon footprint, energy efficiency, and eco-friendliness (mainly derived from industrial by-products) with promising applications. However, SSC’s slow early strength development results in inadequate initial hardening, compromising its durability and limiting its use in practical engineering projects. This study aims to enhance SSC’s early performance by incorporating ordinary Portland cement (OPC), carbide slag (CS), and sodium silicate as alkaline activators alongside anhydrite. The effects of varying proportions of OPC, CS, and sodium silicate on SSC’s compressive strength and hydration mechanism have been investigated experimentally in this study. Results show that using 2% OPC, 2% CS, and 1% sodium silicate as alkaline activators effectively activates slag hydration in SSC-2, achieving a compressive strength of 9.6 MPa at 1 day of hydration. As hydration progresses, SSC’s compressive strength continues to increase. In the early hydration stage, OPC and CS create an alkaline environment for SSC, facilitating rapid slag reaction with anhydrite and sodium silicate, resulting in ettringite and C–S–H formation. Simultaneously, slag hydration produces C–S–H and OH-hydrotalcite, filling voids in the ettringite-formed skeleton structure, leading to a denser microstructure and significantly enhancing SSC’s early compressive strength. From 28 to 90 days of hydration, the ettringite formation rate decreases in the SSC system, but some anhydrite remains, while C–S–H production continues to rise, further enhancing late-stage compressive strength.

Raman spectroscopy is an optical technique that uses inelastic light scattering in response to vibrating molecules to produce chemical fingerprints of tissues, cells, and biofluids. Raman spectroscopy strategies produce high levels of chemical specificity without requiring extensive sample preparation, allowing for the use of advanced optical tools such as microscopes, fiber optics, and lasers that operate in the visible and near-infrared spectral range, making them increasingly suitable for a wide range of medical diagnostic applications. Metal nanoparticles and nonlinear optical effects can improve Raman signals, and optimized fiber optic Raman probes can make real-time, in vivo, single-point observations. Furthermore, diagnostic speed and spatial accuracy can be improved through the multimodal integration of Raman measurements and other technologies. Recent studies have significantly contributed to the improvement of diagnostic speed and accuracy, making them suitable for clinical application. Lung cancer is a prevalent type of respiratory malignancy. However, the use of computed tomography for detection and screening frequently reveals numerous smaller lung nodules, which makes the diagnostic process more challenging from a clinical perspective. While the majority of small nodules detected are benign, there are currently no direct methods for identifying which nodules represent very early-stage lung cancer. Positron emission tomography and other auxiliary diagnostic methods for non-surgical biopsy samples from these small nodules yield low detection rates, which might result in significant expenses and the possibility of complications for patients. While certain subsets of patients can undergo curative treatment, other individuals have a less favorable prognosis and need alternative therapeutic interventions. With the emergence of new methods for treating cancer, such as immunotherapies, which can potentially extend patient survival and even lead to a complete cure in certain instances, it is crucial to determine the most suitable biomarkers and metrics for assessing the effectiveness of these novel compounds. This will ensure that significant treatment outcomes are accurately measured. This review provides a comprehensive overview of the prospects of Raman spectroscopy and its applications in the diagnosis and analysis of lung tumors.

BackgroundPreeclampsia (PE) is a pregnancy complication defined by new onset hypertension and proteinuria or other maternal organ damage after 20 weeks of gestation. Although non-invasive prenatal testing (NIPT) has been widely used to detect fetal chromosomal abnormalities during pregnancy, its performance in combination with maternal risk factors to screen for PE has not been extensively validated. Our aim was to develop and validate classifiers that predict early- or late-onset PE using the maternal plasma cell-free DNA (cfDNA) profile and clinical risk factors.MethodsWe retrospectively collected and analyzed NIPT data of 2,727 pregnant women aged 24–45 years from four hospitals in China, which had previously been used to screen for fetal aneuploidy at 12 + 0 ~ 22 + 6 weeks of gestation. According to the diagnostic criteria for PE and the time of diagnosis (34 weeks of gestation), a total of 143 early-, 580 late-onset PE samples and 2,004 healthy controls were included. The wilcoxon rank sum test was used to identify the cfDNA profile for PE prediction. The Fisher’s exact test and Mann–Whitney U-test were used to compare categorical and continuous variables of clinical risk factors between PE samples and healthy controls, respectively. Machine learning methods were performed to develop and validate PE classifiers based on the cfDNA profile and clinical risk factors.ResultsBy using NIPT data to analyze cfDNA coverages in promoter regions, we found the cfDNA profile, which was differential cfDNA coverages in gene promoter regions between PE and healthy controls, could be used to predict early- and late-onset PE. Maternal age, body mass index, parity, past medical histories and method of conception were significantly differential between PE and healthy pregnant women. With a false positive rate of 10%, the classifiers based on the combination of the cfDNA profile and clinical risk factors predicted early- and late-onset PE in four datasets with an average accuracy of 89 and 80% and an average sensitivity of 63 and 48%, respectively.ConclusionIncorporating cfDNA profiles in classifiers might reduce performance variations in PE models based only on clinical risk factors, potentially expanding the application of NIPT in PE screening in the future.

Cadmium (Cd) contamination of soil can strongly impact human health through the food chain due to uptake by crop plants. Inorganic immobilizing agents such as silicates and phosphates have been shown to effectively reduce Cd transfer from the soil to cereal crops. However, the effects of such agents on total Cd and its bioaccessibility in leafy vegetables are not yet known. Pak choi (Brassica rapa L. ssp. chinensis) was here selected as a representative leafy vegetable to be tested in pots to reveal the effects of silicate–phosphate amendments on soil Cd chemical fractions, total plant Cd levels, and plant bioaccessibility. The collected Cd contaminated soil was mixed with control soil at 1:0, 1:1, 1:4, 0:1 with a view to Cd high/moderate/mild/control soil samples. Three heavy metal-immobilizing agents: wollastonite (W), potassium tripolyphosphate (KTPP), and sodium hexametaphosphate (SHMP) were added to the soil in order to get four different treatment groups, i.e., control (CK), application of wollastonite alone (W), wollastonite co-applied with KTPP (WKTPP), application of wollastonite co-applied with SHMP (WSHMP) for remediation of soils with different levels of Cd contamination. All three treatments increased the effective bio-Cd concentration in the soils with varying levels of contamination, except for W under moderate and heavy Cd contamination. The total Cd concentration in pak choi plants grown in mildly Cd-contaminated soil was elevated by 86.2% after WKTPP treatment compared to the control treatment could function as a phytoremediation aid for mildly Cd-contaminated soil. Using an in vitro digestion method (physiologically based extraction test) combined with transmission electron microscopy, silicate and phosphorus agents were found to reduce the bioaccessibility of Cd in pak choi by up to 66.13% with WSHMP treatment. Application of silicate alone reduced soil bio-Cd concentration through the formation of insoluble complexes and silanol groups with Cd, but the addition of phosphate may have facilitated Cd translocation into pak choi by first co-precipitating with Ca in wollastonite while simultaneously altering soil pH. Meanwhile, wollastonite and phosphate treatments may cause Cd to be firmly enclosed in the cell wall in an insoluble form, reducing its translocation to edible parts and decreasing the bioaccessibility of Cd in pak choi. This study contributes to the mitigation of Cd bioaccessibility in pak choi by reducing soil Cd concentration through in situ remediation and will help us to extend the effects of wollastonite and phosphate on Cd bioaccessibility to other common vegetables. Therefore, this study thus reveals effective strategies for the remediation of soil Cd and the reduction of Cd bioaccessibility in crops based on two indicators: total Cd and Cd bioaccessibility. Our findings contribute to the development of methods for safer cultivation of commonly consumed leafy vegetables and for soil remediation.

IntroductionThe coronavirus disease 2019 (COVID-19) pandemic has affected billions of people worldwide, and the lessons learned need to be concluded to get better prepared for the next pandemic. Early identification of high-risk patients is important for appropriate treatment and distribution of medical resources. A generalizable and easy-to-use COVID-19 severity stratification model is vital and may provide references for clinicians.MethodsThree COVID-19 cohorts (one discovery cohort and two validation cohorts) were included. Longitudinal peripheral blood mononuclear cells were collected from the discovery cohort (n = 39, mild = 15, critical = 24). The immune characteristics of COVID-19 and critical COVID-19 were analyzed by comparison with those of healthy volunteers (n = 16) and patients with mild COVID-19 using mass cytometry by time of flight (CyTOF). Subsequently, machine learning models were developed based on immune signatures and the most valuable laboratory parameters that performed well in distinguishing mild from critical cases. Finally, single-cell RNA sequencing data from a published study (n = 43) and electronic health records from a prospective cohort study (n = 840) were used to verify the role of crucial clinical laboratory and immune signature parameters in the stratification of COVID-19 severity.ResultsPatients with COVID-19 were determined with disturbed glucose and tryptophan metabolism in two major innate immune clusters. Critical patients were further characterized by significant depletion of classical dendritic cells (cDCs), regulatory T cells (Tregs), and CD4+ central memory T cells (Tcm), along with increased systemic interleukin-6 (IL-6), interleukin-12 (IL-12), and lactate dehydrogenase (LDH). The machine learning models based on the level of cDCs and LDH showed great potential for predicting critical cases. The model performances in severity stratification were validated in two cohorts (AUC = 0.77 and 0.88, respectively) infected with different strains in different periods. The reference limits of cDCs and LDH as biomarkers for predicting critical COVID-19 were 1.2% and 270.5 U/L, respectively.ConclusionOverall, we developed and validated a generalizable and easy-to-use COVID-19 severity stratification model using machine learning algorithms. The level of cDCs and LDH will assist clinicians in making quick decisions during future pandemics.

BackgroundDifferences in border zone contribute to different outcomes post-infarction, such as left ventricular aneurysm (LVA) and myocardial infarction (MI). LVA usually forms within 24 h of the onset of MI and may cause heart rupture; however, LVA surgery is best performed 3 months after MI. Few studies have investigated the LVA model, the differences in border zones between LVA and MI, and the mechanism in the border zone.MethodsThe LVA, MI, and SHAM mouse models were used. Echocardiography, Masson’s trichrome staining, and immunofluorescence staining were performed, and RNA sequencing of the border zone was conducted. The adipocyte-conditioned medium-treated hypoxic macrophage cell line and LVA and MI mouse models were employed to determine the effects of the hub gene, adiponectin (ADPN), on macrophages. Quantitative polymerase chain reaction (qPCR), Western blot analysis, transmission electron microscopy, and chromatin immunoprecipitation (ChIP) assays were conducted to elucidate the mechanism in the border zone. Human subepicardial adipose tissue and blood samples were collected to validate the effects of ADPN.ResultsA novel, simple, consistent, and low-cost LVA mouse model was constructed. LVA caused a greater reduction in contractile functions than MI owing to reduced wall thickness and edema in the border zone. ADPN impeded cardiac edema and promoted lymphangiogenesis by increasing macrophage infiltration post-infarction. Adipocyte-derived ADPN promoted M2 polarization and sustained mitochondrial quality via the ADPN/AdipoR2/HMGB1 axis. Mechanistically, ADPN impeded macrophage HMGB1 inflammation and decreased interleukin-6 (IL6) and HMGB1 secretion. The secretion of IL6 and HMGB1 increased ADPN expression via STAT3 and the co-transcription factor, YAP, in adipocytes. Based on ChIP and Dual-Glo luciferase experiments, STAT3 promoted ADPN transcription by binding to its promoter in adipocytes. In vivo, ADPN promoted lymphangiogenesis and decreased myocardial injury after MI. These phenotypes were rescued by macrophage depletion or HMGB1 knockdown in macrophages. Supplying adipocytes overexpressing STAT3 decreased collagen disposition, increased lymphangiogenesis, and impaired myocardial injury. However, these effects were rescued after HMGB1 knockdown in macrophages. Overall, the IL6/ADPN/HMGB1 axis was validated using human subepicardial tissue and blood samples. This axis could serve as an independent factor in overweight MI patients who need coronary artery bypass grafting (CABG) treatment.ConclusionThe IL6/ADPN/HMGB1 loop between adipocytes and macrophages in the border zone contributes to different clinical outcomes post-infarction. Thus, targeting the IL6/ADPN/HMGB1 loop may be a novel therapeutic approach for cardiac lymphatic regulation and reduction of cell senescence post-infarction.