Cancer screening in hospitalized ischemic stroke patients: a multicenter study focused on multiparametric analysis to improve management of occult cancers.

Background/aims: The reciprocal promotion of cancer and stroke occurs due to changes in shared risk factors, such as metabolic pathways and molecular targets, creating a "vicious cycle." Cancer plays a direct or indirect role in the pathogenesis of ischemic stroke (IS), along with the reactive medical approach used in the treatment and clinical management of IS patients, resulting in clinical challenges associated with occult cancer in these patients. The lack of reliable and simple tools hinders the effectiveness of the predictive, preventive, and personalized medicine (PPPM/3PM) approach. Therefore, we conducted a multicenter study that focused on multiparametric analysis to facilitate early diagnosis of occult cancer and personalized treatment for stroke associated with cancer. Methods: Admission routine clinical examination indicators of IS patients were retrospectively collated from the electronic medical records. The training dataset comprised 136 IS patients with concurrent cancer, matched at a 1:1 ratio with a control group. The risk of occult cancer in IS patients was assessed through logistic regression and five alternative machine-learning models. Subsequently, select the model with the highest predictive efficacy to create a nomogram, which is a quantitative tool for predicting diagnosis in clinical practice. Internal validation employed a ten-fold cross-validation, while external validation involved 239 IS patients from six centers. Validation encompassed receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and comparison with models from prior research. Results: The ultimate prediction model was based on logistic regression and incorporated the following variables: regions of ischemic lesions, multiple vascular territories, hypertension, D-dimer, fibrinogen (FIB), and hemoglobin (Hb). The area under the ROC curve (AUC) for the nomogram was 0.871 in the training dataset and 0.834 in the external test dataset. Both calibration curves and DCA underscored the nomogram's strong performance. Conclusions: The nomogram enables early occult cancer diagnosis in hospitalized IS patients and helps to accurately identify the cause of IS, while the promotion of IS stratification makes personalized treatment feasible. The online nomogram based on routine clinical examination indicators of IS patients offered a cost-effective platform for secondary care in the framework of PPPM. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00354-8.

An Investigation into the Performance and Mechanisms of Soymilk-Sized Handmade Xuan Paper at Different Concentrations of Soymilk.

Invaluable paper relics that embody a rich traditional culture have suffered damage, requiring urgent restoration. In this context, the utilization of soymilk as a sizing agent holds great significance and reverence. This study investigates the use of soymilk as a sizing agent for Xuan paper and evaluates its effects on various properties and the long-term behavior of the paper. The findings reveal that the application of soymilk as a sizing agent for Xuan paper imparts distinct properties, including hydrophobicity, improved mechanical properties, and unique chromaticity. These characteristics-arising from the papillae on the surface of the Xuan paper, the protein folding of the soy protein, and hydrogen-bonding interactions between the soy protein and paper fibers-play a crucial role in shaping the paper's unique attributes. From a physicochemical perspective, the aging process leads to multiple changes in paper properties. These changes include acidification, which refers to a decrease in pH, as well as a decline in mechanical strength, an increase in chromaticity, and a decrease in the degree of polymerization (DP) of the paper. The Ekenstam equation is employed to predict the lifespan of the paper, showing longer lifespans for Sheng Xuan paper and a negative correlation between soymilk concentration and lifespan in soymilk-sized paper. Our work provides valuable insights for the preservation and maintenance of paper, highlighting the potential benefits and challenges of using soymilk for surface sizing.

Intense light unleashes male-male courtship behaviour in wild-type Drosophila.

Drosophila courtship studies have elucidated several principles of the neurogenetic organization of complex behaviour. Through an integration across sensory modalities, males perform stereotypic patterns of chasing, courtship song production and copulation attempts. Here we report a serendipitous finding that intense light not only enhances courtship toward female targets but also triggers unexpected courtship behaviours among male flies. Strikingly, in wild-type male-only chambers, we observed extreme behavioural manifestations, such as 'chaining' and 'wheeling', resembling previously reported male-male courtship behaviours in fruitless mutants and in transformants with ectopic mini-white+ overexpression. This male-male courtship was greatly diminished in a variety of visual system mutants, including disrupted phototransduction (norpA), eliminated eye-colour screening pigments (white), or deletion of the R7 photoreceptor cells (sevenless). However, light-induced courtship was unhampered in wing-cut flies, despite their inability to produce courtship song, a major acoustic signal during courtship. Unexpectedly the olfactory mutants orco and sbl displayed unrestrained male-male courtship. Particularly, orco males attained maximum courtship scores under either dim or intense light conditions. Together, our observations support the notion that the innate male courtship behaviour is restrained by olfactory cues under normal conditions but can be unleashed by strong visual stimulation in Drosophila.

Efficacy and Clinical Significance of the Zuogui Pill on Premature Ovarian Failure via the GDF-9/Smad2 Pathway.

Our study aims to investigate the efficacy and clinical significance of the Zuogui pill (ZGP) on premature ovarian failure (POF) via the GDF-9/Smad2 pathway. Changes in clinical symptoms in the control group (treated with Femoston alone) and the treatment group (treated with ZGP combined with Femoston) were assessed before and after treatment. Sex hormone levels, serum inflammatory cytokine levels, and ultrasound parameters were measured before and after treatment. POF rat models were established using cyclophosphamide and the POF rats were treated with Femoston, or ZGP combined with Femoston. GDF-9 and Smad2 expression levels were determined by RT-qPCR. The follicle-stimulating hormone (FSH), luteinizing hormone (LH), interleukin (IL)-6, and IL-21 levels, and the pulsatility index (PI) and resistance index (RI) values were decreased, while the estradiol (E2) and anti-Mullerian hormone (AMH) levels, antral follicle count (AFC), ovarian volume (OV), mean ovarian diameter (MOD), and peak systolic velocity (PSV) values were increased in the treatment group compared to the control group. After treatment with ZGP combined with Femoston, GDF-9 and Smad2 expression in the ovarian tissues of POF rats increased. ZGP has a therapeutic effect on POF via modulation of the GDF-9/Smad2 pathway.

Upconversion boosting pollutants degradation efficiency in wide-spectrum responsive photocatalysts.

Recently, the composite photocatalysts coupled with upconversion materials have received widespread attention due to higher utilization efficiency of solar energy in a wide-spectrum range. Novel heterojunction photocatalysts of CoWO4@NaYF4:Yb3+,Er3+ were designed and developed herein. The structural characterization, morphology and elemental composition analysis demonstrated that heterojunctions between CoWO4 and NaYF4:Yb3+,Er3+ were indeed formed in the composite photocatalysts. Moreover, CoWO4@NaYF4:Yb3+,Er3+ heterojunction photocatalysts exhibited higher pollutants degradation efficiency. Especially, a great enhancement of +87% on the photocatalytic activity was achieved in the heterojunction photocatalyst of 60CoWO4-NaYF4:Yb3+,Er3+ compared with pure CoWO4. The dominant radicals generated from the heterojunction photocatalysts were confirmed as the photo-generated holes (h+) and hydroxyl radicals (⋅OH) through the radical species trapping experiments and fluorescence detection, which is fully in line with the expected band structure characteristics of CoWO4. Eventually, an underlying mechanism was proposed that the enhanced photocatalytic activity should be attributed to the wide-spectrum responsive features of CoWO4@NaYF4:Yb3+,Er3+ heterojunction photocatalysts. Within the heterostructures, CoWO4 photocatalyst can absorb both the UV-Vis light due to its narrow bandgap and the Near-Infrared energy through the upconversion NaYF4:Yb3+,Er3+, thereby utilizing solar energy more efficiently in a wide-spectrum range for photocatalytic reactions.

Investigation on the efficiency of Brucea javanica oil emulsion injection with chemotherapy for treating malignant pleural effusion: A meta-analysis of randomized controlled trials.

Introduction: Systematic evaluation of the clinical efficacy and safety of Brucea javanica oil emulsion injection (BJOEI) in combination with chemotherapy in the treatment of malignant pleural effusion (MPE). Methods: The study searched CNKI, Wanfang database, VIP database, SinoMed, PubMed, Embase, the Cochrane Library, and the Web of Science database and retrieved randomized controlled trials (RCTs) on the treatment of MPE with BJOEI in combination with chemotherapy from seven electronic databases from inception to 31 March 2022. Meta-analysis and sensitivity analysis were performed using Revman 5.4 and Stata 13.0 software. Results: Ultimately, 30 RCTs with 2035 patients were included, including 1002 cases in the control group and 1033 cases in the treatment group. The results of the meta-analysis showed that the overall efficacy rate of BJOEI combined with chemotherapy was higher in the treatment of MPE compared with chemotherapy alone (RR = 1.45, 95%CI: 1.36-1.54, p < 0.00001). And it could improve the Karnofsky (KPS) score (RR = 1.54, 95%CI: 1.41-1.68, p < 0.00001), reduce adverse reactions such as fever (RR = 0.82, 95%CI:0.60-1.12), chest pain (RR = 0.90, 95%CI: 0.67-1.21), gastrointestinal reactions (RR = 0.70, 95%CI: 0.57-0.87, p < 0.005), and leukopenia (RR = 0.51, 95%CI: 0.43-0.61, p < 0.00001). Conclusion: BJOEI combined with chemotherapy has better clinical efficacy than chemotherapy alone in the treatment of MPE. It can further improve KPS score, improve patients' quality of life, and reduce the occurrence of adverse reactions. However, the conclusions of this study need to be confirmed by further randomized, double-blind, controlled trials with large sample size, reasonable design, and strict implementation.

Single-Cell and Bulk RNA Sequencing Reveal Malignant Epithelial Cell Heterogeneity and Prognosis Signatures in Gastric Carcinoma.

Gastric carcinoma (GC) heterogeneity represents a major barrier to accurate diagnosis and treatment. Here, we established a comprehensive single-cell transcriptional atlas to identify the cellular heterogeneity in malignant epithelial cells of GC using single-cell RNA sequencing (scRNA-seq). A total of 49,994 cells from nine patients with paired primary tumor and normal tissues were analyzed by multiple strategies. This study focused on the malignant epithelial cells, which were divided into three subtypes, including pit mucous cells, chief cells, and gastric and intestinal cells. The trajectory analysis results suggest that the differentiation of the three subtypes could be from the pit mucous cells to the chief cells and then to the gastric and intestinal cells. Lauren's histopathology of GC might originate from various subtypes of malignant epithelial cells. The functional enrichment analysis results show that the three subtypes focused on different biological processes (BP) and pathways related to tumor development. In addition, we generated and validated the prognostic signatures for predicting the OS in GC patients by combining the scRNA-seq and bulk RNA sequencing (bulk RNA-seq) datasets. Overall, our study provides a resource for understanding the heterogeneity of GC that will contribute to accurate diagnosis and prognosis.

Abnormal larval neuromuscular junction morphology and physiology in Drosophila prickle isoform mutants with known axonal transport defects and adult seizure behavior.

Previous studies have demonstrated the striking mutational effects of the Drosophila planar cell polarity gene prickle (pk) on larval motor axon microtubule-mediated vesicular transport and on adult epileptic behavior associated with neuronal circuit hyperexcitability. Mutant alleles of the prickle-prickle (pkpk) and prickle-spiny-legs (pksple) isoforms (hereafter referred to as pk and sple alleles, respectively) exhibit differential phenotypes. While both pk and sple affect larval motor axon transport, only sple confers motor circuit and behavior hyperexcitability. However, mutations in the two isoforms apparently counteract to ameliorate adult motor circuit and behavioral hyperexcitability in heteroallelic pkpk/pksple flies. We have further investigated the consequences of altered axonal transport in the development and function of the larval neuromuscular junction (NMJ). We uncovered robust dominant phenotypes in both pk and sple alleles, including synaptic terminal overgrowth (as revealed by anti-HRP and -Dlg immunostaining) and poor vesicle release synchronicity (as indicated by synaptic bouton focal recording). However, we observed recessive alteration of synaptic transmission only in pk/pk larvae, i.e. increased excitatory junctional potential (EJP) amplitude in pk/pk but not in pk/+ or sple/sple. Interestingly, for motor terminal excitability sustained by presynaptic Ca2+ channels, both pk and sple exerted strong effects to produce prolonged depolarization. Notably, only sple acted dominantly whereas pk/+ appeared normal, but was able to suppress the sple phenotypes, i.e. pk/sple appeared normal. Our observations contrast the differential roles of the pk and sple isoforms and highlight their distinct, variable phenotypic expression in the various structural and functional aspects of the larval NMJ.

Drosophila carrying epilepsy-associated variants in the vitamin B6 metabolism gene PNPO display allele- and diet-dependent phenotypes.

Pyridox(am)ine 5 ' -phosphate oxidase (PNPO) catalyzes the rate-limiting step in the synthesis of pyridoxal 5 ' -phosphate (PLP), the active form of vitamin B6 required for the synthesis of neurotransmitters gamma-aminobutyric acid (GABA) and the monoamines. Pathogenic variants in PNPO have been increasingly identified in patients with neonatal epileptic encephalopathy and early-onset epilepsy. These patients often exhibit different types of seizures and variable comorbidities. Recently, the PNPO gene has also been implicated in epilepsy in adults. It is unclear how these phenotypic variations are linked to specific PNPO alleles and to what degree diet can modify their expression. Using CRISPR-Cas9, we generated four knock-in Drosophila alleles, hWT , hR116Q , hD33V , and hR95H , in which the endogenous Drosophila PNPO was replaced by wild-type human PNPO complementary DNA (cDNA) and three epilepsy-associated variants. We found that these knock-in flies exhibited a wide range of phenotypes, including developmental impairments, abnormal locomotor activities, spontaneous seizures, and shortened life span. These phenotypes are allele dependent, varying with the known biochemical severity of these mutations and our characterized molecular defects. We also showed that diet treatments further diversified the phenotypes among alleles, and PLP supplementation at larval and adult stages prevented developmental impairments and seizures in adult flies, respectively. Furthermore, we found that hR95H had a significant dominant-negative effect, rendering heterozygous flies susceptible to seizures and premature death. Together, these results provide biological bases for the various phenotypes resulting from multifunction of PNPO, specific molecular and/or genetic properties of each PNPO variant, and differential allele-diet interactions.

Distinct Aging-Vulnerable and -Resilient Trajectories of Specific Motor Circuit Functions in Oxidation- and Temperature-Stressed Drosophila.

In Drosophila, molecular pathways affecting longevity have been extensively studied. However, corresponding neurophysiological changes underlying aging-related functional and behavioral deteriorations remain to be fully explored. We examined different motor circuits in Drosophila across the life span and uncovered distinctive age-resilient and age-vulnerable trajectories in their established functional properties. In the giant fiber (GF) and downstream circuit elements responsible for the jump-and-flight escape reflex, we observed relatively mild deterioration toward the end of the life span. In contrast, more substantial age-dependent modifications were seen in the plasticity of GF afferent processing, specifically in use dependence and habituation properties. In addition, there were profound changes in different afferent circuits that drive flight motoneuron activities, including flight pattern generation and seizure spike discharges evoked by electroconvulsive stimulation. Importantly, in high-temperature (HT)-reared flies (29°C), the general trends in these age-dependent trajectories were largely maintained, albeit over a compressed time scale, lending support for the common practice of HT rearing for expediting Drosophila aging studies. We discovered that shortened life spans in Cu/Zn superoxide dismutase (Sod) mutant flies were accompanied by altered aging trajectories in motor circuit properties distinct from those in HT-reared flies, highlighting differential effects of oxidative versus temperature stressors. This work helps to identify several age-vulnerable neurophysiological parameters that may serve as quantitative indicators for assessing genetic and environmental influences on aging progression in Drosophila.

Clinical Efficacy and Safety Study of Mifepristone with Misoprostol Treatment in Patients with Missed Abortion.

Currently, medication abortion is widely used in clinical practice in China. The aim of this study was to investigate the effect of mifepristone with misoprostol treatment on the efficacy of patients with missed abortion (MA) and the safety of this drug regimen. 95 patients with MA treated in our hospital from February 2019 to April 2021 were collected as the subjects of this study, and the patients were divided into the control and the research groups according to different treatment modalities. Among them, 46 cases in the control group were treated by diethylstilbestrol combined with oxytocin and 49 cases in the research group were treated by mifepristone combined with misoprostol, and both groups underwent curettage after medication. The rates of complete abortion, time of embryo expulsion, time of operation, intraoperative bleeding, time of postoperative vaginal bleeding, amount of vaginal bleeding, rate of one-time curettage, the levels of serum estradiol (E2), progesterone (P), ß-chorionic gonadotropin (ß-hCG), and interleukin-18 (IL-18), and the incidence of adverse effects in the two groups were examined and compared. Alanine transaminase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and serum creatinine (Scr) were used as indicators to evaluate the safety of the drug. The results showed that the rates of complete abortion and one-time curettage were significantly higher in the study group than in the control group, while the time of embryo expulsion, operation time, intraoperative bleeding, postoperative vaginal bleeding time, and vaginal bleeding were significantly lower than in the control group. The serum E2, P, and ß-hCG levels before curettage in both groups were significantly higher, and IL-18 levels were significantly lower than those at the time of admission, with E2, P, and ß-hCG levels increasing more and IL-18 levels decreasing more in the research group. After drug treatment, no abnormal changes in liver and kidney functions were observed in both groups, and the incidence of adverse reactions was at a similar and lower level in both groups. This shows that mifepristone with misoprostol is a safer and more effective drug regimen for the treatment of MA, which can regulate the levels of serum sex hormones and inflammatory factors in the body, promote the shedding of placental tissue, and create conditions for improving the rate of curettage.

Fly seizure EEG: field potential activity in the Drosophila brain.

Hypersynchronous neural activity is a characteristic feature of seizures. Although many Drosophila mutants of epilepsy-related genes display clear behavioral spasms and motor unit hyperexcitability, field potential measurements of aberrant hypersynchronous activity across brain regions during seizures have yet to be described. Here, we report a straightforward method to observe local field potentials (LFPs) from the Drosophila brain to monitor ensemble neural activity during seizures in behaving tethered flies. High frequency stimulation across the brain reliably triggers a stereotypic sequence of electroconvulsive seizure (ECS) spike discharges readily detectable in the dorsal longitudinal muscle (DLM) and coupled with behavioral spasms. During seizure episodes, the LFP signal displayed characteristic large-amplitude oscillations with a stereotypic temporal correlation to DLM flight muscle spiking. ECS-related LFP events were clearly distinct from rest- and flight-associated LFP patterns. We further characterized the LFP activity during different types of seizures originating from genetic and pharmacological manipulations. In the 'bang-sensitive' sodium channel mutant bangsenseless (bss), the LFP pattern was prolonged, and the temporal correlation between LFP oscillations and DLM discharges was altered. Following administration of the pro-convulsant GABAA blocker picrotoxin, we uncovered a qualitatively different LFP activity pattern, which consisted of a slow (1-Hz), repetitive, waveform, closely coupled with DLM bursting and behavioral spasms. Our approach to record brain LFPs presents an initial framework for electrophysiological analysis of the complex brain-wide activity patterns in the large collection of Drosophila excitability mutants.

Differential effects on neuromuscular physiology between Sod1 loss-of-function mutation and paraquat-induced oxidative stress in Drosophila.

Oxidative stress is thought to be a major contributor to aging processes. Here, we report differential effects on neurotransmission caused by loss-of-function mutations of Superoxide dismutase 1 (Sod1) and by paraquat (PQ) feeding in Drosophila. We demonstrated alterations in Sod1 mutants; the larval neuromuscular junction displayed supernumerary discharges and the adult giant-fiber escape pathway showed increased latency and poor response to repetitive high-frequency stimulation. Even though the concentrations used led to motor coordination defects and lethality, PQ feeding failed to reproduce such performance deficits in these larval and adult preparations, indicating mechanistic distinctions between these genetic and pharmacological manipulations of oxidative stress.

Influence of the type of carrier on ferromagnetism in a Si semiconductor implanted with Cu ions.

Silicon semiconductor samples implanted with Cu ions and samples co-implanted with Cu- and N-ions were prepared by MEVVA and the Kaufman technique. None of the samples showed evidence of secondary phases. The initially n-type Si matrix, when implanted with Cu ions, changed to a p-type semiconductor, and the Cu ions existed as local Cu2+ cations in the p-type environment. As a result, none of the Cu-implanted samples were ferromagnetic at room temperature. The co-implanted samples, on the other hand, showed room-temperature ferromagnetism because the introduction of N ions made the carrier type change from p-type to n-type which is favorable for the appearance of Cu2+. First principles calculations were applied to understand the experimental phenomena. The formation energy was reduced by implanting N ions, and was decreased effectively with the increase in ratio of N to Cu ions. The density of states and spin density of states indicated that the hybridization of s, p and d electrons induced ferromagnetism at 0 K. Particularly, we proposed possible exchange interactions between the Cu2+-N-(N4+)-Cu2+ ions to explain the ferromagnetism mechanism.

Correction to: Competitive sequestration of Ni(II) and Eu(III) on montmorillonite: role of molar Ni:Eu ratios and coexisting oxalate.

In the original publication Fig. 10b was erroneously plotted due to the authors' carelessness and unintentional misoperation.