Towards accurate abdominal tumor segmentation: A 2D model with Position-Aware and Key Slice Feature Sharing.

Abdominal tumor segmentation is a crucial yet challenging step during the screening and diagnosis of tumors. While 3D segmentation models provide powerful performance, they demand substantial computational resources. Additionally, in 3D data, tumors often represent a small portion, leading to imbalanced data and potentially overlooking crucial information. Conversely, 2D segmentation models have a lightweight structure, but disregard the inter-slice correlation, risking the loss of tumor in edge slices. To address these challenges, this paper proposes a novel Position-Aware and Key Slice Feature Sharing 2D tumor segmentation model (PAKS-Net). Leveraging the Swin-Transformer, we effectively model the global features within each slice, facilitating essential information extraction. Furthermore, we introduce a Position-Aware module to capture the spatial relationship between tumors and their corresponding organs, mitigating noise and interference from surrounding organ tissues. To enhance the edge slice segmentation accuracy, we employ key slices to assist in the segmentation of other slices to prioritize tumor regions. Through extensive experiments on three abdominal tumor segmentation CT datasets and a lung tumor segmentation CT dataset, PAKS-Net demonstrates superior performance, reaching 0.893, 0.769, 0.598 and 0.738 tumor DSC on the KiTS19, LiTS17, pancreas and LOTUS datasets, surpassing 3D segmentation models, while remaining computationally efficient with fewer parameters.

PEX3 promotes regenerative repair after myocardial injury in mice through facilitating plasma membrane localization of ITGB3.

The peroxisome is a versatile organelle that performs diverse metabolic functions. PEX3, a critical regulator of the peroxisome, participates in various biological processes associated with the peroxisome. Whether PEX3 is involved in peroxisome-related redox homeostasis and myocardial regenerative repair remains elusive. We investigate that cardiomyocyte-specific PEX3 knockout (Pex3-KO) results in an imbalance of redox homeostasis and disrupts the endogenous proliferation/development at different times and spatial locations. Using Pex3-KO mice and myocardium-targeted intervention approaches, the effects of PEX3 on myocardial regenerative repair during both physiological and pathological stages are explored. Mechanistically, lipid metabolomics reveals that PEX3 promotes myocardial regenerative repair by affecting plasmalogen metabolism. Further, we find that PEX3-regulated plasmalogen activates the AKT/GSK3ß signaling pathway via the plasma membrane localization of ITGB3. Our study indicates that PEX3 may represent a novel therapeutic target for myocardial regenerative repair following injury.

Parasitic behavior and developmental morphology of Mesocomys trabalae (Hymenoptera: Eupelmidae), a promising parasitoid of the Japanese giant silkworm Caligula japonica (Lepidoptera: Saturniidae).

The egg parasitoid Mesocomys trabalae Yao, Yang, and Zhao is used as a biocontrol agent against the emerging defoliator pest Caligula japonica Moore in East Asia. It has been proven that the eggs of Antheraea pernyi Guérin-Méneville can be used as a factitious host for the mass production of M. trabalae. We examined the parasitic behavior and morphological characteristics of the developmental stages of M. trabalae reared on A. pernyi eggs. The parasitic behavior of M. trabalae encompasses 10 steps, involving searching, antennation, locating the oviposition site, drilling, probing, detecting, oviposition, host feeding, grooming, and resting, with the oviposition step further divided into 3 stages. We determined that the parasitoid released an egg during the second stage of the oviposition step, while her body remained in a relatively static state. Among all the steps in parasitic behavior, probing occupied the longest time, accounting for 26.33% of the entire parasitism process. It was followed by oviposition (15.88%), drilling (15.10%), antennation (13.09%), detecting (10.79%), host feeding (10.02%), and the remaining steps, each occupying less than 5.00% of the total time in steps. The pre-emergence of adult M. trabalae comprised of 4 stages: egg (0-1 day), larva (2-6 days), prepupa (7-11 days), pupa (12-20 days), followed by the development into an adult, and it usually took 20-22 days to develop from an egg into an adult at 25°C. This study advances our understanding of the biology of Mesocomys parasitoids and their mass-rearing for use in augmentation programs.

Checkpoint Kinase 1 Stimulates Endogenous Cardiomyocyte Renewal and Cardiac Repair by Binding to Pyruvate Kinase Isoform M2 C-Domain and Activating Cardiac Metabolic Reprogramming in a Porcine Model of Myocardial Ischemia/Reperfusion Injury.

BACKGROUND: The regenerative capacity of the adult mammalian hearts is limited. Numerous studies have explored mechanisms of adult cardiomyocyte cell-cycle withdrawal. This translational study evaluated the effects and underlying mechanism of rhCHK1 (recombinant human checkpoint kinase 1) on the survival and proliferation of cardiomyocyte and myocardial repair after ischemia/reperfusion injury in swine. METHODS AND RESULTS: Intramyocardial injection of rhCHK1 protein (1 mg/kg) encapsulated in hydrogel stimulated cardiomyocyte proliferation and reduced cardiac inflammation response at 3 days after ischemia/reperfusion injury, improved cardiac function and attenuated ventricular remodeling, and reduced the infarct area at 28 days after ischemia/reperfusion injury. Mechanistically, multiomics sequencing analysis demonstrated enrichment of glycolysis and mTOR (mammalian target of rapamycin) pathways after rhCHK1 treatment. Co-Immunoprecipitation (Co-IP) experiments and protein docking prediction showed that CHK1 (checkpoint kinase 1) directly bound to and activated the Serine 37 (S37) and Tyrosine 105 (Y105) sites of PKM2 (pyruvate kinase isoform M2) to promote metabolic reprogramming. We further constructed plasmids that knocked out different CHK1 and PKM2 amino acid domains and transfected them into Human Embryonic Kidney 293T (HEK293T) cells for CO-IP experiments. Results showed that the 1-265 domain of CHK1 directly binds to the 157-400 amino acids of PKM2. Furthermore, hiPSC-CM (human iPS cell-derived cardiomyocyte) in vitro and in vivo experiments both demonstrated that CHK1 stimulated cardiomyocytes renewal and cardiac repair by activating PKM2 C-domain-mediated cardiac metabolic reprogramming. CONCLUSIONS: This study demonstrates that the 1-265 amino acid domain of CHK1 binds to the 157-400 domain of PKM2 and activates PKM2-mediated metabolic reprogramming to promote cardiomyocyte proliferation and myocardial repair after ischemia/reperfusion injury in adult pigs.

Symptom-to-balloon time and risk of ventricular arrhythmias in patients with STEMI undergoing percutaneous coronary intervention: The VERY-STEMI study.

Background: Ventricular arrhythmias (VAs) mainly occur in the early post-myocardial infarction (MI) period. However, studies examining the association between total myocardial ischemia time interval and the risk of new-onset VAs during a long-term follow-up are scarce. Methods: This study (symptom-to-balloon time and VEntricular aRrhYthmias in patients with STEMI, VERY-STEMI study) was a multicenter, observational cohort and real-world study, which included patients with ST-segment elevation MI (STEMI) undergoing percutaneous coronary intervention (PCI). The primary endpoint was cumulative new-onset VAs during follow-up. The secondary endpoints were the major adverse cardiovascular events (MACE) and changes in left ventricular ejection fraction (ΔLVEF, %). Results: A total of 517 patients with STEMI were included and 236 primary endpoint events occurred. After multivariable adjustments, compared to patients with S2BT of 24 h-7d, those with S2BT ≤ 24 h and S2BT > 7d had a lower risk of primary endpoint. RCS showed an inverted U-shaped relationship between S2BT and the primary endpoint, with an S2BT of 68.4 h at the inflection point. Patients with S2BT ≤ 24 h were associated with a lower risk of MACE and a 4.44 increase in LVEF, while there was no significant difference in MACE and LVEF change between the S2BT > 7d group and S2BT of 24 h-7d group. Conclusions: S2BT of 24 h-7d in STEMI patients was associated with a higher risk of VAs during follow-up. There was an inverted U-shaped relationship between S2BT and VAs, with the highest risk at an S2BT of 68.4 h.

Multimodal neuroimaging network associated with executive function in adolescent major depressive disorder patients via cognition-guided magnetic resonance imaging fusion.

Adolescents are high-risk population for major depressive disorder. Executive dysfunction emerges as a common feature of depression and exerts a significant influence on the social functionality of adolescents. This study aimed to identify the multimodal co-varying brain network related to executive function in adolescent with major depressive disorder. A total of 24 adolescent major depressive disorder patients and 43 healthy controls were included and completed the Intra-Extra Dimensional Set Shift Task. Multimodal neuroimaging data, including the amplitude of low-frequency fluctuations from resting-state functional magnetic resonance imaging and gray matter volume from structural magnetic resonance imaging, were combined with executive function using a supervised fusion method named multimodal canonical correlation analysis with reference plus joint independent component analysis. The major depressive disorder showed more total errors than the healthy controls in the Intra-Extra Dimensional Set Shift task. Their performance on the Intra-Extra Dimensional Set Shift Task was negatively related to the 14-item Hamilton Rating Scale for Anxiety score. We discovered an executive function-related multimodal fronto-occipito-temporal network with lower amplitude of low-frequency fluctuation and gray matter volume loadings in major depressive disorder. The gray matter component of the identified network was negatively related to errors made in Intra-Extra Dimensional Set Shift while positively related to stages completed. These findings may help to deepen our understanding of the pathophysiological mechanisms of cognitive dysfunction in adolescent depression.

Neoseiulus mites as biological control agents against Megalurothrips usitatus (Thysanoptera: Thripidae) and Frankliniella intonsa (Thysanoptera: Thripidae) on cowpea crop: laboratory to field.

Megalurothrips usitatus (Bagnall) (Thysanoptera: Thripidae) and Frankliniella intonsa (Trybom) (Thysanoptera: Thripidae) have been detrimental to cowpea production in many countries. Laboratory experiments were conducted to determine the prey stage preference and functional response of 2 predatory mites species, Neoseiulus barkeri (Hughes) (Acari: Phytoseiidae), and Neoseiulus californicus (McGregor) (Acari: Phytoseiidae), towards 2 thrips species (TS), M. usitatus, and F. intonsa, at varying densities and life stages on cowpea. Results shown that Neoseiulus species had a preference for different life stages of prey. Neoseiulus barkeri consumed more M. usitatus nymphs, while N. californicus consumed more F. intonsa (second-instar nymphs). The functional response of the 2 Neoseiulus spp. to nymphs of 2 TS was Type II on cowpea. The higher attack rate coefficient (a') and shorter handling time (Th) values were found on N. barkeri against M. usitatus, and a similar trend was found for those in N. californicus against F. intonsa. Field-caged trials were conducted to evaluate the effectiveness of Neoseiulus spp. in controlling 2 TS. The results have shown that Neoseiulus spp. was effective in controlling the 2 TS, with varying control efficacies at high or low release rates. The study provided valuable information on using Neoseiulus spp. as biological control agents against M. usitatus and F. intonsa in cowpea crops.

Associations between interleukin-13, interleukin-4 and their receptor gene polymorphisms and susceptibility to atopic dermatitis in a Chinese Han population.

Background Atopic dermatitis (AD) is a common skin condition that occurs due to a combined effect of immune dysregulation, skin barrier dysfunction, changes in the cutaneous microbiome, and genetic factors. Recent data from both clinical trials and real-world studies indicate that dupilumab, a biological agent that inhibits interleukin 4 receptor-α is an effective drug in the treatment of AD, which further suggests the important role of IL-13 and IL-4 in the pathogenesis of AD. Objectives To assess the association between gene polymorphisms of IL-13, IL-13 receptor, IL-4, and IL-4 receptor and susceptibility to AD. Methods The single nucleotide polymorphisms (SNPs) of the above-mentioned genes were detected by single base extension (SNaPshot) assay. The association between these SNPs and AD risk was analysed using SPSS software. Results Two hundred and seventy-one subjects including 130 patients with AD and 141 healthy controls were enrolled. There were statistical differences between AD patients and controls in genotype distribution at rs2265753, rs6646259, and rs2254672 of the IL-13 receptor gene (P all < 0.001). Subjects with CG at rs2265753, AG at rs6646259 and TG at rs2254672 had increased risks for AD (P all < 0.001), and subjects with GG at rs2265753, rs6646259, and rs2254672 had reduced risks for AD (P all < 0.001). Limitation This was a single-centre and single-race study, with a relatively small sample size. Conclusions Findings from this study show that rs2265753, rs6646259 and rs2254672 of the IL-13 receptor gene are associated with susceptibility to AD.

Light intensity differentially mediates the life cycle of lepidopteran leaf feeders and stem borers.

BACKGROUND: Leaf feeders, such as Spodoptera frugiperda and Spodoptera litura, and stem borers Ostrinia furnacalis and Chilo suppressalis, occupy two different niches and are well adapted to their particular environments. Borer larvae burrow and inhabit the interior of stems, which are relatively dark. By contrast, the larvae of leaf feeders are exposed to sunlight during feeding. We therefore designed series of experiments to evaluate the effect of light intensity (0, 2000, and 10 000 lx) on these pests with different feeding modes. RESULTS: The development of all four pests was significantly delayed at 0 lx. Importantly, light intensity affected the development of both male and female larvae of borers, but only significantly affected male larvae of leaf feeders. Furthermore, the proportion of female offspring of leaf feeders increased with increasing light intensity (S. frugiperda: 33.89%, 42.26%, 57.41%; S. litura: 38.90%, 51.75%, 65.08%), but no significant differences were found in stem borers. This research also revealed that the survival rate of female leaf feeders did not vary across light intensities, but that of males decreased with increasing light intensity (S. frugiperda: 97.78%, 85.86%, 61.21%; S. litura: 95.83%, 73.54%, 58.99%). CONCLUSION: These results improve our understanding of how light intensity affects sex differences in important lepidopteran pests occupying different feeding niches and their ecological interactions with abiotic factors in agroecosystems. © 2024 Society of Chemical Industry.

Progress of Mitochondrial Function Regulation in Cardiac Regeneration.

Heart failure and myocardial infarction, global health concerns, stem from limited cardiac regeneration post-injury. Myocardial infarction, typically caused by coronary artery blockage, leads to cardiac muscle cell damage, progressing to heart failure. Addressing the adult heart's minimal self-repair capability is crucial, highlighting cardiac regeneration research's importance. Studies reveal a metabolic shift from anaerobic glycolysis to oxidative phosphorylation in neonates as a key factor in impaired cardiac regeneration, with mitochondria being central. The heart's high energy demands rely on a robust mitochondrial network, essential for cellular energy, cardiac health, and regenerative capacity. Mitochondria's influence extends to redox balance regulation, signaling molecule interactions, and apoptosis. Changes in mitochondrial morphology and quantity also impact cardiac cell regeneration. This article reviews mitochondria's multifaceted role in cardiac regeneration, particularly in myocardial infarction and heart failure models. Understanding mitochondrial function in cardiac regeneration aims to enhance myocardial infarction and heart failure treatment methods and insights.

[Clinical study on the treatment of postoperative recurrence of lumbar disc herniation with intervertebral fusion].

OBJECTIVE: To explore clinical effect of different intervertebral fusion devices (cage) in treating postoperative recurrent lumbar disc herniation (LDH). METHODS: One hundred and forty-two LDH patients with recurrence after simple intervertebral disc nucleus pulpoideectomy from January 2019 to January 2021 were retrospectively analyzed. All patients were treated with combined underchannel fixation and interbody fusion and divided into a single anatomical group,two-anatomical group and a single banana group according to types and numbers of implanted cage. There were 51 patients in a single anatomical group,included 29 males and 22 females,aged from 39 to 65 years old with an average of (53.74±5.68) years old;body mass index (BMI) ranged from 18.62 to 28.13 kg·m-2 with an average of (22.08±2.15) kg·m-2;the interval between operation and recurrence ranged from 0.5 to 4.0 years with an average of (2.7±0.8) years;5 patients with L3,4,35 patients with L4,5 and 11 patients with L5S1;a single anatomical cage was implanted. There were 46 patients in two-anatomical group,included 25 males and 21 females,aged from 37 to 66 years old with an average of (54.52±6.02) years old;BMI ranged from 18.25 to 28.44 kg·m-2 with an average of (21.74±1.83) kg·m-2;the interval between operation and recurrence ranged from 0.5 to 5.0 years with an average of (2.7±0.9) years;4 patients with L3,4,32 patients with L4,5 and 10 patients with L5S1;two-anatomical cages were implanted. There were 45 patients in a single banana group,included 22 males and 23 females,aged from 38 to 65 years old with an average of (54.49±6.45) years old;BMI ranged from 18.85 to 28.20 kg·m-2 with an average of (21.63±1.59) kg·m-2;the interval between operation and recurrence ranged from 0.5 to 5.0 years with an average of (2.6±1.0) years;3 patients with L3,4,36 patients with L4,5 and 16 patients with L5S1;a single banana cage was implanted. Operation time,intraoperative blood loss,incision length,postoperative incision drainage volume,hospital stay and complications among 3 groups were observed and compared. The height of intervertebral space before and after operation,curvature of lordosis and the postoperative intervertebral fusion were compared. Visual analogue scale (VAS) and Oswestry disability index (ODI) were used to evaluate degree of lumbar pain and lumbar function before operation,1 and 6 months after operation,respectively. RESULTS: All patients among 3 groups were followed up at least 6 months,and no cases were fell out. There were no significant difference in operation time,intraoperative blood loss,incision length,postoperative incision drainage volume and hospital stay among 3 groups (P>0.05). At 6 months after operation,the height of intervertebral space in two-anatomical group and a single group were [(11.08±1.78) mm,(10.95±1.62) mm],curvature of lordosis were [(12.05±1.86) °,(11.63±1.57) °],which were higher than those in a single dissection group (10.14±1.54) mm,(10.92±1.45) °,and the difference were statistically significant (P<0.05). The interbody fusion rate between two-anatomical and a banana group (95.65%,95.56%) were higher than that in a single anatomical group (78.43%) at 6 months after operation (P<0.05). VAS and ODI of lumbar among 3 groups were decreased at 1 and 6 months after operation (P<0.05). There was no significant difference in complications among 3 groups (P>0.05). CONCLUSION: The three fusion devices could achieve significant results in treating postoperative recurrence of LDH,but the implantation of two-anatomical cage and a single banana cage are more helpful to maintain the height of intervertebral space and lordosis curvature of patients with postoperative recurrence of LDH,and obtain good intervertebral fusion results.

Mutual learning with reliable pseudo label for semi-supervised medical image segmentation.

Semi-supervised learning has garnered significant interest as a method to alleviate the burden of data annotation. Recently, semi-supervised medical image segmentation has garnered significant interest that can alleviate the burden of densely annotated data. Substantial advancements have been achieved by integrating consistency-regularization and pseudo-labeling techniques. The quality of the pseudo-labels is crucial in this regard. Unreliable pseudo-labeling can result in the introduction of noise, leading the model to converge to suboptimal solutions. To address this issue, we propose learning from reliable pseudo-labels. In this paper, we tackle two critical questions in learning from reliable pseudo-labels: which pseudo-labels are reliable and how reliable are they? Specifically, we conduct a comparative analysis of two subnetworks to address both challenges. Initially, we compare the prediction confidence of the two subnetworks. A higher confidence score indicates a more reliable pseudo-label. Subsequently, we utilize intra-class similarity to assess the reliability of the pseudo-labels to address the second challenge. The greater the intra-class similarity of the predicted classes, the more reliable the pseudo-label. The subnetwork selectively incorporates knowledge imparted by the other subnetwork model, contingent on the reliability of the pseudo labels. By reducing the introduction of noise from unreliable pseudo-labels, we are able to improve the performance of segmentation. To demonstrate the superiority of our approach, we conducted an extensive set of experiments on three datasets: Left Atrium, Pancreas-CT and Brats-2019. The experimental results demonstrate that our approach achieves state-of-the-art performance. Code is available at: https://github.com/Jiawei0o0/mutual-learning-with-reliable-pseudo-labels.

Development and validation of a deep-learning model for the detection of non-displaced femoral neck fractures with anteroposterior and lateral hip radiographs.

Background: Hip fractures, including femoral neck fractures, are a significant cause of morbidity and mortality in the elderly population and are typically diagnosed using plain radiography. However, diagnosing non-displaced femoral neck fractures can be challenging due to their subtle appearance on hip radiographs. Previous deep-learning models have shown low accuracy in identifying these fractures on anteroposterior (AP) radiographs; however, no studies have used lateral radiographs. This study aimed to evaluate the potential of using deep-learning with both AP and lateral hip radiographs to automatically identify non-displaced femoral neck fractures. Methods: We conducted a retrospective analysis of patients with femoral neck fractures at The First Affiliated Hospital of Xiamen University. All the hip radiographs were reviewed, and cases of non-displaced femoral neck fractures were included in the study. Additionally, 439 participants with normal hip radiographs were also included in the study. A vision transformer (Vit) model was developed using 1,536 AP and lateral hip radiograph. The model's performance was compared to the performance of two groups of human observers: an expert group comprising orthopedic surgeons and radiologists, and a non-expert group, including emergency physicians and general practice doctors. We also carried out the external validation using two additional data sets to assess the generalizability of the model. Results: The Vit model showed exceptional performance in detecting non-displaced femoral neck fractures on paired AP and lateral hip radiographs, achieving a binary accuracy of 95.8% [95% confidence interval (CI): 94.9%, 96.8%] and an area under the curve (AUC) of 0.988. Compared to the human observers, the model had a higher accuracy of 96.7% (95% CI: 93.9%, 99.5%) on the paired AP and lateral hip radiographs, while the accuracy of the expert group was 90.5% (95% CI: 85.7%, 95.2%). Further, the model maintained good performance during the external validation, with an AUC of 0.959 on the paired AP and lateral views. Conclusions: Our Vit model showed expert-level performance in identifying non-displaced femoral neck fractures on paired AP and lateral hip radiographs. This model has the potential to enhance diagnosis accuracy and improve patient outcomes by reducing the need for additional examinations and preoperative time.

Ontogenetic morphological changes of the venom apparatus in 4 eupelmid egg parasitoids.

Parasitoid wasps, notably egg parasitoids of the family Eupelmidae (Hymenoptera: Chalcidoidea), a key natural enemy of insect pests, offer a sustainable approach to pest management in agriculture. This study investigated the venom apparatus's developmental dynamics across 4 species of eupelmid egg parasitoids: Anastatus. japonicus, Anastatus fulloi, Mesocomys trabalae and Mesocomys albitarsis. A comprehensive anatomical investigation revealed differences in the dimensions of the venom apparatus across different developmental stages in adult females. We found that the venom apparatus of these 4 studied species consists of a venom gland and a reservoir with an associated Dufour's gland. As the length of post-emergence increases, a significant enlargement in the venom apparatus is evident across all the studied parasitoid species. Notably, M. albitarsis consistently exhibites the shortest venom gland length, whereas that of A. fulloi is the longest among the observed species. At the high day age, the width of venom glands of the 2 Mesocomys species surpasses those of the Anastatus species; for the volume of the venom reservoir, there is a steady increase in all 4 species before the age of 6­7 days, with a decline on 8th day, especially for A. japonicus. This research provided new insights into the developmental trajectories of venom apparatus in eupelmid egg parasitoids and the potential impact of venom potency on their success.

2023: A year of accomplishments for the 13 Science Citation Index Expanded- and Emerging Sources Citation Index-indexed Baishideng journals.

In 2023, Baishideng Publishing Group (Baishideng) routinely published 47 open-access journals, including 46 English-language journals and 1 Chinese-language journal. Our successes were accomplished through the collective dedicated efforts of Baishideng staffs, Editorial Board Members, and Peer Reviewers. Among these 47 Baishideng journals, 7 are included in the Science Citation Index Expanded (SCIE) and 6 in the Emerging Sources Citation Index (ESCI). With the support of Baishideng authors, company staffs, Editorial Board Members, and Peer Reviewers, the publication work of 2023 is about to be successfully completed. This editorial summarizes the 2023 activities and accomplishments of the 13 SCIE- and ESCI-indexed Baishideng journals, outlines the Baishideng publishing policy changes and additions made this year, and highlights the unique advantages of Baishideng journals.

Transgenerational hormesis and sublethal effects of five key insecticides for controlling Spodoptera frugiperda on its endoparasitoid Cotesia marginiventris.

BACKGROUND: The endoparasitoid Cotesia marginiventris (Cresson) is a promising biological control agent of the fall armyworm (FAW) Spodoptera frugiperda (Smith). Because the application of insecticides is one of the prime choices in pest management, we evaluated the sublethal and transgenerational effects of the five key insecticides-chlorantraniliprole, emamectin benzoate, spinetoram, Bacillus thuringiensis (Bt), and Mamestra brassicae nucleopolyhedrovirus (MbNPV)-on the parasitoid. RESULTS: Exposure to five insecticides at a concentration causing 10% mortality (LC10 ) caused hormetic effects in the parent generation (F0 ) by increasing the parasitism and reducing the immature duration. Interestingly, the hormetic response was also observed in the offspring generation indirectly exposed to the insecticides. Furthermore, insecticides increased the parasitism rate by 6.32-14.73% in the F1 generation, which was similar to that of the F0 generation (3.96-11.81%) compared with the control. No significant adverse effect was observed on the number of emerged parasitoids of the F1 and F2 generations. However, insecticides had a detrimental impact on body size and fecundity in the F1 and F2 generations, which showed a small body size with shorter hind tibiae and a significant reduction in the female ratio compared with the control; the exception was that chlorantraniliprole significantly improved the female ratio in the F2 generation. CONCLUSIONS: Five insecticides at LC10 induced transgenerational hormetic and sublethal effects on C. marginiventris. Our results provide a scientific basis for a better understanding of the long-term impacts of insecticides at sublethal doses on parasitoids, facilitating the development of improved integrated pest management programs for FAW control. © 2023 Society of Chemical Industry.

Differential effects of sleep deprivation on behavior and microglia in a brain-region-specific manner in young and aged male mice.

Microglia, resident immune cells in the central nervous system, constantly monitor the state of the surrounding brain activity. The animal model induced by sleep deprivation (SD) is widely used to study the pathophysiological mechanisms of insomnia and bipolar disorder. However, it remains unclear whether SD affects behaviors in young and aged male mice and microglia in various brain regions. In this study, we confirmed brain region-specific changes in microglial density and morphology in the accumbens nucleus (Acb), amygdala (AMY), cerebellum (Cb), corpus callosum (cc), caudate putamen, hippocampus (HIP), hypothalamus (HYP), medial prefrontal cortex (mPFC), and thalamus (TH) of young mice. In addition, the density of microglia in old mice was higher than that in young mice. Compared with young mice, old mice showed a markedly increased microglial size, decreased total length of microglial processes, and decreased maximum length. Importantly, we found that 48-h SD decreased microglial density and morphology in old mice, whereas SD increased microglial density and morphology in most observed brain regions in young mice. SD-induced hyperactivity was observed only in young mice but not in old mice. Moreover, microglial density (HIP, AMY, mPFC, CPu) was significantly positively correlated with behaviors in SD- and vehicle-treated young mice. Contrarily, negative correlations were shown between the microglial density (cc, Cb, TH, HYP, Acb, AMY) and behaviors in vehicle-treated young and old mice. These results suggest that SD dysregulates the homeostatic state of microglia in a region- and age-dependent manner. Microglia may be involved in regulating age-related behavioral responses to SD.

Gut microbiota deficiency ameliorates multiple myeloma and myeloma-related bone disease by Th17 cells in mice models.

Purpose: Multiple myeloma, the second most common hematological tumor, is currently incurable. Multiple myeloma-related bone disease is a characteristic clinical symptom that seriously affects the survival and prognosis of patients. In recent years, gut microbiota has been shown to play an important role in the occurrence and development of multiple myeloma. However, whether and how it affects the development of myelomatous bone disease is unclear. Methods: To investigate the mechanism and influence of the microbiota on multiple myeloma and myeloma bone disease, a myeloma-gut microbiota deletion mice model was established. 16S rRNA sequencing was used to analysis of bacterial flora changes. Histochemical staining and bone micro-CT were used to assess the severity of bone disease. Bone marrow tumor load and spleen Th17 cells were detected by flow cytometry. Results: Histochemical staining revealed a reduced tumor burden after eliminating gut microbial communities in mice by administering a mixture of antibiotics. According to the 16S rRNA sequencing of intestinal contents, antibiotic treatment resulted in a significant change in the microbiota of the mice. Bone micro-CT demonstrated that antibiotic treatment could reduce bone lesions caused by myeloma while increasing mineral density, bone volume fraction, trabecular bone thickness, and trabecular number. Meanwhile, histochemical staining of the bone found that the enhanced bone resorption was weakened by the change of flora. These results were consistent with the concentration of IL17 in serum and the frequency of Th17 cells in spleen. Conclusions: Herein, the effects of the gut microbiome on myeloma bone disease are investigated for the first time, providing new insight into its pathogenesis and suggesting that gut microbiota may serve as a therapeutic target in multiple myeloma-associated bone diseases.

SIRT3-dependent mitochondrial redox homeostasis mitigates CHK1 inhibition combined with gemcitabine treatment induced cardiotoxicity in hiPSC-CMs and mice.

Administration of CHK1-targeted anticancer therapies is associated with an increased cumulative risk of cardiac complications, which is further amplified when combined with gemcitabine. However, the underlying mechanisms remain elusive. In this study, we generated hiPSC-CMs and murine models to elucidate the mechanisms underlying CHK1 inhibition combined with gemcitabine-induced cardiotoxicity and identify potential targets for cardioprotection. Mice were intraperitoneally injected with 25 mg/kg CHK1 inhibitor AZD7762 and 20 mg/kg gemcitabine for 3 weeks. hiPSC-CMs and NMCMs were incubated with 0.5 uM AZD7762 and 0.1 uM gemcitabine for 24 h. Both pharmacological inhibition or genetic deletion of CHK1 and administration of gemcitabine induced mtROS overproduction and pyroptosis in cardiomyocytes by disrupting mitochondrial respiration, ultimately causing heart atrophy and cardiac dysfunction in mice. These toxic effects were further exacerbated with combination administration. Using mitochondria-targeting sequence-directed vectors to overexpress CHK1 in cardiomyocyte (CM) mitochondria, we identified the localization of CHK1 in CM mitochondria and its crucial role in maintaining mitochondrial redox homeostasis for the first time. Mitochondrial CHK1 function loss mediated the cardiotoxicity induced by AZD7762 and CHK1-knockout. Mechanistically, mitochondrial CHK1 directly phosphorylates SIRT3 and promotes its expression within mitochondria. On the contrary, both AZD7762 or CHK1-knockout and gemcitabine decreased mitochondrial SIRT3 abundance, thus resulting in respiration dysfunction. Further hiPSC-CMs and mice experiments demonstrated that SIRT3 overexpression maintained mitochondrial function while alleviating CM pyroptosis, and thereby improving mice cardiac function. In summary, our results suggest that targeting SIRT3 could represent a novel therapeutic approach for clinical prevention and treatment of cardiotoxicity induced by CHK1 inhibition and gemcitabine.

Severe thrombocytopenia induced by tirofiban after percutaneous coronary intervention: a case report.

BACKGROUND: Tirofiban is a nonpeptide glycoprotein IIb/IIIa receptor antagonist used widely in patients subjected to percutaneous coronary intervention. While the usage of tirofiban sets an important clinical benefit, severe thrombocytopenia can occur with use of this agent. CASE PRESENTATION: A 76-year-old Chinese man was admitted with 1-month history of sudden onset of chest tightness. He was diagnosed as having subacute inferior myocardial infarction, and percutaneous coronary intervention was performed. After the procedure, patient received tirofiban at 0.15 µg/kg/minute for 4 h. A blood sample was obtained for a complete blood count; severe thrombocytopenia was reported according to routine orders at our hospital. All antiplatelet drugs including tirofiban, aspirin, and clopidogrel were immediately discontinued. The patient received platelet transfusions and was treated with immunoglobulin G. Two days later, the patient's platelet count had increased to 75 × 109/L. There was a significant improvement after day 5, and the platelet count was 112 × 109/L. Seven days after the acute thrombocytopenia, he was discharged with normal platelet count. CONCLUSIONS: Clinicians should be particularly aware of tirofiban-induced thrombocytopenia in routine practice.