Insufficient KIF15 during porcine oocyte ageing induces HDAC6-based microtubule instability.

During aging, oocytes display cytoskeleton dynamics defects and aneuploidy, leading to embryonic aneuploidy, which in turn causes miscarriages, implantation failures, and birth defects. KIF15 (also known as Hklp2), a member of the kinesin-12 superfamily, is a cytoplasmic motor protein reported to be involved in Golgi and vesicle-related transport during mitosis in somatic cells. However, the regulatory mechanisms of KIF15 during meiosis in porcine oocytes and the connection with postovulatory aging remain unclear. In present study, we found that KIF15 is expressed during porcine oocyte maturation, and its localization is dependent on microtubule dynamics. Furthermore, the level of KIF15 expression decreased in postovulatory aged oocytes. The decrease in KIF15 blocked polar body extrusion, thereby hindering oocyte maturation. We demonstrated that KIF15 defects contributed to abnormal spindle morphologies and chromosome misalignment, possibly due to microtubule instability, as evidenced by microtubule depolymerization after cold treatment. Additionally, our data indicated that KIF15 modulates HDAC6 to affect tubulin acetylation in oocytes. Taken together, these results suggest that KIF15 regulates HDAC6-related microtubule stability for spindle organization in porcine oocytes during meiosis, which may contribute to the decline in maturation competence in aged porcine oocytes.

Circulating hypervirulent Marek's disease viruses in vaccinated chicken flocks in Taiwan by genetic analysis of meq oncogene.

Marek's disease (MD) is an important neoplastic disease caused by serotype 1 Marek's disease virus (MDV-1), which results in severe economic losses worldwide. Despite vaccination practices that have controlled the MD epidemic, current increasing MD-suspected cases indicate the persistent viral infections circulating among vaccinated chicken farms in many countries. However, the lack of available information about phylogeny and molecular characterization of circulating MDV-1 field strains in Taiwan reveals a potential risk in MD outbreaks. This study investigated the genetic characteristics of 18 MDV-1 strains obtained from 17 vaccinated chicken flocks in Taiwan between 2018 and 2020. Based on the sequences of the meq oncogene, the phylogenetic analysis demonstrated that the circulating Taiwanese MDV-1 field strains were predominantly in a single cluster that showed high similarity with strains from countries of the East Asian region. Because the strains were obtained from CVI988/Rispens vaccinated chicken flocks and the molecular characteristics of the Meq oncoprotein showed features like vvMDV and vv+MDV strains, the circulating Taiwanese MDV-1 field strains may have higher virulence compared with vvMDV pathotype. In conclusion, the data presented demonstrates the circulation of hypervirulent MDV-1 strains in Taiwan and highlights the importance of routine surveillance and precaution strategies in response to the emergence of enhanced virulent MDV-1.

Subjective and objective cognitive functioning in untreated late-life depression: An exploration centered on comorbid generalized anxiety disorder.

BACKGROUND: Late-Life Depression (LLD) is a prevalent mental health disorder that is often accompanied by cognitive impairments. The objective of this study is to investigate the influence of coexisting Generalized Anxiety Disorder (GAD) on both subjective and objective cognitive abilities in untreated LLD individuals. METHODS: A total of 77 participants aged 60 years and above were recruited for this study, comprising 31 individuals with Major Depressive Disorder (LLD group), 46 with MDD and coexisting Generalized Anxiety Disorder (LLDA group), and 54 healthy controls (HC). Prior to the study, all patients had abstained from psychotropic medication for a minimum of two weeks. Comprehensive neuropsychological assessments were administered to all participants. RESULTS: The LLDA group exhibited substantial disparities in memory, attention, processing speed,executive function,overall cognitive functioning, and subjective cognitive functioning when compared to the HC group. The LLD group displayed deficits in memory, SCWT-W in attention, SCWT-C in processing speed,overall cognitive functioning, and subjective cognitive functioning in comparison to the healthy controls. Although the LLD group achieved lower average scores in executive function, TMTA in processing speed, and DSST in attention than the HC group, no significant distinctions were identified between these groups in these domains. Linear regression analysis unveiled that anxiety symptoms had a significant impact on subjective cognitive deficits among MDD patients, but exhibited a milder influence on objective cognitive performance. After adjusting for the severity of depression, anxiety symptoms were found to affect TMTA in processing speed and subjective cognitive functioning in LLD patients. CONCLUSION: Late-Life Depression (LLD) exhibits pervasive cognitive impairments, particularly in individuals with generalized anxiety disorder, presenting a crucial target for future therapeutic interventions. Among elderly individuals with depression, anxiety symptoms significantly impact subjective cognitive functioning, suggesting its potential utility in distinguishing between depression-associated cognitive decline and pre-dementia conditions.

[Transcriptomic characteristics analysis of bone from chronic osteomyelitis].

OBJECTIVE: To explore the molecular mechanism of chronic osteomyelitis and to clarify the role of MAPK signal pathway in the pathogenesis of chronic osteomyelitis, by collecting and analyzing the transcriptional information of bone tissue in patients with chronic osteomyelitis. METHODS: Four cases of traumatic osteomyelitis in limbs from June 2019 to June 2020 were selected, and the samples of necrotic osteonecrosis from chronic osteomyelitis (necrotic group), and normal bone tissue (control group) were collected. Transcriptome information was collected by Illumina Hiseq Xten high throughput sequencing platform, and the gene expression in bone tissue was calculated by FPKM. The differentially expressed genes were screened by comparing the transcripts of the Necrotic group and control group. Genes were enriched by GO and KEGG. MAP3K7 and NFATC1 were selected as differential targets in the verification experiments, by using rat osteomyelitis animal model and immunohistochemical analysis. RESULTS: A total of 5548 differentially expressed genes were obtained by high throughput sequencing by comparing the necrotic group and control group, including 2701 up-regulated and 2847 down-regulated genes. The genes enriched in MAPK pathway and osteoclast differentiation pathway were screened, the common genes expressed in both MAPK and osteoclast differentiation pathway were (inhibitor of nuclear factor κ subunit Beta, IκBKß), (mitogen-activated protein kinase 7, MAP3K7), (nuclear factor of activated t cells 1, NFATC1) and (nuclear factor Kappa B subunit 2, NFκB2). In rat osteomyelitis model, MAP3K7 and NFATC1 were highly expressed in bone marrow and injured bone tissue. CONCLUSION: Based on the transcriptome analysis, the MAPK signaling and osteoclast differentiation pathways were closely related to chronic osteomyelitis, and the key genes IκBKß, MAP3K7, NFATC1, NFκB2 might be new targets for clinical diagnosis and therapy of chronic osteomyelitis.

Task-related brain activation associated with violence in patients with schizophrenia: A meta-analysis.

This study investigates specific changes in brain function during cognitive and emotional tasks in patients with schizophrenia and a history of violence (VSCZ) compared with non-violent patients with schizophrenia and healthy controls. A comprehensive literature search was conducted at the Web of Science, Medline, and PubMed. Ten studies met the inclusion criteria. In which, eight studies compared brain activation between patients with VSCZ and non-violent patients with schizophrenia, and the former exhibited increased activation at the middle occipital gyrus and rectus compared with the latter. Seven studies compared brain activation between patients with VSCZ and controls, and the former exhibited increased activation at the anterior cingulate cortex, cerebellum VI region, lingual gyrus and fusiform. Subgroup analysis in five studies performing emotional tasks revealed that patients with VSCZ showed increased activation at the middle occipital gyrus compared with non-violent patients with schizophrenia. Our findings suggest that abnormal emotion perception and regulation significantly contribute to the increased risk of violence in patients with schizophrenia. Notably, the middle occipital gyrus and rectus emerge as key neurophysiological correlates associated with this phenomenon.

Food impaction on three-dimensional printed models with periodontal ligament simulation.

OBJECTIVE: This study aims to evaluate food impaction on three-dimensional (3D) printed models with periodontal ligament simulation. MATERIALS AND METHODS: Based on a commercial typodont pair, 3D maxillary and mandibular models were created with no teeth and with tooth sockets that were 1 mm wider than the original ones from 24 to 27 or 34 to 37 for periodontal ligament simulation with vinyl polysiloxane impression material. In total, 35 pairs of 7 combinations, including maxillary/mandibular typodonts in occlusion with maxillary/mandibular 3D models with/without a distal gap of canines on 3D models (tooth 23 or 33) were mounted on hinge articulators and divided into seven groups (n = 5). Each sample experienced the same manual chewing simulation on a customized device. The proximal surfaces were photographed to measure the percentage of food impaction area using ImageJ software. RESULTS: Group with fixed maxillary and mandibular teeth showed more food impaction than other groups with significant differences in the average of maxilla and the average of all proximal areas. CONCLUSION: The flexibility of the periodontal ligament and the degree of freedom of the teeth in their sockets may contribute to the extent of food impaction in proximal spaces.

Unveiling the role of HP1α-HDAC1-STAT1 axis as a therapeutic target for HP1α-positive intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICCA) is a heterogeneous group of malignant tumors characterized by high recurrence rate and poor prognosis. Heterochromatin Protein 1α (HP1α) is one of the most important nonhistone chromosomal proteins involved in transcriptional silencing via heterochromatin formation and structural maintenance. The effect of HP1α on the progression of ICCA remained unclear. METHODS: The effect on the proliferation of ICCA was detected by experiments in two cell lines and two ICCA mouse models. The interaction between HP1α and Histone Deacetylase 1 (HDAC1) was determined using Electrospray Ionization Mass Spectrometry (ESI-MS) and the binding mechanism was studied using immunoprecipitation assays (co-IP). The target gene was screened out by RNA sequencing (RNA-seq). The occupation of DNA binding proteins and histone modifications were predicted by bioinformatic methods and evaluated by Cleavage Under Targets and Tagmentation (CUT & Tag) and Chromatin immunoprecipitation (ChIP). RESULTS: HP1α was upregulated in intrahepatic cholangiocarcinoma (ICCA) tissues and regulated the proliferation of ICCA cells by inhibiting the interferon pathway in a Signal Transducer and Activator of Transcription 1 (STAT1)-dependent manner. Mechanistically, STAT1 is transcriptionally regulated by the HP1α-HDAC1 complex directly and epigenetically via promoter binding and changes in different histone modifications, as validated by high-throughput sequencing. Broad-spectrum HDAC inhibitor (HDACi) activates the interferon pathway and inhibits the proliferation of ICCA cells by downregulating HP1α and targeting the heterodimer. Broad-spectrum HDACi plus interferon preparation regimen was found to improve the antiproliferative effects and delay ICCA development in vivo and in vitro, which took advantage of basal activation as well as direct activation of the interferon pathway. HP1α participates in mediating the cellular resistance to both agents. CONCLUSIONS: HP1α-HDAC1 complex influences interferon pathway activation by directly and epigenetically regulating STAT1 in transcriptional level. The broad-spectrum HDACi plus interferon preparation regimen inhibits ICCA development, providing feasible strategies for ICCA treatment. Targeting the HP1α-HDAC1-STAT1 axis is a possible strategy for treating ICCA, especially HP1α-positive cases.

Advances in the study of gastric organoids as disease models.

Gastric organoids are models created in the laboratory using stem cells and sophisticated three-dimensional cell culture techniques. These models have shown great promise in providing valuable insights into gastric physiology and advanced disease research. This review comprehensively summarizes and analyzes the research advances in culture methods and techniques for adult stem cells and induced pluripotent stem cell-derived organoids, and patient-derived organoids. The potential value of gastric organoids in studying the pathogenesis of stomach-related diseases and facilitating drug screening is initially discussed. The construction of gastric organoids involves several key steps, including cell extraction and culture, three-dimensional structure formation, and functional expression. Simulating the structure and function of the human stomach by disease modeling with gastric organoids provides a platform to study the mechanism of gastric cancer induction by Helicobacter pylori. In addition, in drug screening and development, gastric organoids can be used as a key tool to evaluate drug efficacy and toxicity in preclinical trials. They can also be used for precision medicine according to the specific conditions of patients with gastric cancer, to assess drug resistance, and to predict the possibility of adverse reactions. However, despite the impressive progress in the field of gastric organoids, there are still many unknowns that need to be addressed, especially in the field of regenerative medicine. Meanwhile, the reproducibility and consistency of organoid cultures are major challenges that must be overcome. These challenges have had a significant impact on the development of gastric organoids. Nonetheless, as technology continues to advance, we can foresee more comprehensive research in the construction of gastric organoids. Such research will provide better solutions for the treatment of stomach-related diseases and personalized medicine.

Targeting the PANoptosis signaling pathway for myocardial protection: therapeutic potential of Xian Ling Gu Bao capsule.

Introduction: Myocardial infarction (MI), the most prevalent ischemic heart disease, constitutes a primary cause of global cardiovascular disease with incidence and mortality. The pathogenesis of MI is exceedingly intricate, with PANoptosis playing a pivotal role in its pathological process. Xian Ling Gu Bao capsule (XLGB) contains various active components, including flavonoids, terpenes, and phenylpropanoids, and exhibits a wide range of pharmacological activities. However, it remains unclear whether XLGB can protect the myocardium from damage after MI. This study aimed to investigate the impact of XLGB on isoprenaline (ISO)-induced MI in mice and its potential mechanisms. Methods: This study assessed the protective effects of XLGB against ISO-induced MI through techniques such as echocardiography, HE staining, Masson staining, and enzyme-linked immunosorbent assay (ELISA). Furthermore, the potential mechanisms of XLGB's protective effects on MI were explored using bioinformatics, molecular docking, and molecular dynamics simulations. These mechanisms were further validated through immunofluorescence staining and Western blotting. Results: The results demonstrated that various doses of XLGB exhibited a significant reduction in myocardial injury induced by myocardial infarction. Intriguingly, higher dosages of XLGB displayed superior therapeutic efficacy compared to the positive control metoprolol. This protective effect is primarily achieved through the inhibition of oxidative stress and the inflammatory processes. Furthermore, we have elucidated that XLGB protected the myocardium from MI-induced damage by suppressing PANoptosis, with a critical role played by the NLRP3/Caspase3/RIP1 signaling pathway. Of particular note, the primary compounds of XLGB were found to directly interact with NLRP3/Caspase3/RIP1, a discovery further validated through molecular docking and molecular dynamics simulations. This suggests that NLRP3/Caspase3/RIP1 may be a therapeutic target for XLGB-induced myocardial protection. Conclusion: In summary, our findings reveal a novel property of XLGB: reverses myocardial damage following MI by inhibiting the NLRP3/Caspase3/RIP1-mediated PANoptosis pathway.

Motion sensitive network for action recognition in control and decision-making of autonomous systems.

Spatial-temporal modeling is crucial for action recognition in videos within the field of artificial intelligence. However, robustly extracting motion information remains a primary challenge due to temporal deformations of appearances and variations in motion frequencies between different actions. In order to address these issues, we propose an innovative and effective method called the Motion Sensitive Network (MSN), incorporating the theories of artificial neural networks and key concepts of autonomous system control and decision-making. Specifically, we employ an approach known as Spatial-Temporal Pyramid Motion Extraction (STP-ME) module, adjusting convolution kernel sizes and time intervals synchronously to gather motion information at different temporal scales, aligning with the learning and prediction characteristics of artificial neural networks. Additionally, we introduce a new module called Variable Scale Motion Excitation (DS-ME), utilizing a differential model to capture motion information in resonance with the flexibility of autonomous system control. Particularly, we employ a multi-scale deformable convolutional network to alter the motion scale of the target object before computing temporal differences across consecutive frames, providing theoretical support for the flexibility of autonomous systems. Temporal modeling is a crucial step in understanding environmental changes and actions within autonomous systems, and MSN, by integrating the advantages of Artificial Neural Networks (ANN) in this task, provides an effective framework for the future utilization of artificial neural networks in autonomous systems. We evaluate our proposed method on three challenging action recognition datasets (Kinetics-400, Something-Something V1, and Something-Something V2). The results indicate an improvement in accuracy ranging from 1.1% to 2.2% on the test set. When compared with state-of-the-art (SOTA) methods, the proposed approach achieves a maximum performance of 89.90%. In ablation experiments, the performance gain of this module also shows an increase ranging from 2% to 5.3%. The introduced Motion Sensitive Network (MSN) demonstrates significant potential in various challenging scenarios, providing an initial exploration into integrating artificial neural networks into the domain of autonomous systems.

Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury.

BACKGROUND: Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) plays a crucial role in metabolizing and detoxifying endogenous and exogenous substances. However, its contribution to the progression of liver damage remains unclear. AIM: To determine the role and mechanism of UGT1A1 in liver damage progression. METHODS: We investigated the relationship between UGT1A1 expression and liver injury through clinical research. Additionally, the impact and mechanism of UGT1A1 on the progression of liver injury was analyzed through a mouse model study. RESULTS: Patients with UGT1A1 gene mutations showed varying degrees of liver damage, while patients with acute-on-chronic liver failure (ACLF) exhibited relatively reduced levels of UGT1A1 protein in the liver as compared to patients with chronic hepatitis. This suggests that low UGT1A1 levels may be associated with the progression of liver damage. In mouse models of liver injury induced by carbon tetrachloride (CCl4) and concanavalin A (ConA), the hepatic levels of UGT1A1 protein were found to be increased. In mice with lipopolysaccharide or liver steatosis-mediated liver-injury progression, the hepatic protein levels of UGT1A1 were decreased, which is consistent with the observations in patients with ACLF. UGT1A1 knockout exacerbated CCl4- and ConA-induced liver injury, hepatocyte apoptosis and necroptosis in mice, intensified hepatocyte endoplasmic reticulum (ER) stress and oxidative stress, and disrupted lipid metabolism. CONCLUSION: UGT1A1 is upregulated as a compensatory response during liver injury, and interference with this upregulation process may worsen liver injury. UGT1A1 reduces ER stress, oxidative stress, and lipid metabolism disorder, thereby mitigating hepatocyte apoptosis and necroptosis.

The use of interventional procedures for cancer pain. A brief review.

CONTEXT: Pain is a common experience in people living with cancer. Concerns around opioid prescribing have seen a move toward a multi-modality management approach, which includes interventional pain procedures. PURPOSE: In this paper we discuss the interventional pain procedures used to treat cancer pain at two major tertiary centers in Australia. METHODS AND RESULTS: This expert review provides practical insights on cancer pain management from healthcare providers in different specialties. These insights can be used to guide the management of a wide range of cancer pain types. CONCLUSIONS: Furthermore, this review identifies the need for a systematic and comprehensive approach to the management of cancer pain that is broader than that of a single specialty. With recent advances in pain management procedures, an interdisciplinary approach is essential in order to provide an up to date, patient tailored approach to pain management. This review will help inform the development of a cancer pain intervention registry.

Nodule-CLIP: Lung nodule classification based on multi-modal contrastive learning.

The latest developments in deep learning have demonstrated the importance of CT medical imaging for the classification of pulmonary nodules. However, challenges remain in fully leveraging the relevant medical annotations of pulmonary nodules and distinguishing between the benign and malignant labels of adjacent nodules. Therefore, this paper proposes the Nodule-CLIP model, which deeply mines the potential relationship between CT images, complex attributes of lung nodules, and benign and malignant attributes of lung nodules through a comparative learning method, and optimizes the model in the image feature extraction network by using its similarities and differences to improve its ability to distinguish similar lung nodules. Firstly, we segment the 3D lung nodule information by U-Net to reduce the interference caused by the background of lung nodules and focus on the lung nodule images. Secondly, the image features, class features, and complex attribute features are aligned by contrastive learning and loss function in Nodule-CLIP to achieve lung nodule image optimization and improve classification ability. A series of testing and ablation experiments were conducted on the public dataset LIDC-IDRI, and the final benign and malignant classification rate was 90.6%, and the recall rate was 92.81%. The experimental results show the advantages of this method in terms of lung nodule classification as well as interpretability.

Effect mechanism of capsaicin and dihydrocapsaicin in chili on the oxidative stability of myoglobin in duck meat.

BACKGROUND: Myoglobin (Mb) in duck meat is commonly over-oxidized when heated at high temperatures, which may worsen the color of the meat. Enhancing the oxidative stability of Mb is essential for improving the color of duck meat. Capsaicin and dihydrocapsaicin (CA-DI) in chili exhibit antioxidant properties. This study investigated the effects of CA-DI on the structure and oxidative damage of Mb by fluorescence spectroscopy, differential scanning calorimetry analysis and particle size in duck meat during heat treatment. RESULTS: When the ratio of CA-DI to Mb was 10:1 g kg-1 and heat-treated for 36 min, oxymyoglobin significantly increased, and metmyoglobin significantly decreased compared with the control group (P < 0.05). In parallel, the carbonyl content of Mb in the CA-DI group decreased by 43.40 ± 0.10%, the sulfhydryl content increased by 188 ± 0.21%, and the free radical scavenging activity of Mb was significantly enhanced (P < 0.05). Moreover, the addition of CA-DI resulted in a significant decrease in the particle size of the Mb surface (P < 0.05). When the ratio of CA-DI to Mb was 10:1 g kg-1, CA-DI enhanced the thermal stability and significantly increased the thermal denaturation temperature of Mb. The molecular docking results indicated that hydrophobic interactions and hydrogen bonds were involved in the binding of CA-DI to Mb. CONCLUSION: CA-DI could combine with Mb and improve the oxidation stability of Mb in duck meat. This suggested that CA-DI could be a potential natural antioxidant that improves the color of meat products. © 2024 Society of Chemical Industry.

Treatment outcome and germline predictive factors of ropeginterferon alpha-2b in myeloproliferative neoplasm patients.

BACKGROUND: Studies have shown that some single nucleotide polymorphisms (SNPs) could serve as excellent markers in foretelling the treatment outcome of interferon (IFN) in myeloproliferative neoplasms (MPN). However, most work originated from western countries, and data from different ethnic populations have been lacking. METHODS: To gain insights, targeted sequencing was performed to detect myeloid-associated mutations and SNPs in eight loci across three genes (IFNL4, IFN-γ, and inosine triphosphate pyrophosphatase [ITPA]) to explore their predictive roles in our cohort of 21 ropeginterferon alpha-2b (ROPEG)-treated MPN patients, among whom real-time quantitative PCR was also performed periodically to monitor the JAK2V617F allele burden in 19 JAK2V617F-mutated cases. RESULTS: ELN response criteria were adopted to designate patients as good responders if they achieved complete hematological responses (CHR) within 1 year (CHR1) or attained major molecular responses (MMR), which occurred in 70% and 45% of the patients, respectively. IFNL4 and IFN-γ gene SNPs were infrequent in our population and were thus excluded from further analysis. Two ITPA SNPs rs6051702 A>C and rs1127354 C>A were associated with an inferior CHR1 rate and MMR rate, respectively. The former seemed to be linked to grade 2 or worse hepatotoxicity as well, although the comparison was of borderline significance only (50%, vs. 6.7% in those with common haplotype, p = 0.053). Twelve patients harbored 19 additional somatic mutations in 12 genes, but the trajectory of these mutations varied considerably and was not predictive of any response. CONCLUSIONS: Overall, this study provided valuable information on the ethnics- and genetics-based algorithm in the treatment of MPN.

Transversus Thoracic Muscle Plane Block For Postoperative Pain in Pediatric Cardiac Surgery: A Systematic Review And Meta-Analysis of Randomized And Observational Studies.

OBJECTIVES: Pediatric patients undergoing cardiac surgery usually experience significant surgical pain. Additionally, the effect of poor surgical analgesia creates a pain continuum that extends to the postoperative period. Transversus thoracic muscle plane block (TTMPB) is a novel plane block technique that can provide analgesia to the anterior chest wall. The analgesic role of TTMPB in pediatric cardiac surgery is still uncertain. A meta-analysis was conducted to determine the analgesic efficacy of this procedure. DESIGN AND SETTING: Systematic review and meta-analysis. PubMed, Embase, Web of Science, CENTRAL, WanFang Data, and the China National Knowledge Infrastructure were searched to November 2023, and the Grading of Recommendations Assessment, Development, and Evaluation approach was followed to evaluate the certainty of evidence. PARTICIPANTS: Eligible studies enrolled pediatric patients from 2 months to 12 years old scheduled to undergo cardiac surgery, and randomized them to receive a TTMPB or no block/sham block. MEASUREMENTS AND MAIN RESULTS: Six studies that enrolled 601 pediatric patients were included. Low-certainty evidence from randomized trials showed that, compared with no block or sham block, TTMPB in pediatric patients undergoing cardiac surgery may reduce postoperative modified objective pain score at 12 hours (weighted mean difference [WMD] -2.20, 95% CI -2.73 to -1.68) and 24 hours (WMD -1.76, 95% CI -2.09 to -1.42), intraoperative opioid consumption (WMD -3.83, 95% CI -5.90 to -1.76 µg/kg), postoperative opioid consumption (WMD -2.51, 95% CI -2.84 to -2.18 µg/kg), length of intensive care unit (ICU) stay (WMD -5.56, 95% CI -8.30 to -2.83 hours), and extubation time (WMD -2.13, 95% CI -4.21 to -0.05 hours). Retrospective studies provided very low certainty that the results were consistent with the randomized trials. CONCLUSION: Very low- to low-certainty evidence showed that TTMPB in pediatric patients undergoing cardiac surgery may reduce postoperative pain, opioid consumption, ICU length of stay, and extubation time.

CCNA2 and NEK2 regulate glioblastoma progression by targeting the cell cycle.

Glioblastoma (GBM) is characterized by significant heterogeneity, leading to poor survival outcomes for patients, despite the implementation of comprehensive treatment strategies. The roles of cyclin A2 (CCNA2) and NIMA related kinase 2 (NEK2) have been extensively studied in numerous cancers, but their specific functions in GBM remain to be elucidated. The present study aimed to investigate the potential molecular mechanisms of CCNA2 and NEK2 in GBM. CCNA2 and NEK2 expression and prognosis in glioma were evaluated by bioinformatics methods. In addition, the distribution of CCNA2 and NEK2 expression in GBM subsets was determined using pseudo-time analysis and tricycle position of single-cell sequencing. Gene Expression Omnibus and Kyoto Encyclopedia of Genes and Genome databases were employed and enrichment analyses were conducted to investigate potential signaling pathways in GBM subsets and a nomogram was established to predict 1-, 2- and 3-year overall survival probability in GBM. CCNA2 and NEK2 expression levels were further validated by western blot analysis and immunohistochemical staining in GBM samples. High expression of CCNA2 and NEK2 in glioma indicates poor clinical outcomes. Single-cell sequencing of GBM revealed that these genes were upregulated in a subset of positive neural progenitor cells (P-NPCs), which showed significant proliferation and progression properties and may activate G2M checkpoint pathways. A comprehensive nomogram predicts 1-, 2- and 3-year overall survival probability in GBM by considering P-NPCs, age, chemotherapy and radiotherapy scores. CCNA2 and NEK2 regulate glioblastoma progression by targeting the cell cycle, thus indicating the potential of novel therapy directed to CCNA2 and NEK2 in GBM.

Leave No Photon Behind: Artificial Intelligence in Multiscale Physics of Photocatalyst and Photoreactor Design.

Although solar fuels photocatalysis offers the promise of converting carbon dioxide directly with sunlight as commercially scalable solutions have remained elusive over the past few decades, despite significant advancements in photocatalysis band-gap engineering and atomic site activity. The primary challenge lies not in the discovery of new catalyst materials, which are abundant, but in overcoming the bottlenecks related to material-photoreactor synergy. These factors include achieving photogeneration and charge-carrier recombination at reactive sites, utilizing high mass transfer efficiency supports, maximizing solar collection, and achieving uniform light distribution within a reactor. Addressing this multi-dimensional problem necessitates harnessing machine learning techniques to analyze real-world data from photoreactors and material properties. In this perspective, the challenges are outlined associated with each bottleneck factor, review relevant data analysis studies, and assess the requirements for developing a comprehensive solution that can unlock the full potential of solar fuels photocatalysis technology. Physics-informed machine learning (or Physics Neural Networks) may be the key to advancing this important area from disparate data towards optimal reactor solutions.

Ten-year epidemiology and risk factors of cytomegalovirus infection in hematopoietic stem cell transplantation patients in Taiwan.

BACKGROUND: Cytomegalovirus (CMV) can cause infection and critical diseases in hematopoietic stem cell transplantation (HSCT) recipients. This study aimed to explore the cumulative incidence and risk factors for CMV infection and disease among HSCT recipients in Taiwan. METHODS: This retrospective cohort study using the Taiwan Blood and Marrow Transplantation Registry (TBMTR) included HSCT recipients between 2009 and 2018 in Taiwan. The primary outcome was cumulative incidence of CMV infection or disease at day 100 after HSCT. Secondary outcomes included day 180 cumulative incidence of CMV infection or disease, infection sites, risk factors for CMV infection or disease, survival analysis, and overall survival after CMV infection and disease. RESULTS: There were 4394 HSCT recipients included in the study (2044 auto-HSCT and 2350 allo-HSCT). The cumulative incidence of CMV infection and disease was significantly higher in allo-HSCT than in auto-HSCT patients at day 100 (53.7% vs. 6.0%, P < 0.0001 and 6.1% vs. 0.9%, P < 0.0001). Use of ATG (HR 1.819, p < 0.0001), recipient CMV serostatus positive (HR 2.631, p < 0.0001) and acute GVHD grades ≥ II (HR 1.563, p < 0.0001) were risk factors for CMV infection, while matched donor (HR 0.856, p = 0.0180) and myeloablative conditioning (MAC) (HR 0.674, p < 0.0001) were protective factors. CONCLUSION: The study revealed a significant disparity in terms of the incidence, risk factors, and clinical outcomes of CMV infection and disease between auto and allo-HSCT patients. These findings underscore the importance of considering these factors in the management of HSCT recipients to improve outcomes related to CMV infections.

First Family Case of Hemoglobinopathy Titusville in China with Falsely Low SpO2 and Unmeasurable SaO2.

BACKGROUND: Normal hemoglobin is a tetrameric structure, consisting of two alpha-globin chains and two nonalpha (beta, gamma, delta) chains. Hemoglobinopathies occur when the presence of gene mutations affect the molecular structure or expression of the globin chains. METHODS: We reported the case of a 9-year-old Chinese girl who presented with abnormal low oxygen saturation values on pulse oximetry and no oximetry results were obtained during blood gas analysis (BGA). RESULTS: High-performance liquid chromatography (HPLC) and capillary electrophoresis demonstrated that the presence of a low oxygen affinity hemoglobin variant, characterized as hemoglobin Titusville, was proven by gene sequencing. The patient's mother and aunt also carry the hemoglobin variant, representing the first Chinese family case reported. CONCLUSIONS: Hemoglobin Titusville is a rare genetic hemoglobin structural defect. early diagnosis can help patients and clinicians avoid unnecessary anxiety and costly or excessive clinical investigations.