RNA kinetics influence the response to transcriptional perturbation in leukaemia cell lines.

Therapeutic targeting of dysregulated transcription has emerged as a promising strategy for the treatment of cancers, such as leukaemias. The therapeutic response to small molecule inhibitors of Bromodomain-Containing Proteins (BRD), such as BRD2 and BRD4, P300/cAMP-response element binding protein (CBP) and Cyclin Dependent Kinases (CDKs), is generally attributed to the selective disruption of oncogenic gene expression driven by enhancers, super-enhancers (SEs) and lineage-specific transcription factors (TFs), including the c-MYC oncogene. The selectivity of compounds targeting the transcriptional machinery may be further shaped by post-transcriptional processes. To quantitatively assess the contribution of post-transcriptional regulation in responses to transcription inhibition, we performed multi-omics analyses to accurately measure mRNA production and decay kinetics. We demonstrate that it is not only the selective disruption of mRNA production, but rather mRNA decay rates that largely influence the selectivity associated with transcriptional inhibition. Accordingly, genes down-regulated with transcriptional inhibitors are largely characterized by extremely rapid mRNA production and turnover. In line with this notion, stabilization of the c-MYC transcript through swapping of its 3' untranslated region (UTR) rendered c-MYC insensitive to transcriptional targeting. This failed to negate the impact on c-MYC downstream targets and did not abrogate therapeutic responses. Finally, we provide evidence that modulating post-transcriptional pathways, such as through ELAVL1 targeting, can sensitize long-lived mRNAs to transcriptional inhibition and be considered as a combination therapy approach in leukaemia. Taken together, these data demonstrate that mRNA kinetics influence the therapeutic response to transcriptional perturbation and can be modulated for novel therapeutic outcomes using transcriptional agents in leukaemia.

Characterization of novel phage pK3-24 targeting multidrug-resistant Klebsiella pneumoniae and its therapeutic efficacy in Galleria mellonella larvae.

Klebsiella pneumoniae is a common, conditionally pathogenic bacterium that often has a multidrug-resistant phenotype, leading to failure of antibiotic therapies. It can therefore induce serious diseases, including community-acquired pneumonia and bloodstream infections. As an emerging alternative to antibiotics, phages are considered key to solving the problem of drug-resistant bacterial infections. Here, we report a novel phage, pK3-24, that mainly targets ST447 K. pneumoniae. Phage pK3-24 is a T7-like short-tailed phage with a fast adsorption capacity that forms translucent plaques with halos on bacterial lawns. The optimal multiplicity of infection (MOI) is 0.01, and the average burst size is 50 PFU/mL. Phage pK3-24 shows environmental stability, surviving at below 50°C and at pH values of 6-10. It has a double-stranded DNA genome of 40,327 bp and carries no antibiotic-resistance, virulence, or lysogeny genes. Phylogenetic analysis assigned phage pK3-24 to the genus Przondovirus as a new species. Phage pK3-24 inhibited the production of biofilm. Moreover, treatment with pK3-24 at doses with an MOI > 1 effectively reduced the mortality of Galleria mellonella larvae infected with ST447 K. pneumoniae.

Increased macrolide resistance rate of Mycoplasma pneumoniae correlated with epidemic in Beijing, China in 2023.

We collected respiratory specimens from 128 pediatric patients diagnosed with pneumonia in Beijing in late 2023. Mycoplasma pneumoniae was detected in 77.3% (99/128) patients, with 36.4% (4/11), 82.9% (34/41), 80.3% (61/76) in children aged less than 3 years, 3-6 years, over 7 years, respectively. Mycoplasma pneumoniae (M. pneumoniae) was characterized using P1 gene typing, MLVA typing and sequencing of domain V of the 23S rRNA gene. P1 gene type 1 (P1-1; 76.1%, 54/71) and MLVA type 4-5-7-2 (73.7%, 73/99) were predominant. MLVA identified a new genotype: 3-4-6-2. Macrolide resistance-associated mutations were detected in 100% of samples, with A2063G accounting for 99% and A2064G for 1%. The positive rate of M. pneumoniae was higher compared to previous reports, especially in children less than 3 years, suggesting a M. pneumoniae epidemic showing a younger age trend occurred in late 2023 in Beijing, China. Higher proportions of macrolide-resistant M. pneumoniae, P1-1 and 4-5-7-2 genotype M. pneumoniae indicated increased macrolide resistance rate and genotyping shift phenomenon, which might be attributable to this epidemic. Additionally, complete clinical information from 73 M. pneumoniae pneumonia inpatients were analyzed. The incidence of severe M. pneumoniae pneumonia was 56.2% (41/73). Mycoplasma pneumoniae pneumonia patients exhibited longer duration of fever, with a median value of 10.0 days (IQR, 8.0-13.0), and higher incidence of complications (74.0%, 54/73). However, in this cohort, we found that the severity of M. pneumoniae pneumonia, co-infection, or complications were not associated with M. pneumoniae P1 gene or MLVA types. Clinicians should be aware that patients infected with macrolide-resistant M. pneumoniae exhibited more severe clinical presentations.

Predictive value of spectral dual-detector computed tomography for PD-L1 expression in stage I lung adenocarcinoma: development and validation of a novel nomogram.

Background: Programmed death ligand-1 (PD-L1) expression serves a predictive biomarker for the efficacy of immune checkpoint inhibitors (ICIs) in the treatment of patients with early-stage lung adenocarcinoma (LA). However, only a limited number of studies have explored the relationship between PD-L1 expression and spectral dual-layer detector-based computed tomography (SDCT) quantification, qualitative parameters, and clinical biomarkers. Therefore, this study was conducted to clarify this relationship in stage I LA and to develop a nomogram to assist in preoperative individualized identification of PD-L1-positive expression. Methods: We analyzed SDCT parameters and PD-L1 expression in patients diagnosed with invasive nonmucinous LA through postoperative pathology. Patients were categorized into PD-L1-positive and PD-L1-negative expression groups based on a threshold of 1%. A retrospective set (N=356) was used to develop and internally validate the radiological and biomarker features collected from predictive models. Univariate analysis was employed to reduce dimensionality, and logistic regression was used to establish a nomogram for predicting PD-L1 expression. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curves, and external validation was performed in an independent set (N=80). Results: The proportions of solid components and pleural indentations were higher in the PD-L1-positive group, as indicated by the computed tomography (CT) value, CT at 40 keV (CT40keV; a/v), electron density (ED; a/v), and thymidine kinase 1 (TK1) exhibiting a positive correlation with PD-L1 expression. In contrast, the effective atomic number (Zeff; a/v) showed a negative correlation with PD-L1 expression [r=-0.4266 (Zeff.a), -0.1131 (Zeff.v); P<0.05]. After univariate analysis, 18 parameters were found to be associated with PD-L1 expression. Multiple regression analysis was performed on significant parameters with an area under the curve (AUC) >0.6, and CT value [AUC =0.627; odds ratio (OR) =0.993; P=0.033], CT40keV.a (AUC =0.642; OR =1.006; P=0.025), arterial Zeff (Zeff.a) (AUC =0.756; OR =0.102; P<0.001), arterial ED (ED.a) (AUC =0.641; OR =1.158, P<0.001), venous ED (ED.v) (AUC =0.607; OR =0.864; P<0.001), TK1 (AUC =0.601; OR =1.245; P=0.026), and diameter of solid components (Dsolid) (AUC =0.632; OR =1.058; P=0.04) were found to be independent risk factors for PD-L1 expression in stage I LA. These seven predictive factors were integrated into the development of an SDCT parameter-clinical nomogram, which demonstrated satisfactory discrimination ability in the training set [AUC =0.853; 95% confidence interval (CI): 0.76-0.947], internal validation set (AUC =0.824; 95% CI: 0.775-0.874), and external validation set (AUC =0.825; 95% CI: 0.733-0.918). Decision curve analyses also revealed the highest net benefit for the nomogram across a broad threshold probability range (20-80%), with a clinical impact curve (CIC) indicating its clinical validity. Comparisons with other models demonstrated the superior discriminatory accuracy of the nomogram over any individual variable (all P values <0.05). Conclusions: Quantitative parameters derived from SDCT demonstrated the ability to predict for PD-L1 expression in early-stage LA, with Zeff.a being notably effective. The nomogram established in combination with TK1 showed excellent predictive performance and good calibration. This approach may facilitate the improved noninvasive prediction of PD-L1 expression.

OSApredictor: A tool for prediction of moderate to severe obstructive sleep apnea-hypopnea using readily available patient characteristics.

Sleep apnea is a common sleep disorder. The availability of an easy-to-use sleep apnea predictor would provide a public health benefit by promoting early diagnosis and treatment. Our goal was to develop a prediction tool that used commonly available variables and was accessible to the public through a web site. Using data from polysomnography (PSG) studies that measured the apnea-hypopnea index (AHI), we built a machine learning tool to predict the presence of moderate to severe obstructive sleep apnea (OSA) (defined as AHI ≥15). Our tool employs only seven widely available predictor variables: age, sex, weight, height, pulse oxygen saturation, heart rate and respiratory rate. As a preliminary step, we used 16,958 PSG studies to examine eight machine learning algorithms via five-fold cross validation and determined that XGBoost exhibited superior predictive performance. We then refined the XGBoost predictor by randomly partitioning the data into a training and a test set (13,566 and 3392 PSGs, respectively) and repeatedly subsampling from the training set to construct 1000 training subsets. We evaluated each of the resulting 1000 XGBoost models on the single set-aside test set. The resulting classification tool correctly identified 72.5 % of those with moderate to severe OSA as having the condition (sensitivity) and 62.8 % of those without moderate to-severe OSA as not having it (specificity); overall accuracy was 66 %. We developed a user-friendly publicly available website (https://manticore.niehs.nih.gov/OSApredictor). We hope that our easy-to-use tool will serve as a screening vehicle that enables more patients to be clinically diagnosed and treated for OSA.

Macrophages preserve endothelial cell specialization in the adrenal gland to modulate aldosterone secretion and blood pressure.

Macrophages play crucial roles in organ-specific functions and homeostasis. In the adrenal gland, macrophages closely associate with sinusoidal capillaries in the aldosterone-producing zona glomerulosa. We demonstrate that macrophages preserve capillary specialization and modulate aldosterone secretion. Using macrophage-specific deletion of VEGF-A, single-cell transcriptomics, and functional phenotyping, we found that the loss of VEGF-A depletes PLVAP+ fenestrated endothelial cells in the zona glomerulosa, leading to increased basement membrane collagen IV deposition and subendothelial fibrosis. This results in increased aldosterone secretion, called "haptosecretagogue" signaling. Human aldosterone-producing adenomas also show capillary rarefaction and basement membrane thickening. Mice with myeloid cell-specific VEGF-A deletion exhibit elevated serum aldosterone, hypokalemia, and hypertension, mimicking primary aldosteronism. These findings underscore macrophage-to-endothelial cell signaling as essential for endothelial cell specialization, adrenal gland function, and blood pressure regulation, with broader implications for other endocrine organs.

The transcription factor HIF-1α in NKp46+ ILCs limits chronic intestinal inflammation and fibrosis.

Innate lymphoid cells (ILCs) are critical for intestinal adaptation to microenvironmental challenges, and the gut mucosa is characterized by low oxygen. Adaptation to low oxygen is mediated by hypoxia-inducible transcription factors (HIFs), and the HIF-1α subunit shapes an ILC phenotype upon acute colitis that contributes to intestinal damage. However, the impact of HIF signaling in NKp46+ ILCs in the context of repetitive mucosal damage and chronic inflammation, as it typically occurs during inflammatory bowel disease, is unknown. In chronic colitis, mice lacking the HIF-1α isoform in NKp46+ ILCs show a decrease in NKp46+ ILC1s but a concomitant rise in neutrophils and Ly6Chigh macrophages. Single-nucleus RNA sequencing suggests enhanced interaction of mesenchymal cells with other cell compartments in the colon of HIF-1α KO mice and a loss of mucus-producing enterocytes and intestinal stem cells. This was, furthermore, associated with increased bone morphogenetic pathway-integrin signaling, expansion of fibroblast subsets, and intestinal fibrosis. In summary, this suggests that HIF-1α-mediated ILC1 activation, although detrimental upon acute colitis, protects against excessive inflammation and fibrosis during chronic intestinal damage.

Development of a Recombinase-Aided Amplification Assay for the Rapid Detection of Candida auris.

Candida auris (C. auris) was first discovered in Japan in 2009 and has since spread worldwide. It exhibits strong transmission ability, high multidrug resistance, blood infectivity, and mortality rates. Traditional diagnostic techniques for C. auris have shortcomings, leading to difficulty in its timely diagnosis and identification. Therefore, timely and accurate diagnostic assays for clinical samples are crucial. We developed a novel, rapid recombinase-aided amplification (RAA) assay targeting the 18S rRNA, ITS1, 5.8S rRNA, ITS2, and 28S rRNA genes for C. auris identification. This assay can rapidly amplify DNA at 39 °C in 20 min. The analytical sensitivity and specificity were evaluated. From 241 clinical samples collected from pediatric inpatients, none were detected as C. auris-positive. We then prepared simulated clinical samples by adding 10-fold serial dilutions of C. auris into the samples to test the RAA assay's efficacy and compared it with that of real-time PCR. The assay demonstrated an analytical sensitivity of 10 copies/µL and an analytical specificity of 100%. The lower detection limit of the RAA assay for simulated clinical samples was 101 CFU/mL, which was better than that of real-time PCR (102-103 CFU/mL), demonstrating that the RAA assay may have a better detection efficacy for clinical samples. In summary, the RAA assay has high sensitivity, specificity, and detection efficacy. This assay is a potential new method for detecting C. auris, with simple reaction condition requirements, thus helping to manage C. auris epidemics.

Diagnostic value of carbohydrate antigen 50 in biliary tract cancer: A large-scale multicenter study.

BACKGROUND: To date, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) have been widely used for the screening, diagnosis and prediction of biliary tract cancer (BTC) patients. However, few studies with large sample sizes of carbohydrate antigen 50 (CA50) were reported in BTC patients. METHODS: A total of 1121 patients from the Liver Cancer Clin-Bio Databank of Anhui Hepatobiliary Surgery Union between January 2017 and December 2022 were included in this study (673 in the training cohort and 448 in the validation cohort): among them, 458 with BTC, 178 with hepatocellular carcinoma (HCC), 23 with combined hepatocellular-cholangiocarcinoma, and 462 with nontumor patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the diagnostic efficacy and clinical usefulness. RESULTS: ROC curves obtained by combining CA50, CA19-9, and AFP showed that the AUC value of the diagnostic MODEL 1 was 0.885 (95% CI 0.856-0.885, specificity 70.3%, and sensitivity 84.0%) in the training cohort and 0.879 (0.841-0.917, 76.7%, and 84.3%) in the validation cohort. In addition, comparing iCCA and HCC (235 in the training cohort, 157 in the validation cohort), the AUC values of the diagnostic MODEL 2 were 0.893 (95% CI 0.853-0.933, specificity 96%, and sensitivity 68.6%) in the training cohort and 0.872 (95% CI 0.818-0.927, 94.2%, and 64.6%) in the validation cohort. CONCLUSION: The model combining CA50, CA19-9, and AFP not only has good diagnostic value for BTC but also has good diagnostic value for distinguishing iCCA and HCC.

Inhibition of the ATP synthase increases sensitivity of Escherichia coli carrying mcr-1 to polymyxin B.

Bacterial infections caused by multidrug-resistant (MDR) gram-negative strains carrying the mobile colistin resistance gene mcr-1 are serious threats to world public health due to the lack of effective treatments. Inhibition of the ATP synthase makes bacteria such as Staphylococcus aureus and Klebsiella pneumoniae more sensitive to polymyxin. This provides new strategies for treating infections caused by polymyxins-resistant bacteria carrying mcr-1. Six mcr-1-positive strains were isolated from clinical samples, and all were identified as Escherichia coli. Here we investigated several ATP synthase inhibitors, N,N'-dicyclohexylcarbodiimide (DCCD), resveratrol, and piceatannol, for their antibacterial effects against the mcr-1-positive strains combined with polymyxin B (POL). Checkerboard assay, time-kill assay, biofilm inhibition and eradication assay indicated the significant synergistic effect of ATP synthase inhibitors/POL combination in vitro. Meanwhile, mouse infection model experiment was also performed, showing a 5 log10 reduction of the pathogen after treatment with the resveratrol/POL combination. Moreover, adding adenosine disodium triphosphate (Na2ATP) could inhibit the antibacterial effect of the ATP synthase inhibitors/POL combination. In conclusion, our study confirmed that inhibition of ATP production could increase the susceptibility of bacteria carrying mcr-1 to polymyxins. This provides a new strategy against polymyxins-resistant bacteria infection.

How breaking a sweat affects mood: The mediating role of self-efficacy between physical exercise and emotion regulation ability.

OBJECTIVE: This study investigates the association between physical exercise and emotion regulation abilities among college students, introducing self-efficacy as a mediating variable to analyze the pathway mechanism through which physical exercise affects emotion regulation abilities. METHODS: A cross-sectional study design was employed, utilizing a stratified random sampling method to survey three colleges in Jiangsu Province, China. Physical Activity Rating Scale, Physical Activity Self-efficacy Scale, and Emotional Intelligence Scale were used to measure the college student population. Regression analysis and mediation tests assessed whether self-efficacy mediates the relationship between physical exercise and college students' emotion regulation abilities. A total of 5,430 valid questionnaires were collected. RESULTS: The distribution of college students' physical activities was 77.0% for low, 13.1% for medium, and 9.3% for high levels. Physical activities were significantly and positively correlated with self-efficacy and emotional management abilities (r = 0.298,0.105;P<0.01), and self-efficacy was significantly and positively correlated with emotional management abilities (r = 0.322, P<0.01). Situational motivation and subjective support under self-efficacy were 0.08 and 0.255, respectively, and the adjusted R2 was 0.107. Self-efficacy played a fully mediating role between physical activities and emotional management abilities, with a total effect value of 0.032. The values of the direct and indirect effects were 0.003 and 0.029, accounting for 8.95% and 90.74% of the total effect, respectively. CONCLUSION: The physical exercise behavior of college students is primarily characterized by low intensity. Physical exercise among college students can positively predict their ability to regulate emotions. Self-efficacy fully mediates the relationship between physical exercise and emotion regulation ability among college students. College students can indirectly influence their ability to regulate emotions through physical exercise and self-efficacy.

Influence of physical exercise on negative emotions in college students: chain mediating role of sleep quality and self-rated health.

Background: Negative emotions in college students are a significant factor affecting mental health, with suicide behaviors caused by negative emotions showing an annual increasing trend. Existing studies suggest that physical exercise is essential to alleviate negative feelings, yet the intrinsic mechanisms by which it affects negative emotions have not been fully revealed. Objective: Negative emotions in college students represent a significant issue affecting mental health. This study investigates the relationship between physical exercise and negative emotions among college students, incorporating sleep quality and self-rated health (SRH) as mediators to analyze the pathway mechanism of how physical exercise affects students' negative emotions. Methods: A cross-sectional study design was utilized, employing online questionnaires for investigation. The scales included the Physical Activity Rating Scale-3 (PARS-3), the Depression Anxiety Stress Scales-21 (DASS-21), the Pittsburgh Sleep Quality Index (PSQI), and the 12-Item Short Form Health Survey (SF-12), resulting in the collection of 30,475 valid questionnaires, with a validity rate of 91%. Chain mediation tests and Bootstrap methods were applied for effect analysis. Results: The proportions of university students engaged in low, medium, and high levels of physical exercise were 77.6, 13.1, and 9.3%, respectively. The proportions of students experiencing "very severe" levels of stress, anxiety, and depression were 4.5, 10.9, and 3.6%, respectively. Physical exercise was significantly positively correlated with self-rated health (r = 0.194, p < 0.01), significantly negatively correlated with sleep quality (r = -0.035, p < 0.01), and significantly negatively correlated with stress, anxiety, and depression (r = -0.03, p < 0.01; r = -0.058, p < 0.01; r = -0.055, p < 0.01). Sleep quality was significantly negatively correlated with self-rated health (r = -0.242, p < 0.01). Mediation effect testing indicated that sleep quality and self-rated health partially mediated the relationship between physical exercise and negative emotions, with total effect, total direct effect, and total indirect effect values of -1.702, -0.426, and - 1.277, respectively. Conclusion: College students primarily engage in low-intensity physical activity. Sleep quality and self-rated health mediate the impact of physical exercise on students' negative emotions. A certain level of physical activity can directly affect students' emotional states and indirectly influence their negative emotions via sleep and self-rated health. Regular engagement in physical activities primarily positively impacts emotional states by enhancing mood stability and overall emotional resilience.

Full-Endoscopic Transforaminal Debridement and Decompression for Brucellar Thoracic Spinal Epidural Abscess: A Minimally Invasive Alternative to Open Surgery.

OBJECTIVE: Thoracic spinal epidural abscess (SEA) is a rare but dangerous condition, and traditional surgical methods are accompanied by extensive trauma and approach-related complications. Here we introduce the technique of full-endoscopic transforaminal debridement and decompression and evaluate its feasibility for treating brucellar thoracic SEA. METHODS: We performed thoracic full-endoscopic transforaminal decompression and debridement on two patients with neurological deficits caused by brucellar SEA, which is mainly composed of granulation tissue rather than pus. Postoperative MRI was conducted to confirm the presence of any residual abscess compressing the nerves. Frankel grading was employed to assess the recovery of neurological function, and complications were documented. RESULTS: There were no occurrences of dural tear, postoperative hematoma, or pulmonary complications. Their neurological function had significantly improved after surgery, and postoperative MRI confirmed no residual abscess compressing the spinal cord. During the 2-year follow-up, one patient achieved complete recovery (from Frankel-C to Frankel-E), while another patient improved from Frankel-A to Frankel-D. Neither patient experienced infection recurrence, instability, nor kyphotic deformity. CONCLUSION: We described the novel application of transforaminal endoscopic surgery in brucellar thoracic granulomatous SEA and preliminarily indicated the feasibility of this technique as a minimally invasive alternative to open surgery.

Differences in sleep spindle wave density between patients with diabetes mellitus and matched controls: implications for sensing and regulation of peripheral blood glucose.

Background: Brain waves during sleep are involved in sensing and regulating peripheral glucose level. Whether brain waves in patients with diabetes differ from those of healthy subjects is unknown. We examined the hypothesis that patients with diabetes have reduced sleep spindle waves, a form of brain wave implicated in periphery glucose regulation during sleep. Methods: From a retrospective analysis of polysomnography (PSG) studies on patients who underwent sleep apnea evaluation, we identified 1,214 studies of patients with diabetes mellitus (>66% type 2) and included a sex- and age-matched control subject for each within the scope of our analysis. We similarly identified 376 patients with prediabetes and their matched controls. We extracted spindle characteristics from artifact-removed PSG electroencephalograms and other patient data from records. We used rank-based statistical methods to test hypotheses. We validated our finding on an external PSG dataset. Results: Patients with diabetes mellitus exhibited on average about half the spindle density (median=0.38 spindles/min) during sleep as their matched control subjects (median=0.70 spindles/min) (P<2.2e-16). Compared to controls, spindle loss was more pronounced in female patients than in male patients in the frontal regions of the brain (P=0.04). Patients with prediabetes also exhibited signs of lower spindle density compared to matched controls (P=0.01-0.04). Conclusions: Patients with diabetes have fewer spindle waves that are implicated in glucose regulation than matched controls during sleep. Besides offering a possible explanation for neurological complications from diabetes, our findings open the possibility that reversing/reducing spindle loss could improve the overall health of patients with diabetes mellitus.

Observation on the tilt and decentration of multifocal intraocular lens with optic capture in Berger space for pediatric cataract.

PURPOSE: This study aimed to observe the tilt and decentration of multifocal intraocular lens (IOL) with optic capture in Berger space within 2 years after pediatric cataract surgery. METHODS: This is a prospective observational study. The implantation of multifocal IOL (Tecnis ZMB00) with optic capture in Berger space was performed on 33 patients (48 eyes) with pediatric cataract at Qingdao Eye Hospital. Tilt and decentration of IOL was measured using Scheimpflug system (Pentacam) at 1 month and 2 years postoperatively. RESULTS: All the multifocal IOLs were successfully implanted in Berger space with optic capture and no visually significant complications were detected during the follow-up. The mean tilt of IOLs was 2.779° ± 0.950° in the vertical plane and 2.399° ± 0.898° in the horizontal plane at 1 month postoperatively, and the mean length of the decentration was 0.207 ± 0.081 mm in vertical plane and 0.211 ± 0.090 mm in the horizontal plane. Compared with 1 month after surgery, the angle of tilt decreased by a mean of 0.192° and decentration increased by a mean of 0.014 mm at the vertical meridian at 2 years postoperatively (P = 0.37 and P = 0.27, respectively), meanwhile, tilt increased by 0.265° and decentration increased by 0.012 mm at the horizontal meridian (P = 0.11 and P = 0.22, respectively). CONCLUSIONS: The follow-up results suggest the tilt and decentration of multifocal IOL implantation with optic capture in Berger space remain stable in an acceptable range within 2 years after cataract surgery in children above the age of 5. TRIAL REGISTRATION: The study was approved by the Ethics Committee of Qingdao Eye Hospital, and registered on Chinese Clinical Trial Registry (ChiCTR identifier: 1900023155).

[Interaction between central nervous system and immune system after ischemic stroke and its therapeutic significance of traditional Chinese medicine].

Ischemic stroke is divided into acute phase, subacute phase, and recovery phase, with different pathological and physiological characteristics manifested at each stage. Among them, immune and inflammatory reactions persist for several days and weeks after ischemia. Ischemic stroke not only triggers local inflammation in damaged brain regions but also induces a disorder in the immune system, thereby promoting neuroinflammation and exacerbating brain damage. Therefore, conducting an in-depth analysis of the interaction between the central nervous system and the immune system after ischemic stroke, intervening in the main factors of the interaction between them, blocking pathological cascades, and thereby reducing brain inflammation have become the treatment strategies for ischemic stroke. This study summarizes and sorts out the interaction pathways between the central nervous system and the immune system. The impact of the central nervous system on the immune system can be analyzed from the perspective of the autonomic nervous system, the hypothalamic-pituitary-adrenal axis(HPA), and local inflammatory stimulation. The impact of the immune system on the central nervous system can be analyzed from the dynamic changes of immune cells. At the same time, the relevant progress in the prevention and treatment of traditional Chinese medicine(TCM) is summarized, so as to provide new insights for the analysis of complex mechanisms of TCM in preventing and treating ischemic stroke.

Finite difference-embedded UNet for solving transcranial ultrasound frequency-domain wavefield.

Transcranial ultrasound imaging assumes a growing significance in the detection and monitoring of intracranial lesions and cerebral blood flow. Accurate solution of partial differential equation (PDE) is one of the prerequisites for obtaining transcranial ultrasound wavefields. Grid-based numerical solvers such as finite difference (FD) and finite element methods have limitations including high computational costs and discretization errors. Purely data-driven methods have relatively high demands on training datasets. The fact that physics-informed neural network can only target the same model limits its application. In addition, compared to time-domain approaches, frequency-domain solutions offer advantages of reducing computational complexity and enabling stable and accurate inversions. Therefore, we introduce a framework called FD-embedded UNet (FEUNet) for solving frequency-domain transcranial ultrasound wavefields. The PDE error is calculated using the optimal 9-point FD operator, and it is integrated with the data-driven error to jointly guide the network iterations. We showcase the effectiveness of this approach through experiments involving idealized skull and brain models. FEUNet demonstrates versatility in handling various input scenarios and excels in enhancing prediction accuracy, especially with limited datasets and noisy information. Finally, we provide an overview of the advantages, limitations, and potential avenues for future research in this study.

Key mechanistic features of the trade-off between antibody escape and host cell binding in the SARS-CoV-2 Omicron variant spike proteins.

Since SARS-CoV-2 Omicron variant emerged, it is constantly evolving into multiple sub-variants, including BF.7, BQ.1, BQ.1.1, XBB, XBB.1.5 and the recently emerged BA.2.86 and JN.1. Receptor binding and immune evasion are recognized as two major drivers for evolution of the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein. However, the underlying mechanism of interplay between two factors remains incompletely understood. Herein, we determined the structures of human ACE2 complexed with BF.7, BQ.1, BQ.1.1, XBB and XBB.1.5 RBDs. Based on the ACE2/RBD structures of these sub-variants and a comparison with the known complex structures, we found that R346T substitution in the RBD enhanced ACE2 binding upon an interaction with the residue R493, but not Q493, via a mechanism involving long-range conformation changes. Furthermore, we found that R493Q and F486V exert a balanced impact, through which immune evasion capability was somewhat compromised to achieve an optimal receptor binding. We propose a "two-steps-forward and one-step-backward" model to describe such a compromise between receptor binding affinity and immune evasion during RBD evolution of Omicron sub-variants.

Healable and conductive sulfur iodide for solid-state Li-S batteries.

Solid-state Li-S batteries (SSLSBs) are made of low-cost and abundant materials free of supply chain concerns. Owing to their high theoretical energy densities, they are highly desirable for electric vehicles1-3. However, the development of SSLSBs has been historically plagued by the insulating nature of sulfur4,5 and the poor interfacial contacts induced by its large volume change during cycling6,7, impeding charge transfer among different solid components. Here we report an S9.3I molecular crystal with I2 inserted in the crystalline sulfur structure, which shows a semiconductor-level electrical conductivity (approximately 5.9 × 10-7 S cm-1) at 25 °C; an 11-order-of-magnitude increase over sulfur itself. Iodine introduces new states into the band gap of sulfur and promotes the formation of reactive polysulfides during electrochemical cycling. Further, the material features a low melting point of around 65 °C, which enables repairing of damaged interfaces due to cycling by periodical remelting of the cathode material. As a result, an Li-S9.3I battery demonstrates 400 stable cycles with a specific capacity retention of 87%. The design of this conductive, low-melting-point sulfur iodide material represents a substantial advancement in the chemistry of sulfur materials, and opens the door to the practical realization of SSLSBs.

Efficacy of Forsythia suspensa (Thunb.) Vahl on mouse and rat models of inflammation-related diseases: a meta-analysis.

Objective: To evaluate the efficacy of the fruits of the medicinal plant Forsythia suspensa (Thunb.) Vahl (FS), in treating inflammation-associated diseases through a meta-analysis of animal models, and also probe deeply into the signaling pathways underlying the progression of inflammation. Materials and methods: All data analyses were performed using Review Manager 5.3 and the results are presented as flow diagrams, risk-of-bias summaries, forest plots, and funnel plots. Summary estimates were calculated using a random- or fixed-effect model, depending on the value of I2. Results: Of the 710 records identified in the initial search, 11 were selected for the final meta-analysis. Each study extracted data from the model and treatment groups for analysis, and the results showed that FS alleviated the inflammatory cytokine levels in serum; oxidant indicator: reactive oxygen species; enzymes of liver function; endotoxin and regulatory cells in blood; and improved the antioxidant enzyme superoxide dismutase. Conclusion: FS effectively reversed the change in acute or chronic inflammation indicators in animal models, and the regulation of multiple channel proteins in inflammatory signaling pathways suggests that FS is a good potential drug for inflammatory disease drug therapy.