One step toward precision dosing of caffeine in preterm infants: An external evaluation of published population pharmacokinetic models.

BACKGROUND: Several population pharmacokinetic (PopPK) models of caffeine in preterm infants have been published, but the extrapolation of these models to facilitate model-informed precision dosing (MIPD) in clinical practice is uncertain. This study aimed to comprehensively evaluate their predictive performance using an external, independent dataset. METHODS: Data used for external evaluation were based on an independent cohort of preterm infants. Currently available PopPK models for caffeine in preterm infants were identified and re-established. Prediction- and simulation-based diagnostics were used to assess model predictability. The influence of prior information was assessed using Bayesian forecasting. RESULTS: 120 plasma samples from 76 preterm infants were included in the evaluation dataset. Twelve PopPK models of caffeine in preterm infants were re-established based on our previously published study. Although two models showed superior predictive performance, none of the 12 PopPK models met all the clinical acceptance criteria of these external evaluation items. Besides, the external predictive performances of most models were unsatisfactory in prediction- and simulation-based diagnostics. Nevertheless, the application of Bayesian forecasting significantly improved the predictive performance, even with only one prior observation. CONCLUSIONS: Two models that included the most covariates had the best predictive performance across all external assessments. Inclusion of different covariates, heterogeneity of preterm infant characteristics, and different study designs influenced predictive performance. Thorough evaluation is needed before these PopPK models can be implemented in clinical practice. The implementation of MIPD for caffeine in preterm infants could benefit from the combination of PopPK models and Bayesian forecasting as a helpful tool.

A Hypoxia-Decidual Macrophage Regulatory Axis in Normal Pregnancy and Spontaneous Miscarriage.

The significance of hypoxia at the maternal-fetal interface is proven to be self-explanatory in the context of pregnancy. During the first trimester, low oxygen conditions play a crucial role in processes such as angiogenesis, trophoblast invasion and differentiation, and immune regulation. Recently, there has been increasing research on decidual macrophages, which contribute to the maintenance of immune tolerance, placental and fetal vascular development, and spiral artery remodeling, to investigate the effects of hypoxia on their biological behaviors. On these grounds, this review describes the dynamic changes in oxygen levels at the maternal-fetal interface throughout gestation, summarizing current knowledge on how the hypoxic environment sustains a successful pregnancy by regulating retention, differentiation and efferocytosis of decidual macrophages. Additionally, we explore the relationship between spontaneous miscarriages and an abnormal hypoxia-macrophage axis, shedding light on the underlying mechanisms. However, further studies are essential to elucidate these pathways in greater detail and to develop targeted interventions that could improve pregnancy outcomes.

Effectiveness of microneedle fractional radiofrequency combined with transcutaneous delivery of botulinum toxin in the management of post-acne scars.

BACKGROUND: Post-acne scars are a common sequela of acne, especially prevalent among young people. Delayed treatment not only affects self-perception of beauty but also affects the mental health of patients. OBJECTIVE: This study aims to investigate the clinical efficacy of microneedle fractional radiofrequency (MFR) combined with botulinum toxin A (BoNT/A) in managing post-acne scars. METHODS: This retrospective study involved 63 adult patients with post-acne scars, divided into two groups: group 1 (n = 30) and group 2 (n = 33). Group 1 received treatment with MFR combined with transcutaneous delivery of BoNT/A, whereas group 2 received treatment with MFR alone. The study observed the clinical outcomes in both groups. RESULTS: Based on experimental analysis, the combination of MFR with transcutaneous delivery of BoNT/A demonstrated superior clinical efficacy compared with group 2. There were no significant differences in baseline data or treatment-related pain and adverse reactions between the two groups. However, group 1 exhibited a higher effectiveness rate, lower ECCA score after treatment, higher satisfaction levels, and statistically significant differences compared to group 2. CONCLUSION: MFR combined with transcutaneous delivery of BoNT/A represents an effective and safe alternative for treating acne scars with minimal side effects and complications. SUMMARY STATEMENT: Post-acne scars are a common sequela of acne and combination therapy proves beneficial. Microneedle fractional radiofrequency (MFR) combined with transcutaneous delivery of BoNT/A can be considered an effective and safe alternative for the treatment of acne scars with minimal side effects and complications. It works together through microneedles, radiofrequency, and botulinum toxin. MFR combined with transcutaneous delivery of BoNT/A is based on the direct action of MFR on acne scars and the use of microneedle to create a transient skin microchannel, facilitating BoNT/A penetration into the skin.

Deficiency of geranylgeranyl biphosphate synthase in kidney tubules causes cystic kidney disease.

Polycystic kidney disease (PKD) is a common hereditary kidney disease. Although PKD occurrence is associated with certain gene mutations, its onset regulatory mechanisms are still not well understood. Here, we first report that the key enzyme geranylgeranyl diphosphate synthase (GGPPS) is specifically expressed in renal tubular epithelial cells of mouse kidneys. We aimed to explore the role of GGPPS in PKD. In this study, we established a Ggppsfl/fl:Cdh16cre mouse model and compared its phenotype with that of wild-type mice. A Ggpps-downregulation HK2 cell model was also used to further determine the role of GGPPS. We found that GGPPS was specifically expressed in renal tubular epithelial cells of mouse kidneys. Its expression also increased with age. Low GGPPS expression was observed in human ADPKD tissues. In the Ggppsfl/fl:Cdh16cre mouse model, Ggpps deletion in renal tubular epithelial cells induced the occurrence and development of renal tubule cystic dilation and caused the death of mice after birth due to abnormal renal function. Enhanced proliferation of cyst-lining epithelial cells was also observed after the knockout of Ggpps. These processes were related to the increased rate of Rheb on membrane/cytoplasm and hyperactivation of mTORC1 signaling. In conclusion, the deficiency of GGPPS in kidney tubules induced the formation of renal cysts. It may play a critical role in PKD pathophysiology. A novel therapeutic strategy could be designed according to this work.

Incidence and prevalence of systemic lupus erythematosus in urban China, 2013-2017: A nationwide population-based study.

Systemic lupus erythematosus (SLE) is becoming a growing public health concern due to increasing disease and economic burdens. Epidemiological information about SLE, especially its incidence rate, is limited in developing countries. In the current study, we sought to investigate the incidence, prevalence, and economic burdens of SLE in urban China. We conducted a nationwide population-based cohort study using databases from Urban Employee Basic Medical Insurance and Urban Resident Basic Medical Insurance between 2013 and 2017, covering approximately 300 million residents in 23 provincial regions in China. Incidence rate and prevalence were standardized by age and gender to China's 2010 national census data. Additionally, we calculated the average annual costs and hospital visit rates. A total of 132,258 SLE patients were identified during the study period, with a mean age of 43.03 years (standard deviation: 15.29 years). Of these patients, 81.33% were women. In 2017, the standardized incidence rate of SLE in China was 14.09 (95% confidence interval (CI), 11.95-16.41) per 100,000 person-years, with a higher incidence in women than in men (26.41 vs. 5.92 per 100,000 person-years). Standardized prevalence in 2017 was 47.61 (41.77-53.83), 94.16 (80.67-108.69), and 17.86 (13.84-22.38) per 100,000 people in the overall, female, and male populations, respectively. The average annual rates of increase in prevalence were 21.50%, 19.72%, and 25.67% from 2013 to 2017 in the overall, female, and male populations, respectively. The age-specific incidence rates peaked at 30-49 years old in women and 40-59 years old in men. SLE incident and prevalent cases were most common in North-West China and less common in southern and eastern China. Distinct variations in incidence rates across different regions are also consistent with the varying levels of ultraviolet radiation exposure in China. Additionally, the average estimated annual per-capita cost was 1599.34 US dollars in SLE patients, with the highest costs observed in adolescent and young adult patients among different age groups. The SLE population in China is rapidly expanding, and younger at onset, especially in women, which has placed significant burdens on China's healthcare system.

Development and application of a population pharmacokinetic model repository for caffeine dose tailoring in preterm infants.

BACKGROUND: Considerable interindividual variability for the pharmacokinetics of caffeine in preterm infants has been demonstrated, emphasizing the importance of personalized dosing. This study aimed to develop and apply a repository of currently published population pharmacokinetic (PopPK) models of caffeine in preterm infants to facilitate model-informed precision dosing (MIPD). RESEARCH DESIGN AND METHODS: Literature search was conducted using PubMed, Embase, Scopus, and Web of Science databases. Relevant publications were screened, and their quality was assessed. PopPK models were reestablished to develop the model repository. Covariate effects were evaluated and the concentration-time profiles were simulated. An online simulation and calculation tool was developed as an instance. RESULTS: Twelve PopPK models were finally included in the repository. Preterm infants' age and body size, especially the postnatal age and current weight, were identified as the most clinically critical covariates. Simulated blood concentration-time profiles across these models were comparable. Caffeine citrate-dose regimen should be adjusted according to the age and body size of preterm infants. The developed online tool can be used to facilitate clinical decision-making. CONCLUSIONS: The first developed repository of PopPK models for caffeine in preterm infants has a wide range of potential applications in the MIPD of caffeine.

Facial Action Unit Representation Based on Self-Supervised Learning With Ensembled Priori Constraints.

Facial action units (AUs) focus on a comprehensive set of atomic facial muscle movements for human expression understanding. Based on supervised learning, discriminative AU representation can be achieved from local patches where the AUs are located. Unfortunately, accurate AU localization and characterization are challenged by the tremendous manual annotations, which limits the performance of AU recognition in realistic scenarios. In this study, we propose an end-to-end self-supervised AU representation learning model (SsupAU) to learn AU representations from unlabeled facial videos. Specifically, the input face is decomposed into six components using auto-encoders: five photo-geometric meaningful components, together with 2D flow field AUs. By constructing the canonical neutral face, posed neutral face, and posed expressional face gradually, these components can be disentangled without supervision, therefore the AU representations can be learned. To construct the canonical neutral face without manually labeled ground truth of emotion state or AU intensity, two priori knowledge based assumptions are proposed: 1) identity consistency, which explores the identical albedos and depths of different frames in a face video, and helps to learn the camera color mode as an extra cue for canonical neutral face recovery. 2) average face, which enables the model to discover a 'neutral facial expression' of the canonical neutral face and decouple the AUs in representation learning. To the best of our knowledge, this is the first attempt to design self-supervised AU representation learning method based on the definition of AUs. Substantial experiments on benchmark datasets have demonstrated the superior performance of the proposed work in comparison to other state-of-the-art approaches, as well as an outstanding capability of decomposing input face into meaningful factors for its reconstruction. The code is made available at https://github.com/Sunner4nwpu/SsupAU.

Association of apolipoprotein A1 levels with lumbar bone mineral density and ß-CTX in osteoporotic fracture individuals: a cross-sectional investigation.

Background: The relationship between the levels of high-density lipoprotein (HDL) and bone mineral density (BMD) is controversial. Furthermore, the specific role of apolipoprotein A1 (APOA1), a primary HDL component, in regulating BMD remains unclear. This study aimed to elucidate the correlation between APOA1 levels and lumbar BMD in patients with osteoporotic fracture (OPF) for novel insights into potential therapeutic strategies against osteoporosis. Methods: This study included 587 OPF patients enrolled at the Kunshan Hospital, Affiliated with Jiangsu University between January 2017 and July 2022. The patient's serum APOA1 levels were determined, followed by the assessment of lumbar BMD and C-terminal telopeptide of type I collagen (ß-CTX) as outcome variables. The association of APOA1 levels with lumbar BMD and ß-CTX was assessed via Generalized Estimating Equations (GEE) and spline smoothing plot analyses. A generalized additive model (GAM) helped ascertain non-linear correlations. Moreover, a subgroup analysis was also conducted to validate the result's stability. Results: It was observed that APOA1 levels were positively correlated with lumbar BMD (ß = 0.07, 95% CI: 0.02 to 0.11, p = 0.0045), indicating that increased APOA1 levels were linked with enhanced lumbar BMD. Furthermore, APOA1 levels were negatively related to ß-CTX (ß = -0.19, 95% CI: -0.29 to -0.09, p = 0.0003), suggesting APOA1 might reduce osteolysis. In addition, these findings were robustly supported by subgroup and threshold effect analyses. Conclusion: This study indicated that increased APOA1 levels were correlated with enhanced lumbar BMD and decreased osteolysis in OPF patients. Therefore, APOA1 may inhibit osteoclast activity to prevent further deterioration in osteoporotic patients. However, further research I warranted to validate these conclusions and elucidate the underlying physiologies.

Efficacy and survival outcome of allogeneic stem-cell transplantation in multiple myeloma: meta-analysis in the recent 10 years.

Introduction: Allogeneic hematopoietic cell transplantation (alloHCT) possessed direct cytotoxicity and graft-versus-multiple myeloma effect (GvMM). Growing trials have shown survival benefits of performing alloHCT in both newly diagnosed and relapsed MM. Methods: We aimed to provide a comprehensive analysis in the recent 10 years to verify the efficacy and survival outcome of alloHCT in MM patients. A total of 61 studies which provide data between 14/04/2013 and 14/04/2023 and a total of 15,294 data from MM patients who had undergone alloSCT were included in our study. The best response rates (CR, VGPR, PR) and survival outcomes (1-, 2-, 3-,5-, and 10-year OS, PFS, NRM) were assessed. We further conducted meta-analysis in the NDMM/frontline setting and RRMM/salvage setting independently. Results: The pooled estimate CR, VGPR, and PR rates were 0.45, 0.21, and 0.24, respectively. The pooled estimates of 1-, 2-, 3-, 5-, and 10-year OS were 0.69, 0.57, 0.45, 0.45, and 0.36, respectively; the pooled estimates of 1-, 2-, 3-, 5-, and 10-year PFS were 0.47, 0.35, 0.24, 0.25, and 0.28, respectively; and the pooled estimates of 1-, 2-, 3-, 5-, and 10-year NRM were 0.16, 0.21, 0.16, 0.20, and 0.15, respectively. In the NDMM/upfront setting, the pooled estimate CR rate was 0.54, and those for 5-year OS, PFS, and NRM were 0.69, 0.40, and 0.11, respectively. In a relapsed setting, the pooled estimate CR rate was 0.31, and those for 5-year OS, PFS, and NRM were 0.24, 0.10, and 0.15, respectively. Discussion: Our results showed constant OS, PFS, and NRM from the third year onwards till the 10th year, suggesting that alloSCT has sustained survival benefits. Good response rate and promising survival outcome were observed in the NDMM/ frontline setting. Conclusion: Although comparing with other treatments, alloSCT had a lower response rate and poorer short-term survival outcome, long-term follow-up could reveal survival benefits of alloSCT in MM patients.

Advancements in microenvironment-based therapies: transforming the landscape of multiple myeloma treatment.

Multiple myeloma (MM) is the most prevalent malignant monoclonal disease of plasma cells. There is mounting evidence that interactions with the bone marrow (BM) niche are essential for the differentiation, proliferation, survival, migration, and treatment resistance of myeloma cells. For this reason, gaining a deeper comprehension of how BM microenvironment compartments interact with myeloma cells may inspire new therapeutic ideas that enhance patient outcomes. This review will concentrate on the most recent findings regarding the mechanisms of interaction between microenvironment and MM and highlight research on treatment targeting the BM niche.

A dual-radiomics model for overall survival prediction in early-stage NSCLC patient using pre-treatment CT images.

Introduction: Radiation therapy (RT) is one of the primary treatment options for early-stage non-small cell lung cancer (ES-NSCLC). Therefore, accurately predicting the overall survival (OS) rate following radiotherapy is crucial for implementing personalized treatment strategies. This work aims to develop a dual-radiomics (DR) model to (1) predict 3-year OS in ES-NSCLC patients receiving RT using pre-treatment CT images, and (2) provide explanations between feature importanceand model prediction performance. Methods: The publicly available TCIA Lung1 dataset with 132 ES-NSCLC patients received RT were studied: 89/43 patients in the under/over 3-year OS group. For each patient, two types of radiomic features were examined: 56 handcrafted radiomic features (HRFs) extracted within gross tumor volume, and 512 image deep features (IDFs) extracted using a pre-trained U-Net encoder. They were combined as inputs to an explainable boosting machine (EBM) model for OS prediction. The EBM's mean absolute scores for HRFs and IDFs were used as feature importance explanations. To evaluate identified feature importance, the DR model was compared with EBM using either (1) key or (2) non-key feature type only. Comparison studies with other models, including supporting vector machine (SVM) and random forest (RF), were also included. The performance was evaluated by the area under the receiver operating characteristic curve (AUCROC), accuracy, sensitivity, and specificity with a 100-fold Monte Carlo cross-validation. Results: The DR model showed highestperformance in predicting 3-year OS (AUCROC=0.81 ± 0.04), and EBM scores suggested that IDFs showed significantly greater importance (normalized mean score=0.0019) than HRFs (score=0.0008). The comparison studies showed that EBM with key feature type (IDFs-only demonstrated comparable AUCROC results (0.81 ± 0.04), while EBM with non-key feature type (HRFs-only) showed limited AUCROC (0.64 ± 0.10). The results suggested that feature importance score identified by EBM is highly correlated with OS prediction performance. Both SVM and RF models were unable to explain key feature type while showing limited overall AUCROC=0.66 ± 0.07 and 0.77 ± 0.06, respectively. Accuracy, sensitivity, and specificity showed a similar trend. Discussion: In conclusion, a DR model was successfully developed to predict ES-NSCLC OS based on pre-treatment CT images. The results suggested that the feature importance from DR model is highly correlated to the model prediction power.

Spatial-temporal pattern of ecosystem services and sustainable development in representative mountainous cities: A case study of Chengdu-Chongqing Urban Agglomeration.

The Sustainable Development Goals (SDGs) are essential measure for preserving the balance between human well-being and natural ecosystems. The benefit of preserving ecosystems health play a crucial role in promoting the SDGs by providing stable ecosystem services (ESs). However, the ecological health of mountainous cities is vulnerable, with relative low ecological resilience. To investigate the conflict between ecosystems and sustainable development, this study takes the Chengdu-Chongqing Urban Agglomeration as the study area. The major tasks and results in this study include: (1) using the entropy weighting method and the InVEST model, we combined remote sensing, geographic, and statistical data to quantify three types of SDGs (economic, social, environmental) and four ESs (water yield, soil conservation, habitat quality, carbon storage), and establish a localized sustainable development assessment framework that is applicable to the Chengdu-Chongqing Urban Agglomeration. The results show that from 2014 to 2020, the three types of SDGs exhibited an overall upward trend, with the lowest values occurring in 2016. The gap between different counties has narrowed, but significant regional differences still remain, indicating an unbalanced development status quo. Among the 142 counties, water yield and soil conservation values show a consistent downward trend but occupies significant interannual variations, while habitat quality and carbon storage values increases consistently each year. (2) using Spearman's nonparametric correlation analysis and multiscale geographically weighted regression model to explore the temporal variation and spatial heterogeneity of correlations between county ESs and SDGs. The results showed significant heterogeneity in the spatial trade-offs and synergies between ESs and SDGs, with two pairs of synergies weakening, seven pairs of trade-offs increasing, and the strongest negative correlation between Economic Sustainable Development Goals and habitat quality. (3) we applied the self-organizing mapping neural networks to analyze the spatial clustering characteristics of ESs-SDGs. Based on the spatial clustering effects, we divides the Chengdu-Chongqing Urban Agglomeration into four zones, and different zones have different levels of ESs and SDGs. The targeted strategies should be adopted according to local conditions. This work is of great practical importance in maintaining the stability and sustainable development of the Chengdu-Chongqing Urban Agglomeration ecosystem and provides a scientific reference for the optimal regulation of mountainous cities.

Neuropeptide Y receptor Y8b (npy8br) regulates feeding and digestion in Japanese medaka (Oryzias latipes) larvae: evidence from gene knockout. / 神经肽受体Y8b（npy8br）调节日本青鳉（Oryzias latipes）仔鱼的摄食和消化： æ¥è‡ªåŸºå› æ•²é™¤çš„è¯æ®.

Neuropeptide Y receptor Y8 (NPY8R) is a fish-specific receptor with two subtypes, NPY8AR and NPY8BR. Changes in expression levels during physiological processes or in vivo regulation after ventricular injection suggest that NPY8BR plays an important role in feeding regulation; this has been found in only a few fish, at present. In order to better understand the physiological function of npy8br, especially in digestion, we used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology to generate npy8br-/- Japanese medaka (Oryzias latipes). We found that the deletion of npy8br in medaka larvae affected their feeding and digestion ability, ultimately affecting their growth. Specifically, npy8br deficiency in medaka larvae resulted in decreased feed intake and decreased expression levels of orexigenic genes (npy and agrp). npy8br-/- medaka larvae fed for 10 d (10th day of feeding) still had incompletely digested brine shrimp (Artemia nauplii) in the digestive tract 8 h after feeding, the messenger RNA (mRNA) expression levels of digestion-related genes (amy, lpl, ctra, and ctrb) were significantly decreased, and the activity of amylase, trypsin, and lipase also significantly decreased. The deletion of npy8br in medaka larvae inhibited the growth and significantly decreased the expression of growth-related genes (gh and igf1). Hematoxylin and eosin (H&E) sections of intestinal tissue showed that npy8br-/- medaka larvae had damaged intestine, thinned intestinal wall, and shortened intestinal villi. So far, this is the first npy8br gene knockout model established in fish and the first demonstration that npy8br plays an important role in digestion.

DOT-SLAM: A Stereo Visual Simultaneous Localization and Mapping (SLAM) System with Dynamic Object Tracking Based on Graph Optimization.

Most visual simultaneous localization and mapping (SLAM) systems are based on the assumption of a static environment in autonomous vehicles. However, when dynamic objects, particularly vehicles, occupy a large portion of the image, the localization accuracy of the system decreases significantly. To mitigate this challenge, this paper unveils DOT-SLAM, a novel stereo visual SLAM system that integrates dynamic object tracking through graph optimization. By integrating dynamic object pose estimation into the SLAM system, the system can effectively utilize both foreground and background points for ego vehicle localization and obtain a static feature points map. To rectify the inaccuracies in depth estimation from stereo disparity directly on the foreground points of dynamic objects due to their self-similarity characteristics, a coarse-to-fine depth estimation method based on camera-road plane geometry is presented. This method uses rough depth to guide fine stereo matching, thereby obtaining the 3 dimensions (3D)spatial positions of feature points on dynamic objects. Subsequently, by establishing constraints on the dynamic object's pose using the road plane and non-holonomic constraints (NHCs) of the vehicle, reducing the initial pose uncertainty of dynamic objects leads to more accurate dynamic object initialization. Finally, by considering foreground points, background points, the local road plane, the ego vehicle pose, and dynamic object poses as optimization nodes, through the establishment and joint optimization of a nonlinear model based on graph optimization, accurate six degrees of freedom (DoFs) pose estimations are obtained for both the ego vehicle and dynamic objects. Experimental validation on the KITTI-360 dataset demonstrates that DOT-SLAM effectively utilizes features from the background and dynamic objects in the environment, resulting in more accurate vehicle trajectory estimation and a static environment map. Results obtained from a real-world dataset test reinforce the effectiveness.

Association between systemic inflammatory response index and bone turnover markers in Chinese patients with osteoporotic fractures: a retrospective cross-sectional study.

Background: The systemic inflammatory response index (SIRI) is a novel composite biomarker of inflammation. However, there is limited information on its use in the context of osteoporotic fractures. Hence, this study aimed to investigate the association between baseline SIRI values and bone turnover markers (BTMs) in Chinese patients diagnosed with osteoporotic fractures (OPFs), to offer a more precise method for assessing bone health and inflammation in clinical settings. Methods: A retrospective cross-sectional study was conducted on 3,558 hospitalized patients with OPFs who required surgery or hospitalization at the First People's Hospital of Kunshan City from January 2017 to July 2022. Baseline measurements of SIRI, ß-CTX (beta-C-terminal telopeptide of type I collagen), and P1NP (procollagen type I N-terminal propeptide) were obtained. The analyses were adjusted for variables, including age, sex, body mass index (BMI), and other initial laboratory and clinical findings. Furthermore, multivariable logistic regression, smooth curve fitting, and threshold analysis were also performed. Results: The results revealed a negative correlation between baseline SIRI values and both ß-CTX and P1NP levels. After adjusting for covariates in the regression analysis, each unit increase in SIRI was found to be inked to a reduction of 0.04 (ß = -0.04; 95% confidence interval [CI], -0.05 to -0.03; with p-value <0.001) in ß-CTX levels and a decrease of 3.77 (ß = 3.77; 95% CI, 5.07 to 2.47; with p-value <0.001) in P1NP levels. Furthermore, a curvilinear relationship and threshold effect were also identified. Turning points were identified at SIRI values of 1.41 and 1.63 on the adjusted smooth curve. Conclusion: The results showed a negative correlation between the baseline SIRI value and ß-CTX level, as well as the level of P1NP. This suggests a possible link between the systemic inflammatory response and reduced bone metabolism. If these findings are verified, SIRI has the potential to function as a predictive indicator for BTMs. Nevertheless, additional research is necessary to verify these findings.

The effect of quarantine policy on pollution emission and the usage of private transportation in urban areas.

Governmental policies, regulations, and responses to the pandemic can benefit from a better understanding of people's resulting behaviours before, during, and after COVID-19. To avoid the inelasticity and subjectivity of survey datasets, several studies have already used some objective variables like air pollutants to estimate the potential impacts of COVID-19 on the urban transportation system. However, the usage of reactant gases and a narrow time scale might weaken the results somehow. Here, both the objective passenger volume of public transport and the concentration of private traffic emitted black carbon (BC) from 2018 to 2023 were collected/calculated to decipher the potential relationship between public and private traffic during the COVID-19 period. Our results indicated that the commuting patterns of citizens show significant (p < 0.01) different patterns before, during, and after the pandemic. To be specific, public transportation showed a significant (p < 0.01) positive correlation with private transportation before the pandemic. This public transportation was significantly (p < 0.01) affected by the outbreaks of COVID-19, showing a significant (p < 0.01) negative correlation with private transportation. Such impacts of the virus and governmental policy would affect the long-term behaviour of individuals and even affect public transportation usage after the pandemic. Our results also indicated that such behaviour was mainly linked to the governmental restriction policy and would soon be neglected after the cancellation of the restriction policy in China.

Disruption of cyclin D1 degradation leads to the development of mantle cell lymphoma.

Cyclin D1 has been recognized as an oncogene due to its abnormal upregulation in different types of cancers. Here, we demonstrated that cyclin D1 is SUMOylated, and we identified Itch as a specific E3 ligase recognizing SUMOylated cyclin D1 and mediating SUMO-induced ubiquitination and proteasome degradation of cyclin D1. We generated cyclin D1 mutant mice with mutations in the SUMOylation site, phosphorylation site, or both sites of cyclin D1, and found that double mutant mice developed a Mantle cell lymphoma (MCL)-like phenotype. We showed that arsenic trioxide (ATO) enhances cyclin D1 SUMOylation-mediated degradation through inhibition of cyclin D1 deSUMOylation enzymes, leading to MCL cell apoptosis. Treatment of severe combined immunodeficiency (SCID) mice grafted with MCL cells with ATO resulted in a significant reduction in tumor growth. In this study, we provide novel insights into the mechanisms of MCL tumor development and cyclin D1 regulation and discover a new strategy for MCL treatment.

CRISPR-mediated Sox9 activation and RelA inhibition enhance cell therapy for osteoarthritis.

Osteoarthritis (OA) is a painful and debilitating disease affecting over 500 million people worldwide. Intraarticular injection of mesenchymal stromal cells (MSCs) shows promise for the clinical treatment of OA, but the lack of consistency in MSC preparation and application makes it difficult to further optimize MSC therapy and to properly evaluate the clinical outcomes. In this study, we used Sox9 activation and RelA inhibition, both mediated by the CRISPR-dCas9 technology simultaneously, to engineer MSCs with enhanced chondrogenic potential and downregulated inflammatory responses. We found that both Sox9 and RelA could be fine-tuned to the desired levels, which enhances the chondrogenic and immunomodulatory potentials of the cells. Intraarticular injection of modified cells significantly attenuated cartilage degradation and palliated OA pain compared with the injection of cell culture medium or unmodified cells. Mechanistically, the modified cells promoted the expression of factors beneficial to cartilage integrity, inhibited the production of catabolic enzymes in osteoarthritic joints, and suppressed immune cells. Interestingly, a substantial number of modified cells could survive in the cartilaginous tissues including articular cartilage and meniscus. Together, our results suggest that CRISPR-dCas9-based gene regulation is useful for optimizing MSC therapy for OA.

Superconductivity with T c of 116 K discovered in antimony polyhydrides.

Superconductivity (SC) was experimentally observed for the first time in antimony polyhydride. The diamond anvil cell combined with a laser heating system was used to synthesize the antimony polyhydride sample at high pressure and high temperature. In-situ high pressure transport measurements as a function of temperature with an applied magnetic field were performed to study the SC properties. It was found that the antimony polyhydride samples show superconducting transition with critical temperature T c 116 K at 184 GPa. The investigation of SC at magnetic field revealed the superconducting coherent length of ∼40 Å based on the Ginzburg Landau (GL) equation. Antimony polyhydride superconductor has the second highest T c in addition to sulfur hydride among the polyhydrides of elements from main groups IIIA to VIIA in the periodic table.

Multimode interference methane sensor based on a ZIF-8/PDMS composite film.

A multimode interference methane sensor based on a ZIF-8/PDMS composite film is proposed. The sensing principle is that the refractive index of the ZIF-8/PDMS composite film changes when it adsorbs methane, leading to a measurable optical path difference during the coupling of the cladding higher-order modes and the fundamental mode in the multimode interference fiber (MMI). The environmental methane concentration is then detectable by detecting the wavelength shifts of the interference peaks in the resulted spectrum. Through simulations and experiments aimed at enhancing sensor sensitivity, we optimized three parameters within the sensor structure: the length of the Tapered Single-Mode Fiber (TSMF), the composite film thickness, and the TSMF taper diameter. The experimental results indicate that the sensor's sensitivity reaches a maximum of 0.231 nm%-1. Additionally, the sensor exhibits excellent structural stability and measurement repeatability. The response time is as short as 40 s, and the recovery time ranges between 3 and 5 min. The proposed multimode interferometric methane sensor based on the ZIF-8/PDMS composite film has great potential to support highly sensitive methane concentration detection in many applications.