Epidemic characteristics of measles and efforts to control measles infections in Zhejiang Province, China.

Objectives: Several countries have successfully eliminated measles, and China is making significant strides toward achieving this goal. This study focused on investigating the patterns of measles infections in Zhejiang Province, China, as well as control measures. The objective was to provide valuable insights that could contribute to the development of nationwide elimination strategies. Methods: We analyzed measles surveillance data from 2005 to 2022 in Zhejiang Province. We utilized a joinpoint regression model to examine trends in measles. Additionally, we employed SaTScan software (version 9.5) to identify spatial-temporal clusters. Finally, we used an age-period-cohort model to assess the effects of age, period, and cohort. Results: The age-standardized incidence rate (ASIR) of measles infection in Zhejiang Province from 2005 to 2022 was 5.24 per 100,000, showing a consistent and significant downward trend with an annual percentage change of -24.93% (p<0.05). After 2020, the ASIR for measles infection fell to below 0.1 per 100,000. The majority of measles cases occurred in individuals either without an immunization history or with an unknown immunization status, representing 41.06% and 41.40% of the cases from 2010 to 2022, respectively. According to data from the National Measles Surveillance System, the annual rate of discarded measles cases from 2009 to 2014, and the annual rate of discarded measles and rubella cases from 2015 to 2022, were both above 2 per 100,000, indicating the high sensitivity of the measles surveillance system. Conclusion: The significant reduction in measles incidence from 2005 to 2022 demonstrates substantial progress in Zhejiang Province towards the elimination of measles.

Automated ECL Aptasensing Platform from an Intrarticular Radical Annihilation Route for Distinguishing Glioma Stages.

Nowadays, continuous efforts have been devoted to designing stable and high-efficiency electrochemiluminescence (ECL) emitters as alternatives for tris(2,2'-bipyridine)-ruthenium(II) (Ru(bpy)32+) in medical research. Herein, a novel ECL emitter was obtained by coordinating crystalline covalent triazinyl frameworks (cCTFs) with Ru2+ (termed Ru-cCTFs), which exhibited strong ECL emission by the ligand to metal charge transfer (LMCT) route. After its integration with 4-mercaptopyridine (SH-Py), the resultant SH-Py-Ru-cCTFs achieved 2.3-fold enhancement in the ECL efficiency by employing Ru(bpy)32+ as a standard, which involved a dynamic "intrarticular radical annihilation" ECL pathway. On such foundation, an automated ECL (A-ECL) aptasensor was constructed with an "on-off-on" model and magnetic separation upon linkage of the SH-Py-Ru-cCTFs with streptavidin (SA) magnetic beads (MBs). This automatic assay of miRNA-182 showed a wider linear range from 1.0 to 100.0 fM with a correlation coefficient (R2) of 0.994, a lower limit of detection (LOD) down to 0.28 fM, and faster operation within 41 min. Impressively, this bioassay facilely distinguished the stages of glioma disease from clinical blood samples with high accuracy. Hence, this research sheds light on how to develop advanced ECL luminophores and an automatic method, showing substantial insights into pathogenesis research of gliomas.

An atlas of genetic effects on cellular composition of the tumor microenvironment.

Deciphering the composition of the tumor microenvironment (TME) is critical for understanding tumorigenesis and to design immunotherapies. In the present study, we mapped genetic effects on cell-type proportions using single-cell and bulk RNA sequencing data, identifying 3,494 immunity quantitative trait loci (immunQTLs) across 23 cancer types from The Cancer Genome Atlas. Functional annotation revealed regulatory potential and we further assigned 1,668 genes that regulate TME composition. We constructed a combined immunQTL map by integrating data from European and Chinese colorectal cancer (CRC) samples. A polygenic risk score that incorporates these immunQTLs and hits on a genome-wide association study outperformed in CRC risk stratification within 447,495 multiethnic individuals. Using large-scale population cohorts, we identified that the immunQTL rs1360948 is associated with CRC risk and prognosis. Mechanistically, the rs1360948-G-allele increases CCL2 expression, recruiting regulatory T cells that can exert immunosuppressive effects on CRC progression. Blocking the CCL2-CCR2 axis enhanced anti-programmed cell death protein 1 ligand therapy. Finally, we have established a database (CancerlmmunityQTL2) to serve the research community and advance our understanding of immunogenomic interactions in cancer pathogenesis.

Dissolvable microneedle-based wound dressing transdermally and continuously delivers anti-inflammatory and pro-angiogenic exosomes for diabetic wound treatment.

Due to overactive inflammation and hindered angiogenesis, self-healing of diabetic wounds (DW) remains challenging in the clinic. Platelet-derived exosomes (PLT-Exos), a novel exosome capable of anti-inflammation and pro-angiogenesis, show great potential in DW treatment. However, previous administration of exosomes into skin wounds is topical daub or intradermal injection, which cannot intradermally deliver PLT-Exos into the dermis layer, thus impeding its long-term efficacy in anti-inflammation and pro-angiogenesis. Herein, a dissolvable microneedle-based wound dressing (PLT-Exos@ADMMA-MN) was developed for transdermal and long-term delivery of PLT-Exos. Firstly, a photo-crosslinking methacrylated acellular dermal matrix-based hydrogel (ADMMA-GEL), showing physiochemical tailorability, fast-gelling performance, excellent biocompatibility, and pro-angiogenic capacities, was synthesized as a base material of our dressing. For endowing the dressing with anti-inflammation and pro-angiogenesis, PLT-Exos were encapsulated into ADMMA-GEL with a minimum effective concentration determined by our in-vitro experiments. Then, in-vitro results show that this dressing exhibits excellent properties in anti-inflammation and pro-angiogenesis. Lastly, in-vivo experiments showed that this dressing could continuously and transdermally deliver PLT-Exos into skin wounds to switch local macrophage into M2 phenotype while stimulating neovascularization, thus proving a low-inflammatory and pro-angiogenic microenvironment for DW healing. Collectively, this study provides a novel wound dressing capable of suppressing inflammation and stimulating vascularization for DW treatment.

Regorafenib combined with immune checkpoint inhibitors versus regorafenib monotherapy as a late-line treatment for metastatic colorectal cancer: a single-center, retrospective cohort study.

Background: Few data are available on metastatic colorectal cancer (mCRC) treated with late-line regorafenib monotherapy or combined with other therapies. This study thus aimed to examine regorafenib combined with immune checkpoint inhibitors (ICIs) compared with regorafenib monotherapy in patients with advanced CRC. Methods: This single-center retrospective cohort study included patients with advanced CRC who experienced recurrence and progression after standard first- and second-line treatments treatment from November 2018 to December 2021. The patients received regorafenib plus ICIs or regorafenib monotherapy. Treatment response was evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST). Overall survival (OS) and progression-free survival (PFS) were analyzed via multivariate analysis. Results: The combined group and the monotherapy group included 30 and 43 patients, respectively. The median OS (13.7 vs. 10.1 months; P=0.10) and PFS (4 vs. 3.6 months; P=0.32) were not significantly different between the two groups. In males, the median OS was significantly longer in the combined group compared with the monotherapy group (not reached vs. 8.03 months; P=0.02), but the median PFS showed no significant difference (7.23 vs. 3.90 months; P=0.16). There was no significant difference in OS (P=0.71) or PFS (P=0.89) in females. Eastern Cooperative Oncology Group performance status (ECOG PS) 1 [vs. 0; hazard ratio (HR) =3.13, 95% confidence interval (CI): 1.61-6.10; P<0.001] was independently associated with PFS. ECOG PS 1 (vs. 0; HR =3.63, 95% CI: 1.54-8.56; P=0.003) and combined therapy (vs. monotherapy; HR =0.47, 95% CI: 0.22-0.99; P=0.048) were associated with OS. Conclusions: Regorafenib combined with ICIs led to numerically longer PFS and significantly prolonged OS in patients with mCRC compared to regorafenib monotherapy, especially in male patients.

Global epidemiological trends in the incidence and deaths of acute respiratory infections from 1990 to 2021.

The aim of this study was to investigate the global epidemiological trends in the incidence and deaths of acute respiratory infections (ARIs), encompassing both upper respiratory infections (URIs) and lower respiratory infections (LRIs), from 1990 to 2021. Using data from the Global Burden of Disease study 2021 (GBD 2021), we utilized the average annual percentage change (AAPC) to examine the trends in the age-standardized incidence rate and deaths rate (ASIR and ASDRs) of URIs and LRIs. In 2021, the global ASIR of URIs and LRIs were 166,770.73 (95 % UI: 148,098.16-189,487.93) per 100,000 and 4283.61 (95 % UI: 4057.03-4524.89) per 100,000, respectively. The highest ASIR of URIs occurred in high-sociodemographic index (SDI) regions (232744.64, 95 % UI: 206887.07-261694.81) per 100,000, whereas LRIs occurred in low-SDI regions (9261.1, 95 % UI: 8741.61-9820.86) per 100,000. In 2021, the global ASDRs of URIs and LRIs were 0.28 (95 % UI: 0.09-0.61) per 100,000 and 28.67 (95 % UI: 25.92-31.07) per 100,000, respectively. The highest ASDRs of both URIs and LRIs were observed in low-SDI regions, with 1.1 (95 % UI: 0.08-2.78) per 100,000 and 70.68 (95 % UI: 62.56-78.62) per 100,000, respectively. From 1990 to 2021, the global ASIR for URIs and LRIs decreased, with AAPCs of -0.17 % (95 % CI: 0.17 % to -0.16 %) and -1.28 % (95 % CI: -1.37 % to -1.22 %), respectively. The global ASDRs also decreased (-3.39 % for URIs; -2.46 % for LRIs). However, during the COVID-19 pandemic, the ASIR of URIs increased in many countries, especially in high-SDI regions (rate difference before and during the COVID-19 pandemic in ASIR was 2210.19 per 100,000.) and low-SDI regions (rate difference in ASIR: 111.26 per 100,000). The global incidence and deaths related to ARIs have decreased over the past 32 years. However, it remains a significant public health concern, particularly due to the notable incidence of URIs in high SDI regions and the deaths associated with both URIs and LRIs in low SDI regions. Furthermore, an increase in the incidence of URIs was observed in both high- and low-SDI regions during the COVID-19 pandemic, highlighting the need for increased attention.

Identification of stripe rust resistance gene YrBDT in Chinese landrace wheat Baidatou using BSE-seq and BSR-seq.

KEY MESSAGE: A new stripe rust resistance gene YrBDT in Chinese landrace wheat Baidatou was mapped to a 943.6-kb interval on chromosome arm 6DS and co-segregated with a marker CAPS3 developed from candidate gene TraesCS6D03G0027300. Stripe rust caused by Puccinia striiformis f. sp. tritici (Pst) is a devastating foliar disease of wheat. Chinese landrace wheat Baidatou has shown high resistance to a broad spectrum of Pst races at both the seedling and adult-plant stages for decades in the Longnan region of Gansu province, a hot spot for stripe rust epidemics. Here, we report fine mapping and candidate gene analysis of stripe rust resistance gene YrBDT in Baidatou. Analysis of F1, F2 plants and F2:3 lines indicated that resistance in Baidatou to Pst race CYR31 was conferred by a single dominant gene, temporarily designated YrBDT. Bulked segregant exome capture sequencing (BSE-seq) analysis revealed 61 high-confidence polymorphic SNPs concentrated in a 5.4-Mb interval at the distal of chromosome arm 6DS. Several SNPs and InDels were also identified by genome mining of DNA sampled from the parents and contrasting bulks. The YrBDT locus was mapped to a 943.6-kb (4,658,322-5,601,880 bp) genomic region spanned by markers STS2 and STS3 based on IWGSC RefSeq v2.1, including five putative disease resistance genes. There was high collinearity of the target interval among Chinese Spring RefSeq v2.1, Ae. tauschii AL8/78 and Fielder genomes. The expression level of TraesCS6D03G0027300 showed significant association with Pst infection, and a gene-specific marker CAPS3 developed from TraesCS6D03G0027300 co-segregated with YrBDT suggesting this gene as a candidate of YrBDT. The resistance gene and flanking markers can be used in marker-assisted selection for improvement of stripe rust resistance.

Multifaceted role of GCN2 in tumor adaptation and therapeutic targeting.

Tumor cells voraciously consume nutrients from their environment to facilitate rapid proliferation, necessitating effective strategies to manage nutrient scarcity during tumor growth and progression. A pivotal regulatory mechanism in this context is the Integrated Stress Response (ISR), which ensures cellular homeostasis under conditions such as endoplasmic reticulum stress, the unfolded protein response, and nutrient deprivation. Within the ISR framework, the kinase GCN2 is critical, orchestrating a myriad of cellular processes including the inhibition of protein synthesis, the enhancement of amino acid transport, autophagy initiation, and angiogenesis. These processes collectively enable tumor survival and adaptation under nutrient-limited conditions. Furthermore, GCN2-mediated pathways may induce apoptosis, a property exploited by specific therapeutic agents. Leveraging extensive datasets from TCGA, GEO, and GTEx projects, we conducted a pan-cancer analysis to investigate the prognostic significance of GCN2 expression across diverse cancer types. Our analysis indicates that GCN2 expression significantly varies and correlates with both adverse and favorable prognoses depending on the type of cancer, illustrating its complex role in tumorigenesis. Importantly, GCN2 also modulates the tumor immune microenvironment, influencing immune checkpoint expression and the functionality of immune cells, thereby affecting immunotherapy outcomes. This study highlights the potential of targeting GCN2 with specific inhibitors, as evidenced by their efficacy in preclinical models to augment treatment responses and combat resistance in oncology. These findings advocate for a deeper exploration of GCN2's multifaceted roles, which could pave the way for novel targeted therapies in cancer treatment, aiming to improve clinical outcomes.

Spectacle Lenses With Highly Aspherical Lenslets for Slowing Axial Elongation and Refractive Change in Low-Hyperopic Chinese Children: A Randomized Controlled Trial.

PURPOSE: Spectacle lenses with highly aspherical lenslets (HAL) have been shown to effectively retard myopia progression in myopic children. This study aimed to investigate the impact of spectacle lenses with HAL on refractive and axial length (AL) changes in Chinese children with low amount of hyperopia. DESIGN: Randomized controlled trial. METHODS: A total of 108 Chinese children aged 6.0 to 9.9 years and spherical equivalent refractive error (SERE) from 0.00 to +2.00 D were randomly allocated into two groups: the HAL group and the single vision spectacle lens (SVL) group. Cycloplegic refraction, AL, and uncorrected visual acuity were measured at baseline, 6 and 12 months after lens dispensing. The duration of spectacle lens wear was monitored using a wearable device attached to the spectacle frame and by questionnaire logs provided by participants at each follow-up visit. RESULTS: The 1-year SERE change was -0.19 (-0.32, 0.03) D and -0.23 (-0.36, 0.05) D in the SVL and HAL groups (P = .883). The 1-year AL elongation was 0.24 (0.18, 0.34) mm and 0.19 (0.12, 0.27) mm in the SVL and HAL groups (P = .057). In the HAL group, changes in AL and SERE were significantly correlated to lens wearing time (P < .001 and P = .024, respectively). Participants in the HAL group who wore their lenses for more than 30 hours per week had significantly slower AL elongation (0.11 [0.05, 0.17] mm) compared to their SVL counterparts (0.27 [0.21, 0.33] mm) (P < .001). CONCLUSIONS: Spectacle lenses with HAL significantly reduced AL elongation in low hyperopic children who wore lenses for over 30 hours per week. A dose-response relationship was evident with longer lens wearing time associated with less AL change.

High-resolution oblique coronal MRI at optimal flexed-knee angle: a novel imaging method for enhanced anterior cruciate ligament tear diagnosis.

BACKGROUND: The accuracy of traditional knee MR imaging in diagnosing anterior cruciate ligament tears, especially partial tears, is relatively low, which may lead to misdiagnosis and missed diagnosis. This study aimed to assess the diagnostic performance of a novel imaging method, high-resolution oblique coronal MRI at an optimal flexed-knee Angle, for ACL tears. METHODS: 50 healthy volunteers were scanned with a scan-assisted device for the optimal flexion angle of ACL. For 92 knee trauma patients selected strictly according to inclusion and exclusion criteria, conventional extended-knee scans (control group) and high-resolution oblique coronal scans based on the optimal flexed-knee angle (experimental group) were conducted. Two observers rated ACL visibility blindly on a 5-point scale. Arthroscopy-defined outcomes determined diagnostic metrics for each method and sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated. RESULTS: The average optimal flexion angle for healthy volunteers was approximately 30° (30.3° ± 5.0°). Imaging demonstrated complete visualization of the ACL in 96.7% of images in the experimental group versus 12.0% in the control group. The diagnostic indicators of the experimental group surpassed those of the control group: sensitivity (94.9% vs. 76.3%), specificity (97.0% vs. 81.8%), positive predictive value (98.2% vs. 88.2%), negative predictive value(91.4% vs. 65.9%), and accuracy (95.7% vs. 78.3%). ROC analysis indicated superior diagnostic performance in the experimental group, with an AUC of 0.945 compared with 0.776 for the control group (p < 0.0001). CONCLUSIONS: High-resolution oblique coronal imaging at the optimal 30° flexed-knee angle improved ACL visualization and diagnostic performance compared with conventional techniques.

Establishment and verification of a TME prognosis scoring model based on the acute myeloid leukemia single-cell transcriptome.

The tumor microenvironment (TME) plays an important role in the occurrence and progression of Acute Myeloid Leukemia (AML). Single-cell sequencing has enabled researchers to explore the correlation between TME subgroups and tumor prognosis, distinguish the existence of drug-resistant subgroups of tumor cells, and unravel the complexity of the AML cellular heterogeneity. We used bone marrow immune cell enrichment analysis from public databases to screen prognostic genes, construct prognostic models, and validate their prognostic significance on independent external datasets and patient samples. A total of 18,251 single cells were obtained to establish prognostic scoring models for 10 key genes including CCL5, ETLS2, and IL2RA.The AML cases were divided into two groups: high-risk and low-risk. The low-risk group exhibited a higher survival rate than the high-risk group. The areas under curves (AUC) of 1-, 3- and 5-year survival curves in the TCGA and GEO training sets were greater than 0.8 and 0.6, respectively, indicating effective prediction. The model's prognostic efficacy was confirmed across multiple validation sets. It demonstrated increased expression of ETS2, CCL5, and IL2RA in AML samples compared to controls, which was associated with decreased overall survival (OS). This prognostic scoring model based on tumor immune infiltration provides a reference for developing novel treatment strategies for recurrent/refractory AML.

A comprehensive prognostic and immune infiltration analysis of UBA1 in pan-cancer: A computational analysis and in vitro experiments.

Ubiquitin like modifier activating enzyme 1 (UBA1) plays an important role in immune regulation and cellular function. However, the functional mechanism and role of UBA1 in pan-cancer have not been fully elucidated and its value in haematological tumours (diffuse large B cell lymphoma (DLBC/DLBCL) and acute myeloid leukaemia (AML/LAML)) has not been explored. We conducted a comprehensive analysis of the functional mechanism and role of UBA1 in pan-cancer using multiple databases, including differential expression analysis, clinical pathological staging analysis, prognosis analysis and immune analysis. Then, we confirmed the function of UBA1 in haematological tumours through cell experiments. The results showed that the expression of UBA1 was significantly increased in most cancers and the differential expression of UBA1 was mainly concentrated in digestive tumours, haematological tumours and brain tumours. Moreover, the high expression of UBA1 had poor prognosis in most tumours, which may be related to its involvement in various cancer-related pathways such as cell cycle, as well as its methylation level, protein phosphorylation level, immune cell infiltration and immune therapy response. Cell experiments have confirmed that UBA1 can significantly regulate the cycle progression and apoptosis of DLBCL cells and AML cells. Therefore, UBA1 may be a potential therapeutic target for haematological tumours. In summary, our study not only comprehensively analysed the functional mechanisms and clinical value of UBA1 in pan-cancer, but also validated for the first time the regulatory role of UBA1 in haematological tumours.

Empirical and modified hemostatic resuscitation for liver blast injury combined with seawater immersion: A preliminary study.

PURPOSE: To compare the effects of empirical and modified hemostatic resuscitation for liver blast injury combined with seawater immersion. METHODS: Thirty rabbits were subjected to liver blast injury combined with seawater immersion, and were then divided into 3 groups randomly (n = 10 each): group A (no treatment after immersion), group B (empirical resuscitation with 20 mL hydroxyethyl starch, 50 mg tranexamic acid, 25 IU prothrombin complex concentrate and 50 mg/kg body weight fibrinogen concentrate), and group C (modified resuscitation with additional 10 IU prothrombin complex concentrate and 20 mg/kg body weight fibrinogen concentrate based on group B). Blood samples were gathered at specified moments for assessment of thromboelastography, routine coagulation test, and biochemistry. Mean arterial pressure, heart rate, and survival rate were also documented at each time point. The Kolmogorov-Smirnov test was used to examine the normality of data distribution. Multigroup comparisons were conducted with one-way ANOVA. RESULTS: Liver blast injury combined with seawater immersion resulted in severe coagulo-fibrinolytic derangement as indicated by prolonged prothrombin time (s) (11.53 ± 0.98 vs. 7.61 ± 0.28, p＜0.001), activated partial thromboplastin time (APTT) (s) (33.48 ± 6.66 vs. 18.23 ± 0.89, p＜0.001), reaction time (R) (min) (5.85 ± 0.96 vs. 2.47 ± 0.53, p＜0.001), decreased maximum amplitude (MA) (mm) (53.20 ± 5.99 vs. 74.92 ± 5.76, p＜0.001) and fibrinogen concentration (g/L) (1.188 ± 0.29 vs. 1.890 ± 0.32, p = 0.003), and increased D-dimer concentration (mg/L) (0.379 ± 0.32 vs. 0.051 ± 0.03, p = 0.005). Both empirical and modified hemostatic resuscitation could improve the coagulo-fibrinolytic states and organ function, as indicated by shortened APTT and R values, decreased D-dimer concentration, increased fibrinogen concentration and MA values, lower concentration of blood urea nitrogen and creatine kinase-MB in group B and group C rabbits in comparison to that observed in group A. Further analysis found that the R values (min) (4.67 ± 0.84 vs. 3.66 ± 0.98, p = 0.038), APTT (s) (23.16 ± 2.75 vs. 18.94 ± 1.05, p = 0.001), MA (mm) (60.10 ± 4.74 vs. 70.21 ± 3.01, p < 0.001), and fibrinogen concentration (g/L) (1.675 ± 0.21 vs. 1.937 ± 0.16, p = 0.013) were remarkably improved in group C than in group B at 2 h and 4 h after injury. In addition, the concentration of blood urea nitrogen (mmol/L) (24.11 ± 1.96 vs. 21.00 ± 3.78, p = 0.047) and creatine kinase-MB (U/L) (85.50 ± 13.60 vs. 69.74 ± 8.56, p = 0.013) were lower in group C than in group B at 6 h after injury. The survival rates in group B and group C were significantly higher than those in group A at 4 h and 6 h after injury (p < 0.001), however, there were no statistical differences in survival rates between group B and group C at each time point. CONCLUSIONS: Modified hemostatic resuscitation could improve the coagulation parameters and organ function better than empirical hemostatic resuscitation.

SPGMVC: Multiview Clustering via Partitioning the Signed Prototype Graph.

Multiview clustering (MVC) has been widely studied in machine learning and data mining for its capability of improving clustering performance by fusing the information from multiview data. In the past decade, a large number of MVC methods have made impressive progress, but most of them suffer from computational burdens, especially in large-scale tasks. Binary MVC (BMVC) is proposed to address this issue by representing the large-scale high-dimensional dataset as a group of consensus and low-dimensional binary codes. However, current BMVC-based approaches generate the clustering by executing binary k -means on the obtained binary codes, which fail to capture the embedded geometric information, leading to poor clustering performance. In addition, parameter selection is another "mission impossible" in unsupervised learning tasks including MVC. To tackle these challenges, a framework of multiview clustering via partitioning the signed prototype graph (SPGMVC) is proposed in this work. The SPGMVC framework offers several contributions. First, SPGMVC is designed as a unified framework for MVC. It combines effective technologies, such as consensus binary coding, code compression (CC), signed prototype graph (SPG) partitioning, and prototype-based cluster assignment. Second, SPGMVC partitions the signed graph (SG) based on the relationships between positive and negative edges. By capturing the underlying structure of the data, this partitioning strategy improves clustering accuracy (ACC). CC techniques are applied to reduce the graph's scale, enabling further partitioning and enhancing computational efficiency. Third, SPGMVC employs an alternate minimizing strategy to efficiently handle the optimization problem. This strategy has nearly linear time and space complexity with respect to the data volume, making it suitable for large-scale tasks. Fourth, SPGMVC proposes an automatic parameter selection strategy, eliminating the need for extensive parameter exploration. Comprehensive experiments illustrate the superiority of our model. The implementation of SPGMVC is available at: https://github.com/gepingyang/PSGMVC.

Global years lived with disability for musculoskeletal disorders in adults 70 Years and older from 1990 to 2019, and projections to 2040.

In this article, we provided a comprehensive overview and in-depth analysis of global patterns and temporal trends in years lived with disability (YLDs) for musculoskeletal (MSK) disorders in individuals aged ≥70. Data on YLDs for MSK disorders in individuals aged ≥70 were obtained from the Global Burden of Disease 2019. The average annual percentage change (AAPC) was calculated to assess the temporal trends in the YLDs rate of MSK disorders. A Bayesian Age-Period-Cohort model was used to predict the YLDs rate up to the year 2040. In 2019, the global rate of YLDs for MSK disorders in individuals aged ≥70 were 4819.81 (95 % UI: 3402.91 - 6550.77) per 100,000 persons. The YLDs rate of MSK disorders in female was 1.36 times higher than that in male, and was highest in high SDI regions. From 1990 to 2019, the global YLDs rate showed a slightly downward trend (AAPC = -0.04 %, 95 % CI: -0.06 % to -0.03 %), while it significantly increased in high, low-middle, low SDI regions. Tobacco and high body mass index were the primary risk factors worldwide, while in low SDI regions, occupational risks emerged as the predominant factors. Up to 2040, the global YLDs rate of MSK disorders are expected to increase by 1.78 %, with 36.39 %, 20.66 %, 18.96 % and 5.32 % growth in other MSK disorders, rheumatoid arthritis, neck pain and osteoarthritis. MSK disorders are a significant and continuously growing public health concern among older adults. Tailored interventions should be developed for older adults, taking into account the variations across distributions, trends, and risk factors in terms of sex and SDI levels.

A Serological Survey of Measles and Rubella Antibodies among Different Age Groups in Eastern China.

BACKGROUND: Measles and rubella are vaccine-preventable diseases targeted for elimination in most World Health Organization regions, and China is considered to have momentum towards measles elimination. Therefore, this study aimed to assess the population immunity levels against measles and rubella in Zhejiang Province in China in order to provide valuable insights for informing future public health measures and contributing to the ongoing global campaign against these diseases. MATERIALS AND METHODS: A cross-sectional serological survey was conducted in 2022. A total of 2740 blood samples were collected from healthy individuals spanning the age range of 0-59 years, representing diverse demographic strata across 11 prefectures in Zhejiang Province in China. The sera were tested for measles and rubella IgG antibodies to determine positivity rates and geometric mean concentrations (GMCs). RESULTS: The overall positivity rate for the measles IgG antibody was 85.3%, with a GMC of 588.30 mIU/mL. The positivity rate for the rubella IgG antibody was 70.9%, and the GMC was 35.30 IU/mL. Measles IgG antibody positivity rates across the 0-11 months, 12-23 months, 24-35 months, 3-5 years, 6-9 years, 10-14 years, 15-19 years, 20-29 years, and 30-59 years age groups were 63.1%, 92.5%, 97.0%, 94.0%, 85.8%, 77.3%, 86.9%, 84.9%, and 88.7%, respectively (trend χ2 = 118.34, p < 0.001). Correspondingly, rubella antibody positivity rates for these same age brackets were 55.9%, 87.9%, 94.7%, 88.2%, 69.9%, 54.2%, 72.6%, 67.5%, and 74.3% (trend χ2 = 199.18, p < 0.001). Both univariate and multivariate analyses consistently demonstrated that age, immunization history, and differing economic levels were significant factors contributing to variations in antibody levels. CONCLUSIONS: The seroprevalence of measles and rubella was lower than that required for herd immunity. Periodic vaccination campaigns should be launched to increase immunity.

Genome-wide association study of growth and reproductive traits based on low-coverage whole-genome sequencing in a Chubao black-head goat population.

The Chubao black-head goat is a novel hybrid breed that combines the advantages of Macheng black goats, such as good reproductive performance, strong adaptability, and resistance to rough feeding, with the superior growth and meat characteristics of Boer goats. Given the substantial economic importance of growth (such as birth weight, body height, body length, and chest circumference across different growth stages) and reproductive traits (particularly average litter size after first parity), the aim of this study was to identify significant SNPs and candidate genes associated with these traits in Chubao black-head goats. Through whole-genome sequencing (with 34 goats at approximately 15× coverage and 466 goats at approximately 1× coverage), genotype imputation, and quality control, 22,665,331 SNPs were identified and subsequently used for genetic analyses. Heritability estimates indicated that growth traits exhibit moderate to high heritability (ranging from 0.297 ± 0.071 to 0.535 ± 0.118), while reproductive traits demonstrated low to moderate heritability (with a value of 0.220 ± 0.108). By performing FarmCPU-based genome-wide association studies, we identified 48 potentially significant SNPs associated with growth traits and 7 with reproductive traits. Additionally, 85 candidate genes (such as COL14A1, ZNF148, and TTC39C) linked to growth traits were identified and enriched in pathways associated with fundamental molecular biological activities such as protein deubiquitination, regulation of mRNA stability, and the MAPK signaling pathway. Furthermore, 10 candidate genes (such as SOHLH2, CCNA2, and SOX7) associated with reproductive traits were identified and enriched in pathways related to specific reproductive processes such as oocyte differentiation, endoderm formation, and progesterone-mediated oocyte maturation. Overall, these findings provide valuable preliminary insights into the molecular mechanisms underlying growth and reproductive traits in Chubao black-head goats. However, further functional validation is needed to effectively use these potential SNPs and candidate genes in improving the breeding of these traits in this breed.

Gradual stabilization and narrowing of bone tunnels following primary anterior cruciate ligament reconstruction.

PURPOSE: The purpose of this study is to dynamically assess variations in tunnel diameters following anterior cruciate ligament reconstruction (ACLR) and investigate correlations with patient-reported outcomes (PROs) and graft maturity based on signal-to-noise quotient (SNQ). METHODS: Tunnel diameter and tunnel position were measured using three-dimensional models derived from computed tomography (CT) data. Postoperative graft maturity and integration were evaluated using magnetic resonance imaging (MRI). Clinical outcomes were assessed through PROs, which included the International Knee Documentation Committee Subjective Knee Evaluation Form, Knee Injury and Osteoarthritis Outcome Scores and Lysholm scores. The correlation between tunnel enlargement extent, PROs and SNQ values, as well as correlations between confounding factors, tunnel diameter differences and SNQ were analyzed. RESULTS: A total of 73 participants underwent primary ACLR and scheduled follow-ups. At the segment of the articular aperture, the femoral tunnel was enlarged by 32.3% to 10.4 ± 1.6 mm (p < 0.05), and the tibial tunnel was widened by 17.2% to 9.6 ± 1.2 mm (p < 0.05) at the 6-month follow-up. At 1 year postoperatively, diameters at the articular aperture were not further increased on the femoral (n.s.) and tibial (n.s.) sides. In early postoperative follow-up, the femoral tunnel was anteriorly and distally shifted, coupled with posterior and lateral deviation involving the tibial side, exhibiting minimal migration at 1-year follow-up. The degree of tunnel widening was not correlated with PROs and SNQ values. Age, gender, body mass index (BMI), time from surgery to follow-up, concomitant injuries and autograft type were not correlated with tunnel diameter differences and SNQ. CONCLUSIONS: The femoral and tibial bone tunnels exhibited eccentrical widening and gradually stabilized at 1 year following ACLR. Furthermore, the enlarged bone tunnels were not correlated with unsatisfied PROs and inferior graft maturity. LEVEL OF EVIDENCE: Level IV.

Metabolome and Transcriptome Unveil the Correlated Metabolites and Transcripts with 2-acetyl-1-pyrroline in Fragrant Rice.

Fragrance is a valuable trait in rice varieties, with its aroma significantly influencing consumer preference. In this study, we conducted comprehensive metabolome and transcriptome analyses to elucidate the genetic and biochemical basis of fragrance in the Shangsixiangnuo (SSXN) variety, a fragrant indica rice cultivated in Guangxi, China. Through sensory evaluation and genetic analysis, we confirmed SSXN as strongly fragrant, with an 806 bp deletion in the BADH2 gene associated with fragrance production. In the metabolome analysis, a total of 238, 233, 105 and 60 metabolic compounds exhibited significant changes at the seedling (S), reproductive (R), filling (F), and maturation (M) stages, respectively. We identified four compounds that exhibited significant changes in SSXN across all four development stages. Our analyses revealed a significant upregulation of 2-acetyl-1-pyrroline (2AP), the well-studied aromatic compound, in SSXN compared to the non-fragrant variety. Additionally, correlation analysis identified several metabolites strongly associated with 2AP, including ethanone, 1-(1H-pyrrol-2-yl)-, 1H-pyrrole, and pyrrole. Furthermore, Weighted Gene Co-expression Network Analysis (WGCNA) analysis highlighted the magenta and yellow modules as particularly enriched in aroma-related metabolites, providing insights into the complex aromatic compounds underlying the fragrance of rice. In the transcriptome analysis, a total of 5582, 5506, 4965, and 4599 differential expressed genes (DEGs) were identified across the four developmental stages, with a notable enrichment of the common pathway amino sugar and nucleotide sugar metabolism in all stages. In our correlation analysis between metabolome and transcriptome data, the top three connected metabolites, phenol-, 3-amino-, and 2AP, along with ethanone, 1-(1H-pyrrol-2-yl)-, exhibited strong associations with transcripts, highlighting their potential roles in fragrance biosynthesis. Additionally, the downregulated expression of the P4H4 gene, encoding a procollagen-proline dioxygenase that specifically targets proline, in SSXN suggests its involvement in proline metabolism and potentially in aroma formation pathways. Overall, our study provides comprehensive insights into the genetic and biochemical mechanisms underlying fragrance production in rice, laying the foundation for further research aimed at enhancing fragrance quality in rice breeding programs.

Integrated systematic functional screen and fine-mapping decipher the role and genetic regulation of RPS19 in colorectal cancer development.

Despite genome-wide association studies (GWAS) have identified more than 200 risk loci associated with colorectal cancer (CRC), the causal genes or risk variants within these loci and their biological functions remain not fully revealed. Recently, the genomic locus 19q13.2, with the lead SNP rs1800469 was identified as a crucial CRC risk locus in Asian populations. However, the functional mechanism of this region has not been fully elucidated. Here we employed an RNA interfering-based on-chip approach to screen for the genes essential for cell proliferation in the CRC risk locus 19q13.2. Notably, we found that RPS19 exhibited the most significant effect among the identified genes and acted as a critical oncogene facilitating CRC cell proliferation. Subsequently, combining integrative fine-mapping analysis and a large-scale population study consisting of 6027 cases and 6099 controls, we prioritized rs1025497 as a potential causal candidate for CRC risk, demonstrating that rs1025497[A] allele significantly reduced the risk of CRC (OR 0.70, 95% confidence interval = 0.56-0.83, P = 1.12 × 10-6), which was further validated in UK Biobank cohort comprising 5,313 cases and 21,252 controls. Mechanistically, we experimentally elucidated that variant rs1025497 might acted as an allele-specific silencer, inhibiting the expression level of oncogene RPS19 mediated by the transcription suppressive factor HBP1. Taken together, our sturdy unveils the significant role of RPS19 during CRC pathogenesis and delineates its distal regulatory mechanism mediated by rs1025497, advancing our understanding of the etiology of CRC and provided new insights into the personalized medicine of human cancer.