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Bone infection is a catastrophe in clinical orthopedics. Despite being the standard therapy for osteomyelitis, antibiotic-loaded polymethyl methacrylate (PMMA) cement has low efficiency against bacteria in biofilms. Furthermore, high-dose antibiotic-loaded implants carry risks of bacterial resistance, tissue toxicity, and impairment of local tissue healing. By incorporating borosilicate bioactive glass (BSG) into low-dose gentamicin sulfate (GS)-loaded PMMA cement, an intelligent strategy that synergistically eradicates bacteria and sequentially promotes osseointegration, was devised. Results showed that BSG did not compromises the handling properties of the cement, but actually endowed it with an ionic and alkaline microenvironment, thereby damaging the integrity of bacterial cell walls and membranes, inhibiting ATP synthesis by disrupting the respiratory chain in cell membranes and glycogen metabolism, and elevating reactive oxygen species (ROS) levels by weakening antioxidant components (peroxisomes and carotenoids). These antibacterial characteristics of BSG synergistically reinforced the effectiveness of GS, which was far below the actual clinical dosage, achieving efficient bacterial killing and biofilm clearance by binding to the 30S subunit of ribosomes. Furthermore, the released GS and the ionic and alkaline microenvironment from the implants fostered the osteogenic activity of hBMSCs in vitro and coordinately enhanced osseointegration in vivo. Collectively, this study underscores that BSG incorporation offers a promising strategy for reducing antibiotic dosage while simultaneously enhancing the antibacterial activity and osteogenesis of implants. This approach holds potential for resolving the conflict between bacterial resistance and bone infection.

Abstract Recent genetic studies have linked numerous loci to psychiatric disorders. However, the biological pathways that connect these genetic associations to psychiatric disorders’ specific pathophysiological processes are largely unclear. Endophenotypes, first defined over five decades ago, are heritable traits, independent of disease state that are associated with a disease, encompassing a broad range of neurophysiological, biochemical, endocrinological, neuroanatomical, cognitive, and neuropsychological characteristics. Considering the advancements in genetics and genomics over recent decades, we propose a revised definition of endophenotypes as ‘genetically influenced phenotypes linked to disease or treatment characteristics and their related events.’ We also updated endophenotype criteria to include (1) reliable measurement, (2) association with the disease or its related events, and (3) genetic mediation. ‘Genetic mediation’ is introduced to differentiate between causality and pleiotropic effects and allows non-linear relationships. Furthermore, this updated Endophenotype 2.0 framework expands to encompass genetically regulated responses to disease-related factors, including environmental risks, illness progression, treatment responses, and resilience phenotypes, which may be state-dependent. This broadened definition paves the way for developing new endophenotypes crucial for genetic analyses in psychiatric disorders. Integrating genetics, genomics, and diverse endophenotypes into multi-dimensional mechanistic models is vital for advancing our understanding of psychiatric disorders. Crucially, elucidating the biological underpinnings of endophenotypes will enhance our grasp of psychiatric genetics, thereby improving disease risk prediction and treatment approaches.

Abstract The substitution of microbial fertilizer for chemical fertilizer can not only improve soil fertility but also effectively enhance rice quality. To investigate the effect of different amounts of combined application of chemical fertilizer and microbial fertilizer on the amylose content of rice, this study adopts theoretical calculations to compare the preprocessed Raman spectroscopy information of rice with reduced fertilization and establishes a recognition model for the amylose content of rice, which is used to detect the amylose content in rice. Based on the amylose spectral values measured by Raman spectroscopy and the known starch structure and functional groups, the Raman peaks are mainly distributed in the range of 400 cm− 1 to 1400 cm− 1. The Raman characteristic peaks at 483 cm− 1, 869 cm− 1, 933 cm− 1, 1082 cm− 1, 1126 cm− 1, 1335 cm− 1, 1385 cm− 1, and 1455 cm− 1 exhibit strong vibration modes, which are consistent with its main nutrient component of amylose. By comparing the measured amylose content in the regions treated with microbial fertilizer combined with different amounts of reduced fertilization and the spectral intensity values of amylose measured by Raman spectroscopy, the results show that the treatment of combining conventional amounts of microbial fertilizer with different amounts of reduced chemical fertilizer exhibits a decreasing trend in the amylose content of rice.

Abstract Objective The Ureteral Access Sheath (UAS) has notable benefits but may fail to traverse the ureter in some cases. Our objective was to develop and validate a dynamic online nomogram for patients with ureteral stones who experienced UAS placement failure during retrograde intrarenal surgery (RIRS). Methods This study is a retrospective cohort analysis using medical records from the Second Hospital of Tianjin Medical University. We reviewed the records of patients with ureteral stones who underwent RIRS in 2022 to identify risk factors associated with UAS placement failure. Lasso combined logistic regression was utilized to identify independent risk factors associated with unsuccessful UAS placement in individuals with ureteral stones. Subsequently, a nomogram model was developed to predict the likelihood of failed UAS placement in this patient cohort. The model’s performance was assessed through Receiver Operating Characteristic Curve (ROC) analysis, calibration curve assessment, and Decision Curve Analysis (DCA). Results Significant independent risk factors for unsuccessful UAS placement in patients with ureteral stones included age (OR = 0.95, P

Abstract Background Epigenome‐wide association studies have identified multiple DNA methylation sites (CpGs) associated with alcohol consumption, an important lifestyle risk factor for cardiovascular diseases. This study aimed to test the hypothesis that an alcohol consumption epigenetic risk score (ERS) is associated with blood pressure (BP) traits. Results We implemented an ERS based on a previously reported epigenetic signature of 144 alcohol-associated CpGs in meta-analysis of participants of European ancestry. We found a one-unit increment of ERS was associated with eleven drinks of alcohol consumed per day, on average, across several cohorts (p

BackgroundDeltamethrin (DM) is a broad-spectrum insecticide that is widely used to control agricultural pests. Recently, DM has posed a potential threat to the health of infants and young children, and this is because of the environmental and food pollution that is caused by the extensive use of DM.MethodsIn this study, zebrafish (Danio rerio) embryos were used as experimental animals to quantify the behavioral changes of larvae induced by DM and explore the relationship between DM and acetylcholinesterase activity.ResultsThe results showed that DM caused an increase in coiling movement, heart rate, and apoptosis in the brain in early zebrafish embryos or larvae. It also caused a decrease in the expression of acetylcholinesterase-associated genes and the activity of acetylcholinesterase, which also led to an increase in the acetylcholinesterase content. The transcriptome data also showed that low concentration DM induced acetylcholine-related gene signaling pathways. The above results suggest that low doses of DM may induce neurodegeneration because DM exposure inhibits acetylcholinesterase, leading to brain cell apoptosis and behavioral changes in the zebrafish embryos or larvae. Micro-injection of zebrafish embryos at the 2–4 cell stage knocked down or overexpressed the acetylcholinesterase gene showed that the behavior and enzyme activity of zebrafish had some effects.ConclusionThis study explored the relationship between acetylcholinesterase and the change in zebrafish behavior caused by DM exposure to provide a basis for the treatment of DM poisoning in the aquaculture.

SERINC5 (serine incorporator 5), a member of the serine incorporator family, has been identified as a retrovirus restriction factor that inhibits the fusion of virions with the plasma membrane, thus blocking the release of the viral core into target cells and subsequently attenuating viral infectivity. Several viruses, such as human immunodeficiency virus (HIV), murine leukemia virus (MLV), and equine infectious anemia virus (EIAV), have evolved mechanisms to antagonize the host protein SERINC5 through HIV Nef, MLV glycosylated Gag, and the EIAV S2 protein. These viral proteins degrade SERINC5 on the cell surface through the endolysosomal system. In addition to its direct antiviral ability, SERINC5 also modulates immunity to inhibit the replication of retroviruses and nonretroviruses. This review summarizes the interaction between SERINC5 and viral replication, providing a promising avenue for fighting viral diseases.

Objective: To determine the role of obesity in the development of Parkinson’s disease (PD). Background: Obesity has been reported to be both a risk factor for PD, as well as potentially protective. The Framingham Heart Study (FHS) is a multigenerational longitudinal cohort study that was started in 1948, which is well-known for its cardiovascular health studies. In this study, we utilized the extensive cardiovascular and neurological data to determine if obesity contributes to the risk of the development of PD. Methods: Participants in the FHS Original and Offspring cohorts were included in this study. Controls were selected based on sex and age at baseline examination, 1:10. Cox proportional hazard regression models were used, adjusting for age and sex. PD case status was determined utilizing prior medical and neurological examination data, Framingham Heart Study examinations, and self-report data by a panel of movement disorders neurologists using the UK Brain Bank Criteria (UKBB) and other supporting clinical details after being flagged for review by FHS neurologists. We used p = 30 kg/m2 having HR 0.47 (CI 0.27–0.84; p = 0.01). When the overweight and obese BMI groups were combined, we noted a more robust association, with combined HR of 0.67 (0.41–0.86; p = 0.01). Conclusions: Obesity during mid-life potentially reduces the risk of developing PD; however, additional studies are needed to further explore this association.

Abstract BackgroundSmartphone apps can be used to monitor chronic conditions and offer opportunities for self-assessment conveniently at home. However, few digital studies include older adults. ObjectiveWe aim to describe a new electronic cohort of older adults embedded in the Framingham Heart Study including baseline smartphone survey return rates and survey completion rates by smartphone type (iPhone [Apple Inc] and Android [Google LLC] users). We also aim to report survey results for selected baseline surveys and participant experience with this study’s app. MethodsFramingham Heart Study Offspring and Omni (multiethnic cohort) participants who owned a smartphone were invited to download this study’s app that contained a range of survey types to report on different aspects of health including self-reported measures from the Patient-Reported Outcomes Measurement Information System (PROMIS). iPhone users also completed 4 tasks including 2 cognitive and 2 physical function testing tasks. Baseline survey return and completion rates were calculated for 12 surveys and compared between iPhone and Android users. We calculated standardized scores for the PROMIS surveys. The Mobile App Rating Scale (MARS) was deployed 30 days after enrollment to obtain participant feedback on app functionality and aesthetics. ResultsWe enrolled 611 smartphone users (average age 73.6, SD 6.3 y; n=346, 56.6% women; n=88, 14.4% Omni participants; 478, 78.2% iPhone users) and 596 (97.5%) returned at least 1 baseline survey. iPhone users had higher app survey return rates than Android users for each survey (range 85.5% to 98.3% vs 73.8% to 95.2%, respectively), but survey completion rates did not differ in the 2 smartphone groups. The return rate for the 4 iPhone tasks ranged from 80.9% (380/470) for the gait task to 88.9% (418/470) for the Trail Making Test task. The Electronic Framingham Heart Study participants had better standardized tt ConclusionsWe effectively engaged community-dwelling older adults to use a smartphone app designed to collect health information relevant to older adults. High app survey return rates and very high app survey completion rates were observed along with high participant rating of this study’s app.

Systemic low-grade inflammation is a feature of chronic disease. C-reactive protein (CRP) is a common biomarker of inflammation and used as an indicator of disease risk; however, the role of inflammation in disease is not completely understood. Methylation is an epigenetic modification in the DNA which plays a pivotal role in gene expression. In this study we evaluated differential DNA methylation patterns associated with blood CRP level to elucidate biological pathways and genetic regulatory mechanisms to improve the understanding of chronic inflammation. The racially and ethnically diverse participants in this study were included as 50% White, 41% Black or African American, 7% Hispanic or Latino/a, and 2% Native Hawaiian, Asian American, American Indian, or Alaska Native (total n = 13,433) individuals. We replicated 113 CpG sites from 87 unique loci, of which five were novel (CADM3, NALCN, NLRC5, ZNF792, and cg03282312), across a discovery set of 1,150 CpG sites associated with CRP level (p

Abstract The increasing prevalence of myopia worldwide presents a significant public health challenge. A key strategy to combat myopia is with early detection and prediction in children as such examination allows for effective intervention using readily accessible imaging technique. To this end, we introduced DeepMyopia, an artificial intelligence (AI)-enabled decision support system to detect and predict myopia onset and facilitate targeted interventions for children at risk using routine retinal fundus images. Based on deep learning architecture, DeepMyopia had been trained and internally validated on a large cohort of retinal fundus images (n = 1,638,315) and then externally tested on datasets from seven sites in China (n = 22,060). Our results demonstrated robustness of DeepMyopia, with AUCs of 0.908, 0.813, and 0.810 for 1-, 2-, and 3-year myopia onset prediction with the internal test set, and AUCs of 0.796, 0.808, and 0.767 with the external test set. DeepMyopia also effectively stratified children into low- and high-risk groups (p

Abstract Objectives To investigate the safety of short-term stenting following flexible ureteroscopic lithotripsy (fURL) for patients without preoperative stents. Retaining double-J stent for 1–2 weeks after fURL is a common practice. At present, data on short-term stenting after non-pre-stented fURL is still lacking. Methods 182 patients who met inclusion criteria were retrospectively divided into the 2-days group (2-day removal, 76 cases) and the 1-week group (1-week removal, 106 cases). The study endpoint was stent-associated adverse symptoms assessed by follow-up and completed validated questionnaires on postoperative days (POD) 7 and 12. A postoperative imaging review was performed 1 month after the surgery. Results No statistical differences were found in the patients’ demographic and stone-related characteristics. The 2-days group showed fewer urinary tract symptoms and lower scores on the ureteral stent symptom questionnaire on POD 7: less backache during urination (p = 0.004), less hematuria (p = 0.031), less frequent urination (p = 0.004), lower urinary symptoms index (p

Abstract Background To evaluate the incidence of metabolic syndrome (MetS) in patients with unilateral and bilateral staghorn calculi (SC) and evaluate the impact on the outcome of percutaneous nephrolithotomy (PCNL). Methods The clinical data of patients who underwent PCNL for the treatment of SC between 2019 and 2022 were retrospectively reviewed. SC was divided into unilateral and bilateral. The incidence of MetS was compared between the patients with unilateral SC and the patients with bilateral SC, and the impact on the outcome of PCNL was assessed. Results A total of 1778 patients underwent PCNL between 2019 and 2022. After screening computed tomography, 379 patients were confirmed to have SC, finally, leaving 310 patients with follow-up and complete data to be included in the study. Eighty-four had bilateral SC and 226 had unilateral SC. The patients with bilateral SC had a significantly higher body mass index and higher rates of complete staghorn stones and metabolic syndrome. Higher body mass index, hypertension, diabetes mellitus, hyperlipidaemia, and MetS were present in 62.58%, 44.84%, 21.94%, 60.65% and 27.42% of all patients, respectively. The number of MetS components remained significantly associated with bilateral SC. Specifically, when the number of MetS components increases from 0 to 3–4, the likelihood of developing bilateral staghorn calculi increases by 21.967 times. Eighty-five patients with MetS( +) had a higher rate of overall complications (number (N)(%), 29 (34.12) vs.33 (14.46), P

Objective To explore the influencing factors of spontaneous bacterial peritonitis and the predictive value of multiple inflammatory indicators in elderly alcoholic liver cirrhosis patients. Methods A total of 276 patients with alcoholic cirrhosis hospitalized in Beijing Friendship Hospital, Capital Medical University from January 2020 to June 2023 were selected for retrospective analysis. Seventy-two elderly patients with alcoholic cirrhosis who had spontaneous bacterial peritonitis at admission were included in the observation group, and 204 elderly patients with alcoholic cirrhosis who did not have SBP were included in the control group. The clinical data of patients in the two groups were collected by an electronic medical record system at admission. Multivariate logistic regression model was used to analyze the correlation between inflammatory factors and spontaneous bacterial peritonitis. ROC curve was used to evaluate the diagnostic efficacy of inflammatory factors for spontaneous bacterial peritonitis. Results Univariate analysis showed that the proportion of combined diabetes, hepatic encephalopathy, and upper gastrointestinal bleeding in the observation group was higher than that in the control group, prothrombin time was longer than that in the control group, neutrolphil to lymphocyte ratio(NLR) and C-reactive protein to albumin ratio(CAR) were higher than those in the control group, and lymphocyte to monocyte ratio(LMR) was lower than that in the control group, and the differences were statistically significant (P

The prediction of mine water inflow is of great significance to the safe production of coal mines. The accurate selection of hydrogeological parameters and the selection of calculation methods have a great influence on the accurate prediction of mine water inflow. At the same time, taking into account the actual mining of the mine, the water inflow is not stable from the early stage of mining, but dynamic. In order to improve the accuracy of water inflow prediction and better serve coal mining, based on the analysis of geological and hydrogeological conditions of Donggou Coal Mine in Xinjiang and the selection of accurate hydrogeological parameters, two water inflow prediction methods suitable for Donggou Coal Mine were selected for comparative analysis. The calculation results show that : ① The water inflow calculated by the unsteady flow water release-section flow method shows dynamic change characteristics. After the mining intensity is stable, the change range becomes smaller and finally tends to be stable. ② The predicted water inflow calculated by the large well method and the unsteady flow water release-section flow method is 3396 m3/d, 599.87 − 612.9 m3/d and the actual water inflow 480 m3/d, respectively. The difference with the actual value is in ascending order of magnitude 607.5% > 24.97% − 27.69% ; ③ According to the verification and analysis of the water inflow data generated by the actual mining of the mine, the water inflow calculated by the unsteady flow water release-section flow method is basically consistent with the water inflow generated by the actual mining. The accuracy of the water inflow prediction results is in the order of unsteady flow water release-section flow method > large well method ; ④ In the case of sufficient data and accurate parameters, it is recommended to give priority to the unsteady flow release-section flow method to calculate the water inflow. It is recommended to use the large well method first under the condition that the water supply boundary conditions are poor and meet the requirements of the large well method. On the one hand, the calculation results fully verify the accuracy of the unsteady flow release-section flow method. On the other hand, it provides a reference for the calculation of water inflow in coal mines, and also provides data support for the safe production of Donggou Coal Mine.

Background: Preeclampsia and preterm birth disproportionally affects Black women, but the current understanding of genetic predisposition to preeclampsia and preterm birth is rudimentary. It has been hypothesized that carriers of high-risk genetic variants in the apolipoprotein L1 gene (APOL1) may have an increased risk of preeclampsia and preterm birth. These genetic variants are found only among individuals of recent African ancestry. Previous studies have been small and have yielded inconsistent results. Objective: To examine whether APOL1 genetic variants are associated with risk of preeclampsia or preterm birth. Study design: We conducted a retrospective case-control study of 6616 Black women from the Black Women’s Health Study, a cohort of self-identified Black women in the U.S. Genotype data on APOL1 risk alleles for this case control study were obtained through new genotyping and existing genetic data from a prior case control study of breast cancer using the Illumina Infinium Global Diversity Array or Multi Ethnic Genotyping Array. Primary analyses evaluated risk based on a recessive model, comparing women who carried two APOL1 risk alleles to women who carried zero or one risk allele. We used multivariable logistic regression models to examine associations among 1473 participants with a history of preeclampsia (cases) and 5143 parous women who had not experienced preeclampsia (controls), and among 1296 participants who had a history of preterm birth and 5320 without such history. Results: The odds ratio (OR) of preeclampsia for two APOL1 risk alleles vs. zero or one risk allele was 0.99 (95 % confidence interval (CI): 0.74, 1.32) after adjustment for principal components, genotype platform, and age in 1995. For preterm birth, the comparable multivariable OR was 1.04 (95 % CI: 0.86, 1.25). Conclusions: This large prospective study from a general population of Black women found no evidence of an association of APOL1 genotype with risk of either preeclampsia or preterm birth.

Dermal fibroblasts play a crucial role in the formation of granulation tissue in skin wounds. Consequently, the differentiation, migration, and proliferation of dermal fibroblasts are considered key factors in the skin wound healing process. However, in patients with diabetic foot ulcers, the proliferation and migration of fibroblasts are impaired by reactive oxygen species and inflammatory factors impair. Therefore, a novel magnetic gelatin-hesperidin microrobots drug delivery system was developed using microfluidics. The morphology, motility characteristics, and drug release of the microrobot were assessed, along with its impact on the proliferation and migration of human dermal fibroblasts under high-glucose conditions. Subjected to a rotating magnetic field, the microrobots exhibit precise, controllable, and flexible autonomous motion, achieving a maximum speed of 9.237 μm/s. In vitro drug release experiments revealed that approximately 78% of the drug was released within 30 min. It was demonstrated through cellular experiments that the proliferation of human dermal fibroblasts was actively promoted by the nanorobot, the migration ability of fibroblasts in a high-glucose state was enhanced, and good biocompatibility was exhibited. Hence, our study may provide a novel drug delivery system with significant potential for promoting the healing of diabetic foot wounds.

Surgical advancements for full-thickness macular hole (FTMH) treatment include vitrectomy, membrane peeling, and the inverted flap technique (IFT). IFT, which involves inverting the internal limiting membrane (ILM) flap over the macular hole (MH) or into the MH, improves success rates and visual recovery. However, issues like mis-aspiration during flap handling have been problematic. We introduce the petaloid technique, to position the ILM flap under air during FTMH surgery to evaluate its outcomes. This retrospective study included 28 eyes, with a mean minimum linear diameter (MLD) 472.04 ± 199.7 μm and basal diameter (BD) of 834.95 ± 593.54 μm. Primary closure of MH was achieved in 96.42% of patients, with 3.57% showing persistent MH during the 6-month follow-up. The VA improved significantly from preoperative levels at each postoperative stage, with notable increases at 3 months (0.86 ± 0.49 logMAR; p = 0.0132) and 6 months (0.77 ± 0.41 logMAR; p = 0.000081). The new closure patterns showed Type A in 28.6%, B in 14.3%, C in 28.6%, and D in 25%. Among different types of closure patterns, although VA improved in all types, significant improvement in VA was noted for type A and type C, with notable improvements at the 6-month follow-up for Type A (0.60 ± 0.23 logMAR; p = 0.02) and at the 1-month follow-up for Type C (0.62 ± 0.28 logMAR; p = 0.02). For macular hole retinal detachment in 5 eyes, the average preoperative VA was 1.86 ± 0.19 logMAR, while the final mean postoperative VA showed a significant improvement to 1.1 ± 0.40 logMAR (p = 0.021, paired t-tests). Retinal reattachment was achieved in all cases (5/5) without recurrent detachment post-silicone oil removal. For the prognostic significance of MH shapes identified by OCT, it can be concluded that the shape of macular holes significantly influences visual acuity outcomes at 6 months post-surgery (p = 0.037). The shape of macular holes, particularly Flask-shaped, significantly impacts visual acuity compared to other shape. The modified petaloid technique for treating FTMH proved safe and effective, with no significant complications noted.

Abstract Understanding how to increase soybean yield is crucial for global food security. The genetic and epigenetic factors influencing seed size, a major crop yield determinant, are not fully understood. We explore the role of DNA demethylase GmDMEa in soybean seed size. Our research indicates that GmDMEa negatively correlates with soybean seed size. Using CRISPR-Cas9, we edited GmDMEa in the Dongnong soybean cultivar, known for small seeds. Modified plants had larger seeds and greater yields without altering plant architecture or seed nutrition. GmDMEa preferentially demethylates AT-rich transposable elements, thus activating genes and transcription factors associated with the abscisic acid pathway, which typically decreases seed size. Chromosomal substitution lines confirm that these modifications are inheritable, suggesting a stable epigenetic method to boost seed size in future breeding. Our findings provide insights into epigenetic seed size control and suggest a strategy for improving crop yields through the epigenetic regulation of crucial genes. This work implies that targeted epigenetic modification has practical agricultural applications, potentially enhancing food production without compromising crop quality.

Abstract Deconvolution is an efficient approach for detecting cell-type-specific (cs) transcriptomic signals without cellular segmentation. However, this type of methods may require a reference profile from the same molecular source and tissue type. Here, we present a method to dissect bulk proteome by leveraging tissue-matched transcriptome and proteome without using a proteomics reference panel. Our method also selects the proteins contributing to the cellular heterogeneity shared between bulk transcriptome and proteome. The deconvoluted result enables downstream analyses such as cs-protein Quantitative Trait Loci (cspQTL) mapping. We benchmarked the performance of this multimodal deconvolution approach through CITE-seq pseudo bulk data, a simulation study, and the bulk multi-omics data from human brain normal tissues and breast cancer tumors, individually, showing robust and accurate cell abundance quantification across different datasets. This algorithm is implemented in a tool MICSQTL that also provides cspQTL and multi-omics integrative visualization, available at https://bioconductor.org/packages/MICSQTL .

Background: Percutaneous nephrolithotomy (PCNL) is thought to have an increased risk of infectious complications. This study evaluates the predictability of preoperative midstream urine culture (PMUC), stone culture (SC), and renal pelvis urine culture (RPUC) for post-PCNL systemic inflammatory response syndrome (SIRS) or urosepsis. Method: After literature search in electronic databases (Embase, PubMed, Ovid, Science Direct, and Springer), studies were selected by following precise eligibility criteria. The quality of included studies was assessed, and meta-analyses of proportions were performed to seek culture positivity rates and incidence rates of post-PCNL SIRS/urosepsis. Meta-analyses of odds ratios (OR) were performed to evaluate the odds of positivity between SC and PMUC or RPUC, and the odds of post-PCNL SIRS/urosepsis with SC versus PMUC or RPUC. Results: Nineteen studies (4829 patients) were included. Positivity rates of PMUC, SC, and RPUC were 16 % [95 % CI: 12, 20], 21 % [95 % CI: 16, 26] and 10 % [95 % CI: 7, 14] respectively. The odds of positivity were significantly higher for SC compared to PMUC (OR 1.37 [95%CI: 1.02, 1.84]; p = 0.037) or RPUC (OR 1.65 [95%CI: 1.25, 2.18] p

Background Life's Essential 8 (LE8) is an enhanced metric for cardiovascular health. The interrelations among LE8, biomarkers of aging, and disease risks are unclear. Methods and Results LE8 score was calculated for 5682 Framingham Heart Study participants. We implemented 4 DNA methylation‐based epigenetic age biomarkers, with older epigenetic age hypothesized to represent faster biological aging, and examined whether these biomarkers mediated the associations between the LE8 score and cardiovascular disease (CVD), CVD‐specific mortality, and all‐cause mortality. We found that a 1 SD increase in the LE8 score was associated with a 35% (95% CI, 27–41; P=1.8E‐15) lower risk of incident CVD, a 36% (95% CI, 24–47; P=7E‐7) lower risk of CVD‐specific mortality, and a 29% (95% CI, 22–35; P=7E‐15) lower risk of all‐cause mortality. These associations were partly mediated by epigenetic age biomarkers, particularly the GrimAge and the DunedinPACE scores. The potential mediation effects by epigenetic age biomarkers tended to be more profound in participants with higher genetic risk for older epigenetic age, compared with those with lower genetic risk. For example, in participants with higher GrimAge polygenic scores (greater than median), the mean proportion of mediation was 39%, 39%, and 78% for the association of the LE8 score with incident CVD, CVD‐specific mortality, and all‐cause mortality, respectively. No significant mediation was observed in participants with lower GrimAge polygenic score. Conclusions DNA methylation‐based epigenetic age scores mediate the associations between the LE8 score and incident CVD, CVD‐specific mortality, and all‐cause mortality, particularly in individuals with higher genetic predisposition for older epigenetic age.

BackgroundResting heart rate (HR) and routine physical activity are associated with cardiorespiratory fitness levels. Commercial smartwatches permit remote HR monitoring and step count recording in real-world settings over long periods of time, but the relationship between smartwatch-measured HR and daily steps to cardiorespiratory fitness remains incompletely characterized in the community. ObjectiveThis study aimed to examine the association of nonactive HR and daily steps measured by a smartwatch with a multidimensional fitness assessment via cardiopulmonary exercise testing (CPET) among participants in the electronic Framingham Heart Study. MethodsElectronic Framingham Heart Study participants were enrolled in a research examination (2016-2019) and provided with a study smartwatch that collected longitudinal HR and physical activity data for up to 3 years. At the same examination, the participants underwent CPET on a cycle ergometer. Multivariable linear models were used to test the association of CPET indices with nonactive HR and daily steps from the smartwatch. ResultsWe included 662 participants (mean age 53, SD 9 years; n=391, 59% women, n=599, 91% White; mean nonactive HR 73, SD 6 beats per minute) with a median of 1836 (IQR 889-3559) HR records and a median of 128 (IQR 65-227) watch-wearing days for each individual. In multivariable-adjusted models, lower nonactive HR and higher daily steps were associated with higher peak oxygen uptake (VO2), % predicted peak VO2, and VO2 at the ventilatory anaerobic threshold, with false discovery rate (FDR)–adjusted P values

Abstract Copper ions play a crucial role as cofactors for essential enzymes in cellular processes. However, when the intracellular concentration of copper ions exceeds the homeostatic threshold, they become toxic to cells. In our study, we demonstrated that elesclomol, as a carrier of copper ions, caused an upregulation of protein phosphatase 1 regulatory subunit 15 A (PPP1R15A), which plays a role in regulating substrate selectivity of protein phosphatase 1 during cuproptosis. Mechanistically, we investigated that PPP1R15A activated translation initiation by dephosphorylating eukaryotic translation initiation factor 2 subunit alpha at the S51 residue through protein phosphatase 1 and phosphorylating eukaryotic translation initiation factor 4E binding protein 1 at the T70 residue. In addition, PPP1R15A reduced H3K4 methylation by altering the phosphorylation of histone methyltransferases, which led to the silencing of MYC and G2M phase arrest.

目的 系统评价急性缺血性卒中静脉溶栓后症状性颅内出血预测模型的特征，为静脉溶栓临床决策提供参考。 方法 检索中国知网、万方数据知识服务平台、维普资讯、PubMed、Embase、Web of Science和The Cochrane Library数据库，收集急性缺血性卒中静脉溶栓后症状性颅内出血预测模型相关研究信息，检索时限为建库至2022年12月18日。由2位研究员独立筛选文献、提取资料并评价偏倚风险后对纳入模型的基本特征和方法论进行系统评价。 结果 纳入20项研究，共30个预测模型。纳入模型ROC曲线的AUC值范围为0.42～0.94。24个（80%）预测模型的整体预测性能较好，模型对不同结局的定义和算法的区分度有明显差异。最常见的预测因子包括NIHSS评分、年龄、梗死的影像学征象或评分、血糖、收缩压和抗血小板药物。 结论 急性缺血性卒中静脉溶栓后症状性颅内出血预测模型呈现出建模算法多样化、模型性能更佳化、预测因素多元化等特点，但总体偏倚风险较高，未来研究还需要进一步校准模型。此外，应更加关注模型的更新与外部验证，提高其外推性及临床效用，从而发挥模型更大的临床价值。 Abstract: Objective To systematically evaluate the prediction models of symptomatic intracerebral hemorrhage after intravenous thrombolysis in acute ischemic stroke and to provide a reference for clinical decision-making of intravenous thrombolysis. Methods CNKI, WanFang Data, VIP, PubMed, Embase, Web of Science, and The Cochrane Library databases were searched to collect relevant studies, with a timeframe for searching the database from the establishment of the database to December 18, 2022. Two researchers independently screened the literature, extracted the data, assessed the risk of bias, and then systematically evaluated the basic characteristics and methodology of the included models. Results Twenty studies were included, with a total of 30 prediction models. The AUC of the included models ranged from 0.42 to 0.94. The overall predictive performance of the 24 (80%) prediction models was good, with significant differences in model differentiation across outcome definitions and algorithms. The most common predictors were NIHSS score, age, imaging signs or scores of infarction, blood glucose, systolic blood pressure, and antiplatelet drugs. Conclusions In recent years, the prediction models of symptomatic intracerebral hemorrhage after intravenous thrombolysis in acute ischemic stroke have shown the characteristics of diversified modeling algorithms, better model performance, and diversified predictors. However, the overall risk of bias was high, and future studies need to calibrate the models further. More attention should be paid to updating and externally validating the models to improve extrapolation and clinical utility and utilize the models’ clinical practice implications.

Neural decoding is still a challenging and a hot topic in neurocomputing science. Recently, many studies have shown that brain network patterns containing rich spatiotemporal structural information represent the brain’s activation information under external stimuli. In the traditional method, brain network features are directly obtained using the standard machine learning method and provide to a classifier, subsequently decoding external stimuli. However, this method cannot effectively extract the multidimensional structural information hidden in the brain network. Furthermore, studies on tensors have show that the tensor decomposition model can fully mine unique spatiotemporal structural characteristics of a spatiotemporal structure in data with a multidimensional structure. This research proposed a stimulus-constrained Tensor Brain Network (s-TBN) model that involves the tensor decomposition and stimulus category-constraint information. The model was verified on real neuroimaging data obtained via magnetoencephalograph and functional mangetic resonance imaging). Experimental results show that the s-TBN model achieve accuracy matrices of greater than 11.06% and 18.46% on the accuracy matrix compared with other methods on two modal datasets. These results prove the superiority of extracting discriminative characteristics using the STN model, especially for decoding object stimuli with semantic information.

Lignin is one of the building blocks of plant cell walls, and the study of the spectral characterization of its cleavage process can help to monitor the production and reuse of straw after decay. In this paper, four theoretical model structures of lignin formed by lignin G monomers and connected by β-O-4 bonding type were optimized and calculated based on the density functional theory using the B3LYP/3-21g and B3LYP/6-311g basis sets. The results showed that the theoretical infrared spectra of lignin increased sequentially in the absorption peaks of 1500 cm−1 blue shift and 2932 cm−1 and 1200 cm−1 red shift, while the latter three theoretical models showed new infrared absorption peaks of 716 cm−1 and 823 cm−1 due to the presence of the β-O-4 structure, which is of great value for the theoretical spectral study of organic macromolecules and also provides data support for the spectral change in lignin in the degradation of graminaceous plants.

The storage time of rice determines its quality and nutritional value, and the longer the storage time, the greater the impact. In this study, different excitation wavelengths (405 nm, 365 nm, 310 nm) were used to detect the fluorescence spectrum of “Dongdao 12” brown rice. Support vector machine (SVM), K-nearest neighbor (KNN), and wide neural network (WNN) were used for modeling and analysis. Under the excitation of 310 nm, the accuracy of WNN classification is up to 99.2%. In order to reduce the scattering effect and other interference in the data, multiplicative scatter correction (MSC), standard normal variable (SNV), and Savitzky–Goray smoothing (SG) preprocessing methods were used. The results showed that SG + KNN classification achieved an accuracy of 99.3% under 310 nm excitation. In order to further improve the classification accuracy, the original spectrum and the preprocessed spectrum under different excitation light sources were fused. The classification accuracy of all methods was improved, and the original data fusion was combined with the WNN model to reach 100%. It shows that fluorescence spectroscopy has excellent potential in identifying rice storage years.

The origin of agricultural products significantly influences their quality and safety. Fluorescence spectroscopy was used to analyse Japonica rice 830, grown in different areas of Jilin Province, by examining rice seed, brown rice, and rice flour from 12 origins. Fluorescence spectra were pre-processed through normalisation and smoothing to remove noise. These processed spectra were input into decision trees, support vector machines (SVMs), K-nearest neighbour (KNN), and neural network models for classification. The analysis revealed that the combined four models achieved an average classification accuracy of 98.05% with a computation time of 180 s, while the reduced-scale models improved accuracy to 98.36% and reduced computation time to 11.25 s. Additionally, prediction models using standard rice starch content values across different states achieved R² values over 0.8. This method provides a rapid, precise approach for assessing rice quality and origin, demonstrating significant potential for application in rice analysis.

Introduction: Acute kidney injury (AKI) is a prevalent renal disorder. The occurrence of AKI may promote the formation of renal calcium oxalate stones by exerting continuous effects on renal tubular epithelial cells (TECs). We aimed to delineate the molecular interplay between AKI and nephrolithiasis. Methods: A mild (20 min) and severe (30 min) renal ischemia-reperfusion injury model was established in mice. Seven days after injury, calcium oxalate stones were induced using glyoxylate (Gly) to evaluate the impact of AKI on the formation of kidney stones. Transcriptome sequencing was performed on TECs to elucidate the relationship between AKI severity and kidney stones. Key transcription factors (TFs) regulating differential gene transcription levels were identified using motif analysis, and pioglitazone, ginkgetin, and fludarabine were used for targeted therapy to validate key TFs as potential targets for kidney stone treatment. Results: Severe AKI led to increased deposition of calcium oxalate crystals in renal, impaired kidney function, and upregulation of kidney stone-related gene expression. In contrast, mild AKI was associated with decreased crystal deposition, preserved kidney function, and downregulation of similar gene expression. Transcriptomic analysis revealed that genes associated with inflammation and cell adhesion pathways were significantly upregulated after severe AKI, while genes related to energy metabolism pathways were significantly upregulated after mild AKI. An integrative bioinformatic analysis uncovered a TF regulatory network within TECs, pinpointing that PKNOX1 was involved in the upregulation of inflammation-related genes after severe AKI, and inhibiting PKNOX1 function with pioglitazone could simultaneously reduce the increase of calcium oxalate crystals after severe AKI in kidney. On the other hand, motif analysis also revealed the protective role of STAT1 in the kidneys after mild AKI, enhancing the function of STAT1 with ginkgetin could reduce kidney stone formation, while the specific inhibitor of STAT1, fludarabine, could eliminate the therapeutic effects of mild AKI on kidney stones. Conclusion: Inadequate repair of TECs after severe AKI increases the risk of kidney stone formation, with the upregulation of inflammation-related genes regulated by PKNOX1 playing a role in this process. Inhibiting PKNOX1 function can reduce kidney stone formation. Conversely, after mild AKI, effective cell repair through upregulation of STAT1 expression can protect TEC function and reduce stone formation, and activating STAT1 function can also achieve the goal of treating kidney stones.

The positional accuracy of satellite imagery is essential for remote sensing cameras. However, vibrations and temperature changes during launch and operation can alter the exterior orientation parameters of remote sensing cameras, significantly reducing image positional accuracy. To address this issue, this article proposes an exterior orientation parameter variation real-time monitoring system (EOPV-RTMS). This system employs lasers to establish a full-link active optical monitoring path, which is free from time and space constraints. By simultaneously receiving star and laser signals with the star tracker, the system monitors changes in the exterior orientation parameters of the remote sensing camera in real time. Based on the in-orbit calibration geometric model, a new theoretical model and process for the calibration of exterior orientation parameters are proposed, and the accuracy and effectiveness of the system design are verified by ground experiments. The results indicate that, under the condition of a centroid extraction error of 0.1 pixel for the star tracker, the EOPV-RTMS achieves a measurement accuracy of up to 0.6″(3σ) for a single image. Displacement variation experiments validate that the measurement error of the system deviates by at most 0.05″ from the theoretical calculation results. The proposed EOPV-RTMS provides a new design solution for improving in-orbit calibration technology and image positional accuracy.

Abstract Background Metabolite signatures of long-term alcohol consumption are lacking. To better understand the molecular basis linking alcohol drinking and cardiovascular disease (CVD), we investigated circulating metabolites associated with long-term alcohol consumption and examined whether these metabolites were associated with incident CVD. Methods Cumulative average alcohol consumption (g/day) was derived from the total consumption of beer, wine, and liquor on average of 19 years in 2428 Framingham Heart Study Offspring participants (mean age 56 years, 52% women). We used linear mixed models to investigate the associations of alcohol consumption with 211 log-transformed plasma metabolites, adjusting for age, sex, batch, smoking, diet, physical activity, BMI, and familial relationship. Cox models were used to test the association of alcohol-related metabolite scores with fatal and nonfatal incident CVD (myocardial infarction, coronary heart disease, stroke, and heart failure). Results We identified 60 metabolites associated with cumulative average alcohol consumption (p

Abstract Background The sperm flagellum is an evolutionarily conserved specialized organelle responsible for sperm motility and male fertility. Deleterious mutations in genes involved in the sperm flagellum assembly can often cause sperm motility defects and male infertility. The murine Dnali1 gene encodes a protein that is known to interact with the cytoplasmic dynein heavy chain 1. Results A Dnali1-mutated mouse model was generated by inducing a nonsense mutation in the Dnali1 gene. The Dnali1-mutated male mice presented impaired sperm motility and were completely infertile. Although no obviously abnormal sperm morphology was observed in Dnali1-mutated male mice, the ultrastructural structure of sperm flagellum was disrupted, displaying as an asymmetrical distribution of the longitudinal columns (LCs). Notably, infertile Dnali1-mutated male mice were able to obtain offspring via ICSI. Conclusions Our results uncover a role of DNALI1 in sperm motility and male fertility in mice, and demonstrate that ICSI overcomes Dnali1-associated male infertility, thus providing guidance for the diagnosis and genetic counseling of DNALI1-associated human infertility.

Abstract Background Insulin resistance (IR) is a major risk factor for Alzheimer’s disease (AD) dementia. The mechanisms by which IR predisposes to AD are not well-understood. Epigenetic studies may help identify molecular signatures of IR associated with AD, thus improving our understanding of the biological and regulatory mechanisms linking IR and AD. Methods We conducted an epigenome-wide association study of IR, quantified using the homeostatic model assessment of IR (HOMA-IR) and adjusted for body mass index, in 3,167 participants from the Framingham Heart Study (FHS) without type 2 diabetes at the time of blood draw used for methylation measurement. We identified DNA methylation markers associated with IR at the genome-wide level accounting for multiple testing (P

In this study, yak bone collagen hydrolysate (YBCH) was produced by mixed proteases and provided to standard-diet mice at a different dose (low dose (LD), medium dose (MD), and high dose (HD)) to investigate its effects on the composition of gut microbiota and short-chain fatty acids (SCFA) production. It was found that YBCH was mainly composed of small molecular peptides whose molecular weight below 2000 Da. Notably, supplementation with different doses of YBCH could significantly downregulate the ratio of Firmicutes to Bacteroidetes in the fecal microbiota. At the family level, the Lachnospiraceae abundance was significantly reduced in the YBCH gavage groups (mean reduction ratio 41.7 %, 35.2 %, and 36.4 % for LD, MD, and HD group, respectively). The predicted functions of gut microbes in the MD group were significantly increased at “lipid metabolism” and “glycan biosynthesis and metabolism”. Moreover, the SCFA production in the YBCH groups was elevated. Especially, the concentration of acetic acid, propionic acid, and butyric acid in the MD group was separately increased 79.7 %, 89.2 %, and 78.8 % than that in the NC group. These results indicated that YBCH might be applied in the development of functional food for intestinal microecological regulation.

Abstract Mitochondria carry their own circular genome and disruption of the mitochondrial genome is associated with various aging-related diseases. Unlike the nuclear genome, mitochondrial DNA (mtDNA) can be present at 1000 s to 10,000 s copies in somatic cells and variants may exist in a state of heteroplasmy, where only a fraction of the DNA molecules harbors a particular variant. We quantify mtDNA heteroplasmy in 194,871 participants in the UK Biobank and find that heteroplasmy is associated with a 1.5-fold increased risk of all-cause mortality. Additionally, we functionally characterize mtDNA single nucleotide variants (SNVs) using a constraint-based score, mitochondrial local constraint score sum (MSS) and find it associated with all-cause mortality, and with the prevalence and incidence of cancer and cancer-related mortality, particularly leukemia. These results indicate that mitochondria may have a functional role in certain cancers, and mitochondrial heteroplasmic SNVs may serve as a prognostic marker for cancer, especially for leukemia.

BackgroundShort-term blood pressure variability (BPV) is associated with arterial stiffness in patients with hypertension. Few studies have examined associations between arterial stiffness and digital home BPV over a mid- to long-term time span, irrespective of underlying hypertension. ObjectiveThis study aims to investigate if arterial stiffness traits were associated with subsequent mid- to long-term home BPV in the electronic Framingham Heart Study (eFHS). We hypothesized that higher arterial stiffness was associated with higher home BPV over up to 1-year follow-up. MethodsAt a Framingham Heart Study research examination (2016-2019), participants underwent arterial tonometry to acquire measures of arterial stiffness (carotid-femoral pulse wave velocity [CFPWV]; forward pressure wave amplitude [FWA]) and wave reflection (reflection coefficient [RC]). Participants who agreed to enroll in eFHS were provided with a digital blood pressure (BP) cuff to measure home BP weekly over up to 1-year follow-up. Participants with less than 3 weeks of BP readings were excluded. Linear regression models were used to examine associations of arterial measures with average real variability (ARV) of week-to-week home systolic (SBP) and diastolic (DBP) BP adjusting for important covariates. We obtained ARV as an average of the absolute differences of consecutive home BP measurements. ARV considers not only the dispersion of the BP readings around the mean but also the order of BP readings. In addition, ARV is more sensitive to measurement-to-measurement BPV compared with traditional BPV measures. ResultsAmong 857 eFHS participants (mean age 54, SD 9 years; 508/857, 59% women; mean SBP/DBP 119/76 mm Hg; 405/857, 47% hypertension), 1 SD increment in FWA was associated with 0.16 (95% CI 0.09-0.23) SD increments in ARV of home SBP and 0.08 (95% CI 0.01-0.15) SD increments in ARV of home DBP; 1 SD increment in RC was associated with 0.14 (95% CI 0.07-0.22) SD increments in ARV of home SBP and 0.11 (95% CI 0.04-0.19) SD increments in ARV of home DBP. After adjusting for important covariates, there was no significant association between CFPWV and ARV of home SBP, and similarly, no significant association existed between CFPWV and ARV of home DBP (P>.05). ConclusionsIn eFHS, higher FWA and RC were associated with higher mid- to long-term ARV of week-to-week home SBP and DBP over 1-year follow-up in individuals across the BP spectrum. Our findings suggest that higher aortic stiffness and wave reflection are associated with higher week-to-week variation of BP in a home-based setting over a mid- to long-term time span.

Abstract Expression quantitative trait methylation (eQTM) analysis identifies DNA CpG sites at which methylation is associated with gene expression. The present study describes an eQTM resource of CpG-transcript pairs derived from whole blood DNA methylation and RNA sequencing gene expression data in 2115 Framingham Heart Study participants. We identified 70,047 significant cis CpG-transcript pairs at p

Abstract Identifying genes whose expression is associated with schizophrenia (SCZ) risk by transcriptome-wide association studies (TWAS) facilitates downstream experimental studies. Here, we integrated multiple published datasets of TWAS, gene coexpression, and differential gene expression analysis to prioritize SCZ candidate genes for functional study. Convergent evidence prioritized Propionyl-CoA Carboxylase Subunit Beta (PCCB), a nuclear-encoded mitochondrial gene, as an SCZ risk gene. However, the PCCB’s contribution to SCZ risk has not been investigated before. Using dual luciferase reporter assay, we identified that SCZ-associated SNPs rs6791142 and rs35874192, two eQTL SNPs for PCCB, showed differential allelic effects on transcriptional activities. PCCB knockdown in human forebrain organoids (hFOs) followed by RNA sequencing analysis revealed dysregulation of genes enriched with multiple neuronal functions including gamma-aminobutyric acid (GABA)-ergic synapse. The metabolomic and mitochondrial function analyses confirmed the decreased GABA levels resulted from inhibited tricarboxylic acid cycle in PCCB knockdown hFOs. Multielectrode array recording analysis showed that PCCB knockdown in hFOs resulted into SCZ-related phenotypes including hyper-neuroactivities and decreased synchronization of neural network. In summary, this study utilized hFOs-based multi-omics analyses and revealed that PCCB downregulation may contribute to SCZ risk through regulating GABAergic pathways, highlighting the mitochondrial function in SCZ.

The regeneration of alveolar bone is still clinical challenge, particularly accompanied with diabetes, causing metabolic disorder with a protracted low-grade inflammatory phenotype. As a result, the anticipated loading of biomaterials is highly suspicious in spontaneous modulation of cells function, which is mostly disturbed by constant inflammation. In this study, we developed glucose and hydrogen peroxide dual-responsive borosilicate glass (BSG) scaffolds loaded with epigallocatechin gallate (EGCG) to synergistically modulate the abnormal inflammation of diabetic alveolar bone defects. It was found that the release of EGCG by BSG could directly regulate the shift of macrophages from M1 to the M2 phenotype by promoting autophagy and lessening the inhibition of autophagic flux. Moreover, EGCG can also indirectly regulate the polarization phenotype of macrophages by reducing the activation of NF-κb in stem cells and restoring its immunoregulatory capacity. Therefore, the addition of EGCG to BSG scaffold in diabetes allows for a more striking modulation of the macrophage phenotype in a timely manner. The altered macrophage phenotype reduces local inflammation and thus increases the ability to repair diabetic alveolar bone, showing promise for the treatment of alveolar defect in diabetic patients.