Muscularis macrophages controlled by NLRP3 maintain the homeostasis of excitatory neurons.

Peristaltic movements in gut are essential to propel ingested materials through the gastrointestinal tract. Intestinal resident macrophages play an important role in this physiological function through protecting enteric neurons. However, it is incompletely clear how individuals maintain the homeostasis of gut motility. Here we found that NLRP3 is a critical factor in controlling loss of muscularis resident macrophages (MMs), and demonstrate that MMs are involved in the homeostasis of excitatory neurons such as choline acetyltransferase (ChAT)+ and vesicular glutamate transporter 2 (VGLUT2)+ but not inhibitory neuronal nitric oxide synthase (nNOS)+ neurons. NLRP3 knockout (KO) mice had enhanced gut motility and increased neurons, especially excitatory ChAT+ and VGLUT2+ neurons. Single cell analyses showed that there had increased resident macrophages, especially MMs in NLRP3 KO mice. The MM proportion in the resident macrophages was markedly higher than those in wild-type (WT) or caspase 1/11 KO mice. Deletion of the MMs and transplantation of the NLRP3 KO bone marrow cells showed that survival of the gut excitatory ChAT+ and VGLUT2+ neurons was dependent on the MMs. Gut microbiota metabolites ß-hydroxybutyrate (BHB) could promote gut motility through protecting MMs from pyroptosis. Thus, our data suggest that MMs regulated by NLRP3 maintain the homeostasis of excitatory neurons.

Interplay between mesenchymal stem cells and macrophages: Promoting bone tissue repair.

The repair of bone tissue damage is a complex process that is well-orchestrated in time and space, a focus and difficulty in orthopedic treatment. In recent years, the success of mesenchymal stem cells (MSCs)-mediated bone repair in clinical trials of large-area bone defects and bone necrosis has made it a candidate in bone tissue repair engineering and regenerative medicine. MSCs are closely related to macrophages. On one hand, MSCs regulate the immune regulatory function by influencing macrophages proliferation, infiltration, and phenotype polarization, while also affecting the osteoclasts differentiation of macrophages. On the other hand, macrophages activate MSCs and mediate the multilineage differentiation of MSCs by regulating the immune microenvironment. The cross-talk between MSCs and macrophages plays a crucial role in regulating the immune system and in promoting tissue regeneration. Making full use of the relationship between MSCs and macrophages will enhance the efficacy of MSCs therapy in bone tissue repair, and will also provide a reference for further application of MSCs in other diseases.

SnSe2 Quantum Dots and Chlorhexidine Acetate Suppress Synergistically Non-radiative Recombination Loss for High Efficiency and Stability Perovskite Solar Cells.

Non-radiative recombination losses limit the property of perovskite solar cells (PSCs). Here, a synergistic strategy of SnSe2QDs doping into SnO2 and chlorhexidine acetate (CA) coating on the surface of perovskite is proposed. The introduction of 2D SnSe2QDs reduces the oxygen vacancy defects and increases the carrier mobility of SnO2. The optimized SnO2 as a buried interface obviously improves the crystallization quality of perovskite. The CA containing abundant active sites of ─NH2/─NH─, ─C═N, CO, ─Cl groups passivate the defects on the surface and grain boundary of perovskite. The alkyl chain of CA also improves the hydrophobicity of perovskite. Moreover, the synergism of SnSe2QDs and CA releases the residual stress and regulates the energy level arrangement at the top and bottom interface of perovskite. Benefiting from these advantages, the bulk and interface non-radiative recombination loss is greatly suppressed and thereby increases the carrier transport and extraction in devices. As a result, the best power conversion efficiency (PCE) of 23.41% for rigid PSCs and the best PCE of 21.84% for flexible PSCs are reached. The rigid PSC maintains 89% of initial efficiency after storing nitrogen for 3100 h. The flexible PSCs retain 87% of the initial PCE after 5000 bending cycles at a bending radius of 5 mm.

Downregulation of Serum PTEN Expression in Mercury-Exposed Population and PI3K/AKT Pathway-Induced Inflammation.

Objective: This study investigated the impact of occupational mercury (Hg) exposure on human gene transcription and expression, and its potential biological mechanisms. Methods: Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation. Hg-exposed cell models and PTEN low-expression models were established in vitro using 293T cells. PTEN gene expression was assessed using qRT-PCR, and Western blotting was used to measure PTEN, AKT, and PI3K protein levels. IL-6 expression was determined by ELISA. Results: Combined findings from gene expression microarray analysis, bioinformatics, and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group. In the Hg-exposed cell model (25 and 10 µmol/L), a significant decrease in PTEN expression was observed, accompanied by a significant increase in PI3K, AKT, and IL-6 expression. Similarly, a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K, AKT, and IL-6 levels. Conclusion: This is the first study to report that Hg exposure downregulates the PTEN gene, activates the PI3K/AKT regulatory pathway, and increases the expression of inflammatory factors, ultimately resulting in kidney inflammation.

Anxiety and depression in nasopharyngeal carcinoma patients and network analysis to identify central symptoms: A cross-sectional study from a high-incidence area.

PURPOSE: To determine the prevalence of anxiety and depression in patients with nasopharyngeal carcinoma (NPC) and to identify central symptoms and bridge symptoms among psychiatric disorders. METHODS: This cross-sectional study recruited patients with NPC in Guangzhou, China from May 2022, to October 2022. The General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used for screening anxiety and depression, respectively. Network analysis was conducted to evaluate the centrality and connectivity of the symptoms of anxiety, depression, quality of life (QoL) and insomnia. RESULTS: A total of 2806 respondents with complete GAD-7 and PHQ-9 scores out of 3828 were enrolled. The incidence of anxiety in the whole population was 26.5% (depression, 28.5%; either anxiety or depression, 34.8%). Anxiety was highest at caner diagnosis (34.2%), while depression reached a peak at late-stage radiotherapy (48.5%). Both moderate and severe anxiety and depression were exacerbated during radiotherapy. Coexisting anxiety and depression occurred in 58.3% of those with either anxiety or depression. The generated network showed that anxiety and depression symptoms were closely connected; insomnia was strongly connected with QoL. "Sad mood", "Lack of energy", and "Trouble relaxing" were the most important items in the network. Insomnia was the most significant bridge item that connected symptom groups. CONCLUSION: Patients with NPC are facing alarming disturbances of psychiatric disorders; tailored strategies should be implemented for high-risk patients. Besides, central symptoms (sad mood, lack of energy, and trouble relaxing) and bridge symptoms (insomnia) may be potential interventional targets in future clinical practice.

Effects of Dexamethasone on Postoperative Glycemic Control in Patients After Primary Total Joint Arthroplasty: A Randomized Double-Blind Controlled Trial.

BACKGROUND: In patients undergoing total joint arthroplasty, the use of dexamethasone (DEX) may cause perioperative blood glucose (BG) disorders, leading to complications even in patients who do not have diabetes. We aimed to evaluate the effects of different DEX doses on perioperative BG levels. METHODS: A total of 135 patients who do not have diabetes were randomized into three groups: preoperative intravenous (IV) injection of normal saline (Group A, the placebo group), preoperative IV injection of 10 mg DEX (Group B), and preoperative IV injection of 20 mg DEX (Group C). Postoperative fasting BG (FBG) levels were designated as the primary outcome, while postoperative postprandial BG (PBG) levels were assigned as the secondary outcome. The incidence of complications was recorded. We also investigated the risk factors for FBG ≥ 140 mg/dL and PBG ≥ 180 mg/dL. RESULTS: The FBG levels were higher in Groups B and C than in Group A on postoperative days (PODs) 0 and 1. The PBG levels were lower for Groups A and B compared to Group C on POD 1. No differences in FBG or PBG were detected beyond POD 1. Elevated preoperative glycosylated hemoglobin A1c levels increased the risk of FBG ≥ 140 mg/dL and PBG ≥ 180 mg/dL, respectively. However, preoperative IV injection of DEX was not associated with FBG ≥ 140 mg/dL or PBG ≥ 180 mg/dL. No differences were found in postoperative complications among the three groups. CONCLUSIONS: The preoperative IV administration of 10 or 20 mg DEX in patients who do not have diabetes showed transient effects on postoperative BG after total joint arthroplasty. The preoperative glycosylated hemoglobin A1c level threshold (regardless of the administration or dosage of DEX) that increased the risk for the occurrence of FBG ≥ 140 mg/dL and PBG ≥ 180 mg/dL was 5.75 and 5.85%, respectively.

Electrochemiluminescence-Based Single-Particle Tracking of the Biomolecules Moving along Intercellular Membrane Nanotubes between Live Cells.

Electrochemiluminescence (ECL) imaging, a rapidly evolving technology, has attracted significant attention in the field of cellular imaging. However, its primary limitation lies in its inability to analyze the motion behaviors of individual particles in live cellular environments. In this study, we leveraged the exceptional ECL properties of quantum dots (QDs) and the excellent electrochemical properties of carbon dots (CDs) to develop a high-brightness ECL nanoprobe (CDs-QDs) for real-time ECL imaging between living cells. This nanoprobe has excellent signal-to-noise ratio imaging capabilities for the single-particle tracking (SPT) of biomolecules. Our finding elucidated the enhanced ECL mechanism of CDs-QDs in the presence of reactive oxygen species through photoluminescence, electrochemistry, and ECL techniques. We further tracked the movement of single particles on membrane nanotubes between live cells and confirmed that the ECL-based SPT technique using CD-QD nanoparticles is an effective approach for monitoring the transport behaviors of biomolecules on membrane nanotubes between live cells. This opens a promising avenue for the advancement of ECL-based single-particle detection and the dynamic quantitative imaging of biomolecules.

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins.

Cyclic annulation involving diaryliodonium salts is an efficient tool for the construction of two or more chemical bonds in a one-pot process. Ortho-functionalized diaryliodonium salts have showcased distinct reactivity in the exploration of benzocyclization or arylocyclization. With this strategy of ortho-ester-substituted diaryliodonium salts, herein, we utilized a copper catalyst to activate the C-I bond of diaryliodonium salts in the generation of aryl radicals, thus resulting in an annulation reaction with naphthols and substituted phenols. This approach yielded a diverse array of 3,4-benzocoumarin derivatives bearing various substituents.

Redox Relay-Induced C-S Radical Cross-Coupling Strategy: Application in Nontraditional Site-Selective Thiocyanation of Quinoxalinones.

Oxidative cross-coupling is a powerful strategy to form C-heteroatom bonds. However, oxidative cross-coupling for constructing C-S bond is still a challenge due to sulfur overoxidation and poisoning transition-metal catalysts. Now, electrochemical redox relay using sulfur radicals formed in situ from inorganic sulfur source offers a solution to this problem. Herein, electrochemical redox relay-induced C-S radical cross-coupling of quinoxalinones and ammonium thiocyanate with bromine anion as mediator is presented. The electrochemical redox relay comprised initially the formation of sulfur radical via indirect electrochemical oxidation, simultaneous electrochemical reduction of the imine bond, electro-oxidation-triggered radical coupling involving dearomatization-rearomatization, and the reformation of the imine bond through anodic oxidation. Applying this strategy, various quinoxalinones bearing multifarious electron-deficient/-rich substituents at different positions were well compatible with moderate to excellent yields and good steric hindrance compatibility under constant current conditions in an undivided cell without transition-metal catalysts and additional redox reagents. Synthetic applications of this methodology were demonstrated through gram-scale preparation and follow-up transformation. Notably, such a unique strategy may offer new opportunities for the development of new quinoxalinone-core leads.

Green preparation of CaO-based CO2 adsorbent by calcium-induced hydrogenation of shell wastes at room/moderate temperature.

Capturing CO2 using clamshell/eggshell-derived CaO adsorbent can not only reduce carbon emissions but also alleviate the impact of trash on the environment. However, organic acid was usually used, high-temperature calcination was often performed, and CO2 was inevitably released during preparing CaO adsorbents from shell wastes. In this work, CaO-based CO2 adsorbent was greenly prepared by calcium-induced hydrogenation of clamshell and eggshell wastes in one pot at room/moderate temperature. CO2 adsorption experiments were performed in a thermogravimetric analyzer (TGA). The adsorption performance of the adsorbents obtained from the mechanochemical reaction (BM-C/E-CaO) was superior to that of the adsorbents obtained from the thermochemical reaction (Cal-C/E-CaO). The CO2 adsorption capacity of BM-C-CaO at 650 °C is up to 36.82 wt%, but the adsorption decay rate of the sample after 20 carbonation/calcination cycles is only 30.17%. This study offers an alternative energy-saving method for greenly preparing CaO-based adsorbent from shell wastes.

Investigation on vehicle occupant dummy applicability for under-foot impact loading conditions.

PURPOSE: Under-foot impact loadings can cause serious lower limb injuries in many activities, such as automobile collisions and underbody explosions to military vehicles. The present study aims to compare the biomechanical responses of the mainstream vehicle occupant dummies with the human body lower limb model and analyze their robustness and applicability for assessing lower limb injury risk in under-foot impact loading environments. METHODS: The Hybrid III model, the test device for human occupant restraint (THOR) model, and a hybrid human body model with the human active lower limb model were adopted for under-foot impact analysis regarding different impact velocities and initial lower limb postures. RESULTS: The results show that the 2 dummy models have larger peak tibial axial force and higher sensitivity to the impact velocities and initial postures than the human lower limb model. In particular, the Hybrid III dummy model presented extremely larger peak tibial axial forces than the human lower limb model. In the case of minimal difference in tibial axial force, Hybrid III's tibial axial force (7.5 kN) is still 312.5% that of human active lower limb's (2.4 kN). Even with closer peak tibial axial force values, the biomechanical response curve shapes of the THOR model show significant differences from the human lower limb model. CONCLUSION: Based on the present results, the Hybrid III dummy cannot be used to evaluate the lower limb injury risk in under-foot loading environments. In contrast, potential improvement in ankle biofidelity and related soft tissues of the THOR dummy can be implemented in the future for better applicability.

Efficacy of botulinum toxin A combined with extracorporeal shockwave therapy in post-stroke spasticity: a systematic review.

Objectives: In recent years, there has been an increase in the number of randomized clinical trials of BTX-A combined with ESWT for the treatment of post-stroke spasticity. This has made it possible to observe the benefits of combination therapy in clinical practice. Therefore, this paper reviews the effectiveness of BTX-A in combination with ESWT for the treatment of post-stroke spasticity. Methods: By October 2023, a systematic review was conducted in the databases PubMed, Cochrane, Embase, Medline, Web of Science, China National Knowledge Infrastructure, Wan Fang Database, China Biology Medicine disc and China Science and Technology Journal Database were systematically searched. We included randomized controlled trials that reported outcome metrics such as MAS, FMA, and MBI score. Studies were excluded if MAS was not reported. The quality of the included studies was assessed by the Cochrane Collaboration's tool for assessing risk of bias, and the AMSTAR quality rating scale was selected for self-assessment. Results: A total of 70 articles were included in the initial search, and six were ultimately included. The results of the included studies showed that the combination therapy was effective in reducing MAS scores and improving FMA and MBI scores in patients with spasticity compared to the control group. Combination therapy has also been shown to improve joint mobility and reduce pain in spastic limbs. Conclusion: Cumulative evidence from clinical randomized controlled trial studies suggests that the combination therapy is effective in reducing lower limb spasticity and improving mobility after stroke. However, more clinical trials are still needed to corroborate the evidence regarding the efficacy of BTX-A combined with shockwave therapy. Systematic Review Registration: The system review can be searched in the PROSPERO database (CRD42023476654).

Childhood urbanicity is associated with emotional episodic memory-related striatal function and common variation in NTRK2.

BACKGROUND: Childhoods in urban or rural environments may differentially affect the risk of neuropsychiatric disorders, possibly through memory processing and neural response to emotional stimuli. Genetic factors may not only influence individuals' choices of residence but also modulate how the living environment affects responses to episodic memory. METHODS: We investigated the effects of childhood urbanicity on episodic memory in 410 adults (discovery sample) and 72 adults (replication sample) with comparable socioeconomic statuses in Beijing, China, distinguishing between those with rural backgrounds (resided in rural areas before age 12 and relocated to urban areas at or after age 12) and urban backgrounds (resided in cities before age 12). We examined the effect of childhood urbanicity on brain function across encoding and retrieval sessions using an fMRI episodic memory paradigm involving the processing of neutral or aversive pictures. Moreover, genetic association analyses were conducted to understand the potential genetic underpinnings that might contribute to memory processing and neural mechanisms influenced by early-life urban or rural environments. RESULTS: Episodic memory retrieval accuracy for more difficult neutral stimuli was similar between those with urban and rural childhoods, whereas aversive stimuli elicited higher retrieval accuracy in the urban group (P = 0.023). For aversive stimuli, subjects with urban childhood had relatively decreased engagement of the striatum at encoding and decreased engagement of the hippocampus at retrieval. This more efficient striatal encoding of aversive stimuli in those with urban childhoods was associated with common variation in neurotrophic tyrosine kinase receptor type 2 (NTRK2) (right striatum: P = 1.58×10-6). These findings were confirmed in the replication sample. CONCLUSIONS: We suggest that this differential striatal processing of aversive stimuli observed in individuals with urban or rural childhoods may represent mechanisms by which childhood urbanicity may affect brain circuits, heightening behavioral responses to negative stressors associated with urban environments. NTRK2-associated neural processes in the striatum may play a role in these processes.

Association between genetically proxied PCSK9 inhibition and systemic lupus erythematosus risk: A mendelian randomization study.

BACKGROUND: Preclinical and epidemiological studies suggest that proprotein convertase subtilisin/kexin type 9 (PCSK9) had a potential effect on the development of SLE, but it was unclear whether a causal relationship exists. We aimed to investigate the association between genetically proxied inhibition of PCSK9 and the risk of SLE using a two-sample Mendelian randomization (MR) approach. METHODS: Single nucleotide polymorphisms (SNPs) associated with PCSK9 were extracted from pooled data obtained from the Global Lipid Genetics Consortium (GLGC) Genome-wide Association Study (GWAS) related to LDL-c levels, which was used as a proxy for PCSK9 inhibition. Pooled statistics for SLE were obtained from an independent GWAS dataset including 5201 SLE patients and 9066 controls. Inverse variance-weighted random-effects models were used to examine the association between genetically proxied inhibition of PCSK9 and the risk of SLE. MR-Egger, weighted median, weighted mode, Simple mode, and co-location analyses were used as sensitivity analyses to test the robustness of the analyses. RESULTS: Genetically proxied inhibition of PCSK9 was associated with a reduced risk of SLE (OR = 0.51, 95% CI = 0.34 to 0.77, p = .001). This finding was replicated in an earlier GLGC GWAS analysis (OR = 0.59, 95% CI = 0.40 to 0.87, p = .007). Sensitivity analysis ensured that the results were robust. Co-localization analysis did not find evidence of shared causal variation between PCSK9 and SLE. CONCLUSIONS: This Mendelian randomization study showed that PCSK9 was associated with SLE pathogenesis, and its inhibition was associated with a reduced risk of SLE. This study has offered a prospective therapeutic avenue for intervening in the progression of SLE by inhibiting PCSK9 levels.

Excited-state Engineering Enables Efficient Deep-blue Light-emitting Diodes Exhibiting BT.2020 Color Gamut.

Organic luminescent materials that exhibit thermally activated delayed fluorescence (TADF) can convert non-emissive triplet excitons into emissive singlet states through a reverse intersystem crossing (RISC) process. Therefore, they have tremendous potential for applications in organic light-emitting diodes (OLEDs). However, with the development of ultra-high definition 4K/8K display technologies, designing efficient deep-blue TADF materials to achieve the Commission Internationale de l'Éclairage (CIE) coordinates fulfilling BT.2020 remains a significant challenge. Here, we propose an effective approach to design deep-blue TADF molecules based on hybrid long- and short-range charge-transfer by incorporation of multiple donor moieties into organoboron multiple resonance acceptors. The resulting TADF molecule exhibits deep-blue emission at 414 nm with a full width at half maximum (FWHM) of 29 nm, together with a thousand-fold increase in RISC rate. OLEDs based on our champion material achieved a record maximum external quantum efficiency (EQE) of 22.8% with CIE coordinates of (0.163, 0.046), approaching the coordinates of the BT.2020 blue standard. Moreover, TADF-assisted fluorescence devices employing our designed material as a sensitizer exhibited an exceptional EQE of 33.1%. Our work thus provides a blueprint for future development of efficient deep-blue TADF emitters, representing an important milestone towards meeting the blue color gamut standard of BT.2020. This article is protected by copyright. All rights reserved.

Impact of guideline-directed medical therapy on systolic blood pressure and cardiovascular outcomes in patients with heart failure and low blood pressure: A systematic review and meta-analysis.

AIMS: Existing research indicates that patients with heart failure (HF) may have restricted access to guideline-directed medical therapy (GDMT) when their blood pressure (BP) is comparatively low. However, recent clinical trials suggest that HF patients with low BP could still benefit from certain HF medications, which have a minimal impact on BP. This systematic review and meta-analysis was conducted to determine whether this applies to all GDMT. METHODS AND RESULTS: A systematic search of MEDLINE and EMBASE was conducted for studies published from inception to 10 January 2024. Randomized controlled trials were selected if they reported on the longitudinal change of systolic BP (SBP) due to GDMT, or the risks of cardiovascular events in HF patients based on SBP categories. Weighted mean difference (WMD), hazard ratio or relative risk, and corresponding 95% confidence intervals (CI) were pooled for meta-analysis where possible. Data from 20 studies, encompassing information on 84 782 individuals, were analysed. Overall, GDMT is associated with lower SBP (WMD, -2.16; 95% CI -2.86 to -1.46), with no significant difference between baseline low and non-low BP subgroups (interaction p = 0.810). However, SBP of the treatment group increased by 5.8 mmHg from baseline in the low SBP subgroup during follow-up, while it decreased by 4.0 mmHg in the baseline non-low SBP subgroup. GDMT demonstrated similar cardiovascular benefits and risk of hypotension between low and non-low SBP subgroups (interaction p = 0.318 and 0.903, respectively). CONCLUSIONS: Guideline-directed medical therapy is associated with a negligible decrease in SBP, but can provide similar cardiovascular benefits in both low and non-low SBP HF patients, with no significant interaction with SBP as to hypotension. Therefore, GDMT should be initiated and maintained in HF patients with low BP.

UPLC-Q-TOF/MS analysis of chemical components of single decoction and combined decoction of Qige decoction reveals the differences between various preparation processes.

The aim of this work was to explore the differences between various pharmaceutical processes in combined solutions of a single decoction (QGHBY) and a combined decoction (QGHJY) of Qi-Ge decoction from the perspective of chemical composition changes, so as to further guide the clinical application of drugs. A combined solution of a single decoction and a combined decoction of Astragali Radix, Puerariae Lobatae Radix and Citri Reticulatae Chachiensis Pericarpium was prepared with the same technological parameters. The chemical components of the two were detected and identified based on UPLC-Q-TOF/MS, and the different components were determined by principal component analysis. Eighty-eight compounds were identified in the pharmaceutical solution of Qi-Ge decoction. Principal component analysis revealed 11 different components of QGHBY and QGHJY with the conditions of Variable Importance in Projection (VIP) ≥ 1, fold change ≥ 2 and p < 0.05, among which hesperidin, hesperitin, isosinensetin, sinensetin and 5-demethylnobiletin were the components of Citri Reticulatae Chachiensis Pericarpium. The levels of these 11 different components in QGHJY were higher than those of QGHBY. The combined decoction is beneficial for the dissolution of flavonoids and other chemical components, and there is a significant difference in the content of chemical components between modern herbal concentrate granules and traditional decoctions.

Long-term trends in Alzheimer's disease and other dementias deaths with high body mass index in China from 1990 to 2019, and projections up to 2042.

BACKGROUND: In China, the rising prevalence of high Body Mass Index (BMI) is linked to increasing health issues, including Alzheimer's disease (AD). This study analyzes mortality trends related to AD and other dementias associated with high BMI from 1990 to 2019, considering age, period, and birth cohort effects, and forecasts future trends. METHODS: We analyzed mortality data for AD and other dementias linked to high BMI in Chinese residents from the Global Burden of Disease 2019 database. Using Joinpoint regression, we examined age-standardized mortality rate (ASMR) trends and calculated annual and average annual percentage changes (APC and AAPC). Age-period-cohort models provided deeper insights, with Bayesian models used to project future ASMR trends to 2042. RESULTS: From 1990 to 2019, the ASMR for AD and other dementias associated with high BMI in China showed an overall increasing trend. Females had a lower increase rate than males, yet their overall levels remained higher. Specifically, the ASMR for males increased by an average of 2.70% per year, peaking between 2006 and 2010, while for females, it increased by an average of 2.29% per year, also peaking in the same period. Age-period-cohort analysis revealed increasing mortality relative risk with age and period, but a decrease with birth cohort. Projections suggest a continued rise in ASMR by 2042, with rates for males and females expected to be 2.48/100,000 and 2.94/100,000, respectively. CONCLUSION: The increasing mortality trend from AD and other dementias associated with high BMI highlights the urgent need for policy interventions focused on overweight prevention, particularly vital for addressing the health challenges in China's aging population.

Conserved intronic secondary structures with concealed branch sites regulate alternative splicing of poison exons.

Alternative splicing (AS) generates multiple RNA isoforms and increases the complexities of transcriptomes and proteomes. However, it remains unclear how RNA structures contribute to AS regulation. Here, we systematically search transcriptomes for secondary structures with concealed branch sites (BSs) in the alternatively spliced introns and predict thousands of them from six organisms, of which many are evolutionarily conserved. Intriguingly, a highly conserved stem-loop structure with concealed BSs is found in animal SF3B3 genes and colocalizes with a downstream poison exon (PE). Destabilization of this structure allows increased usage of the BSs and results in enhanced PE inclusion in human and Drosophila cells, leading to decreased expression of SF3B3. This structure is experimentally validated using an in-cell SHAPE-MaP assay. Through RNA interference screens of 28 RNA-binding proteins, we find that this stem-loop structure is sensitive to U2 factors. Furthermore, we find that SF3B3 also facilitates DNA repair and protects genome stability by enhancing interaction between ERCC6/CSB and arrested RNA polymerase II. Importantly, both Drosophila and human cells with the secondary structure mutated by genome editing exhibit altered DNA repair in vivo. This study provides a novel and common mechanism for AS regulation of PEs and reveals a physiological function of SF3B3 in DNA repair.

Deep Learning Model for Prediction of Bronchopulmonary Dysplasia in Preterm Infants Using Chest Radiographs.

Bronchopulmonary dysplasia (BPD) is common in preterm infants and may result in pulmonary vascular disease, compromising lung function. This study aimed to employ artificial intelligence (AI) techniques to help physicians accurately diagnose BPD in preterm infants in a timely and efficient manner. This retrospective study involves two datasets: a lung region segmentation dataset comprising 1491 chest radiographs of infants, and a BPD prediction dataset comprising 1021 chest radiographs of preterm infants. Transfer learning of a pre-trained machine learning model was employed for lung region segmentation and image fusion for BPD prediction to enhance the performance of the AI model. The lung segmentation model uses transfer learning to achieve a dice score of 0.960 for preterm infants with ≤ 168 h postnatal age. The BPD prediction model exhibited superior diagnostic performance compared to that of experts and demonstrated consistent performance for chest radiographs obtained at ≤ 24 h postnatal age, and those obtained at 25 to 168 h postnatal age. This study is the first to use deep learning on preterm chest radiographs for lung segmentation to develop a BPD prediction model with an early detection time of less than 24 h. Additionally, this study compared the model's performance according to both NICHD and Jensen criteria for BPD. Results demonstrate that the AI model surpasses the diagnostic accuracy of experts in predicting lung development in preterm infants.