Mediation effect of illness acceptance between perceived social support and self-management behaviors in rural elderly with coronary heart disease.

OBJECTIVE: To explore the relationship between perceived social support, acceptance of illness, and self-management behaviors and the mediating role of acceptance of illness in perceived social support and self-management behaviors. METHODS: Between August 2022 and February 2023, 731 rural older adults with coronary heart disease in Feicheng City participated in this study. Correlation analysis was used to analyze the relationship between variables, and mediating effects were analyzed using AMOS 23.0 software. RESULTS: Perceived social support and acceptance of illness were positively correlated with self-management behaviors. Acceptance of illness mediated the relationship between the perceived social support and the three dimensions of self-management behavior. CONCLUSION: These findings contribute to the understanding that increased perceived social support and acceptance of illness are more likely to improve self-management behaviors.

Whether mTICI 3 or mTICI 2b is better in patients with vertebrobasilar artery occlusion undergoing endovascular treatment depends on pc-ASPECTS.

BACKGROUND: The clinical relevance of differentiating between mTICI (modified Thrombolysis In Cerebral Infarction) 2b and mTICI 3 in patients with vertebrobasilar artery occlusion (VBAO) remains unclear. This study aimed to investigate whether mTICI 3 improves functional outcomes compared with mTICI 2b in patients with VBAO and whether this improvement differs according to extent of ischemic damage. METHODS: This retrospective study enrolled patients with VBAO within 24 hours of the estimated occlusion time at 65 stroke centers in a nationwide registration in China. The primary outcome was favorable functional outcome (modified Rankin scale score 0-3) at 90 days. Patients were matched by final mTICI grade using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Logistic regression and ordinal regression models were used to assess the impact of mTICI 2b versus mTICI 3 grading on prognosis, based on different extent of ischemia damage (posterior circulation Alberta Stroke Program Early CT Score-pc-ASPECTS of 9-10, 7-8, and 3-6) and treatment strategies (bridging therapy and direct endovascular therapy (EVT)). RESULTS: A total of 2075 patients with VBAO and successful reperfusion were included, 652 patients (31.4%) achieved mTICI 2b and 1423 patients (68.6%) achieved mTICI 3. After adjustment for confounders, achieving mTICI 3 following EVT in patients with VBAO and pc-ASPECTS 9-10 (OR 1.54, 95% CI 1.16 to 2.03) and pc-ASPECTS 7-8 (OR 1.80, 95% CI (1.26 to 2.56) were associated with favorable functional outcome compared with mTICI 2b, especially in those receiving direct EVT. However, in patients with pc-ASPECTS≤6, functional outcomes at 90 days did not differ between mTICI 3 and mTICI 2b (OR 1.12, 95% CI 0.67 to 1.88), irrespective of using bridging therapy or direct EVT. CONCLUSION: In patients with VBAO undergoing EVT with pc-ASPECTS>6, achieving mTICI 3 favors better outcomes compared with mTICI 2b, especially in those receiving direct EVT. However, in patients with pc-ASPECTS≤6, mTICI 3 did not improve functional outcomes compared with mTICI 2b. Interventionalists should carefully assess the risk-benefit of additional maneuvers once mTICI 2b reperfusion is restored in EVT for patients with VBAO and pc-ASPECTS≤6. Further studies are needed to guide treatment decisions in these cases.

Transformable 3D curved high-density liquid metal coils - an integrated unit for general soft actuation, sensing and communication.

Rigid solenoid coils have long been indispensable in modern intelligent devices. However, their sparse structure and challenging preparation of flexible coils for soft robots impose limitations. Here, a transformable 3D curved high-density liquid metal coil (HD-LMC) is introduced that surpasses the structural density level of enameled wire. The fabrication technique employed for high-density channels in elastomers is universally applicable. Such HD-LMCs demonstrated excellent performance in pressure, temperature, non-contact distance sensors, and near-field communication. Soft electromagnetic actuators thus achieved significantly improved the electromagnetic force and power density. Moreover, precise control of swinging tail motion enables a bionic pufferfish to swim. Finally, HD-LMC is further utilized to successfully implement a soft rotary robot with integrated sensing and actuation capabilities. This groundbreaking research provides a theoretical and experimental basis for expanding the applications of liquid metal-based multi-dimensional complex flexible electronics and is expected to be widely used in liquid metal-integrated robotic systems.

Dynamic hydrazone crosslinked salecan/chondroitin sulfate hydrogel platform as a promising wound healing Strategy: A comparative study on antibiotic and probiotic delivery.

Natural polysaccharide-based active-ingredient carriers have been a source of great concern for a long time. In order to explore potential antibiotics and probiotics carriers, a novel injectable chondroitin sulfate/salecan (CS) hydrogel was constructed by forming dynamic hydrazone bonds. Scanning electron microscope (SEM), proton nuclear magnetic resonance (1H NMR), Fourier transform infrared spectroscopy (FTIR), bacteriostatic test, and rheological experiments were used to investigate the chemical structure, inherent morphology, and enzymatic corruption of the hydrogel in vitro. The resulting hydrogels exhibited ideal probiotics loading capacity, drug release behavior, excellent antimicrobial activity and variable properties. Crucially, owing to its exceptional biocompatibility and reversible crosslinking network, this hydrogel can function as a three-dimensional extracellular matrix for cells, enabling cells to maintain high vitality and proliferation, and promote wound healing. The aforementioned findings indicated that this novel hydrogel can be a promising candidate as an active-ingredient carrier and scaffold material for tissue engineering.

Vertebrobasilar Artery Occlusion Treatment Outcomes Within 24 hours of Estimated Occlusion Time.

BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the efficacy and safety of endovascular treatment (EVT) in patients with acute vertebrobasilar artery occlusion (VBAO) within 24 hours of estimated occlusion time (EOT) and to evaluate the effect of early and late time window in a cohort of patients with VBAO treated with EVT. METHODS: Retrospective analysis was conducted on patients within 24 hours of the EOT in 65 stroke centers in China. Favorable outcome was defined as modified Rankin Scale ≤3 at 90 days. Patients were divided into the medical management (MM) group and the EVT group. Times were dichotomized into early (EOT ≤6 hours) and late (>6 hours) time windows. Multivariate logical regression models were used to evaluate the efficacy and safety of EVT and the effect of time windows on outcomes in EVT patients. RESULTS: Among 4124 patients, 2473 and 1651 patients were included in the early and late windows, respectively. 1702 patients received MM and 2422 were treated with EVT. EVT was associated with a higher rate of a favorable outcome at 90 days both in early (odds ratio [OR] 2.16, 95% CI 1.94-2.41) and late (OR 1.89, 95% CI 1.65-2.17) time windows. No differences were found regarding favorable outcome (OR 0.95, 95% CI 0.87-1.03) between VBAO patients treated with EVT within and beyond 6 hours. CONCLUSION: Patients with acute VBAO who received EVT within 24 hours were associated with improved favorable outcome compared with patients who received MM. EVT beyond 6 hours is feasible and safe with no increase in symptomatic intracranial hemorrhage.

The effect of femtosecond laser-assisted in situ keratomileusis on contrast sensitivity.

The benefits of femtosecond laser-assisted in situ keratomileusis (FS-LASIK) for correcting vision, particularly in terms of spherical equivalent (SE) and visual acuity (VA), have gained broad recognition. Nevertheless, it has remained uncertain whether FS-LASIK has a positive impact on contrast sensitivity (CS). In this study, we measured CS on seven participants by the quick contrast sensitivity function (qCSF) and compared CS before and after the surgery at two time points (1 day and 7 days after) by the repeated measures analysis of variance (ANOVA). Then, we clarified the underlying mechanisms using the perceptual template model (PTM). Furthermore, we investigated the relationship among SE, VA, and CS employing the Pearson correlation test. We found that (1) CS exhibited significant improvements on postoperative day 1, with further enhancements observed up to postoperative day 7, (2) CS improvements were dependent on spatial frequency (SF) and external noise, (3) CS improvements were attributed to the reduction of internal noise and the enhancement of the perceptual template, (4) VA and SE demonstrated significant improvement post-surgery, and (5) no significant correlations were observed among SE, VA, and CS, possibly due to limitations in sample size and lighting conditions. These findings contribute to our comprehension of FS-LASIK and provide a great indicator for assessing the outcomes of visual surgery.

Effects of the teach-back method on the health status of patients with chronic obstructive pulmonary disease: a real-world community-based cluster-randomized controlled trial.

Background: The teach-back method (TBM), also known as the "show-me" method, is a technique for verifying patients' understanding of health-related information that has been recommended for improving health literacy. However, the research on TBM effect on the outcomes of chronic obstructive pulmonary disease (COPD) patients is limited. Therefore, the aim of this study was to examine the effect of a TBM intervention on the health status of COPD patients. Methods: This real-world community-based cluster-randomized controlled trial enrolled 1,688 patients with COPD from 18 communities in China. Participants received either TBM plus usual care (UC) or UC only. General practitioners were trained in TBM before the intervention. The primary outcomes were depression and anxiety symptoms, as measured by the Hospital Anxiety and Depression Scale (HADS). The secondary outcomes were health-related quality of life and dyspnea, as measured by the COPD Assessment Test (CAT). Dyspnea was assessed using the modified Medical Research Council (mMRC) dyspnea scale. Data on acute exacerbations and deaths were extracted from medical records. Lung function was expressed as the forced expiratory volume in 1 second as a percentage of the predicted value [FEV1 (% pred)]. Results: In total, 336 of the 853 COPD patients in the intervention group (TBM plus UC) had comorbid depression, compared with 329 of the 835 in the control group (UC only). The TBM group showed a significantly greater improvement in HADS depression and anxiety subscale scores (HADS-D and HADS-A, respectively) than the UC group at12 months (t =8.34, P<0.001; t=12.18, P<0.001). The CAT and mMRC scores were significantly lower in the TBM than UC group at 12 months (t=8.43, P<0.001; t=7.23, P<0.001). The numbers of acute exacerbations and deaths were significantly lower in the TBM than UC group at 12 months (mean MCF values were 0.35 and 0.56, respectively [difference of 0.22; 95% confidence interval (CI): -0.41, -0.02; χ2=9.63, P<0.001]. The FEV1 (% pred) was significantly higher in the TBM than UC group at 12 months (t=7.45, P<0.001). Conclusions: General practitioners can use TBM interventions to effectively reduce anxiety, depression, and dyspnea symptoms, decrease the frequency of exacerbations and likelihood of death, and improve health-related quality of life and pulmonary function in patients with COPD. Trial Registration: The trial was registered on the Chinese Clinical Trials Registry (reference: ChiCTR-TRC-12001958).

Role of tenofovir dipivoxil in gut microbiota recovery from HBV-infection induced dysbiosis.

BACKGROUND: Studies have found dysbiosis of the gut microbiota in individuals infected with the hepatitis B virus (HBV). Tenofovir dipivoxil (TDF) is one of the preferred oral antiviral drugs used for the treatment of chronic hepatitis B (CHB), but the extent to which TDF is able to affect the gut microbiota and inflammatory factors of a patient remains largely unexplored. In this study, we collected stool samples from HBV patients prior to medication and from CHB patients treated with TDF. RESULTS: The gut microbiota and inflammatory factors were assessed in 42 healthy subjects (HC group), 109 HBV-infected subjects, including 48 CHB patients who were not medicated with nucleoside analogue drugs (No-NAs group), and 61 CHB patients who were medicated with TDF (TDF group). 16 S rRNA sequencing revealed that TDF treatment caused significant changes in the gut microbiota of HBV-infected individuals; however, the gut microbiota of HBV-infected individuals did not fully recover to a pre-dysbiosis state. The relative abundance of Bacteroidota gradually decreased from the HC group to the No-NAs and TDF groups. The relative abundance of Fusobacteriota was significantly higher in the No-NAs group than in the HC group. At the genus level, Dialister, Eubacterium_hallii_group, Halomonas, Collinsella, Sphingomonas, Xanthomonadaceae_unclassified, and Rhizobiaceae_unclassified were overrepresented; while the abundance of Bacteroides and Fusobacterium decreased significantly in the No-NAs and TDF groups. CONCLUSIONS: This study showed that TDF treatment significantly improved the regulation of the gut microbiota and aided in dysbiosis recovery. We did not observe significant improvement in serum inflammatory factor concentrations, which may be related to the relatively short duration of TDF administration in this study.

Well-Being and Cardiovascular Health: Insights From the UK Biobank Study.

BACKGROUND: Cardiovascular diseases (CVDs) are a leading global health concern. Emerging evidence suggests a potential protective role of well-being in reducing CVD risk. METHODS AND RESULTS: We conducted a cohort analysis using the UK Biobank data set, encompassing 121 317 participants. We assessed the well-being of participants using a well-being index derived from baseline questionnaires. Well-being categories were derived by latent class analysis using general happiness and satisfaction with family, friendships, health, and finance situations. The relationship between well-being and 4 major CVDs was analyzed using Cox proportional hazards models and Mendelian randomization. The study also examined the impacts of well-being on lifestyle factors and inflammatory markers, and its mediating role in the well-being-CVD relationship. Higher well-being was associated with a significantly reduced risk of various CVDs. Latent class analysis identified 4 distinct well-being groups (low, variable, moderate-to-high, and high satisfaction), with higher satisfaction levels generally associated with lower risk of CVDs. Mendelian randomization suggested potential causal relationships between well-being and reduced risk of CVDs. Participants with greater well-being demonstrated healthier behaviors and lower levels of inflammatory markers. Mediation analysis indicated that lifestyle and inflammatory markers partially mediated the relationship between well-being and CVDs. CONCLUSIONS: This study demonstrates a robust inverse association between well-being and the risks of CVDs, suggesting that enhancing well-being may be a viable strategy for CVD prevention. The role of lifestyle factors and inflammation as a mediator provides insight into possible biological pathways linking psychological states and cardiovascular health.

COF-derived porous nitrogen-doped carbon for removal of emerging organic contaminants and efficient uranium extraction from seawater.

The development of adsorbents for efficient and highly selective seawater extraction of uranium was instrumental in fostering sustainable progress in energy and addressing the prevailing energy crisis. However, the complex background composition of the marine environment, including radionuclides, organic pollutants, and a large number of co-existing heavy metal ions, were non-negligible obstacles to the extraction of uranium from seawater. The present investigation successfully employed a self-templated approach to synthesize porous nitrogen-doped carbon (PNC) derived from COF, which exhibited tremendous potential as an adsorbent for pollutant removal in environmental treatment. LZU1@PNC not only retained the structural features of the original COF-LZU1, but also overcame the acid-base instability problem commonly found in COFs. Subsequently, the removal process of two typical water pollutants on the material was investigated using 2,4-DCP and [UO2(CO3)3]4-. The results demonstrated that LZU1@PNC exhibited superior removal performance for the target pollutants compared to COF-LZU1, owing to its larger specific surface area and abundant defect structure. After six desorption-regeneration cycles, LZU1@PNC still maintained a high removal rate of the target contaminants, demonstrating the stability of this material and its excellent recyclability. In addition, based on various characterization techniques, the removal mechanism of 2,4-DCP was presumed to be mainly electrostatic attraction, hydrogen bonding, and π-π stacking interactions. Conversely, the elimination process of [UO2(CO3)3]4- predominantly relied on surface complexation phenomena. The present investigation provided new perspectives and stimulated a broader study of other COF-derived carbon materials and their modifications as adsorbents for uranium extraction from seawater and other applications.

Role of SbNRT1.1B in cadmium accumulation is attributed to nitrate uptake and glutathione-dependent phytochelatins biosynthesis.

Phytoremediation of cadmium (Cd)-polluted soil by using sweet sorghum displays a tremendous potential as it is a fast-growing, high biomass and Cd tolerant energy plant. Previous study has demonstrated SbNRT1.1B expression change is in accordance with enhanced Cd accumulation by external nitrate supply in sweet sorghum. Nevertheless, underlying mechanism of SbNRT1.1B response to Cd stress is still elusive. SbNRT1.1B exhibited a positive response to Cd stress in sweet sorghum. Overexpressing SbNRT1.1B increased primary root length, shoot fresh weight, nitrate and chlorophyll concentrations compared with Col-0 under Cd stress, while complementary SbNRT1.1B rescued these decreased values in mutant chl1-5. Cd concentrations in overexpressing SbNRT1.1B, complementary SbNRT1.1B and Col-0 lines were 3.2-4.1, 2.5-3.1 and 1.2-2.1 folds of that in chl1-5. Consistent with Cd concentrations, non-protein thiol (NPT), reduced glutathione (GSH) and phytochelatins (PCs) concentrations as well as the related genes expression levels showed the same trends under Cd stress. GSH biosynthesis inhibitor failed to reverse the patterns of GSH-dependent PCs concentrations changes in different lines, suggesting that SbNRT1.1B plays an upstream role in GSH-dependent PCs biosynthesis under Cd treatment. Altogether, SbNRT1.1B enhances nitrate concentrations contributing to increased chlorophyll concentrations and GSH-dependent PCs metabolites biosynthesis, thereby improving growth and Cd concentrations in plants.

Fecal microbiota transplantation as a new way for OVA-induced atopic dermatitis of juvenile mice.

Children all over the world suffer from atopic dermatitis (AD), a prevalent condition that impairs their health. Corticosteroids, which have long-term negative effects, are frequently used to treat AD. There has been a growing body of research on the gut microbiota's function in AD. Nevertheless, the function and underlying mechanisms of fecal microbiota transplantation (FMT) in AD children remain to be established. Therefore, in order to assess the preventive effects of FMT treatment on AD and investigate the mechanisms, we constructed an ovalbumin (OVA)-induced juvenile mouse AD model in this investigation. This study explored the role and mechanism of FMT treatment in AD through 16S RNA sequencing, pathological histological staining, molecular biology, and Flow cytometry. Results demonstrated that the FMT treatment improved the gut microbiota's diversity and composition, bringing it back to a level similar to that of a close donor. Following FMT treatment, OVA-specific antibodies were inhibited, immunoglobulin (Ig) E production was decreased, the quantity of mast cells and eosinophils was decreased, and specific inflammatory markers in the skin and serum were decreased. Further mechanistic studies revealed that FMT treatment induced CD103+ DCs and programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) expression in skin-draining lymph nodes and promoted Treg production to induce immune tolerance and suppress skin inflammation. Meanwhile, changes in the gut microbiota were substantially correlated with Th2 cytokines, OVA-specific antibodies, and PD-L1/PD-1. In conclusion, FMT regulates the Th1/Th2 immunological balance and the gut microbiota. It may also inhibit AD-induced allergy responses through the PD-L1/PD-1 pathway, and providing a unique idea and possibly a fresh approach to the treatment of AD.

An activity-based sensing fluorogenic probe for monitoring O-methyltransferase in plants.

Activity-based sensing probes are powerful tools for monitoring enzymatic activities in complex biological samples such as cellular and live animals; however, their application in plants remains challenging. Herein, fourteen activity-based fluorescent probes were assayed against Arabidopsis O-methyltransferases (AtOMTs). One probe, 3-BTD, displayed a high selectivity, reactivity, and fluorescence response toward AtOMTs especially the isoform AtCCoAOMT. We further characterized the features of this probe and explored whether it could be used to detect OMT activities in living plant cells. Our results show that 3-BTD can be used to visualize OMT activity in Arabidopsis, and no fluorescent signal was observed in the comt/ccoaomt double mutant, indicating that it has good specificity. Interestingly, in contrast to the observation that AtCCoAOMT-YFP accumulated in both cytoplasm and nucleus, OMT enzymatic activity tracked by 3-BTD probe was found only in the cytoplasm. This underscores the importance of activity-based sensing in studying protein function. Moreover, 3-BTD can be successfully applied in OMT visualization of different plants. This study indicates that 3-BTD can serve as a potential probe for in situ monitoring the real activity of OMT in multiple plants and provides a strategy for visualizing the activity of other enzymes in plants.

Clinical study on improving the diagnostic accuracy of adult elbow joint cartilage injury by multisequence magnetic resonance imaging.

BACKGROUND: Due to frequent and high-risk sports activities, the elbow joint is susceptible to injury, especially to cartilage tissue, which can cause pain, limited movement and even loss of joint function. AIM: To evaluate magnetic resonance imaging (MRI) multisequence imaging for improving the diagnostic accuracy of adult elbow cartilage injury. METHODS: A total of 60 patients diagnosed with elbow cartilage injury in our hospital from January 2020 to December 2021 were enrolled in this retrospective study. We analyzed the accuracy of conventional MRI sequences (T1-weighted imaging, T2-weighted imaging, proton density weighted imaging, and T2 star weighted image) and Three-Dimensional Coronary Imaging by Spiral Scanning (3D-CISS) in the diagnosis of elbow cartilage injury. Arthroscopy was used as the gold standard to evaluate the diagnostic effect of single and combination sequences in different injury degrees and the consistency with arthroscopy. RESULTS: The diagnostic accuracy of 3D-CISS sequence was 89.34% ± 4.98%, the sensitivity was 90%, and the specificity was 88.33%, which showed the best performance among all sequences (P < 0.05). The combined application of the whole sequence had the highest accuracy in all sequence combinations, the accuracy of mild injury was 91.30%, the accuracy of moderate injury was 96.15%, and the accuracy of severe injury was 93.33% (P < 0.05). Compared with arthroscopy, the combination of all MRI sequences had the highest consistency of 91.67%, and the kappa value reached 0.890 (P < 0.001). CONCLUSION: Combination of 3D-CISS and each sequence had significant advantages in improving MRI diagnostic accuracy of elbow cartilage injuries in adults. Multisequence MRI is recommended to ensure the best diagnosis and treatment.

Improving UASS pesticide application: optimizing and validating drift and deposition simulations.

BACKGROUND: As unmanned aerial spraying systems (UASS) usage grows rapidly worldwide, a critical research study was conducted to optimize the simulation of UASS applications, aiming to enhance pesticide delivery efficiency and reduce environmental impact. The study examined several key aspects for accurate simulation of UASS application with lattice Boltzmann method (LBM). Based on these discussions, the most suitable grid size and simulation parameters were selected to create a robust model for optimizing UASS performance in various pest management scenarios, potentially leading to more targeted and sustainable pest control practices. RESULTS: The effect of stability parameter, grid size around the rotor and near ground, and parameters at wake flow were carefully analyzed to improve the precision of pesticide drift predictions and deposition patterns. Optimal grid sizes were identified as 0.2 m generally, 0.025 m near rotors, and a 0.1 + 0.2 m scheme for ground proximity, with finer grids improving accuracy but increasing computation time. Wake resolution and threshold significantly influenced simulation results, while wake distance had minimal impact beyond a certain point. The LBM's accuracy was validated by comparing simulated downwash flow and droplet deposition with field test data. CONCLUSION: This study optimized UASS simulation parameters, balancing computational efficiency with accuracy. The validated model enhances our ability to design more effective UASS for pest management, potentially leading to more precise and targeted pesticide applications. These advancements contribute to the development of sustainable pest control strategies, aiming to reduce pesticide usage and environmental impact while maintaining crop protection efficacy. © 2024 Society of Chemical Industry.

Overexpression of PRDM16 attenuates acute kidney injury progression: genetic and pharmacological approaches.

Acute kidney injury (AKI) presents as a condition marked by a sudden and rapid decrease in kidney function over a short timeframe, resulting from diverse causes. As a transcription factor, PR domain-containing 16 (PRDM16), has recently been implicated in brown fat biogenesis and heart diseases. Our recent works indicated that PRDM16 could suppress the occurrence of renal interstitial fibrosis in diabetic kidney disorder. Nonetheless, the effect and regulatory mechanism of PRDM16 in AKI remain elusive. Our study demonstrated that PRDM16 inhibited apoptosis induced by ischemic/reperfusion (I/R) in BUMPT (Boston University mouse kidney proximal tubular) cells and HK-2(Human Kidney-2) cells. Mechanistically, PRDM16 not only bound to the promoter region of S100 Calcium Binding Protein A6 (S100A6)and upregulated its expression but also interacted with its amino acids 945-949, 957-960, and 981-984 to suppress the p38MAPK and JNK axes via inhibition of PKC-η activity and mitochondrial reactive oxygen species (ROS) production. Furthermore, cisplatin- and I/R-stimulated AKI progression were ameliorated in PRDM16 proximal-tubule-specific knockin mice, whereas exacerbated in PRDM16 knockout proximal-tubule-specific mice). Moreover, we observed that formononetin ameliorated I/R- and cisplatin-triggered AKI progression in mice. Taken together, these findings reveal a novel self-protective mechanism in AKI, whereby PRDM16 regulates the S100A6/PKC-η/ROS/p38MAPK and JNK pathways to inhibit AKI progression.

Genetics of cell-type-specific post-transcriptional gene regulation during human neurogenesis.

The function of some genetic variants associated with brain-relevant traits has been explained through colocalization with expression quantitative trait loci (eQTL) conducted in bulk postmortem adult brain tissue. However, many brain-trait associated loci have unknown cellular or molecular function. These genetic variants may exert context-specific function on different molecular phenotypes including post-transcriptional changes. Here, we identified genetic regulation of RNA editing and alternative polyadenylation (APA) within a cell-type-specific population of human neural progenitors and neurons. More RNA editing and isoforms utilizing longer polyadenylation sequences were observed in neurons, likely due to higher expression of genes encoding the proteins mediating these post-transcriptional events. We also detected hundreds of cell-type-specific editing quantitative trait loci (edQTLs) and alternative polyadenylation QTLs (apaQTLs). We found colocalizations of a neuron edQTL in CCDC88A with educational attainment and a progenitor apaQTL in EP300 with schizophrenia, suggesting that genetically mediated post-transcriptional regulation during brain development leads to differences in brain function.

Transcriptome analysis of potassium-mediated cadmium accumulation in sweet sorghum.

Cadmium (Cd) pollution in the soil is a serious environmental issue worldwide. Phytoextraction of Cd-polluted soil is a cost-effective, sustainable and environmentally-friendly strategy. Agricultural fertilizer management is beneficial for promoting the Cd phytoremediation efficiency. Potassium (K) is the nutrient required in the largest amount cation by plants. Sweet sorghum exhibits a substantial phytoremediation potential of Cd-polluted soil. Clarifying the mechanism of K-mediated Cd accumulation in sweet sorghum is imperative. Sweet sorghum plants were grown hydroponically with an extra K supply in the presence or absence of Cd treatment. An extra K application significantly increased plant growth under non-Cd addition, while K lost the profitable effect under Cd stress. K supplementation remarkably enhanced Cd concentrations and Cd accumulation in shoots and roots of sweet sorghum. Transcriptome analysis demonstrated that zinc ion transport, cysteine and methionine metabolism, flavonoid biosynthesis and phenylpropanoid biosynthesis pathways might contribute to the increased Cd accumulation as affected by an extra K supply. Furthermore, SbZIP9, SbSTP8, SbYS1, SbMAG and SbFOMT-like were targeted as they closely correlated with both plant growth and Cd stress in sweet sorghum. SbFOMT-like showed an independent pathway, while SbZIP9, SbSTP8, SbYS1 and SbMAG displayed positive correlations mutually. Notably, SbZIP9 and SbFOMT-like were highly expressed when compared with other target genes. Taken together, SbZIP9 and SbFOMT-like were upregulated and downregulated by an extra K supply under Cd stress, suggesting that SbZIP9 and SbFOMT-like enhances and declines Cd accumulation as regulated by K addition in sweet sorghum respectively.

Arginine Accelerates Sulfur Fluoride Exchange and Phosphorus Fluoride Exchange Reactions between Proteins.

Sulfur fluoride exchange (SuFEx) and phosphorus fluoride exchange (PFEx) click chemistries are advancing research across multiple disciplines. By genetically incorporating latent bioreactive unnatural amino acids (Uaas), these chemistries have been integrated into proteins, enabling precise covalent linkages with biological macromolecules and paving the way for new applications. However, their suboptimal reaction rates in proteins limit effectiveness, and traditional catalytic methods for small molecules are often incompatible with biological systems or in vivo applications. We demonstrated that introducing an arginine adjacent to the latent bioreactive Uaa significantly boosts SuFEx and PFEx reaction rates between proteins. This method is effective across various Uaas, target residues, and protein environments. Notably, it also enables efficient SuFEx reactions in acidic conditions, common in certain cellular compartments and tumor microenvironments, which typically hinder SuFEx reactions. Furthermore, we developed the first covalent cell engager that substantially enhances natural killer cell activation through improved covalent interaction facilitated by arginine. These findings provide mechanistic insights and offer a biocompatible strategy to harness these robust chemistries for advancing biological research and developing new biotherapeutics.

Endovascular treatment effect in vertebrobasilar artery occlusion patients with posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) <6.

BACKGROUND: Endovascular treatment (EVT) has revolutionized the standard treatment of vertebrobasilar artery occlusion (VBAO) with moderate infarct core, but its effectiveness in patients with a low posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) is unclear. This study aimed to assess EVT effects in VBAO patients with pc-ASPECTS <6. METHODS: This retrospective study enrolled patients with VBAO within 24 hours of the estimated occlusion time at 65 stroke centers in a nationwide registration in China. The primary outcome was a favorable shift in the modified Rankin Scale (mRS) at 90 days. The secondary outcomes included a favorable outcome (mRS 0-3) and functional independence (mRS 0-2). Propensity score matching and inverse probability of treatment weighting were used to compare the outcomes of patients treated with EVT and those with best medical management. RESULTS: A total of 431 patients with VBAO and pc-ASPECTS <6 were included. EVT was associated with a favorable shift in the mRS score at 90 days (OR 1.72, 95% CI 1.19 to 2.5), a higher probability of a favorable outcome (OR 1.66, 95% CI 1.02 to 2.74), and improved functional independence (OR 1.76, 95% CI 1.06 to 2.96). EVT also significantly reduced the risk of 90-day mortality (OR 0.62, 95% CI 0.40 to 0.96), but increased the risk of symptomatic intracranial hemorrhage (OR 2.76, 95% CI 1.06 to 8.58). CONCLUSION: The results of this study suggest that EVT may be a safe and effective treatment option for patients with VBAO and pc-ASPECTS <6. Further studies are needed to investigate the effect of EVT in patients with pc-ASPECTS <6 and to identify patients who may benefit from EVT.