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Abstract Catalytic asymmetric hydroboration of unsaturated bonds has been recognized as the most straightforward method for the construction of chiral organoboron compounds. Although catalytic asymmetric hydroboration of alkenes has been well-developed, enantioselective hydroboration of allenes still remains rare probably due to the challenges in controlling the enantio-, stereo-, and regioselectivity. Additionally, the hydroboration products might go through over-borohydride, making the catalytic asymmetric dihydroboration of allenes challenging. Here, we report a cobalt-catalyzed asymmetric dihydroboration of allenes using a ligand relay strategy with two simple ligands. This protocol shows excellent enantio-, stereo-, and regioselectivity with positive functional group compatibilities in the construction of chiral 1,4-diboronate products. The applications of this reaction are demonstrated by various product derivatizations, gram-scale reactions, and the preparation of artigenin analogues. Mechanistic studies indicate that the achiral ligand controls the first hydroboration of allenes, and the chiral oxazoline iminopyridine ligand is responsible for the subsequent isomerization and asymmetric hydroboration.

Abstract Nipah virus infection, one of the top priority diseases recognized by the World Health Organization, underscores the urgent need to develop effective countermeasures against potential epidemics and pandemics. Here, we identify a fully human single-domain antibody that targets a highly conserved cryptic epitope situated at the dimeric interface of the Nipah virus G protein (receptor binding protein, RBP), as elucidated through structures by high-resolution cryo-electron microscopy (cryo-EM). This unique binding mode disrupts the tetramerization of the G protein, consequently obstructing the activation of the F protein and inhibiting viral membrane fusion. Furthermore, our investigations reveal that this compact antibody displays enhanced permeability across the blood-brain barrier (BBB) and demonstrates superior efficacy in eliminating pseudovirus within the brain in a murine model of Nipah virus infection, particularly compared to the well-characterized antibody m102.4 in an IgG1 format. Consequently, this single-domain antibody holds promise as a therapeutic candidate to prevent Nipah virus infections and has potential implications for vaccine development.

Abstract The relationship of weight change has extended to accelerated ageing, yet little is known about the association between weight change and anti-aging protein α-Klotho. This study included 10,972 subjects from the National Health and Nutrition Examination Survey 2007–2016. Participants were measured body weight and height at baseline and recalled weight at young adulthood and middle adulthood. α-Klotho concentrations were quantified. Generalized linear regression models were used to assess the association between weight change and α-Klotho. Across adulthood, maximal overweight, non-obese to obese, and stable obesity were consistently associated with lower serum Klotho levels. Compared with participants who remained at normal weight, from middle to late adulthood, participants experiencing maximal overweight, moving from the non-obese to obese, and maintaining obesity had 27.97 (95% CI: − 46.57 to − 9.36), 39.16 (95% CI: − 61.15 to − 17.18), and 34.55 (95% CI: − 55.73 to − 13.37) pg/ml lower α-Klotho, respectively; similarly, from young to late adulthood, those had 29.21 (95% CI: − 47.00 to − 11.42) , 34.14 (95% CI: − 52.88 to − 15.40), and 36.61 (95% CI: − 65.01 to − 8.21) lower, respectively. Interestingly, from middle to late adulthood, the absolute weight change values of 590 participants who changed from obese to non-obese were negatively associated with serum α-Klotho. Each 1 kg of weight loss during the process of changing from obese to non-obese brought about a relative increase in α-Klotho levels of 3.03 pg/ml. The findings suggest the potential role of weight management across adulthood for aging.

Abstract Biological ion channels exhibit high selectivity and permeability of ions because of their asymmetrical pore structures and surface chemistries. Here, we demonstrate a biomimetic nanofluidic channel (BNC) with an asymmetrical structure and glycyl-L-proline (GLP) -functionalization for ultrafast, selective, and unidirectional Dy3+ extraction over other lanthanide (Ln3+) ions with very similar electronic configurations. The selective extraction mainly depends on the amplified chemical affinity differences between the Ln3+ ions and GLPs in nanoconfinement. In particular, the conductivities of Ln3+ ions across the BNC even reach up to two orders of magnitude higher than in a bulk solution, and a high Dy3+/Nd3+ selectivity of approximately 60 could be achieved. The designed BNC can effectively extract Dy3+ ions with ultralow concentrations and thereby purify Nd3+ ions to an ultimate content of 99.8 wt.%, which contribute to the recycling of rare earth resources and environmental protection. Theoretical simulations reveal that the BNC preferentially binds to Dy3+ ion due to its highest affinity among Ln3+ ions in nanoconfinement, which attributes to the coupling of ion radius and coordination matching. These findings suggest that BNC-based ion selectivity system provides alternative routes to achieving highly efficient lanthanide separation.

Mango has frequently encountered severe climate and environmental challenges such as low temperatures, seriously affecting the sustainable development of the industry. In the study, physiological measurements showed that the activities of superoxide dismutase (SOD) and peroxidase (POD) were found to be higher in Jinhuang (JH) mango plants than those of Tainong (TN) mango plants under cold stress, indicating cold tolerant (JH) and non-cold tolerant (TN) mango varieties were firstly determined. Subsequently, transcriptomics showed 8,337 and 7,996 differentially expressed genes (DEGs) were respectively identified in JH and TN mango varieties treated at 4 °C for 36 h, while more DEGs (10,683 and 10,723) were screened when treated at 4 °C for 72 h. Quantitative real-time PCR (qRT-PCR) of the selected DEGs confirmed their transcriptional levels displayed agreement to the transcriptome data. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed two primary cold resistant regulation pathways, photosynthesis-antenna proteins pathway and photosynthesis pathway, were both significant annotated in the two mango varieties, indicating share the common regulation mechanism response to cold stress. However, five specific cold resistant pathways, such as amino acid and carbohydrate metabolisms, were identified in JH mango variety with cold stress for longer duration, indicating the specific regulation pathways in the cold tolerant mango varieties. Furthermore, 43 ethylene-responsive transcription factors (ERFs) were significantly annotated in JH mango after cold-treated for 72 h comparing with the control group, and three of them ERF109-1, ERF017-1 and ERF017-2 were highly expressed, which may play important regulatory roles in plant cold resistance. These results provided insights into the primary and specific molecular mechanisms of different mango varieties resistance to chill.

Abstract Background The circadian clock, also known as the circadian rhythm, is responsible for predicting daily and seasonal changes in the environment, and adjusting various physiological and developmental processes to the appropriate times during plant growth and development. The circadian clock controls the expression of the Lhcb gene, which encodes the chlorophyll a/b binding protein. However, the roles of the Lhcb gene in tea plant remain unclear. Results In this study, a total of 16 CsLhcb genes were identified based on the tea plant genome, which were distributed on 8 chromosomes of the tea plant. The promoter regions of CsLhcb genes have a variety of cis-acting elements including hormonal, abiotic stress responses and light response elements. The CsLhcb family genes are involved in the light response process in tea plant. The photosynthetic parameter of tea leaves showed rhythmic changes during the two photoperiod periods (48 h). Stomata are basically open during the day and closed at night. Real-time quantitative PCR results showed that most of the CsLhcb family genes were highly expressed during the day, but were less expressed at night. Conclusions Results indicated that CsLhcb genes were involved in the circadian clock process of tea plant, it also provided potential references for further understanding of the function of CsLhcb gene family in tea plant.

Abstract Background Mango (Mangifera indica L.) is grown in Hainan, Guangdong, Yunnan, Sichuan, and Fujian provinces and Guanxi autonomous region of China. However, trees growing in these areas suffer severe cold stress during winter, which affects the yield. To this regard, data on global metabolome and transcriptome profiles of leaves are limited. Here, we used combined metabolome and transcriptome analyses of leaves of three mango cultivars with different cold stress tolerance, i.e. Jinhuang (J)—tolerant, Tainung (T) and Guiremang No. 82 (G)—susceptible, after 24 (LF), 48 (MF) and 72 (HF) hours of cold. Results A total of 1,323 metabolites belonging to 12 compound classes were detected. Of these, amino acids and derivatives, nucleotides and derivatives, and lipids accumulated in higher quantities after cold stress exposure in the three cultivars. Notably, Jinhuang leaves showed increasing accumulation trends of flavonoids, terpenoids, lignans and coumarins, and alkaloids with exposure time. Among the phytohormones, jasmonic acid and abscisic acid levels decreased, while N6-isopentenyladenine increased with cold stress time. Transcriptome analysis led to the identification of 22,526 differentially expressed genes. Many genes enriched in photosynthesis, antenna proteins, flavonoid, terpenoid (di- and sesquiterpenoids) and alkaloid biosynthesis pathways were upregulated in Jihuang leaves. Moreover, expression changes related to phytohormones, MAPK (including calcium and H2O2), and the ICE-CBF-COR signalling cascade indicate involvement of these pathways in cold stress responses. Conclusion Cold stress tolerance in mango leaves is associated with regulation of primary and secondary metabolite biosynthesis pathways. Jasmonic acid, abscisic acid, and cytokinins are potential regulators of cold stress responses in mango leaves.

Abstract Background Mango (Mangifera indica L.) faces escalating challenges from increasing drought stress due to erratic climate patterns, threatening yields, and quality. Understanding mango's drought response mechanisms is pivotal for resilience and food security. Results Our RNA-seq analyses unveil 12,752 differentially expressed genes linked to stress signaling, hormone regulation, and osmotic adjustment. Weighted Gene Co-expression Network Analysis identified three essential genes—WRKY transcription factor 3, polyamine oxidase 4, and protein MEI2-like 1—as drought defense components. WRKY3 having a role in stress signaling and defense validates its importance. Polyamine oxidase 4, vital in stress adaptation, enhances drought defense. Protein MEI2-like 1's significance emerges, hinting at novel roles in stress responses. Metabolite profiling illuminated Mango’s metabolic responses to drought stress by presenting 990 differentially abundant metabolites, mainly related to amino acids, phenolic acids, and flavonoids, contributing to a deeper understanding of adaptation strategies. The integration between genes and metabolites provided valuable insights by revealing the correlation of WRKY3, polyamine oxidase 4 and MEI2-like 1 with amino acids, D-sphingnosine and 2,5-Dimethyl pyrazine. Conclusions This study provides insights into mango's adaptive tactics, guiding future research for fortified crop resilience and sustainable agriculture. Harnessing key genes and metabolites holds promise for innovative strategies enhancing drought tolerance in mango cultivation, contributing to global food security efforts.

Abstract Deformable attention only focuses on a small group of key sample-points around the reference point and make itself be able to capture dynamically the local features of input feature map without considering the size of the feature map. Its introduction into point cloud registration will be quicker and easier to extract local geometric features from point cloud than attention. Therefore, we propose a point cloud registration method based on Spatial Deformable Transformer (SDT). SDT consists of a deformable self-attention module and a cross-attention module where the deformable self-attention module is used to enhance local geometric feature representation and the cross-attention module is employed to enhance feature discriminative capability of spatial correspondences. The experimental results show that compared to state-of-the-art registration methods, SDT has a better matching recall, inlier ratio, and registration recall on 3DMatch and 3DLoMatch scene, and has a better generalization ability and time efficiency on ModelNet40 and ModelLoNet40 scene.

The methyltransferase SETD3 is an enzyme essential for catalyzing histidine-73 methylation on β-Actin, thereby promoting its polymerization and regulating muscle contraction. Although increasing evidence suggests that SETD3 is involved in multiple physiological or pathological events, its biological functions remain incompletely understood. In this study, we utilize in situ proximity labeling combined with mass spectrometry analysis to detect potential interacting partners of SETD3. Unexpectedly, we find that many splicing factors are associated with SETD3. Genome-wide RNA sequencing reveals that SETD3 regulates pre-mRNA splicing events, predominantly influencing exon skipping. Biochemical and bioinformatic analyses suggest that SETD3 interacts with hnRNPK, and they collaboratively regulate exon skipping in a common subset of genes. Functionally, we demonstrate that SETD3 and hnRNPK are required for retention of exon 7 skipping in the FNIP1 gene. This promotes FNIP1-mediated nuclear translocation of the transcription factor TFEB and the subsequent induction of lysosomal and mitochondrial biogenesis. Overall, this study uncovers a novel function of SETD3 in modulating mRNA exon splicing.

Clear aligner therapy is a rapidly developing orthodontic treatment. 3D-printing technology, which enables the creation of complex geometric structures with high precision, has been used in dentistry. This article aims to summarize the various aspects of 3D-printing clear aligners and give an outlook on their future development. The traditional thermoforming technology is introduced and the principle and application of 3D-printed clear aligners and materials are introduced, as well as the application prospects of 3D-printed clear aligners. According to PRISMA statement, the relevant literature of 3D-printing clear aligner was searched in PubMed, Web of Science, Embase and other databases. We searched the related words in the MESH database and then carried out advanced searches. We read systematic review and conference papers to find the articles related to the subject and manually added and excluded articles by reading the title and abstract. The production of clear aligners combines computer-aided 3D analysis, personalized design and digital molding technology. The thickness and edges of the 3D-printed clear aligner can be digitally controlled, which allows appliance more efficiently fitted. Presently, the array of clear resins suitable for 3D-printing include photo polymeric clear methacrylate-based resin (Dental LT) (Form Labs, Somerville, Mass), aliphatic vinyl ester-polyurethane polymer (Tera Harz TC-85) (Graphy, Seoul, South Korea). They all have good biocompatibility. But no such material is currently approved on the market. Developing biocompatible resins and further improving the material’s mechanical properties will be critical for the combination of 3D-printing and clear aligners. However, the literature on 3D-printed clear aligners is limited and lacks clinical application. Further in vivo and in vitro tests, as well as additional exploration in conjunction with corresponding cytological tests, are required for the research on available materials and machinery for 3D-printing clear aligners.

Objectives: To elucidate and compare the genetic, clinical, ancillary diagnostic, and pathological characteristics across different Gerstmann-Sträussler-Scheinker disease (GSS) phenotypes and explore the underlying causes of the phenotypic heterogeneities. Methods: The genetic, clinical, ancillary diagnostic, and pathological profiles of GSS patients reported in the literature were obtained and analyzed. Additionally, 3 patients with genetically confirmed GSS from our unit were included. Based on clinical presentation, patients were classified into typical GSS, Creutzfeldt-Jakob disease (CJD)-like GSS, GSS with dementia, and other categories. Results: A total of 329 GSS cases were included with a 1.13:1 female-to-male ratio, median onset age 44, and median duration 4 years. Of the 294 categorized patients, 50.7% had typical GSS, 24.8% showed CJD-like GSS, and 16.3% presented with GSS with dementia. Clinical classification varied significantly based on genotype, with P102L more common in typical GSS and A117V prevalent in CJD-like GSS. Polymorphism at codon 129 has no effect on GSS phenotype, but the 129 M allele acts as a protective factor in GSS patients in Asia and North America. Moderate to severe spongiform degeneration and the presence of PK-resistant small fragments migrating at

Introduction Severe septic cardiomyopathy (SCM) is one of the main causes of refractory septic shock (RSS), with a high mortality. The application of venoarterial extracorporeal membrane oxygenation (ECMO) to support the impaired cardiac function in patients with septic shock remains controversial. Moreover, no prospective studies have been taken to address whether venoarterial ECMO treatment could improve the outcome of patients with sepsis-induced cardiogenic shock. The objective of this study is to assess whether venoarterial ECMO treatment can improve the 30-day survival rate of patients with sepsis-induced refractory cardiogenic shock.Methods and analysis ExtraCorporeal Membrane Oxygenation in the therapy for REfractory Septic shock with Cardiac function Under Estimated is a prospective, multicentre, non-randomised, cohort study on the application of ECMO in SCM. At least 64 patients with SCM and RSS will be enrolled in an estimated ratio of 1:1.5. Participants taking venoarterial ECMO during the period of study are referred to as cohort 1, and patients receiving only conventional therapy without ECMO belong to cohort 2. The primary outcome is survival in a 30-day follow-up period. Other end points include survival to intensive care unit (ICU) discharge, hospital survival, 6-month survival, quality of life for long-term survival (EQ-5D score), successful rate of ECMO weaning, long-term survivors’ cardiac function, the number of days alive without continuous renal replacement therapy, mechanical ventilation and vasopressor, ICU and hospital length of stay, the rate of complications potentially related to ECMO treatment.Ethics and dissemination The trial has been approved by the Clinical Research and Application Institutional Review Board of the Second Affiliated Hospital of Guangzhou Medical University (2020-hs-51). Participants will be screened and enrolled from ICU patients with septic shock by clinicians, with no public advertisement for recruitment. Results will be disseminated in research journals and through conference presentations.Trial registration number NCT05184296.

Soluble Triggering Receptor Expressed on Myeloid Cells 2 (sTREM2) plays a crucial role in the pathogenesis of Alzheimer’s disease (AD). This review comprehensively examines sTREM2’s involvement in AD, focusing on its regulatory functions in microglial responses, neuroinflammation, and interactions with key pathological processes. We discuss the dynamic changes in sTREM2 levels in cerebrospinal fluid and plasma throughout AD progression, highlighting its potential as a therapeutic target. Furthermore, we explore the impact of genetic variants on sTREM2 expression and its interplay with other AD risk genes. The evidence presented in this review suggests that modulating sTREM2 activity could influence AD trajectory, making it a promising avenue for future research and drug development. By providing a holistic understanding of sTREM2’s multifaceted role in AD, this review aims to guide future studies and inspire novel therapeutic strategies.

Rechargeable zinc (Zn) metal batteries have long been plagued by dendrite growth and parasitic reactions due to the absence of a stable Zn-ion conductive solid-electrolyte interphase (SEI). Although the current strategies assist in suppressing dendritic Zn growth, it is still a challenge to obtain the operation-stability of Zn anode with high Coulombic efficiency (CE) required to implement a sustainable and long-cycling life of Zn metal batteries. In this perspective, we summarize the advantages of the functional gradient interphase (FGI) and try to fundamentally understand the transport behaviors of Zn ions, based on recently an article understanding Zn chemistry. The correlation between the function-orientated design of gradient interphase and key challenges of Zn metal anodes in accelerating Zn2+ transport kinetics, improving electrode reversibility, and inhibiting Zn dendrite growth and side reactions was particularly emphasized. Finally, the rational design and innovative directions are provided for the development and application of functional gradient interphase in rechargeable Zn metal battery systems.

This paper presents a robust point cloud registration method based on a multi-scale covariance matrix descriptor and an accurate transformation estimation. Compared with state-of-the-art feature descriptors, such as FPH, 3DSC, spin image, etc., our proposed multi-scale covariance matrix descriptor is superior for dealing with registration problems in a higher noise environment since the mean operation in generating the covariance matrix can filter out most of the noise-damaged samples or outliers and also make itself robust to noise. Compared with transformation estimation, such as feature matching, clustering, ICP, RANSAC, etc., our transformation estimation is able to find a better optimal transformation between a pair of point clouds since our transformation estimation is a multi-level point cloud transformation estimator including feature matching, coarse transformation estimation based on clustering, and a fine transformation estimation based on ICP. Experiment findings reveal that our proposed feature descriptor and transformation estimation outperforms state-of-the-art feature descriptors and transformation estimation, and registration effectiveness based on our registration framework of point cloud is extremely successful in the Stanford 3D Scanning Repository, the SpaceTime dataset, and the Kinect dataset, where the Stanford 3D Scanning Repository is known for its comprehensive collection of high-quality 3D scans, and the SpaceTime dataset and the Kinect dataset are captured by a SpaceTime Stereo scanner and a low-cost Microsoft Kinect scanner, respectively.

Unconfined compressive strength (UCS) is a critical property for assessing the engineering performances of sustainable materials, such as cement–fly ash mortar (CFAM), in the design of construction engineering projects. The experimental determination of UCS is time-consuming and expensive. Therefore, the present study aims to model the UCS of CFAM with boosting machine learning methods. First, an extensive database consisting of 395 experimental data points derived from the literature was developed. Then, three typical boosting machine learning models were employed to model the UCS based on the database, including gradient boosting regressor (GBR), light gradient boosting machine (LGBM), and Ada-Boost regressor (ABR). Additionally, the importance of different input parameters was quantitatively analyzed using the SHapley Additive exPlanations (SHAP) approach. Finally, the best boosting machine learning model’s prediction accuracy was compared to ten other commonly used machine learning models. The results indicate that the GBR model outperformed the LGBM and ABR models in predicting the UCS of the CFAM. The GBR model demonstrated significant accuracy, with no significant difference between the measured and predicted UCS values. The SHAP interpretations revealed that the curing time (T) was the most critical feature influencing the UCS values. At the same time, the chemical composition of the fly ash, particularly Al2O3, was more influential than the fly-ash dosage (FAD) or water-to-binder ratio (W/B) in determining the UCS values. Overall, this study demonstrates that SHAP boosting machine learning technology can be a useful tool for modeling and predicting UCS values of CFAM with good accuracy. It could also be helpful for CFAM design by saving time and costs on experimental tests.

Abstract Single‐domain antibody–drug conjugates (sdADCs) have been proven to have deeper solid tumor penetration and intratumor accumulation capabilities due to their smaller size compared with traditional IgG format ADCs. However, one of the key challenges for improving clinical outcomes of sdADCs is their abbreviated in vivo half‐life. In this study, we innovatively fused an antihuman serum albumin (αHSA) nanobody to a sdADCs targeting oncofetal antigen 5T4, conferring serum albumin binding to enhance the pharmacokinetic profiles of sdADCs. The fusion protein was conjugated with monomethyl auristatin E (MMAE) at s224c site mutation. The conjugate exhibited potent cytotoxicity against various tumor cells. Compared with the nonalbumin‐binding counterparts, the conjugate exhibited a 10‐fold extended half‐life in wild‐type mice and fivefold prolonged serum half‐life in BxPC‐3 xenograft tumor models as well as enhanced tumor accumulation and retention in mice. Consequently, n501–αHSA–MMAE showed potent antitumor effects, which were comparable to n501–MMAE in pancreatic cancer BxPC‐3 xenograft tumor models; however, in human ovarian teratoma PA‐1 xenograft tumor models, n501–αHSA–MMAE significantly improved antitumor efficacy. Moreover, the conjugate showed mitigated hepatotoxicity. In summary, our results suggested that fusion to albumin‐binding moiety as a viable strategy can enhance the therapeutic potential of sdADCs through optimized pharmacokinetics.

Tubulin plays an essential role in cortical development, and TUBA1A encodes a major neuronal α-tubulin. Neonatal mutations in TUBA1A are associated with severe brain malformations, and approximately 70% of patients with reported cases of TUBA1A mutations exhibit lissencephaly. We report the case of a 1-year-old boy with the TUBA1A nascent mutation c.1204C >T, p.Arg402Cys, resulting in lissencephaly, developmental delay, and seizures, with a brain MRI showing normal cortical formation in the bilateral frontal lobes, smooth temporo-parieto-occipital gyri and shallow sulcus. This case has not been described in any previous report; thus, the present case provides new insights into the broad disease phenotype and diagnosis associated with TUBA1A mutations. In addition, we have summarized the gene mutation sites, neuroradiological findings, and clinical details of cases previously described in the literature and discussed the differences that exist between individual cases of TUBA1A mutations through a longitudinal comparative analysis of similar cases. The complexity of the disease is revealed, and the importance of confirming the genetic diagnosis from the beginning of the disease is emphasized, which can effectively shorten the diagnostic delay and help clinicians provide genetic and therapeutic counseling.

Summary: N(6)-methyladenosine (m6A) critically regulates RNA dynamics in various biological processes. The m6A demethylase ALKBH5 promotes tumorigenesis of glioblastoma, while the intricate web that orchestrates its regulation remains enigmatic. Here, we discover that cell density affects ALKBH5 subcellular localization and m6A dynamics. Mechanistically, ALKBH5 is phosphorylated by the large tumor suppressor kinase 2 (LATS2), preventing its nuclear export and enhancing protein stability. Furthermore, phosphorylated ALKBH5 reciprocally erases m6A from LATS2 mRNA, thereby stabilizing this transcript. Unexpectedly, LATS2 depletion suppresses glioblastoma stem cell self-renewal independent of yes-associated protein activation. Additionally, deficiency in either LATS2 or ALKBH5 phosphorylation impedes tumor progression in mouse xenograft models. Moreover, high levels of LATS2 expression and ALKBH5 phosphorylation are associated with tumor malignancy in patients with gliomas. Collectively, our study unveils an oncogenic positive feedback loop between LATS2 and ALKBH5, revealing a non-canonical branch of the Hippo pathway for RNA processing and suggesting potential anti-cancer interventions.

BackgroundMore and more evidence suggests a close association between depression and hepatobiliary diseases, but its causal relationship is not yet clear.MethodUsing genome-wide association studies (GWAS) to summarize data, independent genetic variations associated with depression were selected as instrumental variables. Firstly, we designed a univariate Mendelian randomization (UVMR) analysis with two samples and simultaneously conducted reverse validation to evaluate the potential bidirectional causal relationship between depression and various hepatobiliary diseases. Secondly, we conducted a multivariate Mendelian randomization (MVMR) analysis on diseases closely related to depression, exploring the mediating effects of waist to hip ratio, hypertension, and daytime nap. The mediating effects were obtained through MVMR. For UVMR and MVMR, inverse variance weighted method (IVW) is considered the most important analytical method. Sensitivity analysis was conducted using Cochran’Q, MR Egger, and Leave-one-out methods.ResultsUVMR analysis showed that depression may increase the risk of non-alcoholic fatty liver disease (OR, 1.22; 95% CI, 1.03-1.46; p=0.0248) in liver diseases, while depression does not increase the risk of other liver diseases; In biliary and pancreatic related diseases, depression may increase the risk of cholelithiasis (OR, 1.26; 95% CI, 1.05-1.50; p=0.0120), chronic pancreatitis (OR, 1.61; 95% CI, 1.10-2.35; p=0.0140), and cholecystitis (OR, 1.23; 95% CI, 1.03-1.48; p=0.0250). In addition, through reverse validation, we found that non-alcoholic fatty liver disease, cholelithiasis, chronic pancreatitis, cholecystitis, or the inability to increase the risk of depression (p>0.05). The waist to hip ratio, hypertension, and daytime nap play a certain role in the process of depression leading to non-alcoholic fatty liver disease, with a mediating effect of 35.8%.ConclusionDepression is a susceptibility factor for non-alcoholic fatty liver disease, and the causal effect of genetic susceptibility to depression on non-alcoholic fatty liver disease is mediated by waist-hip ratio, hypertension, and daytime nap.

Abstract Background Vertebral compression fractures (VCFs) are common clinical problems that arise from various reasons. The differential diagnosis of benign and malignant VCFs is challenging. This study was designed to develop and validate a radiomics model to predict benign and malignant VCFs with 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT). Results Twenty-six features (9 PET features and 17 CT features) and eight clinical variables (age, SUVmax, SUVpeak, SULmax, SULpeak, osteolytic destruction, fracture line, and appendices/posterior vertebrae involvement) were ultimately selected. The area under the curve (AUCs) of the radiomics and clinical–radiomics models were significantly different from that of the clinical model in both the training group (0.986, 0.987 vs. 0.884, p 0.05). The accuracies of the radiomics and clinical–radiomics models were 94.0% and 95.0% in the training group and 93.2% and 93.2% in the test group, respectively. The three models all showed good calibration (Hosmer–Lemeshow test, p > 0.05). According to the decision curve analysis (DCA), the radiomics model and clinical–radiomics model exhibited higher overall net benefit than the clinical model. Conclusions The PET/CT-based radiomics and clinical–radiomics models showed good performance in distinguishing between malignant and benign VCFs. The radiomics method may be valuable for treatment decision-making.

Abstract Shellfish with rigid shells prevent damage to their delicate internal cores, and their soft bonding muscles drive the opening and closing of the shells. This synergism of rigid and soft materials provides shellfish with unique environmental adaptation. Inspired by the structural characteristics of mussels, a riveting layer was introduced into hydrogel-plastic hybrids for bonding hydrogel networks and plastic substrates. The bonding strength of the hydrogel on the polypropylene (PP) substrate was approximately 1.52 MPa, and the interface toughness reached 1450 J m−2. Furthermore, the integration of plastics and microscale hydrogels, as well as abscised or prefabricated hydrogels, could also be fabricated through the same process. By using this strategy, a hydrogel-plastic hybrid-based device with temperature responsiveness and scratch resistance was fabricated and could mimic the basic activities of mussels. This work improves the functional materials used in programmable engineering systems and could facilitate the construction of intelligent robots.

Abstract The benefits of mHealth interventions in uncontrolled hypertension are unclear. To determine whether mHealth effectively improves the control rate of uncontrolled hypertension. PubMed, Web of Science, EMBASE, Scopus, and Cochrane Library were searched for randomized controlled trials (RCTs) from January 2007 to September 2022. The intervention group consisted of mHealth intervention, and the control group was usual care. Random‐effects meta‐analysis models were used to assess pooled mHealth intervention effects and CIs. The primary outcome was the blood pressure (BP) control rate of uncontrolled hypertension. The secondary outcome was the change of BP. Thirteen RCTs were included in this meta‐analysis, of which eight reported the successful BP control rate, 13 reported the change of systolic blood pressure (SBP), and 11 reported the change in diastolic blood pressure (DBP). The mean age of trial participants ranged from 47.7 to 66.9 years old, with a female composition ratio of 40.0%–66.1%. The duration of follow‐up ranged from 3 to 18 months. This study showed a more robust effect size for improving BP control rate by mHealth interventions than usual care (57.5% vs. 40.8% of successful control rate; odds ratio [OR], 2.19 [95% CI, 1.32—3.62]). Furthermore, mHealth significantly reduced SBP by 4.45 mm Hg and DBP by 2.47 mm Hg, and subgroup analysis did not observe the major source of heterogeneity. This meta‐analysis found that mHealth could significantly improve the uncontrolled hypertension control rate and might be a feasible, acceptable, and effective tool for uncontrolled hypertension management.

ABSTRACT Objective To assess the proportion of clinically diagnosed MM2‐type sporadic Creutzfeldt–Jakob disease (sCJD) in a Chinese cohort, describe the clinical features of MM2‐cortical (MM2C) and MM2‐thalamic (MM2T) type sCJD to improve the early detection of MM2‐type sCJD. Methods A total of 209 patients with sCJD admitted to the Xuanwu Hospital between February 2012 and August 2022 were reviewed. The patients were classified into probable MM2C, MM2T‐type sCJD, and other types of sCJD according to current clinical diagnostic criteria. Clinical and ancillary data were compared between the groups. Results Fifty‐one (24.4%) patients were clinically diagnosed with MM2‐type sCJD, of which 44 were diagnosed with MM2C‐type sCJD and 7 with MM2T‐type sCJD. In the absence of RT‐QuIC, 27 (61.3%) patients of MM2C‐type sCJD did not meet the US CDC sCJD criteria for possible sCJD on admission, even though the mean period from onset to admission was 6.0 months. However, all of these patients had cortical hyperintensity on DWI. Compared to the other types of sCJD, MM2C‐type sCJD was associated with slower disease progression and the absence of the typical clinical features of sCJD; the MM2T‐type sCJD group had a higher proportion of males, earlier age of onset, longer duration of disease, and a higher incidence of bilateral thalamic hypometabolism/hypoperfusion. Interpretation In the absence of multiple typical sCJD symptoms within 6 months, the presence of cortical hyperintensity on DWI should raise concerns for MM2C‐type sCJD after excluding other etiologies. Bilateral thalamic hypometabolism/hypoperfusion may be more helpful in the clinical diagnosis of MM2T‐type sCJD.

Introduction Mild cognitive impairment (MCI) is an important intervenable stage for the prevention of dementia. Hypertension is associated with impaired cognition, and when combined with MCI, it may lead to a poor prognosis. Digital computerised cognitive training (CCT) has recently become a potential instrument for improving cognition, but evidence for its efficacy remains limited. This study aims to evaluate the efficacy of a digital adaptive CCT intervention in older patients with hypertension and MCI.Methods and analysis The multicentre, double-blinded, randomised, actively -controlled clinical trial will recruit 200 older (≥60 years) patients with hypertension and MCI from 11 hospitals across China. Participants will be randomly assigned in a 1:1 ratio to the intervention group (multidomain adaptative CCT) and active control group (non-adaptive cognitive training) for 12-week cognitive training for 30 min/day and 5 days/week. Those who have completed their 12-week training in the intervention group will be rerandomised into the continuation and discontinuation training groups. All participants will be followed up to 24 weeks. Neuropsychological assessments and structural and functional 7.0 T MRI will be obtained at baseline and at 12-week and 24-week follow-up. The primary outcome is the possible improvement of global cognitive function at 12 weeks, as measured by the Basic Cognitive Aptitude Tests. Secondary and exploratory endpoints include the major cognitive domain function improvement, self-efficacy, mental health, quality of life and MRI measurements of the brain.Ethics and dissemination The trial has been approved by the institutional review board of Beijing Anzhen Hospital and thereafter by all other participating centres. Trial findings will be disseminated in peer-reviewed journals and conference presentations.Trial registration number NCT05704270.

Ensemble modeling is a chief strategy for probabilistic forecasting. In weather forecasting, analog ensemble, which operates under the principle that weather patterns often repeat, and dynamical ensemble, which generates equally likely trajectories of future weather by perturbing the initial and boundary conditions, constitute the two most common approaches to making ensembles. That said, in the field of solar forecasting, nor is there any head-to-head comparison made thus far in regard to understanding the relative performance of these two competing approaches; this work seeks to fill the gap. Four years (2017–2020) of operational forecasts, at seven locations, from the European Centre for Medium-Range Weather Forecasts (ECMWF) are used, and both the raw and post-processed versions of the ensemble irradiance forecasts are verified in a fair and thorough fashion. Three classical post-processing methods, namely, Bayesian model averaging, nonhomogeneous Gaussian regression, and quantile regression, are applied to both the analog ensemble forecasts derived from ECMWF’s high-resolution control forecasts and dynamical ensemble forecasts from ECMWF’s Ensemble Prediction System. It is found that analog ensemble before post-processing possesses some advantage in terms of calibration over dynamical ensemble; their average reliability values are 0.6 W/m2 and 8.2 W/m2, respectively. However, dynamical ensemble after post-processing becomes generally more attractive, obtaining an average continuous ranked probability score of 49.0 W/m2, against 51.7 W/m2 for AnEn.

Ion channels play a vital role in regulating the flow of ions across cell membranes to maintain physiological functions. Mimicking this biological process and fabricating artificial nano-/micro-channels with similar functions are expected to solve challenges involving ion transport in fields such as energy, environment, and human health. As a flexible and controllable preparation technology, supramolecular self-assembly is a powerful tool for designing biomimetic channels for specific purposes. Although various artificial channels have been reported, ever-increasing research interest in their application potential call for a bridge between design principles and engineering applications. In this Perspective, we summarized the recent advances in this new field and analyzed the working mechanism based on the grounded theory of supramolecular chemistry and nanofluidic systems. To promote the progress of this field, the opportunities and key challenges in this field for future research and applications are highlighted.

Highlights The first construct of a multi-field-coupled synergistic ion transport system (MSITS) in Li+ extraction is proposed. Effectively suppress the ion concentration polarization effect of the ion-enrichment zone at the membrane interface. The MSITS equipped with heterogeneous membrane exhibited outstanding separation performance with Li+ flux of 367.4 mmol m−2 h−1 and Li+/Co2+ selectivity of 216,412, outperforming previous reports.

Abstract In recent years, the incidence of lung cancer is increasing. Lung cancer has become one of the most malignant tumors with the highest incidence in the world, which seriously affects people’s health. The most important cause of death of lung cancer is metastasis. Therefore, it is crucial to understand the mechanism of lung cancer progression and metastasis. This review article discusses the physiological functions, pathological states and disorders of the lung and intestine based on the concepts of traditional Chinese medicine (TCM), and analyzes the etiology and mechanisms of lung cancer formation from the perspective of TCM. From the theory of “the exterior and interior of the lung and gastrointestinal tract”, the theory of “the lung-intestinal axis” and the progression and metastasis of lung cancer, we proposed e “lung-gut co-treatment” therapy for lung cancer. This study provides ideas for studying the mechanism of lung cancer and the comprehensive alternative treatment for lung cancer patients.

Phosphates play a crucial role in drug design, but their negative charge and high polarity make the transmembrane transport of phosphate species challenging. This leads to poor bioavailability of phosphate drugs. Combretastatin-A4 phosphate (CA4P) is such an anticancer monoester phosphate compound, but its absorption and clinical applicability are greatly limited. Therefore, developing carrier systems to effectively deliver phosphate drugs like CA4P is essential. Anion receptors have been found to facilitate the transmembrane transport of anions through hydrogen bonding. In this study, we developed a tripodal hexaurea anion receptor (L1) capable of binding anionic CA4P through hydrogen bonding, with a binding constant larger than 104 M−1 in a DMSO/water mixed solvent. L1 demonstrated superior binding ability compared to other common anions, and exhibited negligible cell cytotoxicity, making it a promising candidate for future use as a carrier for drug delivery.

Insufficient denitrification and limited phosphorus uptake hinder nitrogen and phosphorus removal in constructed wetlands (CWs). Sponge iron is a promising material for the removal of phosphorus and nitrogen because of its strong reducing power, high electronegativity, and inexpensive cost. The influence of factors including initial solution pH, dosage, and the Fe/C ratio was investigated. A vertical flow CW with sponge iron (CW-I) was established, and a traditional gravel bed (CW-G) was used as a control group. The kinetic analysis demonstrated that for both nitrogen and phosphorus, pseudo-second-order kinetics were superior. The theoretical adsorption capacities of sponge iron for nitrate (NO3−-N) and phosphate (PO43−-P) were 1294.5 mg/kg and 583.6 mg/kg, respectively. Under different hydraulic retention times (HRT), CW-I had better total nitrogen (TN) and total phosphorus (TP) removal efficiencies (6.08–15.18% and 5.00–20.67%, respectively) than CW-G. The enhancing effect of sponge iron on nitrogen and phosphorus removal was best when HRT was 48 h. The increase in HRT improved not only the nitrogen and phosphorus removal effects of CWs but also the reduction capacity of iron and the phosphorus removal effect. The main mechanisms of synergistic nitrogen and phosphorus removal were chemical reduction, ion exchange, electrostatic adsorption, and precipitation formation.

Abstract Phosphorylation of Ser10 of histone H3 (H3S10p), together with the adjacent methylation of Lys9 (H3K9me), has been proposed to function as a ‘phospho‐methyl switch’ to regulate mitotic chromatin architecture. Despite of immense understanding of the roles of H3S10 phosphorylation, how H3K9me2 are dynamically regulated during mitosis is poorly understood. Here, it is identified that Plk1 kinase phosphorylates the H3K9me1/2 methyltransferase G9a/EHMT2 at Thr1045 (pT1045) during early mitosis, which attenuates its catalytic activity toward H3K9me2. Cells bearing Thr1045 phosphomimic mutant of G9a (T1045E) show decreased H3K9me2 levels, increased chromatin accessibility, and delayed mitotic progression. By contrast, dephosphorylation of pT1045 during late mitosis by the protein phosphatase PPP2CB reactivates G9a activity and upregulates H3K9me2 levels, correlated with decreased levels of H3S10p. Therefore, the results provide a mechanistic explanation of the essential of a ‘phospho‐methyl switch’ and highlight the importance of Plk1 and PPP2CB‐mediated dynamic regulation of G9a activity in chromatin organization and mitotic progression.

IntroductionRecent studies have highlighted the vital role of gut microbiota in traumatic brain injury (TBI). Fecal microbiota transplantation (FMT) is an effective means of regulating the microbiota–gut–brain axis, while the beneficial effect and potential mechanisms of FMT against TBI remain unclear. Here, we elucidated the anti-neuroinflammatory effect and possible mechanism of FMT against TBI in mice via regulating the microbiota–gut–brain axis.MethodsThe TBI mouse model was established by heavy object falling impact and then treated with FMT. The neurological deficits, neuropathological change, synaptic damage, microglia activation, and neuroinflammatory cytokine production were assessed, and the intestinal pathological change and gut microbiota composition were also evaluated. Moreover, the population of Treg cells in the spleen was measured.ResultsOur results showed that FMT treatment significantly alleviated neurological deficits and neuropathological changes and improved synaptic damage by increasing the levels of the synaptic plasticity-related protein such as postsynaptic density protein 95 (PSD-95) and synapsin I in the TBI mice model. Moreover, FMT could inhibit the activation of microglia and reduce the production of the inflammatory cytokine TNF-α, alleviating the inflammatory response of TBI mice. Meanwhile, FMT treatment could attenuate intestinal histopathologic changes and gut microbiota dysbiosis and increase the Treg cell population in TBI mice.ConclusionThese findings elucidated that FMT treatment effectively suppressed the TBI-induced neuroinflammation via regulating the gut microbiota–gut–brain axis, and its mechanism was involved in the regulation of peripheral immune cells, which implied a novel strategy against TBI.

Abstract Introduction Creutzfeldt-Jakob disease (CJD) is a fatal and irreversible neurodegenerative disease. Identification of inexpensive and easy-to-implement biomarkers of CJD which could predict disease severity and patient survival is important for improving disease management. The aim of this study was to assess the predictive value of peripheral neutrophil to lymphocyte ratio (NLR), high-density lipoprotein (HDL), monocyte to HDL ratio (MHR) and neutrophil to HDL ratio (NHR) for CJD. Methods Patients with definite or probable CJD admitted to the Neurology Department of Xuanwu Hospital from 2014 to 2021 were enrolled and followed up until April 2022. Clinical information including sex, age, Barth Index, survival time and results of auxiliary examination were collected, and NLR, HDL, NHR and MHR were measured for all enrolled patients. The associations between NLR, HDL, NHR and MHR, and disease severity (evaluated by Barth Index), survival time and auxiliary examinations were evaluated. Results A total of 88 CJD patients were enrolled and all were deceased. NLR (r = -0.341, p = 0.001), NHR (r = -0.346, p = 0.001) and MHR (r = -0.327, p = 0.002) were significantly associated with disease severity. Higher NHR (HR = 2.344, 95% CI = 1.277–4.303 p = 0.006) and lower HDL (HR = 0.567, 95% CI = 0.346–0.930, p = 0.025) were associated with shorter survival time in the CJD patients. Conclusions Peripheral inflammatory biomarkers, especially NHR, were associated with disease severity and survival duration. These findings provide new insights into the mechanisms and treatment strategies of CJD.

Abstract Background Behavioral variant frontotemporal dementia (bvFTD) is predominantly considered a dysfunction in cortico-cortical transmission, with limited direct investigation of cortical-subcortical transmission. Thus, we aimed to characterize the metabolic connectivity between areas of the limbic cortico-striato-thalamic-cortical (CSTC) circuit in presymptomatic and symptomatic bvFTD patients. Methods Thirty-three bvFTD patients and 33 unrelated healthy controls were recruited for this study. Additionally, six asymptomatic carriers of the MAPT P301L mutation were compared with 12 non-carriers who were all from the same family of bvFTD. Each participant underwent neuropsychological assessment, genetic testing, and a hybrid PET/MRI scan. Seed-based metabolic connectivity based on [18F]-fluorodeoxyglucose PET between the main components within the limbic CSTC circuit was explored according to the Oxford-GSK-Imanova Striatal Connectivity Atlas. Results BvFTD patients exhibited reduced metabolic connectivity between the relays in the limbic CSTC circuit, which included the frontal region (ventromedial prefrontal cortex, orbitofrontal cortex, rectus gyrus, and anterior cingulate cortex), the limbic striatum, and thalamus compared to controls. In the bvFTD patients, the involvement of the limbic CSTC circuit was associated with the severity of behavior disruption, as measured by the frontal behavior inventory, the disinhibition subscale, and the apathy subscale. Notably, asymptomatic MAPT carriers had weakened frontostriatal connectivity but enhanced striatothalamus and thalamofrontal connectivity within the limbic CSTC circuit compared with noncarriers. Conclusion These findings suggested that aberrant metabolic connectivity within the limbic CSTC circuit is present in symptomatic and even asymptomatic stages of bvFTD. Thus, metabolic connectivity patterns could be used as a potential biomarker to detect the presymptomatic stage and track disease progression.

Abstract Background The commonly used technique for treating unstable pelvic fractures with sacroiliac screws and anterior internal fixator (INFIX) is prone to complications, such as injury to the pelvic vasculature and nerves, life-threatening bleeding, lateral femoral cutaneous neuritis, and wound infection. This study investigated the clinical effects of using a modified percutaneous iliosacral screw and INFIX technique for treating unstable pelvic fractures. Methods A retrospective analysis of minimally invasive internal fixation using modified incision of an anterior-ring INFIX application combined with modified percutaneous iliosacral screw placement was performed for 22 cases of unstable pelvic fractures from January 2017 to December 2018. Based on the Tile classification, there were 4 type B1, 7 type B2, 5 type B3 and 6 type C1 injuries. Preoperatively, the length and orientation of the internal fixation were computer-simulated and measured. On postoperative day 3, pelvic radiographs and three-dimensional computed tomograms were used to assess fracture reduction and fixation. All patients were regularly followed up at 4 weeks, 12 weeks, 6 months, 12 months, 24 months and annually thereafter. Fracture healing, complications, visual analogue scale (VAS) scores, the quality of fracture repositioning and Majeed score were assessed during follow-up. Results All patients were followed up for a mean of 25.23 ± 1.48 months. All fractures healed without loss of reduction and no patient showed evidence of delayed union or nonunion. Two years postoperatively, the mean VAS score was 0.32 ± 0.09 and the mean Majeed score was 94.32 ± 1.86. Conclusion The modified percutaneous iliosacral screw technique increases the anterior tilt of the sacroiliac screw by shifting the entry point posteriorly to increase the safety of the screw placement. Downward modification of the INFIX incision reduces the risk of lateral femoral cutaneous nerve injury. This technique is safe, effective and well tolerated by patients.

The current work demonstrates the fabrication of kaolin supported Au nanoparticles (Au NPs-kaolin) mediated by Thymbra spicata extract as green reductant and capping agent without any toxic reagent. Physicochemical characteristics of the said nanocomposite were elucidated by field emission scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, elemental mapping, X-ray diffraction and inductively coupled plasma techniques. The figures of the TEM display the black dots signifying Au NPs being dispersed over the kaolin surface. Size of spherical Au NPs are around 10–15 nm. In the in vivo, we established a rat calvaria defect model using a combination of collagen scaffold and nanoparticle. The experimental group was divided into three classifications: control, collagen matrix and nanoparticle with collagen. Histological analyses showed that nanoparticle increased bone formation activity when used in conjunction with collagen matrix. In the nanoparticle group, grafted materials were still present until 12 weeks after treatment, as evidenced by foreign body reactions showing multinucleated giant cells in chronic inflammatory vascular connective tissue. Other results revealed that the nanoparticle increased bone formation activity when used with collagen matrix. All groups showed almost the same histological findings until 7 weeks. In the experimental groups, new bone formation activity was found continuously up to 12 weeks.