Search

As an important halophyte in the Yellow River Delta, the Amaranthaceae C3Suaeda salsa (L.) Pall. has attracted much attention for the "red carpet" landscape, and could be simply divided into red and green phenotypes according to the betacyanin content in the fleshy leaves. However, S. salsa has not been sequenced yet, which limited people's understanding of this species at the molecular level. We constructed a high‐quality chromosome‐scale reference genome by combining high‐throughput sequencing, PacBio single molecule real‐time sequencing, and Hi‐C sequencing techniques with a genome size of 445.10 Mb and contigs N50 of 2.94 Mb. Through the annotation of the S. salsa genome, 298.76 Mb of the repetitive sequences and 23 965 protein‐coding genes were identified, of which the proportion of long terminal repeats type in the repetitive sequences was the most abundant, about 50.74% of the S. salsa genome. Comparative genomics indicated that S. salsa underwent a whole‐genome duplication event about 146.15 million years ago (Ma), and the estimated divergence time between S. salsa and Suaeda aralocaspica was about 16.9 Ma. A total of four betacyanins including betanidin, celosianin II, amaranthin and 6′‐O‐malonyl‐celosianin II were identified and purified in both phenotypes, while two significantly up‐regulated betacyanins (celosianin II and amaranthin) may be the main reason for the red color in red phenotype. In addition, we also performed transcriptomics and metabolomics in both phenotypes to explore the molecular mechanisms of pigment synthesis, and a series of structural genes and transcription factors concerning with betacyanin production were selected in S. salsa. [ABSTRACT FROM AUTHOR]

Cell therapies such as CAR−T have demonstrated significant clinical successes, driving the investigation of immune cell surface engineering using natural and synthetic materials to enhance their therapeutic performance. However, many of these materials do not fully replicate the dynamic nature of the extracellular matrix (ECM). This study presents a cell surface engineering strategy that utilizes phase‐separated peptide coacervates to decorate the surface of immune cells. We meticulously designed a tripeptide, Fmoc−Lys−Gly−Dopa−OH (KGdelta; Fmoc=fluorenylmethyloxycarbonyl; delta=Dopa, dihydroxyphenylalanine), that forms coacervates in aqueous solution via phase separation. These coacervates, mirroring the phase separation properties of ECM proteins, coat the natural killer (NK) cell surface with the assistance of Fe3+ ions and create an outer layer capable of encapsulating monoclonal antibodies (mAb), such as Trastuzumab. The antibody‐embedded coacervate layer equips the NK cells with the ability to recognize cancer cells and eliminate them through enhanced antibody‐dependent cellular cytotoxicity (ADCC). This work thus presents a unique strategy of cell surface functionalization and demonstrates its use in displaying cancer‐targeting mAb for cancer therapies, highlighting its potential application in the field of cancer therapy. [ABSTRACT FROM AUTHOR]

Cell therapies such as CAR−T have demonstrated significant clinical successes, driving the investigation of immune cell surface engineering using natural and synthetic materials to enhance their therapeutic performance. However, many of these materials do not fully replicate the dynamic nature of the extracellular matrix (ECM). This study presents a cell surface engineering strategy that utilizes phase‐separated peptide coacervates to decorate the surface of immune cells. We meticulously designed a tripeptide, Fmoc−Lys−Gly−Dopa−OH (KGdelta; Fmoc=fluorenylmethyloxycarbonyl; delta=Dopa, dihydroxyphenylalanine), that forms coacervates in aqueous solution via phase separation. These coacervates, mirroring the phase separation properties of ECM proteins, coat the natural killer (NK) cell surface with the assistance of Fe3+ ions and create an outer layer capable of encapsulating monoclonal antibodies (mAb), such as Trastuzumab. The antibody‐embedded coacervate layer equips the NK cells with the ability to recognize cancer cells and eliminate them through enhanced antibody‐dependent cellular cytotoxicity (ADCC). This work thus presents a unique strategy of cell surface functionalization and demonstrates its use in displaying cancer‐targeting mAb for cancer therapies, highlighting its potential application in the field of cancer therapy. [ABSTRACT FROM AUTHOR]

Background: There is a critical need for a rapid and sensitive pathogen detection method for septic patients. This study aimed to investigate the diagnostic efficacy of Digital droplet polymerase chain reaction (ddPCR) in identifying pathogens among suspected septic patients. Methods: We conducted a prospective pilot diagnostic study to clinically validate the multiplex ddPCR panel in diagnosing suspected septic patients. A total of 100 sepsis episodes of 89 patients were included in the study. Results: In comparison to blood culture, the ddPCR panel exhibited an overall sensitivity of 75.0% and a specificity of 69.7%, ddPCR yielded an additional detection rate of 17.0% for sepsis cases overall, with a turnaround time of 2.5 h. The sensitivity of ddPCR in the empirical antibiotic treatment and the non-empirical antibiotic treatment group were 78.6% versus 80.0% (p > 0.05). Antimicrobial resistance genes were identified in a total of 13 samples. Whenever ddPCR detected the genes beta-lactamase-Klebsiella pneumoniae carbapenemase (blaKPC) or beta-lactamase-New Delhi metallo (blaNDM), these findings corresponded to the cultivation of carbapenem-resistant gram-negative bacteria. Dynamic ddPCR monitoring revealed a consistent alignment between the quantitative ddPCR results and the trends observed in C-reactive protein and procalcitonin levels. Conclusions: Compared to blood culture, ddPCR exhibited higher sensitivity for pathogen diagnosis in suspected septic patients, and it provided pathogen and drug resistance information in a shorter time. The quantitative results of ddPCR generally aligned with the trends seen in C-reactive protein and procalcitonin levels, indicating that ddPCR can serve as a dynamic monitoring tool for pathogen load in septic patients. [ABSTRACT FROM AUTHOR]

The development of portable and sustainable power sources is crucial for the advancement of flexible electronics. Thermoelectric devices, made from ductile inorganic thermoelectric materials, present an optimal solution due to their remarkable deformability and their ability to efficiently convert heat into electricity. Nevertheless, the scarcity of these materials underscores the pressing need to further explore the material landscape and to devise strategies that enhance both mechanical and thermoelectric properties. The van der Waals layered semiconductor GeAs has emerged as a ductile thermoelectric material. In this study, we utilized a state-of-the-art first-principles approach to examine the mechanical and thermoelectric properties of GeAs in configurations ranging from monolayer to tetralayer. Our research reveals that as GeAs is thinned to a monolayer, its bendability increases significantly, and its structure becomes stiffer. Moreover, reducing the material to a monolayer results in a 10-fold improvement in the thermoelectric figure of merit, ZT, boosting the power factor and lowering lattice thermal conductivity. At 300 K, ZT reaches a value of one, and at 600 K, it doubles. These findings highlight a promising route to achieve exceptional flexibility and superior thermoelectric conversion efficiency by dimension reduction. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is a degenerative disease that affects synovial joints and leads to significant pain and disability, particularly in older adults. Infiltration of macrophages plays a key role in the progression of OA. However, the mechanisms underlying macrophage recruitment in OA are not fully understood. Methods: The Serglycin (SRGN) expression pattern was analyzed, along with its association with macrophage infiltration in OA, using bioinformatic methods. SRGN expression in chondrocytes was altered by small interfering RNA (siRNA) and plasmids. Conditioned media (CM) was obtained from transfected chondrocytes to establish a co-culture model of chondrocytes and THP-1 derived macrophages. The impact of SRGN on macrophage recruitment was evaluated using a transwell assay. Furthermore, the regulatory effect of SRGN on CCL3 was validated through qPCR, WB, and ELISA experiments. Results: In OA patients, the upregulation of SRGN positively correlated with K-L grade and macrophage infiltration. It was found that SRGN expression and secretion were up-regulated in OA and that it can promote macrophage migration in vitro. Further investigation showed that SRGN affects macrophage migration by regulating the expression of CCL3. Conclusion: SRGN in chondrocytes plays a role in promoting the recruitment of THP-1 derived macrophages in vitro by regulating production of CCL3. [ABSTRACT FROM AUTHOR]

Ecological models hold significant potential for advancing lake research. In this study, we employed CiteSpace, a bibliometric analysis tool, and VOSviewer, a visualisation software, to facilitate a comprehensive understanding of recent advancements in ecological modelling within the context of lake research. The objective was to furnish valuable references in support of the widespread application of ecological models in aquatic environments. Using the 4688 articles collected in the Web of Science (WoS) core database as the sample data source, conducting corresponding data mining and quantitative analysis through visualisation analysis software such as CiteSpace and VOSviewer. From the perspectives of literature output patterns, keyword co‐occurrence networks and future research directions, in‐depth quantitative and visual analysis is carried out on the current status of research on lake ecological models, research institutions, journal publication situations, prolific authors and research hot topics. Through meticulous examination of literature and organisational categorisation techniques, we systematically scrutinised and synthesised the present state, limitations and noteworthy considerations associated with models such as EFDC, CE‐QUAL‐W2, DYRESM‐CAEDYM, AQUATOX, Vollenweider, PCLake, MIKE, WASP and Deflt3D in the context of lake research. Our findings reveal that research focal points from 2002 to 2022 encompass climate change, the ramifications of eutrophication on aquatic ecosystems and the effects of phytoplankton and resuspended sediments on lake management. [ABSTRACT FROM AUTHOR]

Serine–arginine (SR) proteins are splicing factors that play essential roles in both constitutive and alternative pre-mRNA splicing. Phosphorylation of their C-terminal RS domains by SR protein kinases (SRPKs) regulates their localization and diverse cellular activities. Dysregulation of phosphorylation has been implicated in many human diseases, including cancers. Here, we report the development of a covalent protein–protein interaction inhibitor, C-DBS, that targets a lysine residue within the SRPK-specific docking groove to block the interaction and phosphorylation of the prototypic SR protein SRSF1. C-DBS exhibits high specificity and conjugation efficiency both in vitro and in cellulo. This self-cell-penetrating inhibitor attenuates the phosphorylation of endogenous SR proteins and subsequently inhibits the angiogenesis, migration, and invasion of cancer cells. These findings provide a new foundation for the development of covalent SRPK inhibitors for combatting diseases such as cancer and viral infections and overcoming the resistance encountered by ATP-competitive inhibitors. The binding and phosphorylation of serine–arginine-rich (SR) proteins by SR protein kinases (SRPKs) is essential to regulate target gene expression, however, the efficient inhibition of this interaction and phosphorylation remains underexplored. Here, the authors develop a covalent inhibitor that targets the lysine residue within the SRPK-specific docking groove, to block interaction and phosphorylation of the prototypic SR protein SRSF1. [ABSTRACT FROM AUTHOR]

The nuclear-encoded mitochondrial protein Tu translation elongation factor, mitochondrial (TUFM) is well-known for its role in mitochondrial protein translation. Originally discovered in yeast, TUFM demonstrates significant evolutionary conservation from prokaryotes to eukaryotes. Dysregulation of TUFM has been associated with mitochondrial disorders. Although early hypothesis suggests that TUFM is localized within mitochondria, recent studies identify its presence in the cytoplasm, with this subcellular distribution being linked to distinct functions of TUFM. Significantly, in addition to its established function in mitochondrial protein quality control, recent research indicates a broader involvement of TUFM in the regulation of programmed cell death processes (e.g., autophagy, apoptosis, necroptosis, and pyroptosis) and its diverse roles in viral infection, cancer, and other disease conditions. This review seeks to offer a current summary of TUFM's biological functions and its complex regulatory mechanisms in human health and disease. Insight into these intricate pathways controlled by TUFM may lead to the potential development of targeted therapies for a range of human diseases. [ABSTRACT FROM AUTHOR]

Background: To investigate the causal associations of serum urate (SUA) with stroke risk and prognosis using Mendelian randomization (MR) and the potential mediating role of stroke risk factors in the causal pathways. Methods: We used the random-effects inverse variance weighting (IVW) as our primary method. We initially performed two-sample univariable MR (UVMR) to identify the causal associations of SUA (n = 437,354) with any stroke (AS, FinnGen: n = 311,635; MEGASTROKE: n = 446,696), ischemic stroke (IS, FinnGen: n = 212,774; MEGASTROKE: n = 440,328), intracranial hemorrhage (ICH, FinnGen: n = 343,663; ISGC: n = 3,026), functional outcome after ischemic stroke at 90d (n = 4,363), and motor recovery within 24 months after stroke (n = 488), and then multivariable MR (MVMR) to estimate the direct causal effects of SUA on these outcomes, adjusting for potential confounders. Finally, we further conducted a two-step MR to investigate the potential mediating role of body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and estimated glomerular filtration rate (eGFR) in the identified causal pathways. Results: Genetically predicted elevated SUA levels were significantly associated with increased risk of AS (meta-analysis: OR = 1.09, 95% CI [1.04-1.13], p = 3.69e-05) and IS (meta-analysis: OR = 1.10, 95% CI [1.01-1.19], p = 0.021) and with improved poor functional outcome after ischemic stroke at 90d (OR = 0.81, 95% CI [0.72-0.90], p = 1.79e-04) and motor recovery within 24 months after stroke (OR = 1.42, 95% CI [1.23-1.64], p = 2.15e-06). In MVMR, SBP and DBP significantly attenuated the causal effects of SUA on AS, IS, and functional outcome after ischemic stroke at 90d and motor recovery within 24 months after stroke. Further mediation analyses showed that SBP mediated 52.4 and 34.5% of the effects of SUA on AS and IS, while DBP mediated 28.5 and 23.4% of the causal effects, respectively. Conclusion: This study supports the dual role of genetically predicted SUA in increasing stroke risk, especially ischemic stroke risk, and in improving functional outcome and motor recovery. SBP and DBP are key mediators lying on the causal pathways of SUA with AS and IS. [ABSTRACT FROM AUTHOR]

Background: Exercise has been reported to be associated with a reduced risk of nonalcoholic fatty liver disease (NAFLD), but there is no consensus on the role of weight changes in this association. This study aims to investigate whether the impact of exercise on NAFLD is mainly dependent on weight changes or is inherent to exercise itself. Methods: The study recruited 1671 Chinese NAFLD-free adults in 2019, and collected their exercise habits as well as 3 years of medical examination data including anthropometric measurements, blood biochemistry parameters, and liver ultrasound results. Univariate and multivariate logistic regression models were employed to examine the impact of exercise habits on NAFLD risk, with mediation analysis utilized to estimate the magnitude of the role of weight maintenance in the association between exercise and NAFLD. Results: After adjusting for confounders, moderate to high-intensity exercisers were 1.56 times (95% CIs = 1.09–2.22) more likely to successfully control their body weight, and therefore the weight-controlled group had a lower NAFLD risk of 34.9% (95% CIs = 21.8%–56.0%) compared to the weight-gain group. Mediation analysis reveals that exercise can significantly reduce the risk of NAFLD both through weight maintenance (37.1%) and independent of weight maintenance (62.9%). Conclusion: It might be more crucial to emphasize the adoption of regular moderate to high-intensity exercise for preventing NAFLD in the general population, rather than solely focusing on weight maintenance. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC), one of the most common malignancies in the world, urgently requires more treatment strategies. Although there has been much research on probiotics, limited research has been done in treating cancer. The purpose of this study was to investigate the role of Bifidobacterium longum (B. longum) in the prevention and treatment of CRC. Through Cell Counting Kit-8 and Colony Formation Assays, 8 h and a B. longum count of 1 × 108 CFU/ml were chosen as the best cocultivation conditions with CRC cells. The role of B. longum in inhibiting the progression of CRC cells was verified by a series of functional and immunofluorescence assays. For instance, in vivo assays have verified that B. longum could alleviate CRC progression. In addition, according to the results of in vivo assays and clinical statistical analysis, B. longum could reduce diarrhea symptoms. Mechanistically, by 16S and RNA sequencing, it was found that B. longum could affect the development of CRC by regulating the composition of gut microbes and enhancing immune function. The B. longum might inhibit the occurrence and development of CRC and relieve diarrhea symptoms by regulating intestinal microbes and immune function. [ABSTRACT FROM AUTHOR]

Background: Senescent astrocytes play crucial roles in age-associated neurodegenerative diseases, including Parkinson's disease (PD). Metformin, a drug widely used for treating diabetes, exerts longevity effects and neuroprotective activities. However, its effect on astrocyte senescence in PD remains to be defined. Methods: Long culture-induced replicative senescence model and 1-methyl-4-phenylpyridinium/α-synuclein aggregate-induced premature senescence model, and a mouse model of PD were used to investigate the effect of metformin on astrocyte senescence in vivo and in vitro. Immunofluorescence staining and flow cytometric analyses were performed to evaluate the mitochondrial function. We stereotactically injected AAV carrying GFAP-promoter-cGAS-shRNA to mouse substantia nigra pars compacta regions to specifically reduce astrocytic cGAS expression to clarify the potential molecular mechanism by which metformin inhibited the astrocyte senescence in PD. Results: We showed that metformin inhibited the astrocyte senescence in vitro and in PD mice. Mechanistically, metformin normalized mitochondrial function to reduce mitochondrial DNA release through mitofusin 2 (Mfn2), leading to inactivation of cGAS-STING, which delayed astrocyte senescence and prevented neurodegeneration. Mfn2 overexpression in astrocytes reversed the inhibitory role of metformin in cGAS-STING activation and astrocyte senescence. More importantly, metformin ameliorated dopamine neuron injury and behavioral deficits in mice by reducing the accumulation of senescent astrocytes via inhibition of astrocytic cGAS activation. Deletion of astrocytic cGAS abolished the suppressive effects of metformin on astrocyte senescence and neurodegeneration. Conclusions: This work reveals that metformin delays astrocyte senescence via inhibiting astrocytic Mfn2-cGAS activation and suggest that metformin is a promising therapeutic agent for age-associated neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Background: General obesity is a well-established risk factor for gallstone disease (GSD), but whether central obesity contributes additional independent risk remains controversial. We aimed to comprehensively clarify the effect of body fat distribution on GSD. Methods: We first investigated the observational association of central adiposity, characterized by waist-to-hip ratio (WHR), with GSD risk using data from UK Biobank (N=472,050). We then explored the genetic relationship using summary statistics from the largest genome-wide association study of GSD (ncase=43,639, ncontrol=506,798) as well as WHR, with and without adjusting for body mass index (BMI) (WHR: n=697,734; WHRadjBMI: n=694,649). Results: Observational analysis demonstrated an increased risk of GSD with one unit increase in WHR (HR=1.18, 95%CI=1.14-1.21). A positive WHR-GSD genetic correlation (rg =0.41, P=1.42×10-52) was observed, driven by yet independent of BMI (WHRadjBMI: rg =0.19, P=6.89×10-16). Cross-trait meta-analysis identified four novel pleiotropic loci underlying WHR and GSD with biological mechanisms outside of BMI. Mendelian randomization confirmed a robust WHR-GSD causal relationship (OR=1.50, 95%CI=1.35-1.65) which attenuated yet remained significant after adjusting for BMI (OR=1.17, 95%CI=1.09-1.26). Furthermore, observational analysis confirmed a positive association between general obesity and GSD, corroborated by a shared genetic basis (rg =0.40, P=2.16×10-43), multiple novel pleiotropic loci (N=11) and a causal relationship (OR=1.67, 95%CI=1.56-1.78). Conclusion: Both observational and genetic analyses consistently provide evidence on an association of central obesity with an increased risk of GSD, independent of general obesity. Our work highlights the need of considering both general and central obesity in the clinical management of GSD. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative joint disease that affects millions worldwide. Synovitis and macrophage polarization are important factors in the development of OA. However, the specific components of synovial fluid (SF) responsible for promoting macrophage polarization remain unclear. Semi-quantitative antibody arrays were used to outline the proteome of SF. Differential expression analysis and GO/KEGG were performed on the obtained data. Immunohistochemistry and ELISA were used to investigate the relationship between SF S100A12 levels and synovitis levels in clinalclinical samples. In vitro cell experiments were conducted to investigate the effect of S100A12 on macrophage polarization. Public databases were utilized to predict and construct an S100A12-centered lncRNA-miRNA-mRNA competing endogenous RNA network, which was preliminarily validated using GEO datasets. The study outlines the protein profile in OA and non-OA SF. The results showed that the S100A12 level was significantly increased in OA SF and inflammatory chondrocytes. The OA synovium had more severe synovitis and higher levels of S100A12 than non-OA synovium. Exogenous S100A12 upregulated the levels of M1 markers and phosphorylated p65 and promoted p65 nuclear translocation, while pretreatment with BAY 11–7082 reversed these changes. It was also discovered that LINC00894 was upregulated in OA and significantly correlated with S100A12, potentially regulating S100A12 expression by acting as a miRNA sponge. This study demonstrated that S100A12 promotes M1 macrophage polarization through the NF-κB pathway, and found that LINC00894 has the potential to regulate the expression of S100A12 as a therapeutic approach. [ABSTRACT FROM AUTHOR]

Pulmonary invasive fungal infection in immunocompromised hosts is difficult to diagnose, and current tools for diagnosis or monitoring of response to antifungal treatments have inherent limitations. Droplet digital PCR (ddPCR) has emerged as a promising tool for pulmonary pathogen detection with high sensitivity. This study presents a novel ddPCR panel for rapid and sensitive identification of pulmonary fungal pathogens. First, a ddPCR method for detecting three fungal genera, including Pneumocystis, Aspergillus, and Cryptococcus, was established and evaluated. Then, the clinical validation performance of ddPCR was compared with that of qPCR using 170 specimens, and the 6 specimens with inconsistent results were further verified by metagenomics next-generation sequencing, which yielded results consistent with the ddPCR findings. Finally, the area under the ROC curve (AUC) was used to evaluate the efficiency of ddPCR. While the qPCR identified 16 (9.41%) cases of Aspergillus and 6 (3.53%) cases of Pneumocystis, ddPCR detected 20 (11.76%) Aspergillus cases and 8 (4.71%) Pneumocystis cases. The AUC for Aspergillus, Cryptococcus, and Pneumocystis was 0.974, 0.998, and 0.975, respectively. These findings demonstrated that the ddPCR assay is a highly sensitive method for identifying pathogens responsible for invasive fungal pulmonary infections, and is a promising tool for early diagnosis. [ABSTRACT FROM AUTHOR]

Background: To investigate whether accurate placement of sustentaculum tali screws have the impacts on the clinical efficacy of calcaneal fractures. Methods: A retrospective analysis of 72 cases (73 feet) of calcaneal fractures from September 2015 to September 2019 treated with open reduction and internal fixation with sustentaculum tali screws was conducted. Patients were divided into the sustentaculum tali fixation group (ST group) and the sustentaculum fragment fixation group (STF group) according to the location of the sustentaculum tali screw placement. The functional outcomes at preoperative, 7 days and 1 year postoperative were collected and analyzed. Results: In the ST group (40 feet), the Gissane's angle altered from (109.89 ± 12.13)° to (121.23 ± 9.34)° and (119.08 ± 8.31)° at 7 days and 1 year postoperative, respectively. For Böhler’s angles altered from (11.44 ± 5.94)°, to (31.39 ± 7.54)°, and (30.61 ± 7.94)° at 7 days and 1 year postoperative, respectively. In the STF group (33 feet), Gissane’s angle altered from (110.47 ± 14.45)°, to (122.08 ± 8.84)°, and (120.67 ± 9.07)° and Böhler’s angle altered from (11.32 ± 6.77)°, to (28.82 ± 8.52)°, and (28.25 ± 9.13)° (P < 0.001). However, there was no statistically significant difference in functional outcomes at 1 week after surgery and 1 year after surgery (P > 0.05). The AOFAS scores at the final follow-up of the two groups: ST group (88.95 ± 6.16) and STF group (89.78 ± 8.76); VAS scores, ST group (0.83 ± 0.98) and STF group (1.03 ± 1.59), all differences were not statistically significant (P > 0.05). Conclusion: The position of sustentaculum tali screws has no significant difference on the short-term clinical outcome in patients with calcaneal fractures, while reliable fixation of screws to sustentaculum tali fragment can achieve similar clinical outcome. Level of evidence V. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are membrane‐enclosed nanovesicles secreted by cells into the extracellular space and contain functional biomolecules, e.g. signaling receptors, bioactive lipids, nucleic acids, and proteins, which can serve as biomarkers. Neurons and glial cells secrete EVs, contributing to various physiological and pathological aspects of brain diseases. EVs confer their role in the bidirectional crosstalk between the central nervous system (CNS) and the periphery owing to their distinctive ability to cross the unique blood–brain barrier (BBB). Thus, EVs in the blood, cerebrospinal fluid (CSF), and urine can be intriguing biomarkers, enabling the minimally invasive diagnosis of CNS diseases. Although there has been an enormous interest in evaluating EVs as promising biomarkers, the lack of ultra‐sensitive approaches for isolating and detecting brain‐derived EVs (BDEVs) has hindered the development of efficient biomarkers. This review presents the recent salient findings of exosomal biomarkers, focusing on brain disorders. We summarize highly sensitive sensors for EV detection and state‐of‐the‐art methods for single EV detection. Finally, the prospect of developing advanced EV analysis approaches for the non‐invasive diagnosis of brain diseases is presented. [ABSTRACT FROM AUTHOR]

Targeted immunotherapies capitalize on the exceptional binding capabilities of antibodies to stimulate a host response that effectuates long‐lived tumor destruction. One example is the conjugation of immunoglobulins (IgGs) to immune effector cells, which equips the cells with the ability to recognize and accurately kill malignant cells through a process called antibody‐dependent cellular cytotoxicity (ADCC). In this study, a chemoenzymatic reaction is developed that specifically functionalizes a single tyrosine (Tyr, Y) residue, Y296, in the Fc domain of therapeutic IgGs. A one‐pot reaction that combines the tyrosinase‐catalyzed oxidation of tyrosine to o‐quinone with a subsequent [3+2] photoaddition with vinyl ether is employed. This reaction installs fluorescent molecules or bioorthogonal groups at Y296 of IgGs or the C‐terminal Y‐tag of an engineered nanobody. The Tyr‐specific reaction is utilized in constructing monofunctionalized antibody‐drug conjugates (ADCs) and antibody/nanobody‐conjugated effector cells, such as natural killer cells or macrophages. These results demonstrate the potential of site‐selective antibody reactions for enhancing targeted cancer immunotherapy. [ABSTRACT FROM AUTHOR]

The construction of bioactive scaffolds with a suitable microenvironment for tissue regeneration provides a great promise for improving clinical treatment of osteochondral and full-thickness articular cartilage defects. Hydrogels of polysaccharides, such as alginate, agarose, chitosan, cellulose, hyaluronic acid, and dextran, biomimic the structure of the extracellular matrix (ECM), are exceptionally biocompatible scaffold material for tissue regeneration. The application of polysaccharide hydrogels combined with 3-dimensional (3D) printing technology can precisely distribute cell-loaded biomaterials, construct complex 3D living tissues with optimal structure and mechanical properties for osteochondral and cartilage repair. This review highlights recent advances in the development of polysaccharide-based hydrogel materials for promoting bone and cartilage tissue repair. We also highlight recent advances in 3D bioprinting polysaccharide-based hydrogel materials in cartilage regeneration. The cell type and the development of 3D bioprinting technology were described. In addition, the formation of polysaccharide – protein-based is also discussed. We outline the future trends of 3D printing including machine learning, near-infrared photopolymerization, 4D printing, and a combination of self-assembly and live-cell 3D printing-based methods. [ABSTRACT FROM AUTHOR]

Hydroxycarboxylic acid receptor 2 (HCAR2) belongs to the family of class A G protein-coupled receptors with key roles in regulating lipolysis and free fatty acid formation in humans. It is deeply involved in many pathophysiological processes and serves as an attractive target for the treatment of cardiovascular, neoplastic, autoimmune, neurodegenerative, inflammatory, and metabolic diseases. Here, we report four cryo-EM structures of human HCAR2–Gi1 complexes with or without agonists, including the drugs niacin (2.69 Å) and acipimox (3.23 Å), the highly subtype-specific agonist MK-6892 (3.25 Å), and apo form (3.28 Å). Combined with molecular dynamics simulation and functional analysis, we have revealed the recognition mechanism of HCAR2 for different agonists and summarized the general pharmacophore features of HCAR2 agonists, which are based on three key residues R1113.36, S17945.52, and Y2847.43. Notably, the MK-6892–HCAR2 structure shows an extended binding pocket relative to other agonist-bound HCAR2 complexes. In addition, the key residues that determine the ligand selectivity between the HCAR2 and HCAR3 are also illuminated. Our findings provide structural insights into the ligand recognition, selectivity, activation, and G protein coupling mechanism of HCAR2, which shed light on the design of new HCAR2-targeting drugs for greater efficacy, higher selectivity, and fewer or no side effects. [ABSTRACT FROM AUTHOR]

Background: Tibiotalocalcaneal (TTC) arthrodesis with a retrograde intramedullary nail for severe tibiotalar and talocalcaneal arthritis has a high fusion rate; however, no studies have focused on how to handle the fibula intraoperatively to achieve better results. This study aimed to compare the efficacies of various fibular procedures. Methods: We retrospectively reviewed the cases of severe tibiotalar and talocalcaneal arthritis in adults treated with TTC arthrodesis using a retrograde intramedullary nail between January 2012 and July 2017. The patients were divided into three groups according to different fibular procedures: Fibular osteotomy (FO), fibular strut (FS), and fibular preservation (FP). Functional outcomes and pain were assessed using the American Orthopedic Foot and Ankle Society (AOFAS) ankle and hindfoot score and visual analog scales (VAS), respectively. The operation time, fusion time, radiographic evaluation, and complications were also recorded. Results: Fifty-eight patients with an average age of 53.2 (range, 32–69) years were enrolled in the final analysis. The numbers of patients enrolled in the three groups were 21, 19, and 18 in the FO, FS, and FP groups, respectively. The mean postoperative follow-up time was 66.0 (range, 60–78) months. All groups showed a high fusion rate (90.5% for FO, 94.7% for FS, and 94.4% for FP) and significant improvement in AOFAS ankle and hindfoot scores and VAS scores at the latest follow-up. There were no significant differences in these parameters among the three groups. The mean operation time of FS (131.3 ± 17.1 min) was longer than that of FO (119.3 ± 11.7 min) and FS (112.2 ± 12.6 min), but the fusion time was shorter (15.1 ± 2.8 weeks for FS, 17.2 ± 1.9 weeks for FO, and 16.8 ± 1.9 weeks for FP). Statistically significant differences were observed in these parameters. Conclusions: TTC arthrodesis using a retrograde intramedullary nail is an effective procedure with a high rate of fusion to treat severe tibiotalar and talocalcaneal arthritis in adults; however, FSs can shorten fusion time when compared with FO and FP. Level of clinical evidence: Level 3. [ABSTRACT FROM AUTHOR]

Cellular membranes, including the plasma and endosome membranes, are barriers to outside proteins. Various vehicles have been devised to deliver proteins across the plasma membrane, but in many cases, the payload gets trapped in the endosome. Here we designed a photo‐responsive phase‐separating fluorescent molecule (PPFM) with a molecular weight of 666.8 daltons. The PPFM compound condensates as fluorescent droplets in the aqueous solution by liquid‐liquid phase separation (LLPS), which disintegrate upon photoirradiation with a 405 nm light‐emitting diode (LED) lamp within 20 min or a 405 nm laser within 3 min. The PPFM coacervates recruit a wide range of peptides and proteins and deliver them into mammalian cells. Photolysis disperses the payload from condensates into the cytosolic space. Altogether, a type of small molecules that are photo‐responsive and phase separating are discovered; their coacervates can serve as transmembrane vehicles for intracellular delivery of proteins, whereas photo illumination triggers the cytosolic distribution of the payload. [ABSTRACT FROM AUTHOR]

Cellular membranes, including the plasma and endosome membranes, are barriers to outside proteins. Various vehicles have been devised to deliver proteins across the plasma membrane, but in many cases, the payload gets trapped in the endosome. Here we designed a photo‐responsive phase‐separating fluorescent molecule (PPFM) with a molecular weight of 666.8 daltons. The PPFM compound condensates as fluorescent droplets in the aqueous solution by liquid‐liquid phase separation (LLPS), which disintegrate upon photoirradiation with a 405 nm light‐emitting diode (LED) lamp within 20 min or a 405 nm laser within 3 min. The PPFM coacervates recruit a wide range of peptides and proteins and deliver them into mammalian cells. Photolysis disperses the payload from condensates into the cytosolic space. Altogether, a type of small molecules that are photo‐responsive and phase separating are discovered; their coacervates can serve as transmembrane vehicles for intracellular delivery of proteins, whereas photo illumination triggers the cytosolic distribution of the payload. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA), a common joint disorder with articular cartilage degradation as the main pathological change, is the major source of pain and disability worldwide. Despite current treatments, the overall treatment outcome is unsatisfactory. Thus, patients with severe OA often require joint replacement surgery. In recent years, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic option for preclinical and clinical palliation of OA. MSC-derived exosomes (MSC-Exos) carrying bioactive molecules of the parental cells, including non-coding RNAs (ncRNAs) and proteins, have demonstrated a significant impact on the modulation of various physiological behaviors of cells in the joint cavity, making them promising candidates for cell-free therapy for OA. This review provides a comprehensive overview of the biosynthesis and composition of MSC-Exos and their mechanisms of action in OA. We also discussed the potential of MSC-Exos as a therapeutic tool for modulating intercellular communication in OA. Additionally, we explored bioengineering approaches to enhance MSC-Exos' therapeutic potential, which may help to overcome challenges and achieve clinically meaningful OA therapies. [ABSTRACT FROM AUTHOR]

Repeated neonatal exposures to sevoflurane induce long-term cognitive impairment that has been reported to have sex-dependent differences. Exercise promotes learning and memory by releasing lactate from the muscle. The study tested the hypothesis that lactate may improve long-term cognitive impairment induced by repeated neonatal exposures to sevoflurane through SIRT1-mediated regulation of adult hippocampal neurogenesis and synaptic plasticity. C57BL/6 mice of both genders were exposed to 3% sevoflurane for 2 h daily from postnatal day 6 (P6) to P8. In the intervention experiments, mice received lactate at 1 g/kg intraperitoneally once daily from P21 to P41. Behavioral tests including open field (OF), object location (OL), novel object recognition (NOR), and fear conditioning (FC) tests were performed to assess cognitive function. The number of 5-Bromo-2′- deoxyuridine positive (BrdU+) cells and BrdU+/DCX+ (doublecortin) co-labeled cells, expressions of brain-derived neurotrophic factor (BDNF), activity-regulated cytoskeletal-associated protein (Arc), early growth response 1 (Egr-1), SIRT1, PGC-1α and FNDC5, and long-term potentiation (LTP) were evaluated in the hippocampus. Repeated exposures to sevoflurane induced deficits in OL, NOR and contextual FC tests in male but not female mice. Similarly, adult hippocampal neurogenesis, synaptic plasticity-related proteins and hippocampal LTP were impaired after repeated exposures to sevoflurane in male but not female mice, which could rescue by lactate treatment. Our study suggests that repeated neonatal exposures to sevoflurane inhibit adult hippocampal neurogenesis and induce defects of synaptic plasticity in male but not female mice, which may contribute to long-term cognitive impairment. Lactate treatment rescues these abnormalities through activation of SIRT1. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease 2019 (COVID-19) pandemic has exerted a profound influence on humans. Increasing evidence shows that immune response is crucial in influencing the risk of infection and disease severity. Observational studies suggest an association between COVID-19 and immunoglobulin G (IgG) N-glycosylation traits, but the causal relevance of these traits in COVID-19 susceptibility and severity remains controversial. Methods: We conducted a two-sample Mendelian randomization (MR) analysis to explore the causal association between 77 IgG N-glycosylation traits and COVID-19 susceptibility, hospitalization, and severity using summary-level data from genome-wide association studies (GWAS) and applying multiple methods including inverse-variance weighting (IVW), MR Egger, and weighted median. We also used Cochran's Q statistic and leave-one-out analysis to detect heterogeneity across each single nucleotide polymorphism (SNP). Additionally, we used the MR-Egger intercept test, MR-PRESSO global test, and PhenoScanner tool to detect and remove SNPs with horizontal pleiotropy and to ensure the reliability of our results. Results: We found significant causal associations between genetically predicted IgG N-glycosylation traits and COVID-19 susceptibility, hospitalization, and severity. Specifically, we observed reduced risk of COVID-19 with the genetically predicted increased IgG N-glycan trait IGP45 (OR = 0.95, 95% CI = 0.92-0.98; FDR = 0.019). IGP22 and IGP30 were associated with a higher risk of COVID-19 hospitalization and severity. Two (IGP2 and IGP77) and five (IGP10, IGP14, IGP34, IGP36, and IGP50) IgG N-glycosylation traits were causally associated with a decreased risk of COVID-19 hospitalization and severity, respectively. Sensitivity analyses did not identify any horizontal pleiotropy. Conclusions: Our study provides evidence that genetically elevated IgG Nglycosylation traits may have a causal effect on diverse COVID-19 outcomes. Our findings have potential implications for developing targeted interventions to improve COVID-19 outcomes by modulating IgG N-glycosylation levels. [ABSTRACT FROM AUTHOR]

Background: This study aimed to analyze quantitative correlation between the posterior malleolus fracture and fixation and the rotational stability of the ankle and to explore supplementary surgical indications for posterior malleolus fracture. Methods: Twenty fresh frozen cadaver specimens were selected and dissected. Based on the tibial insertion of the ligament complex, the model for the supination external rotation stage 3 ankle fracture with a posterior malleolar fragment and syndesmosis diastasis was created. The area threshold of the posterior tibial insertion of posterior malleolus fracture was biomechanically assessed and the difference of the antirotating ability stiffness of the ankle between simple posterior malleolus fixation and simple syndesmotic fixation was analyzed statistically. Results: The tibial insertion of posterior inferior tibiofibular ligament and inferior transverse tibiofibular ligament complex was relatively broad, and its width decreased as the distance from the joint line increased. Biomechanical analysis showed that: the threshold of posterior area of posterior malleolus fracture was 1/4S; posterior malleolus fixation provided better rotational stability than syndesmotic fixation (P < 0.01). Conclusion: The surgical indications for posterior malleolus fracture should consider simultaneously the restoration of the axial and rotational stability of the ankle. Simple posterior malleolus fracture fixation is recommended when the syndesmosis is unstable and the area ratio of posterior tibial insertion of posterior malleolus fracture is greater than or equal to 1/4. Syndesmotic fixation is proposed to restore and maintain the rotational stability of the ankle when the syndesmosis is unstable and the area ratio is less than 1/4. Regardless of the area ratio, the surgical indication only depends on the impact of the posterior malleolus fracture on the axial stability of tibiotalar joint, the involved articular surface area, and the displacement degree of posterior malleolus fragment, when the syndesmosis is stable. [ABSTRACT FROM AUTHOR]

Early in the COVID-19 pandemic, data suggested that males had a higher risk of developing severe disease and that androgen deprivation therapy might be associated with protection. Combined with the fact that TMPRSS2 (transmembrane serine protease 2), a host entry factor for the SARS-CoV- 2 virus, was a well-known androgen-regulated gene, this led to an upsurge of research investigating androgen receptor (AR)-targeting drugs. Proxalutamide, an AR antagonist, was shown in initial clinical studies to benefit COVID-19 patients; however, further validation is needed as one study was retracted. Due to continued interest in proxalutamide, which is in phase 3 trials, we examined its ability to impact SARS-CoV- 2 infection and downstream inflammatory responses. Proxalutamide exerted similar effects as enzalutamide, an AR antagonist prescribed for advanced prostate cancer, in decreasing AR signaling and expression of TMPRSS2 and angiotensin-converting enzyme 2 (ACE2), the SARS-CoV- 2 receptor. However, proxalutamide led to degradation of AR protein, which was not observed with enzalutamide. Proxalutamide inhibited SARS-CoV- 2 infection with an IC50 value of 97 nM, compared to 281 nM for enzalutamide. Importantly, proxalutamide inhibited infection by multiple SARS-CoV- 2 variants and synergized with remdesivir. Proxalutamide protected against cell death in response to tumor necrosis factor alpha and interferon gamma, and overall survival of mice was increased with proxalutamide treatment prior to cytokine exposure. Mechanistically, we found that proxalutamide increased levels of NRF2, an essential transcription factor that mediates antioxidant responses, and decreased lung inflammation. These data provide compelling evidence that proxalutamide can prevent SARS-CoV- 2 infection and cytokine-induced lung damage, suggesting that promising clinical data may emerge from ongoing phase 3 trials. [ABSTRACT FROM AUTHOR]

Background: This study explores the latest epidemiological characteristics of posterior malleolus fracture and compares the epidemiological differences of posterior malleolus fracture in different periods, regions, and adult age groups. Methods: Clinical information of inpatients with posterior malleolus fracture in Shanghai Tongji Hospital and Karamay Central Hospital from January 2014 to February 2022 was reviewed and collected. The imaging data of patients were acquired using the Picture Archiving and Communication Systems. A statistical analysis was performed as to gender, current age, year of admission, injury mechanism, fracture type, and posterior malleolus fracture classification. Moreover, a comparative analysis was conducted on the injury mechanisms and morphological differences of posterior malleolus fracture at different periods, regions, and age groups. Results: A total of 472 patients (210 patients from Shanghai Tongji Hospital and 262 patients from Karamay Central Hospital) with posterior malleolus fracture and an average age of 48.7 ± 15.6 were included in this study. The peak of posterior malleolus fracture occurs in the age group of 50–59. The injury mechanisms mainly involve low-energy fall and sprain (411 cases, 87.1%), followed by traffic accidents (52 cases, 11.0%), and fall injury from height (9 cases, 1.9%). With aging, the number of fall and sprain cases increases and reaches the peak at the age of 50–59, followed by progressive decline. Traffic accidents presents a relatively flat small peak in the age group of 40–59. The number of cases according to different fracture types shows the following ascending order: trimalleolar fracture-supination external rotation (335 cases, 71.0%) > bimalleolar fracture (60 cases, 12.7%) > trimalleolar fracture-pronation extorsion (43 cases, 9.1%) > posterior malleolus + tibial shaft fracture (19 cases, 4.0%) > simple posterior malleolus fracture (15 cases, 3.2%). The numbers of cases corresponding to the Haraguchi I Type, II Type, and III Type of posterior malleolus fractures were 369 (78.2%), 49 (10.4%), and 54 (11.4%), respectively. The Tongji IIA Type represented the highest number of cases (249 cases, 52.8%), followed by the IIB Type (120 cases, 25.4%), I Type (54 cases, 11.4%), IIIB Type (36 cases, 7.6%), and IIIA type (13 cases, 2.8%). The trimalleolar fracture-supination external rotation, Haraguchi I Type and Tongji IIA Type of posterior malleolus fractures all presented an obvious peak of incidence in the age group of 50–59. However, no obvious statistical difference was observed in the injury mechanism, Haraguchi classification, and Tongji classification of posterior malleolus fractures among different years and regions in recent years (P > 0.05). Conclusions: The injury mechanism of posterior malleolus fracture mainly involves low-energy fall and sprain cases. The trimalleolar fracture-supination external rotation, Haraguchi I type and Tongji IIA type of posterior malleolus fracture are predilection fracture types, and all present an obvious incidence peak in the age group of 50–59. Elderly patients have high risks of falling and their bones are more fragile, conditions which are potential risk factors of posterior malleolus fracture. Early positive control has important significance. This study provides references for relevant basic and clinical studies of posterior malleolus fracture. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the genetic factors promoting widespread Q6 dissemination of tet(X4) between Escherichia coli and to characterize the genetic contexts of tet(X4). Methods: We isolated E. coli from feces, water, soil and flies collected across a largescale chicken farm in China in 2020. Antimicrobial susceptibility testing and PFGE typing were used to identify tigecycline resistance and assess clonal relationships among isolates. Plasmids present and genome sequences were analyzed by conjugation, S1 pulsed-field gel electrophoresis (PFGE), plasmid stability testing and whole-genome sequencing. Results: A total of 204 tigecycline-resistant E. coli were isolated from 662 samples. Of these, we identified 165 tet(X4)-carrying E. coli and these strains exhibited a high degree of multidrug resistance. Based on the geographical location distribution of the sampled areas, number of samples in each area and isolation rate of tigecyclineresistant strains and tet(X4)-carrying isolates, 72 tet(X4)-positive isolates were selected for further investigation. Tigecycline resistance was shown to be mobile in 72 isolates and three types of tet(X4)-carrying plasmids were identified, they were IncHI1 (n= 67), IncX1 (n= 3) and pO111-like/IncFIA(HI1) (n= 2). The pO111-like/IncFIA(HI1) is a novel plasmid capable of transferring tet(X4). The transfer efficiency of IncHI1 plasmids was extremely high in most cases and IncHI1 plasmids were stable when transferred into common recipient strains. The genetic structures flanked by IS1, IS26 and ISCR2 containing tet(X4) were complex and varied in different plasmids. Discussion: The widespread dissemination of tigecycline-resistant E. coli is a major threat to public health. This data suggests careful use of tetracycline on farms is important to limit spread of resistance to tigecycline. Multiple mobile elements carrying tet(X4) are in circulation with IncHI1 plasmids the dominant vector in this setting. [ABSTRACT FROM AUTHOR]

To avoid the production of drug resistance during the antibiotic treatment of wound infection, the use of antimicrobial peptides (AMPs) has been strongly developed. However, its application is limited by low bioavailability, rapid degradation of AMP, and the difficulty of deep-tissue bacterial elimination. To solve this problem, AMP and recombinant type III humanized collagen (Col III)-contained microneedle patches were designed to achieve slow and controlled release of AMP and Col III to effectively eliminate the bacteria in the deep wound tissue and promote wound healing. AMP (KKLRLKIAFK) coupled with Cy3 was encapsulated in the nanogel (CGA-NPs), which was formed by chitosan (CS) and gum arabic (GA) through electrostatic interactions. Microneedle (MN) patches were dissolved after penetrating the infected skin and biofilm formed by Staphylococcus aureus to release CGA-NPs. AMPs was released responding to the infected microenvironment to efficiently kill bacteria, and Col III was beneficial to promote wound healing. This is a strategy for the design and application of a microneedle-based antimicrobial drug delivery system. [ABSTRACT FROM AUTHOR]

Earthquakes are a significant factor that contributes to tailings dam failure. Generally, the seismic stability of a tailings dam can be increased by improving the dynamic properties of tailings. The dynamic properties of tailings can be improved effectively using polymers. In this study, the dynamic properties of polyacrylamide-reinforced tailings were investigated via a sequence of dynamic triaxial tests. The content of polyacrylamide in the test sample was 0.3%. Test results show that the cyclic liquefaction resistance, initial dynamic shear modulus, dynamic shear modulus, and dynamic shear modulus ratio of polyacrylamide-reinforced tailings were slightly greater than those of unreinforced tailings. The damping ratio of polyacrylamide-reinforced tailings was lower than that of unreinforced tailings when the dynamic shear strain exceeded 0.038%. The increase in the dynamic pore water pressure of polyacrylamide-reinforced tailings during cyclic loading decelerated significantly compared with that of unreinforced tailings. The revised Zeng model can effectively described the changes in dynamic pore-water pressure of unreinforced and polyacrylamide-reinforced tailings. The polyacrylamide can improve the structural stability of the tailings specimen and also improve the dynamic properties of the tailings, thereby enhancing the seismic stability of the tailings dam. [ABSTRACT FROM AUTHOR]

Employee recognition, an incentive method widely used in management practice, plays an important role in the organization. Although extant studies have confirmed its effectiveness, little attention has been paid to its spillover effect. Based on the Social Cognitive Theory and Affective Events Theory, this study argues that employee recognition encounter can trigger cognitive and behavioral reactions. Through perceived organizational justice and workplace wellbeing, a chain-mediating effect connects witnessing employee recognition to work engagement. This research adopts the empirical research method by asking the participants to do the weekly survey (four times in 1 month), and 258 samples are collected. Using SPSS20.0 and its PROCESS macro module, hypotheses are tested. The results indicate (1) employees who witness leaders’ recognition of colleagues will (a) perceive higher organizational justice and (b) be more engaged in work. (2) Perceived organizational justice will mediate the positive relationship between employee recognition encounters with (a) workplace wellbeing and (b) work engagement. (3) Perceived organizational justice and workplace wellbeing will have a chain-mediating effect in the path of employee recognition encounter and work engagement. The results provide both practical and theoretical contribution to employee recognition. [ABSTRACT FROM AUTHOR]

Background: DNA methylation plays an important role in Parkinson's disease (PD) pathogenesis. DNA methyltransferase 1 (DNMT1) is critical for maintaining DNA methylation in mammals. The link between DNMT1 polymorphisms and PD remains elusive. Methods: The DNMT1 gene contained a total of 28 single nucleotide polymorphisms (SNPs). Four representing tag-SNPs (rs16999593, rs2162560, rs11880553, and rs9305012) were identified and genotyped in a Han Chinese population comprising 712 PD patients and 696 controls. Association analyses were performed at gene-wide significance (p < 1.8 x 10-3). Results: Rs9305012, but not the other 3 tag-SNPs, was gene-wide significantly associated with PD risk (p = 0.8 x 10-3). The rs9305012/C was a protective allele against PD (p = 1.5 x 10-3, OR 0.786, 95% CI 0.677-0.912). No significant association was observed in individual genders or PD subtypes. Haplotypes of the 4 tag-SNPs showed a significant overall distribution difference between PD patients and controls (p < 1 x 10-4). The 3-allele ACC module in the order of rs2162560, rs11880553, and rs9305012 was the highest-risk haplotype associated with PD (p < 1x 10-4, OR 2.439, 95% CI 1.563-3.704). Rs9305012 displayed certain probability to affect transcription factor binding and target gene expression based on functional annotation analyses. Conclusion: The DNMT1 variant rs9305012 together with its haplotypes may gene-wide significantly modulate PD susceptibility. Our results support a role of DNMT1 in PD pathogenesis and provide novel insights into the genetic connection in between. [ABSTRACT FROM AUTHOR]

Introduction: With the rapid development of China’s “gig economy,” the on-call work model has grown increasingly prevalent in China and has attracted a large number of rural migrant workers with its low employment threshold. However, this irregular employment mode may negatively impact the mental health of workers. Methods: This paper uses an ordinal logistic regression model to study the relationship between Chinese rural migrant workers’ on-call work and their depression. Results: The results showed that after controlling for relevant variables, the odds ratio of depressive mood among rural migrant workers engaged in on-call work was 1.22 (95% CI 1.04–1.43) compared with rural migrant workers who did not need to be on call. In further heterogeneity research, we found that on-call work is more likely to aggravate the depression risk of rural migrant workers who are highly dependent on the internet and have low-wage incomes. Discussion: This research suggests that appropriate measures should be taken to mitigate the negative impact of on-call work on the mental health of rural migrant workers, and more attention needs to be paid to the mental health of lower salaried and gig workers. This paper provides a valuable sample of Chinese rural migrant workers for theoretical research on the relationship between on-call work and mental health and confirms the relationship between the two. These results contribute new ideas to the theory and practice of psychological crisis intervention aimed at Chinese rural migrant workers. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Electrochemistry is the property of Journal of Electrochemistry Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Medical Biochemistry is the property of Society of Medical Biochemists of Serbia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)