[Analysis of influencing factors of early femoral head necrosis after femoral neck fracture and construction of nomogram prediction model].

OBJECTIVE: To explore the risk factors of early femoral head necrosis in patients with femoral neck fracture after operation, and to establish a nomogram prediction model. METHODS: A total of 167 patients with femoral neck fracture from January 2020 to April 2022 were selected and divided into necrosis group and non-necrosis group according to whether femoral head necrosis occurred in the early postoperative period. There were 21 males and 17 females in the necrosis group, aged from 33 to 72 years old, with an average of (53.49±10.96) years old, and the time from injury to operation ranged from 40 to 67 hours, with average time of(53.46±7.23) hours. There were 72 males and 57 females in the non-necrosis group, aged from 18 to 83 years, with an average of (52.78±12.55) years old, and the time from injury to operation was 18 to 65 hours, with an average time of(39.88±7.79) hours. The potential influencing factors, including patient gender, diabetes mellitus, hypertension, chronic liver disease, posterior inclination angle of the femoral head, operation mode, fracture displacement, fracture line location, preoperative braking traction, screw arrangement mode, reduction quality, age, body mass index(BMI), and injury to operation time were subjected to single factor analysis. Logistic multivariate regression analysis was conducted for factors with a significance level of P<0.05. RESULTS: The incidence of femoral head necrosis in 167 patients with femoral neck fracture was 22.76%. The following factors were identified as independent risk factors for early postoperative femoral head necrosis in patients with femoral neck fractures:coexisting diabetes[OR=5.139, 95%CI(1.405, 18.793), P=0.013], displaced fracture [OR=3.723, 95%CI(1.105, 12.541), P=0.034], preoperative immobilization[OR=3.444, 95%CI(1.038, 11.427), P=0.043], quality of reduction [OR=3.524, 95%CI(1.676, 7.411), P=0.001], and time from injury to surgery[OR=1.270, 95%CI(1.154, 1.399), P=0.000]. The Hosmer-Lemeshow goodness-of-fit test(χ2=3.951, P=0.862), the area under the receiver operator characteristic(ROC) curve was 0.944[P<0.001, 95%CI(0.903, 0.987)], with a sensitivity of 89.50%, the specificity was 88.40%, the maximum Youden index was 0.779, and the overall trend of the model correction curve was close to the ideal curve. Model regression equation was Z=1.637 × diabetes + 1.314× fracture displacement+1.237 × preoperative braking traction+1.260 × reduction quality + 0.239×injury to operation time-18.310. CONCLUSION: The occurrence of early femoral head necrosis in patients with femoral neck fracture postoperatively is affected by multiple factors. The risk early warning model established according to the factors has good predictive efficacy.

Distinct Species-Specific and Toxigenic Metabolic Profiles for 6PPD and 6PPD Quinone by P450 Enzymes: Insights from In Vitro and In Silico Studies.

The tire rubber antioxidant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its quinone product (6PPDQ) are prevalent emerging contaminants, yet their biotransformation profiles remain poorly understood, hampering the assessment of environmental and health risks. This study investigated the phase-I metabolism of 6PPD and 6PPDQ across aquatic and mammalian species through in vitro liver microsome (LM) incubations and in silico simulations. A total of 40 metabolites from seven pathways were identified using the highly sensitive nano-electrospray ionization mass spectrometry. Notably, 6PPDQ was consistently detected as a 6PPD metabolite with an approximate 2% yield, highlighting biotransformation as a neglected indirect exposure pathway for 6PPDQ in organisms. 6PPDQ was calculated to form through a facile two-step phenyl hydroxylation of 6PPD, catalyzed by cytochrome P450 enzymes. Distinct species-specific metabolic kinetics were observed, with fish LM demonstrating retarded biotransformation rates for 6PPD and 6PPDQ compared to mammalian LM, suggesting the vulnerability of aquatic vertebrates to these contaminants. Intriguingly, two novel coupled metabolites were identified for 6PPD, which were predicted to exhibit elevated toxicity compared to 6PPDQ and result from C-N oxidative coupling by P450s. These unveiled metabolic profiles offer valuable insights for the risk assessment of 6PPD and 6PPDQ, which may inform future studies and regulatory actions.

Prevalence and correlates of probable rapid eye movement sleep behavior disorder among middle-aged and older adults in a psychiatric outpatient clinic: A cross-sectional survey.

OBJECTIVE: Rapid eye movement sleep behavior disorder (RBD) is often underdiagnosed among people living with mental disorders. The present study aimed to investigate the prevalence of probable RBD (pRBD) and its associated factors among middle-aged and older adults in a psychiatric outpatient clinic. METHODS: We conducted a cross-sectional survey among 2907 people aged 45-80 years who visited the outpatient clinic between March 1 and August 31, 2022 in a psychiatric hospital. A cutoff score ≥5 on the RBD Screening Questionnaire (RBDSQ) was used to indicate the presence of probable RBD (pRBD). Potential factors associated with pRBD were also assessed with a structured checklist. The association between these factors and the presence of pRBD was examined with logistic regression. RESULTS: The response rate was 64.3 %. Among 1868 respondents [age 58.5 ± 9.6 years, male n = 738 (39.5 %), female n = 1130 (60.5 %)], 15.9 % (95 % CI 14.2-17.6 %) screened positive for pRBD. Occupational exposure to chemicals; positive family history of psychotic disorders; a late start of mental health care; a medical history of autonomic dysfunction; mood problems; and use of antidepressants, hypnotics, and acetylcholinesterase inhibitors were associated with an increased likelihood of having pRBD (P < 0.05 for all). CONCLUSION: pRBD is common among outpatients with mental disorders, especially in mental disorders due to neurological diseases and physical conditions, mood disorders and anxiety or somatoform disorders. The findings highlight the importance of identifying sleep behavior disorders among people living with mental disorders in clinical practice.

Emissions of volatile organic compounds from Chinese coal-fired power plants: Characteristics, source profile, inventories, and impacts.

Volatile organic compounds (VOCs) are key precursors for secondary organic aerosols (SOA) and ozone, imposing severe impacts on human health and environment. Considering the massive coal consumption, coal fired power plants (CFPPs) in China are non-negligible VOCs contributors, whose emission characteristics remain inadequately understood. Here, we investigated emission characteristics of 117 VOCs by field tests in four typical CFPPs, and a latest localized CFPPs source profile was compiled by integrating literature reviews. Then speciated-VOCs emission inventories for 2018-2022 were established based on dynamic emission factors and unit-level activity data. The results suggested that oxygenated VOCs (OVOCs) constituted the dominant group (76.5 %), with propionaldehyde (32.0 %) and formaldehyde (24.5 %) being the predominant species. OVOCs (93.2 %) and aromatics (77.4 %) were identified as the primary contributors to ozone and SOA, respectively. Driven by both the rise in coal consumption and technological advancements, nationwide VOCs emissions decreased from 83,393 t in 2018 to 53,251 t in 2022. Regional disparities and varying rates of decline in provincial emissions were evident, with VOCs emissions predominantly concentrated in northern and eastern provinces. Neimenggu, Shandong, Shanxi, Jiangsu, and Guangdong were identified as the top five provinces with the highest emissions. We believe this study would be conducive to a more comprehensive understanding and effective control of VOCs emissions from CFPPs in China.

Unraveling Mechanism for Microstructure Engineering toward High-Capacity Nickel-Rich Cathode Materials.

Microstructural engineering on nickel-rich layered oxide (NRLO) cathode materials is considered a promising approach to increase both the capacity and lifespan of lithium-ion batteries by introducing high valence-state elements. However, rational regulation on NRLO microstructures based on a deep understanding of its capacity enhancement mechanism remains challenging. Herein for the first time, it is demonstrated that an increase of 14 mAh g-1 in reversible capacity at the first cycle can be achieved via tailoring the micro and nano structure of NRLO through introducing tungsten. Aberration-corrected scanning transmission electron microscopy (STEM) characterization reveals that the formation of a modified microstructure featured as coherent spinel twin boundaries. Theoretical modeling and electrochemical investigations further demonstrate that the capacity increase mechanism is related to such coherent spinel twin boundaries, which can lower the Li+ diffusion barrier and thus allow more Li+ to participate in deeper phase transitions. Meanwhile, the surface and grain boundaries of NRLOs are found to be modified by generating a dense and uniform LiWxOy phase, which further extends its cycle life by reducing side reactions with electrolytes. This work enables a comprehensive understanding of the capacity-increased mechanism and endows the remarkable potential of microstructural engineering for capacity- and lifespan-increased NRLOs.

Effects of Ratoon Rice Cropping Patterns on Greenhouse Gas Emissions and Yield in Double-Season Rice Regions.

The ratoon rice cropping pattern is an alternative to the double-season rice cropping pattern in central China due to its comparable annual yield and relatively lower cost and labor requirements. However, the impact of the ratoon rice cropping pattern on greenhouse gas (GHG) emissions and yields in the double-season rice region requires further investigation. Here, we compared two cropping patterns, fallow-double season rice (DR) and fallow-ratoon rice (RR), by using two early-season rice varieties (ZJZ17, LY287) and two late-season rice varieties (WY103, TY390) for DR, and two ratoon rice varieties (YLY911, LY6326) for RR. The six varieties constituted four treatments, including DR1 (ZJZ17 + WY103), DR2 (LY287 + TY390), RR1 (YLY911), and RR2 (LY6326). The experimental results showed that conversion from DR to RR cropping pattern significantly altered the GHG emissions, global warming potential (GWP), and GWP per unit yield (yield-scaled GWP). Compared with DR, the RR cropping pattern significantly increased cumulative methane (CH4), nitrous oxide (N2O), and carbon dioxide (CO2) emissions by 65.73%, 30.56%, and 47.13%, respectively, in the first cropping season. Conversely, in the second cropping season, the RR cropping pattern effectively reduced cumulative CH4, N2O, and CO2 emissions by 79.86%, 27.18%, and 30.31%, respectively. RR led to significantly lower annual cumulative CH4 emissions, but no significant difference in cumulative annual N2O and CO2 emissions compared with DR. In total, the RR cropping pattern reduced the annual GWP by 7.38% and the annual yield-scaled GWP by 2.48% when compared to the DR cropping pattern. Rice variety also showed certain effects on the yields and GHG emissions in different RR cropping patterns. Compared with RR1, RR2 significantly increased annual yield while decreasing annual GWP and annual yield-scaled GWP. In conclusion, the LY6326 RR cropping pattern may be a highly promising strategy to simultaneously reduce GWP and maintain high grain yield in double-season rice regions in central China.

Ag-thiolate interactions to enable an ultrasensitive and stretchable MXene strain sensor with high temporospatial resolution.

High-sensitivity strain sensing elements with a wide strain range, fast response, high stability, and small sensing areas are desirable for constructing strain sensor arrays with high temporospatial resolution. However, current strain sensors rely on crack-based conductive materials having an inherent tradeoff between their sensing area and performance. Here, we present a molecular-level crack modulation strategy in which we use layer-by-layer assembly to introduce strong, dynamic, and reversible coordination bonds in an MXene and silver nanowire-matrixed conductive film. We use this approach to fabricate a crack-based stretchable strain sensor with a very small sensing area (0.25 mm2). It also exhibits an ultrawide working strain range (0.001-37%), high sensitivity (gauge factor ~500 at 0.001% and >150,000 at 35%), fast response time, low hysteresis, and excellent long-term stability. Based on this high-performance sensing element and facile assembly process, a stretchable strain sensor array with a device density of 100 sensors per cm2 is realized. We demonstrate the practical use of the high-density strain sensor array as a multichannel pulse sensing system for monitoring pulses in terms of their spatiotemporal resolution.

R3 strain and Fe-Mn modified biochar reduce Cd absorption capacity of roots and available Cd content of soil by affecting rice rhizosphere and endosphere key flora.

Microorganisms have a significant role in regulating the absorption and transportation of Cd in the soil-plant system. However, the mechanism by which key microbial taxa play a part in response to the absorption and transportation of Cd in rice under Cd stress requires further exploration. In this study, the cadmium-tolerant endophytic bacterium Herbaspirillum sp. R3 (R3) and Fe-Mn-modified biochar (Fe-Mn) were, respectively, applied to cadmium-contaminated rice paddies to investigate the effects of key bacterial taxa in the soil-rice system on the absorption and transportation of Cd in rice under different treatments. The results showed that both R3 and Fe-Mn treatments considerably decreased the content of cadmium in roots, stems and leaves of rice at the peak tillering stage by 17.24-49.28% in comparison to the control (CK). The cadmium content reduction effect of R3 treatment is better than that of Fe-Mn treatment. Further analysis revealed that the key bacterial taxa in rice roots under R3 treatment were Sideroxydans and Actinobacteria, and that their abundance showed a substantial positive correlation and a significant negative correlation with the capacity of rice roots to assimilate Cd from the surroundings, respectively. The significant increase in soil pH under Fe-Mn treatment, significant reduction in the relative abundances of Acidobacteria, Verrucomicrobia, Subdivision3 genera incertae sedis, Sideroxydans, Geobacter, Gp1, and Gp3, and the significant increase in the relative abundance of Thiobacillus among the soil bacterial taxa may be the main reasons for the decrease in available Cd content of the soil. In addition, both the R3 and Fe-Mn treatments showed some growth-promoting effects on rice, which may be related to their promotion of transformations of soil available nutrients. This paper describes the possible microbial mechanisms by which strain R3 and Fe-Mn biochar reduce Cd uptake in rice, providing a theoretical basis for the remediation of Cd contamination in rice and soil by utilizing key microbial taxa.

Sja-let-7 suppresses the development of liver fibrosis via Schistosoma japonicum extracellular vesicles.

Schistosomiasis is a fatal zoonotic parasitic disease that also threatens human health. The main pathological features of schistosomiasis are granulomatous inflammation and subsequent liver fibrosis, which is a complex, chronic, and progressive disease. Extracellular vesicles (EVs) derived from schistosome eggs are broadly involved in host-parasite communication and act as important contributors to schistosome-induced liver fibrosis. However, it remains unclear whether substances secreted by the EVs of Schistosoma japonicum, a long-term parasitic "partner" in the hepatic portal vein of the host, also participate in liver fibrosis. Here, we report that EVs derived from S. japonicum worms attenuated liver fibrosis by delivering sja-let-7 into hepatic stellate cells (HSCs). Mechanistically, activation of HSCs was reduced by targeting collagen type I alpha 2 chain (Col1α2) and downregulation of the TGF-ß/Smad signaling pathway both in vivo and in vitro. Overall, these results contribute to further understanding of the molecular mechanisms underlying host-parasite interactions and identified the sja-let-7/Col1α2/TGF-ß/Smad axis as a potential target for treatment of schistosomiasis-related liver fibrosis.

Design of Solid Polycationic Electrolyte to Enable Durable Chloride-Ion Batteries.

The high energy density and cost-effectiveness of chloride-ion batteries (CIBs) make them promising alternatives to lithium-ion batteries. However, the development of CIBs is greatly restricted by the lack of compatible electrolytes to support cost-effective anodes. Herein, we present a rationally designed solid polycationic electrolyte (SPE) to enable room-temperature chloride-ion batteries utilizing aluminum (Al) metal as an anode. This SPE endows the CIB configuration with improved air stability and safety (i.e. free of flammability and liquid leakage). A high ionic conductivity (1.3×10-2 S cm-1 at 25 °C) has been achieved by the well-tailored coordination structure of the SPE. Meanwhile, the solid polycationic electrolyte ensures stable electrodes|electrolyte interfaces, which effectively inhibit the growth of dendrites on the Al anodes and degradation of the FeOCl cathodes. The Al|SPE|FeOCl chloride-ion batteries showcased a high discharge capacity around 250 mAh g-1 (based on the cathodes) and extended lifespan. Our electrolyte design opens a new avenue for developing low-cost chloride-ion batteries.

The Printability, Microstructure, and Mechanical Properties of Fe80-xMnxCo10Cr10 High-Entropy Alloys Fabricated by Laser Powder Bed Fusion Additive Manufacturing.

This work investigated the effect of Fe/Mn ratio on the microstructure and mechanical properties of non-equimolar Fe80-xMnxCo10Cr10 (x = 30% and 50%) high-entropy alloys (HEAs) fabricated by laser powder bed fusion (LPBF) additive manufacturing. Process optimization was conducted to achieve fully dense Fe30Mn50Co10Cr10 and Fe50Mn30Co10Cr10 HEAs using a volumetric energy density of 105.82 J·mm-3. The LPBF-printed Fe30Mn50Co10Cr10 HEA exhibited a single face-centered cubic (FCC) phase, while the Fe50Mn30Co10Cr10 HEA featured a hexagonal close-packed (HCP) phase within the FCC matrix. Notably, the fraction of HCP phase in the Fe50Mn30Co10Cr10 HEAs increased from 0.94 to 28.10%, with the deformation strain ranging from 0 to 20%. The single-phase Fe30Mn50Co10Cr10 HEA demonstrated a remarkable combination of high yield strength (580.65 MPa) and elongation (32.5%), which surpassed those achieved in the FeMnCoCr HEA system. Comparatively, the dual-phase Fe50Mn30Co10Cr10 HEA exhibited inferior yield strength (487.60 MPa) and elongation (22.3%). However, it displayed superior ultimate tensile strength (744.90 MPa) compared to that in the Fe30Mn50Co10Cr10 HEA (687.70 MPa). The presence of FCC/HCP interfaces obtained in the Fe50Mn30Co10Cr10 HEA resulted in stress concentration and crack expansion, thereby leading to reduced ductility but enhanced resistance against grain slip deformation. Consequently, these interfaces facilitated an earlier attainment of yield limit point and contributed to increased ultimate tensile strength in the Fe50Mn30Co10Cr10 HEA. These findings provide valuable insights into the microstructure evolution and mechanical behavior of LPBF-printed metastable FeMnCoCr HEAs.

Microvascular activation and exocytosis after exposure to the serum from mismatched recipients by using donor microvascular cultures.

BACKGROUND: Microvascular injury resulting from activation and exocytosis are early signs of tissue damage caused by allografting. However, humoral anti-graft reactions are not easily detectable in transplant biopsies. The aim of this study was to establish a bioassay to recapitulate this process in a prospective approach. METHODS: The study was executed by using our previously established protocol to isolate and freeze the donors' microvascular endothelial cells (MVEC) at the transplantation (34 living-related donors and 26 cadaver donors); and to collect sera from the recipients before the transplantation, one-, three- and six-months after transplantation. The activation and exocytosis of the MVEC were determined by incubating the donors' cultures with the recipients' sera. We determined if there was any endothelial activation by quantifying the releases of monocyte chemotactic protein-1 (MCP-1) and interleukin 8 (IL-8) in supernatants and the expressions of membrane intercellular adhesion molecule-1 (CD54) and intercellular adhesion molecule-1 (CD106) by flow cytometry. Endothelial exocytosis was determined by quantifying soluble E-selectin (CD62E) and cytoplasmic von Willebrand Factor (vWF) in supernatants. Endothelial activation or exocytosis was considered positive when the fold change (≧1.5) of post-transplantation to pre-transplantation was reached. We also monitored serum PRA and cytokines using Luminex multiple-plex and cytometric bead-based assay respectively. RESULTS: We found 41.2% recipients (14 out of 34, ranging from 1.5 to 5.2 folds, p < 0.05) exhibited positive MVEC activation in the first month after transplantation as determined by IL-8 levels; 26.5% recipients (9 out of 34, ranging from 1.5 to 11.8 folds, p < 0.05) by MCP-1 levels. In the group of three months post-transplantation, 70.6% patients were positive (12 out of 17, ranging from 1.8 to 87.1 folds, p < 0.05) by IL-8 increased levels; 24% recipients (4 out of 17, ranging from 1.8 to 50.5 folds, p < 0.05) measured by MCP-1 levels. However, these changes disappeared six months after transplantation. Flow cytometric data showed that a time-dependent of CD54+ and CD106+ expressions existed over the course of six months. Most CD54+ and CD106+ cells were CD31- (platelet-endothelial cell adhesion molecule-1), though CD31+/CD106+ (37.5%, 3 out of 8) and CD31+/CD106+ (25%. 2 out of 8) were seen. When comparing donor MVEC activation to their recipient's proinflammatory cytokine levels or PRA status, we could not draw a conclusion regarding the connections between them. The sera collected from recipients at either one- or three-months after allografting did not significantly induce the release of either soluble CD62E or vWF (p > 0.05), indicating exocytosis was not significantly involved in the acute phase of allografting. CONCLUSIONS: This bioassay enables us to detect the activation and exocytosis of donor MVEC elicited by respective sera from mismatched kidney recipients.

Molecular and functional characterization of Schistosoma japonicum annexin A13.

Schistosomiasis is a neglected tropical disease that affects humans and animals in tropical and subtropical regions worldwide. Schistosome eggs are responsible for the pathogenesis and transmission of schistosomiasis, thus reducing egg production is vital for prevention and control of schistosomiasis. However, the mechanisms underlying schistosome reproduction remain unclear. Annexin proteins (ANXs) are involved in the physiological and pathological functions of schistosomes, but the specific regulatory mechanisms and roles of ANX A13 in the development of Schistosoma japonicum and host-parasite interactions remain poorly understood. Therefore, in this study, the expression profiles of SjANX A13 at different life cycle stages of S. japonicum were assessed using quantitative PCR. In addition, the expression profiles of the homolog in S. mansoni were analyzed in reference to public datasets. The results of RNA interference showed that knockdown of SjANX A13 significantly affected the development and egg production of female worms in vivo. The results of an immune protection assay showed that recombinant SjANX A13 increased production of immunoglobulin G-specific antibodies. Finally, co-culture of S. japonicum exosomes with LX-2 cells using a transwell system demonstrated that SjANX A13 is involved in host-parasite interactions via exosomes. Collectively, these results will help to clarify the roles of SjANX A13 in the development of S. japonicum and host-parasite interactions as a potential vaccine candidate.

Soil bacterial community composition in rice-turtle coculture systems with different planting years.

The rice-turtle coculture system is the most special rice-fish integrated farming system. In this study, we selected four paddy fields, including a rice monoculture paddy and three rice-turtle paddies with different planting years, to investigate the soil bacterial community composition with Illumina MiSeq sequencing technology. The results indicated that the contents of soil available nitrogen (AN), soil available phosphorus (AP) and soil organic matter (OM) in 9th year of rice-turtle paddy (RT9) were increased by 5.40%, 51.11% and 23.33% compared with rice monoculture paddy (CK), respectively. Significant differences of Acidobacteria, Desulfobacteria, Crenarchaeota were observed among the different rice farming systems. The relative abundance of Methylomonadaceae, Methylococcaceae and Methylophilaceae in RT9 was significantly higher than that in other treatments. RT9 had significantly lower relative abundance of Acidobacteria, but significantly higher relative abundance of Proteobacteria than other treatments. Redundancy analysis showed that soil AN and AP contents were the major factors influencing the abundance of the dominant microbes, wherein Methylomonadaceae, Methylococcaceae and Methylophilaceae were positively correlated with OM. The findings revealed the rice-turtle coculture system in the 9th year had higher soil nutrients and soil bacterial diversity, but there was also a risk of increasing methane emissions.

Sja-Let-7 Attenuates Carbon Tetrachloride-Induced Liver Fibrosis in a Mouse Model via Col1α2.

Liver fibrosis (LF) is a chronic progressive disease with no definitive treatment. The aim of this study was to assess helminth-derived molecules as potential therapeutic targets to prevent or reverse LF. A mouse model of carbon tetrachloride (CCL4)-induced LF was established and sja-let-7 was overexpressed by treatment with a miRNA agomir once per week. After four weeks, serum biochemistry, hepatic hydroxyproline content measurements, liver histology, mRNA expression profiling of fibrotic markers, the dual-luciferase reporter assay, and fluorescence in situ hybridization (FISH) were performed. Administration of the sja-let-7 agomir markedly ameliorated hepatosplenomegaly and reduced the liver hydroxyproline content. Liver histological analysis showed significant reductions in collagen deposition in the sja-let-7 agomir-treated mice. Additionally, the mRNA levels of both pro-fibrotic markers and pro-inflammatory cytokines were diminished after treatment. Furthermore, the dual-luciferase reporter assay and FISH identified the α2 chain of collagen type 1 (Col1α2) as the direct target of sja-let-7. Accordingly, the progression of LF was attenuated by targeting Col1α2 and the TGF-ß/Smad signaling pathway.

Extracellular vesicle-packaged circBIRC6 from cancer-associated fibroblasts induce platinum resistance via SUMOylation modulation in pancreatic cancer.

BACKGROUND: Cancer-associated fibroblasts (CAFs) play pivotal roles in chemoresistance of pancreatic ductal adenocarcinoma (PDAC). However, the underlying mechanisms are poorly understood. Revealing the cross-talk network between tumor stroma and pancreatic cancer and developing effective strategies against oxaliplatin resistance are highly desired in the clinic. METHODS: High-throughput sequence was used to screened the key circRNAs transmitted by extracellular vesicles (EVs) from CAFs to pancreatic cancer cells. The associations between EV-packaged circBIRC6 and chemotherapy responsiveness were validated in a cohort of 82 cases of advanced PDAC patients. Then, the effects of EV-packaged circBIRC6 on CAF-induced oxaliplatin resistance were investigated by flow cytometry, colony formation, viability of pancreatic cancer organoids in vitro and by xenograft models in vivo. RNA pulldown, RNA immunoprecipitation, and sites mutation assays were used to reveal the underlying mechanism. RESULTS: We identified a circRNA, circBIRC6, is significantly upregulated in CAF-derived EVs and is positively associated with oxaliplatin-based chemoresistance. In vitro and in vivo functional assays showed that CAF-derived EV-packaged circBIRC6 enhance oxaliplatin resistance of pancreatic cancer cells and organoids via regulating the non-homologous end joining (NHEJ) dependent DNA repair. Mechanistically, circBIRC6 directly binds with XRCC4 and enhanced the interaction of XRCC4 with SUMO1 at the lysine 115 residue, which facilitated XRCC4 chromatin localization. XRCC4K115R mutation dramatically abrogated the EV-packaged circBIRC6 induced effect. Moreover, combination of antisense oligonucleotide inhibitors against circBIRC6 with Olaparib dramatically suppressed chemoresistance in patient-derived xenograft models. CONCLUSIONS: Our study revealed that EV-packaged circBIRC6 confer oxaliplatin resistance in PDAC by mediating SUMOylation of XRCC4, introducing a promising predictive and therapeutic target for PDAC on oxaliplatin resistance.

Diagnostic Efficacy of Plasma-Based Real-Time PCR for Schistosomiasis Japonica in Mice before and after Treatment with Praziquantel.

The prevalence of schistosomiasis japonica in China is now characterized by a low epidemic rate and low-intensity infections. Some diagnostic methods with high sensitivity and specificity are urgently needed to better monitor this disease in the current situation. In this study, the detection efficacy of a real-time fluorescent quantitative PCR (qPCR) assay was assessed for schistosomiasis japonica in mice, and before and after treatment with praziquantel (PZQ). Our results showed that the sensitivity of the qPCR was 99.3% (152/153, 95% CI: 96.41-99.98%) and its specificity was 100% (77/77, 95% CI: 95.32-100%) in mice infected with different numbers of Schistosoma japonicum. After the oral administration of PZQ, mice infected with 10 cercariae or 40 cercariae were all Schistosoma japonicum-negative 6 weeks after treatment. However, the negativity rates on a soluble egg antigen (SEA)-based enzyme-linked immunosorbent assay (ELISA) were only 34.8% (8/23, 10 cercariae group) and 6.7% (1/15, 40 cercariae group) at the sixth week after PZQ treatment. These results demonstrated that the qPCR method had good sensitivity and specificity, and suggested that its sensitivity correlated with the infection intensity in mice. Moreover, this method had better potential utility for evaluating the treatment efficacy of PZQ in schistosome-infected mice than SEA-based ELISA.

The effects of earthworm inoculation on cadmium-contaminated rice field in Southern China: a pot experiment and a field test.

Currently, the effects of earthworm inoculation on cadmium-contaminated rice field remain unclear. In this study, four treatments were tested, including rice monoculture (CK), earthworm inoculation with low density (L, 30 g/m2), middle density (M, 60 g/m2), and high density (H, 90 g/m2). The pot and field experiment were conducted in Hunan Province, China. In the pot experiment, the H treatment significantly decreased the available cadmium concentration in 0 ~ 20 cm soil by 5.21% ~ 16.51%, and the M treatment significantly decreased in 0 ~ 10 cm soil by 7.29% ~ 8.96%. The H treatment significantly decreased the total cadmium concentration in 0 ~ 5 cm soil by 10.36%. Moreover, the earthworm inoculation treatments significantly reduced cadmium accumulation in rice organs. In the field experiment, the M and H treatment decreased the available cadmium concentration in 0 ~ 20 cm soil by 14.05% ~ 47.52% and the H treatment decreased the total cadmium concentration in 0 ~ 20 cm soil by 0.78% ~ 5.75% although there was no significant difference. Furthermore, the earthworm inoculation treatments significantly decreased cadmium accumulation in part of rice organs. In conclusion, this study recommends that earthworm inoculation is an effective method of controlling cadmium contamination for rice production.

A high propensity for excessive daytime sleepiness independent of lifestyle is associated with cognitive performance in community-dwelling older adults.

Objective: The relationship between excessive daytime sleepiness (EDS) and cognitive performance of older adults remains unclear, especially when a healthy lifestyle is considered. The study aimed to explore the association between EDS in passive and active situations and general cognitive function among community-dwelling older adults. Methods: Two hundred and seventy-one older adults aged 60 and above were recruited from the community cohort in Shangrao. All study participants were free of depression and dementia. The Chinese version of the Epworth Sleepiness Scale (CESS) was used to evaluate EDS. Using the item scores of CESS, the presence of EDS among all study participants were grouped as non-EDS, passive situation-related EDS (PSR-EDS), active situation-related EDS (ASR-EDS), and high sleep propensity (HSP). The Hong Kong Brief Cognitive Test (HKBC) was used to assess cognitive function. Chinese healthy lifestyle metrics were scored based on AHA Life Simple-7. The multivariate logistic regression model was used to estimate the association between the presence of EDS and cognitive function. Results: The PSR-EDS (n = 29, 20.8 ± 5.3) and the HSP groups (n = 21, 19.8 ± 4.8) scored lower with HKBC than in the non-EDS group (n = 213, 23.2 ± 4.9). The subdomain performance of language in the HSP group was poorer than in the non-EDS group (ps < 0.05). Relative to non-EDS, HSP (OR = 3.848, 95% CI = 1.398-10.591) was associated with an increased risk of poor cognitive performance after adjusting age, sex, education, and healthy lifestyle metrics. Conclusion: High propensity for excessive daytime sleepiness, irrespective of lifestyle, is associated with poorer cognitive performance among community-dwelling older adults. The findings may provide empirical evidence to support sleepiness intervention for reducing the risk of cognitive decline.

DiGeorge syndrome critical region gene 2 (DGCR2), a schizophrenia risk gene, regulates dendritic spine development through cell adhesion.

BACKGROUND: Dendritic spines are the sites of excitatory synapses on pyramidal neurons, and their development is crucial for neural circuits and brain functions. The spine shape, size, or number alterations are associated with neurological disorders, including schizophrenia. DiGeorge syndrome critical region gene 2 (DGCR2) is one of the deleted genes within the 22q11.2 deletion syndrome (22q11DS), which is a high risk for developing schizophrenia. DGCR2 expression was reduced in schizophrenics. However, the pathophysiological mechanism of DGCR2 in schizophrenia or 22q11DS is still unclear. RESULTS: Here, we report that DGCR2 expression was increased during the neurodevelopmental period and enriched in the postsynaptic densities (PSDs). DGCR2-deficient hippocampal neurons formed fewer spines. In agreement, glutamatergic transmission and synaptic plasticity were decreased in the hippocampus of DGCR2-deficient mice. Further molecular studies showed that the extracellular domain (ECD) of DGCR2 is responsible for its transcellular interaction with cell adhesion molecule Neurexin1 (NRXN1) and spine development. Consequently, abnormal behaviors, like anxiety, were observed in DGCR2-deficient mice. CONCLUSIONS: These observations indicate that DGCR2 is a novel cell adhesion molecule required for spine development and synaptic plasticity, and its deficiency induces abnormal behaviors in mice. This study provides a potential pathophysiological mechanism of DGCR2 in 22q11DS and related mental disorders.