Mitigated dissemination of antibiotic resistance genes by nanoscale zero-valent iron and iron oxides during anaerobic digestion: Roles of microbial succession and regulation.

Nanoscale zero-valent iron (ZVI) and the oxides have been documented as an effective approach for mitigating the dissemination of antibiotic resistance genes (ARGs) during anaerobic digestion (AD). However, the mechanism of ARGs dissemination mitigated by nanoscale ZVI and iron oxides remain unclear. Here, we investigated the influencing mechanisms of nanoscale ZVI and iron oxides on ARGs dissemination during AD. qPCR results indicated that nanoscale ZVI and iron oxides significantly declined the total ARGs abundances, and the strongest inhibiting effect was observed by 10 g/L nanoscale ZVI. Mantel test showed ARGs distribution was positively correlated with physiochemical properties, integrons and microbial community, among which microbial community primarily contributed to ARGs dissemination (39.74%). Furthermore, redundancy and null model analyses suggested the dominant and potential ARGs host was Fastidiosipila, and homogeneous selection in the determinism factors was the largest factor for driving Fastidiosipila variation, confirming the inhibition of Fastidiosipila was primary reason for mitigating ARGs dissemination by nanoscale ZVI and iron oxides. These results were related to the inhibition of ARGs transfer related functions. This work provides novel evidence for mitigating ARGs dissemination through regulating microbial succession and regulation induced by ZVI and iron oxides.

Clinical efficacy and kinematic analysis of Chinese knotting technique-assisted posterior cruciate ligament reconstruction: A retrospective analysis.

To investigate the clinical efficacy and knee joint kinematic changes of posterior cruciate ligament (PCL) reconstruction assisted by Chinese knotting technique (CKT). A retrospective analysis was conducted on 88 cases of PCL reconstructive surgery admitted between September 2016 and September 2020. All patients were operated on by the same senior doctor and his team. The patients were divided into 2 groups according to whether the CKT was applied, with 44 cases in each group. Both groups received active rehabilitation treatment after surgery. All patients were followed up for more than 2 years. International knee documentation committee, hospital for special surgery (HSS), and Lysholm scores were used to evaluate the clinical efficacy of the 2 methods at 3, 12, and 24 months after surgery. The motion cycle and kinematic indices of the knee joint were measured by the Opti_Knee three-dimensional motion measurement system before surgery and at 3, 12, and 24 months after surgery. A secondary arthroscopic examination was performed at 12 months after surgery, MAS score was used to evaluate the secondary endoscopic examination of PCL. All the patients had wound healing in stage I without infection. International Knee in both sets Documentation Committee scores, HSS scores and Lysholm scores were gradually improved at all time points (P < .05); compared with the traditional group, the HSS score was higher in the reduction group 12 months after surgery (P < .05), but there was no significant difference at 24 months after surgery. 12 months and 24 months after 3 dimensional motion measurement system using Opti_Knee showed a reduction group before and after displacement and displacement of upper and lower range than the traditional group (P < 0. 05). One year after surgery, the good and good rate of MAS score reduction group was higher than traditional group. CKT assisted PCL reconstruction can improve the subjective function score of the affected knee joint and the results of secondary microscopy. Satisfactory knee kinematic function can be obtained in the early stage, and the anteroposteric relaxation of the knee joint can be reduced.

CARM1 hypermethylates the NuRD chromatin remodeling complex to promote cell cycle gene expression and breast cancer development.

Protein arginine methyltransferase CARM1 has been shown to methylate a large number of non-histone proteins, and play important roles in gene transcriptional activation, cell cycle progress, and tumorigenesis. However, the critical substrates through which CARM1 exerts its functions remain to be fully characterized. Here, we reported that CARM1 directly interacts with the GATAD2A/2B subunit in the nucleosome remodeling and deacetylase (NuRD) complex, expanding the activities of NuRD to include protein arginine methylation. CARM1 and NuRD bind and activate a large cohort of genes with implications in cell cycle control to facilitate the G1 to S phase transition. This gene activation process requires CARM1 to hypermethylate GATAD2A/2B at a cluster of arginines, which is critical for the recruitment of the NuRD complex. The clinical significance of this gene activation mechanism is underscored by the high expression of CARM1 and NuRD in breast cancers, and the fact that knockdown CARM1 and NuRD inhibits cancer cell growth in vitro and tumorigenesis in vivo. Targeting CARM1-mediated GATAD2A/2B methylation with CARM1 specific inhibitors potently inhibit breast cancer cell growth in vitro and tumorigenesis in vivo. These findings reveal a gene activation program that requires arginine methylation established by CARM1 on a key chromatin remodeler, and targeting such methylation might represent a promising therapeutic avenue in the clinic.

Effects of O2/Ar Ratio on Preparation and Dielectric Properties of CaZrO3 Films by Radio Frequency (RF) Magnetron Sputtering.

CaZrO3 (CZO) thin films were deposited on Pt/Ti/SiO2/Si substrates at 450 °C by radio-frequency magnetron sputtering technology. The microstructures and dielectric properties of CZO thin films were investigated. X-ray diffraction analysis reveals that the perovskite orthogonal CZO phase would be promoted by a higher O2 partial pressure in the flow ratio of O2/Ar after thin films were annealed at 700 °C for 3 h in air. The films prepared under the flow ratio of O2/Ar (20:40, 30:40 and 40:40) show the main perovskite crystal phase of CaZrO3 with a small amount of Ca0.2Zr0.8O1.8. The main crystal phase was Ca0.2Zr0.8O1.8 when the film was deposited under an O2/Ar ratio of 40:10. The annealed film with a 40:40 O2/Ar ratio exhibits a dielectric performance with a high dielectric constant (εr) of 25 at 1 MHz, a temperature coefficient of permittivity of not more than 122.7 ppm/°C from 0 °C to 125 °C, and a low leakage current density of about 2 × 10-7 A/cm2 at 30 V with an ohmic conduction mechanism.

Study on the High-Temperature Interaction between Coke and Iron Ores with Different Layer Thicknesses.

Coke plays a key role as the skeleton of the charge column in BF. The gas path formed by the coke layer in the BF has a decisive influence on gas permeability. At high temperatures, the interface between coke and ore undergoes a melting reaction of coke and a reduction reaction of ore. The better the reducibility of the ore, the more conducive it is to the coupling reaction of ore and coke. The melting loss reaction of coke becomes more intense, and the corresponding strength of coke will decrease, which will affect the permeability of the blast furnace and is not conducive to the smooth operation of the blast furnace. Especially with a deterioration in iron ore quality, BF operation faces severe challenges, which makes it necessary to find an effective way to strengthen BF operation. In this study, a melting-dropping furnace was used to develop and clarify the high-temperature interaction between coke and iron ores with different layer thicknesses. The influencing factors were studied by establishing a gas permeability mathematical model and observing the metallographic microscope images of samples after the coke solution loss reaction. The relationships between coke layer thickness, distribution of gas flow, and pressure drop were obtained. The results showed that, under certain conditions, the gas permeability property of a furnace burden has been improved after the coke layer thickness increased. Upon observing the size of coke particles at the interface reaction site, the degree of melting loss reaction can be determined. A smaller particle size indicates more melting loss reaction. A dripping eigenvalue for molten metal was introduced to evaluate the dynamic changes in the comprehensive dripping properties of molten metal of furnace burden, which showed that the dripping eigenvalue for the molten metal could deteriorate because of the unruly thickness and the coke layer thickness should be limited through considering the operational indicators of the blast furnace.

Open Distal Femur Fractures Treated with Bone Cement Intramedullary Support Combined with Locked Plate Fixation.

Objective: The objective of this study was to assess the short-term clinical efficacy of the short-term clinical efficacy of bone cement intramedullary support combined with locked plate fixation in the treatment of such fractures. Methods: A retrospective study including 21 patients was reviewed at an urban level one trauma center. There were 17 males and 4 females, with a mean age of 33.9 years. Gustilo grade was II (12 cases), III-A (6 cases), III-B (2 cases), and III-C (1 case). Two fractures were AO-OTA type 33A3, 9 cases were type 33C2, and 10 cases were type 33C3. After the first stage debridement and temporary external fixation, all patients received bone cement intramedullary support combined with locked plate fixation through an anterolateral incision at the second stage.. The perioperative complications, need for bone graft, alignment, and radiographic union were recorded. At 1-year follow-up, the range of knee motion was recorded, and functional results were evaluated by the Hospital for Special Surgery (HSS) knee score. Results: All 21 patients were followed up for 12-36 months, with an average of 18.7 months. 1 case had superficial wound infection, and 2 cases had partial skin edge necrosis of the original open wound. After symptomatic dressing changes, they all healed well. 4 cases had autogenous bone grafting. 18 patients (85.7%) achieved radiographic union, with a mean union time of 6.2 months. Two patients underwent secondary operation 9 months after surgery due to nonunion and finally united after autologous bone grafting. One patient developed a deep infection 8 months after surgery and was successfully treated with Masquelet technique. Finally, bone union was achieved 7 months after surgery. The alignment was good in 17 patients (81.0%). No deep infection or hardware failure occurred during 1-year follow-up. The average range of knee extension and flexion was 5.2 ° and 106.8 °, respectively. The HSS score averaged 83.6. Conclusions: Bone cement intramedullary support combined with locked plate fixation was an effective treatment modality of open distal femur fractures with high union rate, low complication, adequate alignment and satisfactory functional outcomes.

Exopolysaccharides of Paenibacillus polymyxa: A review.

Paenibacillus polymyxa (P. polymyxa) is a member of the genus Paenibacillus, which is a rod-shaped, spore-forming gram-positive bacterium. P. polymyxa is a source of many metabolically active substances, including polypeptides, volatile organic compounds, phytohormone, hydrolytic enzymes, exopolysaccharide (EPS), etc. Due to the wide range of compounds that it produces, P. polymyxa has been extensively studied as a plant growth promoting bacterium which provides a direct benefit to plants through the improvement of N fixation from the atmosphere and enhancement of the solubilization of phosphorus and the uptake of iron in the soil, and phytohormones production. Among the metabolites from P. polymyxa, EPS exhibits many activities, for example, antioxidant, immunomodulating, anti-tumor and many others. EPS has various applications in food, agriculture, environmental protection. Particularly, in the field of sustainable agriculture, P. polymyxa EPS can be served as a biofilm to colonize microbes, and also can act as a nutrient sink on the roots of plants in the rhizosphere. Therefore, this paper would provide a comprehensive review of the advancements of diverse aspects of EPS from P. polymyxa, including the production, extraction, structure, biosynthesis, bioactivity and applications, etc. It would provide a direction for future research on P. polymyxa EPS.

Targeting PRMT1-mediated SRSF1 methylation to suppress oncogenic exon inclusion events and breast tumorigenesis.

PRMT1 plays a vital role in breast tumorigenesis; however, the underlying molecular mechanisms remain incompletely understood. Herein, we show that PRMT1 plays a critical role in RNA alternative splicing, with a preference for exon inclusion. PRMT1 methylome profiling identifies that PRMT1 methylates the splicing factor SRSF1, which is critical for SRSF1 phosphorylation, SRSF1 binding with RNA, and exon inclusion. In breast tumors, PRMT1 overexpression is associated with increased SRSF1 arginine methylation and aberrant exon inclusion, which are critical for breast cancer cell growth. In addition, we identify a selective PRMT1 inhibitor, iPRMT1, which potently inhibits PRMT1-mediated SRSF1 methylation, exon inclusion, and breast cancer cell growth. Combination treatment with iPRMT1 and inhibitors targeting SRSF1 phosphorylation exhibits an additive effect of suppressing breast cancer cell growth. In conclusion, our study dissects a mechanism underlying PRMT1-mediated RNA alternative splicing. Thus, PRMT1 has great potential as a therapeutic target in breast cancer treatment.

[Ultrasonic Composite Iron-carbon Activated Persulfate for Treating Organic Wastewater].

A coupling system of ultrasonic composite iron-carbon activated persulfate (US/PS/Fe-C) was built to treat a triphenylmethane derivative, crystal violet (CV). The results revealed that US/PS/Fe-C ternary system had a good coupling effect. The structure and surface morphology of commercial Fe-C and self-made Fe-C catalysts were analyzed using an X-ray diffractometer (XRD) and scanning electron microscope (SEM), respectively. Finally, commercial Fe-C was used to study the effects of different factors on the CV of US/PS/Fe-C ternary coupling degradation, and the optimum conditions were as follows:PDS concentration 2 mmol·L-1, iron-carbon catalyst 1 g·L-1, pH without adjustment, and the removal rate of 15 mg·L-1 CV reached 90% after 30 min. To explore the effects of anions and cations on the system, it was observed that Mg2+ and NO3- had almost no effect on the treatment of the system, and Mn2+, Cl-, and CO32- had a certain effect on the treatment of the system, whereas Fe2+ could promote the reaction at low concentration and inhibit the reaction at high concentration. By adding different quenchants, it was concluded that there were four types of active substances:1O2, SO4-·,·O2-, and·OH.

Treatment options for digital nerve injury: a systematic review and meta-analysis.

BACKGROUND: Surgical treatment of finger nerve injury is common for hand trauma. However, there are various surgical options with different functional outcomes. The aims of this study are to compare the outcomes of various finger nerve surgeries and to identify factors associated with the postsurgical outcomes via a systematic review and meta-analysis. METHODS: The literature related to digital nerve repairs were retrieved comprehensively by searching the online databases of PubMed from January 1, 1965, to August 31, 2021. Data extraction, assessment of bias risk and the quality evaluation were then performed. Meta-analysis was performed using the postoperative static 2-point discrimination (S2PD) value, moving 2-point discrimination (M2PD) value, and Semmes-Weinstein monofilament testing (SWMF) good rate, modified Highet classification of nerve recovery good rate. Statistical analysis was performed using the R (V.3.6.3) software. The random effects model was used for the analysis. A systematic review was also performed on the other influencing factors especially the type of injury and postoperative complications of digital nerve repair. RESULTS: Sixty-six studies with 2446 cases were included in this study. The polyglycolic acid conduit group has the best S2PD value (6.71 mm), while the neurorrhaphy group has the best M2PD value (4.91 mm). End-to-side coaptation has the highest modified Highet's scoring (98%), and autologous nerve graft has the highest SWMF (91%). Age, the size of the gap, and the type of injury were factors that may affect recovery. The type of injury has an impact on the postoperative outcome of neurorrhaphy. Complications reported in the studies were mainly neuroma, cold sensitivity, paresthesia, postoperative infection, and pain. CONCLUSION: Our study demonstrated that the results of surgical treatment of digital nerve injury are generally satisfactory; however, no nerve repair method has absolute advantages. When choosing a surgical approach to repair finger nerve injury, we must comprehensively consider various factors, especially the gap size of the nerve defect, and postoperative complications. Type of study/level of evidence Therapeutic IV.

Factors associated with heterochronic gastric cancer development post-endoscopic mucosal dissection in early gastric cancer patients.

BACKGROUND: Endoscopic mucosal resection is an innovative method for treating early gastric cancer and has been widely used in clinical practice. AIM: To analyze the factors associated with the development of heterochronic gastric cancer in patients with early gastric cancer who had undergone endoscopic mucosal dissection (EMD). METHODS: A cohort of patients with early gastric cancer treated using EMD was retrospectively analyzed, and patients who developed heterochronic gastric cancer after the surgery were compared with those who did not. The effects of patient age, sex, tumor size, pathological type, and surgical technique on the development of heterochronic gastric cancer were assessed using statistical analysis. RESULTS: Of the 300 patients with early gastric cancer, 150 patients developed heterochronic gastric cancer after EMD. Statistical analysis revealed that patient age (P value = XX), sex (P value = XX), tumor size (P value = XX), pathological type (P value = XX), and surgical technique (P value = XX) were significantly associated with the occurrence of heterochronic gastric cancer. CONCLUSION: Age, sex, tumor size, pathological type, and surgical technique are key factors influencing the occurrence of heterochronic gastric cancer after EMD in patients with early gastric cancer. To address these factors, postoperative follow-up and management should be strengthened to improve the prognosis and survival rate of patients.

The Role of circTmeff-1 in Morphine Addiction Memory of Mice.

In addition to the essential pharmacological effects of opioids, situational cues associated with drug addiction memory are key triggers for drug seeking. CircRNAs, an emerging hotspot regulator in crown genetics, play an important role in central nervous system-related diseases. However, the internal mediating mechanism of circRNAs in the field of drug reward and addiction memory remains unknown. Here, we trained mice on a conditional place preference (CPP) model and collected nucleus accumbens (NAc) tissues from day 1 (T0) and day 8 (T1) for high-throughput RNA sequencing. QRT-PCR analysis revealed that circTmeff-1 was highly expressed in the NAc core but not in the NAc shell, suggesting that it plays a role in addiction memory formation. Meanwhile, the down-regulation of circTmeff-1 by adeno-associated viruses in the NAc core or shell could inhibit the morphine CPP scores. Subsequently, the GO and KEGG analyses indicated that circTmeff-1 might regulate the addiction memory via the MAPK and AMPK pathways. These findings suggest that circTmeff-1 in NAc plays a crucial role in morphine-dependent memory formation.

cdh23 affects congenital hearing loss through regulating purine metabolism.

Introduction: The pathogenic gene CDH23 plays a pivotal role in tip links, which is indispensable for mechanoelectrical transduction in the hair cells. However, the underlying molecular mechanism and signal regulatory networks that influence deafness is still largely unknown. Methods: In this study, a congenital deafness family, whole exome sequencing revealed a new mutation in the pathogenic gene CDH23, subsequently; the mutation has been validated using Sanger sequencing method. Then CRISPR/Cas9 technology was employed to knockout zebrafish cdh23 gene. Startle response experiment was used to compare with wide-type, the response to sound stimulation between wide-type and cdh23-/-. To further illustrate the molecular mechanisms underlying congenital deafness, comparative transcriptomic profiling and multiple bioinformatics analyses were performed. Results: The YO-PRO-1 assay result showed that in cdh23 deficient embryos, the YO-PRO-1 signal in inner ear and lateral line neuromast hair cells were completely lost. Startle response experiment showed that compared with wide-type, the response to sound stimulation decreased significantly in cdh23 mutant larvae. Comparative transcriptomic showed that the candidate genes such as atp1b2b and myof could affect hearing by regulating ATP production and purine metabolism in a synergetic way with cdh23. RT-qPCR results further confirmed the transcriptomics results. Further compensatory experiment showed that ATP treated cdh23-/- embryos can partially recover the mutant phenotype. Conclusion: In conclusion, our study may shed light on deciphering the principal mechanism and provide a potential therapeutic method for congenital hearing loss under the condition of CDH23 mutation.

The growth inhibitory effects and non-targeted metabolomic profiling of Microcystis aeruginosa treated by Scenedesmus sp.

The health of the aquatic ecosystem has recently been severely affected by cyanobacterial blooms brought on by eutrophication. Therefore, it is critical to develop efficient and secure methods to control dangerous cyanobacteria, such as Microcystis aeruginosa. In this research, we tested the inhibition of M. aeruginosa growth by a Scenedesmus sp. strain isolated from a culture pond. Scenedesmus sp. culture filtrate that had been lyophilized was added to M. aeruginosa, and cultivation for seven days, the cell density, chlorophyll a (Chl-a) concentration, maximum quantum yield of photosystem II (Fv/Fm), the activities of superoxide dismutase (SOD), catalase (CAT), and the concentration of malondialdehyde (MDA) and glutathione (GSH) were measured. Moreover, non-targeted metabolomics was carried out to provide light on the inhibitory mechanism in order to better understand the metabolic response. According to the results, M. aeruginosa is effectively inhibited by the lyophilized Scenedesmus sp. culture filtrate at a rate of 51.2%. Additionally, the lyophilized Scenedesmus sp. clearly inhibit the photosystem and damages the antioxidant defense system of M. aeruginosa cells, resulting in oxidative damage, which worsens membrane lipid peroxidation, according to changes in Chl-a, Fv/Fm, SOD, CAT enzyme activities and MDA, GSH. Metabolomics analysis revealed that the secondary metabolites of Scenedesmus sp. significantly interfere with the metabolism of M. aeruginosa involved in amino acid synthesis, membrane creation and oxidative stress, which is coherent with the morphology and physiology outcomes. These results demonstrate that the secondary metabolites of Scenedesmus sp. exert algal inhibition effect by breaked the membrane structure, destroyed the photosynthetic system of microalgae, inhibited amino acid synthesis, reduced antioxidant capacity, and eventually caused algal cell lysis and death. Our research provides a reliable basis for the biological control of cyanobacterial blooms on the one hand, and on other hand supply application of non-targeted metabolome on the study of microalgae allelochemicals.

[Establishment of anterior cruciate ligament reconstruction model in cynomolgus monkey with autogenous hamstring tendon transplantation].

Objective: To investigate the feasibility of establishing an anterior cruciate ligament (ACL) reconstruction model using hamstring tendon autograft in cynomolgus monkeys. Methods: Twelve healthy adult male cynomolgus monkeys, weighing 8-13 kg, were randomly divided into two groups ( n=6). In the experimental group, the ACL reconstruction model of the right lower limb was prepared by using a single bundle of hamstring tendon, and the ACL of the right lower limb was only cut off in the control group. The survival of animals in the two groups was observed after operation. Before operation and at 3, 6, and 12 months after operation, the knee range of motion, thigh circumference, and calf circumference of the two groups were measured; the anterior tibial translation D-value (ATTD) was measured by Ligs joint ligament digital body examination instrument under the loads of 13-20 N, respectively. At the same time, the experimental group underwent MRI examination to observe the graft morphology and the signal/ noise quotient (SNQ) was caculated. Results: All animals survived to the end of the experiment. In the experimental group, the knee range of motion, thigh circumference, and calf circumference decreased first and then gradually increased after operation; the above indexes were significantly lower at 3 and 6 months after operation than before operation ( P<0.05), and no significant difference was found between pre-operation and 12 months after operation ( P>0.05). In the control group, there was no significant change in knee range of motion after operation, showing no significant difference between pre- and post-operation ( P>0.05), but the thigh circumference and calf circumference gradually significantly decreased with time ( P<0.05), and the difference was significant when compared with those before operation ( P<0.05). At 6 and 12 months after operation, the thigh circumference and calf circumference were significantly larger in the experimental group than in the control group ( P<0.05). At 3 and 6 months after operation, the knee range of motion was significantly smaller in the experimental group than in the control group ( P<0.05). Under the loading condition of 13-20 N, the ATTD in the experimental group increased first and then decreased after operation; and the ATTD significantly increased at 3, 6 months after operation when compared with the value before operation ( P<0.05). But there was no significant difference between the pre-operation and 12 months after operation ( P>0.05). There was no significant change in ATTD in the control group at 3, 6, and 12 months after operation ( P>0.05), and which were significantly higher than those before operation ( P<0.05). At each time point after operation, the ATTD was significantly smaller in the experimental group than in the control group under the same load ( P<0.05). The MRI examination of the experimental group showed that the ACL boundary gradually became clear after reconstruction and was covered by the synovial membrane. The SNQ at each time point after operation was significantly higher than that before operation, but gradually decreased with time, and the differences between time points were significant ( P<0.05). Conclusion: The ACL reconstruction model in cynomolgus monkey with autogenous hamstring tendon transplantation was successfully established.

Buffering effect of the economizer against PCDD/Fs in flue gas from solid waste incineration plants.

The emission of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) from solid waste incineration is always a crucial concern for the society. Less attention has been paid to differentiate its formation and migration in the low temperature range of economizer, leading to a fuzzy understanding on the control of PCDD/Fs before flue gas cleaning. This study first reveals the buffering effect against PCDD/Fs in the economizer, which is contrary to the well-known memory effect, and first recognizes the intrinsic mechanism by 36 sets of full-scale experimental data under three typical operating conditions. Results indicated that the buffering effect, which includes interception and releasing, could remove averagely 82.9 % of PCDD/Fs in flue gas and reconcile PCDD/Fs profiles. The interception effect is dominant and in compliance with the condensation law. The low temperature range of economizer is exactly suitable for the condensation of lowly chlorinated congeners, which condense behind highly chlorinated ones. The releasing effect was non-staple but stimulated by the sudden change of operating condition, proving that PCDD/Fs formation rarely exists in the economizer. The buffering effect is mainly controlled by the physical migration of PCDD/Fs among different phases. The condensation of PCDD/Fs leads to their migration from vapor phase to aerosol and solid phases during flue gas cooling in the economizer. There is no need for excessive anxiety about PCDD/Fs formation in the economizer because it rarely exists. Intensifying the condensation process of PCDD/Fs in the economizer can help relieve the pressure of end-of-pipe measures for PCDD/Fs control.

Roles of nucleus accumbens shell small-conductance calcium-activated potassium channels in the conditioned fear freezing.

BACKGROUND: Posttraumatic stress disorder (PTSD), a psychiatric disorder caused by stressful events, is characterized by long-lasting fear memory. The nucleus accumbens shell (NAcS) is a key brain region that regulates fear-associated behavior. Small-conductance calcium-activated potassium channels (SK channels) play a key role in regulating the excitability of NAcS medium spiny neurons (MSNs) but their mechanisms of action in fear freezing are unclear. METHOD: We established an animal model of traumatic memory using conditioned fear freezing paradigm, and investigated the alterations in SK channels of NAc MSNs subsequent to fear conditioning in mice. We then utilized an adeno-associated virus (AAV) transfection system to overexpress the SK3 subunit and explore the function of the NAcS MSNs SK3 channel in conditioned fear freezing. RESULTS: Fear conditioning activated NAcS MSNs with enhanced excitability and reduced the SK channel-mediated medium after-hyperpolarization (mAHP) amplitude. The expression of NAcS SK3 were also reduced time-dependently. The overexpression of NAcS SK3 impaired conditioned fear consolidation without affecting conditioned fear expression, and blocked fear conditioning-induced alterations in NAcS MSNs excitability and mAHP amplitude. Additionally, the amplitudes of mEPSC, AMPAR/NMDAR ratio, and membrane surface GluA1/A2 expression in NAcS MSNs was increased by fear conditioning and returned to normal levels upon SK3 overexpression, indicating that fear conditioning-induced decrease of SK3 expression caused postsynaptic excitation by facilitating AMPAR transmission to the membrane. CONCLUSION: These findings show that the NAcS MSNs SK3 channel plays a critical role in conditioned fear consolidation and that it may influence PTSD pathogenesis, making it a potential therapeutic target against PTSD.

Non-negligible health risks caused by inhalation exposure to aldehydes and ketones during food waste treatments in megacity Shanghai.

Aldehydes and ketones in urban air continue to receive regulatory and scientific attention for their environmental prevalence and potential health hazard. However, current knowledge of the health risks and losses caused by these pollutants in food waste (FW) treatment processes is still limited, especially under long-term exposure. Here, we presented the first comprehensive assessment of chronic exposure to 21 aldehydes and ketones in urban FW-air environments (e.g., storage site, mechanical dewatering, and composting) by coupling substantial measured data (383 samples) with Monte Carlo-based probabilistic health risk and impact assessment models. The results showed that acetaldehyde, acetone, 2-butanone and cyclohexanone were consistently the predominant pollutants, although the significant differences in pollution profiles across treatment sites and seasons (Adonis test, P < 0.001). According to the risk assessment results, the estimated cancer risk (CR; mean range: 1.6 × 10-5-1.12 × 10-4) and non-cancer risk (NCR; mean range: 2.98-22.7) triggered by aldehydes and ketones were both unacceptable in most cases (CR: 37.8%-99.3%; NCR: 54.2%-99.8%), and even reached the limit of concern to CR (1 × 10-4) in some exposure scenarios (6.18%-16.9%). Application of DALYs (disability adjusted life years) as a metric for predicting the damage suggested that exposure of workers to aldehydes and ketones over 20 years of working in FW-air environments could result in 0.02-0.14 DALYs per person. Acetaldehyde was the most harmful constituent of all targeted pollutants, which contributed to the vast majority of health risks (>88%) and losses (>90%). This study highlights aldehydes and ketones in FW treatments may be the critical pollutants to pose inhalation risks.

Detection of Alpha Fetoprotein Based on AIEgen Nanosphere Labeled Aptamer Combined with Sandwich Structure of Magnetic Gold Nanocomposites.

As a biomarker, alpha-fetoprotein (AFP) is valuable for detecting some tumors in men, non-pregnant women, and children. However, the detection sensitivity in some methods needs to be improved. Therefore, developing a simple, reliable, and sensitive detection method for AFP is important for non-malignant diseases. An aptamer binding was developed based on aggregation-induced emission luminogen (AIEgen) nanosphere labeled with Fe3O4@MPTMS@AuNPs. AFP was detected with a sandwich structure of AuNPs magnetic composite particles. An aggregation-induced emission (AIE) molecule and polystyrene (PS) nanosphere complex were assembled, enhancing the fluorescence and improving the sensitivity of detection. The limit of detection (LOD) was at a given level of 1.429 pg/mL, which can best be achieved in serum samples. Finally, the results obtained showed the complex to be promising in practical applications.