Molecular basis of A. thaliana KEOPS complex in biosynthesizing tRNA t6A.

In archaea and eukaryotes, the evolutionarily conserved KEOPS is composed of four core subunits-Kae1, Bud32, Cgi121 and Pcc1, and a fifth Gon7/Pcc2 that is found in fungi and metazoa. KEOPS cooperates with Sua5/YRDC to catalyze the biosynthesis of tRNA N6-threonylcarbamoyladenosine (t6A), an essential modification needed for fitness of cellular organisms. Biochemical and structural characterizations of KEOPSs from archaea, yeast and humans have determined a t6A-catalytic role for Kae1 and auxiliary roles for other subunits. However, the precise molecular workings of KEOPSs still remain poorly understood. Here, we investigated the biochemical functions of A. thaliana KEOPS and determined a cryo-EM structure of A. thaliana KEOPS dimer. We show that A. thaliana KEOPS is composed of KAE1, BUD32, CGI121 and PCC1, which adopts a conserved overall arrangement. PCC1 dimerization leads to a KEOPS dimer that is needed for an active t6A-catalytic KEOPS-tRNA assembly. BUD32 participates in direct binding of tRNA to KEOPS and modulates the t6A-catalytic activity of KEOPS via its C-terminal tail and ATP to ADP hydrolysis. CGI121 promotes the binding of tRNA to KEOPS and potentiates the t6A-catalytic activity of KEOPS. These data and findings provide insights into mechanistic understanding of KEOPS machineries.

Novel markers of MCL1 inhibitor sensitivity in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer sub-type with limited treatment options and poor prognosis. Currently, standard treatments for TNBC include surgery, chemotherapy, and anti-PDL1 therapy. These therapies have limited efficacy in advanced stages. Myeloid-cell leukemia 1 (MCL1) is an anti-apoptotic BCL2 family protein. High expression of MCL1 contributes to chemotherapy resistance and is associated with a worse prognosis in TNBC. MCL1 inhibitors are in clinical trials for TNBC, but response rates to these inhibitors can vary and predictive markers are lacking. Currently, we identified a 4-member (AXL, ETS1, IL6, EFEMP1) gene signature (GS) that predicts MCL1 inhibitor sensitivity in TNBC cells. Factors encoded by these genes regulate signaling pathways to promote MCL1 inhibitor resistance. Small molecule inhibitors of the GS factors can overcome resistance and sensitize otherwise resistant TNBC cells to MCL1 inhibitor treatment. These findings offer insights into potential therapeutic strategies and tumor stratification for MCL1 inhibitor use in TNBC.

Interpretable artificial intelligence model for accurate identification of medical conditions using immune repertoire.

Underlying medical conditions, such as cancer, kidney disease and heart failure, are associated with a higher risk for severe COVID-19. Accurate classification of COVID-19 patients with underlying medical conditions is critical for personalized treatment decision and prognosis estimation. In this study, we propose an interpretable artificial intelligence model termed VDJMiner to mine the underlying medical conditions and predict the prognosis of COVID-19 patients according to their immune repertoires. In a cohort of more than 1400 COVID-19 patients, VDJMiner accurately identifies multiple underlying medical conditions, including cancers, chronic kidney disease, autoimmune disease, diabetes, congestive heart failure, coronary artery disease, asthma and chronic obstructive pulmonary disease, with an average area under the receiver operating characteristic curve (AUC) of 0.961. Meanwhile, in this same cohort, VDJMiner achieves an AUC of 0.922 in predicting severe COVID-19. Moreover, VDJMiner achieves an accuracy of 0.857 in predicting the response of COVID-19 patients to tocilizumab treatment on the leave-one-out test. Additionally, VDJMiner interpretively mines and scores V(D)J gene segments of the T-cell receptors that are associated with the disease. The identified associations between single-cell V(D)J gene segments and COVID-19 are highly consistent with previous studies. The source code of VDJMiner is publicly accessible at https://github.com/TencentAILabHealthcare/VDJMiner. The web server of VDJMiner is available at https://gene.ai.tencent.com/VDJMiner/.

Mixed lineage kinase 3 and CD70 cooperation sensitize trastuzumab-resistant HER2+ breast cancer by ceramide-loaded nanoparticles.

Trastuzumab is the first-line therapy for human epidermal growth factor receptor 2-positive (HER2+) breast cancer, but often patients develop acquired resistance. Although other agents are in clinical use to treat trastuzumab-resistant (TR) breast cancer; still, the patients develop recurrent metastatic disease. One of the primary mechanisms of acquired resistance is the shedding/loss of the HER2 extracellular domain, where trastuzumab binds. We envisioned any new agent acting downstream of the HER2 should overcome trastuzumab resistance. The mixed lineage kinase 3 (MLK3) activation by trastuzumab is necessary for promoting cell death in HER2+ breast cancer. We designed nanoparticles loaded with MLK3 agonist ceramide (PPP-CNP) and tested their efficacy in sensitizing TR cell lines, patient-derived organoids, and patient-derived xenograft (PDX). The PPP-CNP activated MLK3, its downstream JNK kinase activity, and down-regulated AKT pathway signaling in TR cell lines and PDX. The activation of MLK3 and down-regulation of AKT signaling by PPP-CNP induced cell death and inhibited cellular proliferation in TR cells and PDX. The apoptosis in TR cells was dependent on increased CD70 protein expression and caspase-9 and caspase-3 activities by PPP-CNP. The PPP-CNP treatment alike increased the expression of CD70, CD27, cleaved caspase-9, and caspase-3 with a concurrent tumor burden reduction of TR PDX. Moreover, the expressions of CD70 and ceramide levels were lower in TR than sensitive HER2+ human breast tumors. Our in vitro and preclinical animal models suggest that activating the MLK3-CD70 axis by the PPP-CNP could sensitize/overcome trastuzumab resistance in HER2+ breast cancer.

Characterization of Firmiana danxiaensis plastomes and comparative analysis of Firmiana: insight into its phylogeny and evolution.

BACKGROUND: Firmiana danxiaensis is a critically endangered and ecologically important tree currently only found in four locations in Danxia or Karst habitats in northern Guangdong Province, China. The specialized habitat preference makes it an ideal model species for study of adaptive evolution. Meanwhile, the phylogenetic relationships of F. danxiaensis in four locations under two landforms are unclear. Therefore, we sequenced its complete chloroplast (cp.) genomes and conducted comprehensive interspecific and intrageneric plastome studies. RESULTS: The F. danxiaensis plastomes in four locations showed a typical quadripartite and circular structure that ranged from 160,832 to 161,206 bp in size, with 112 unique genes encoded. Comparative genomics showed that the plastomes of F. danxiaensis were relatively conserved with high similarity of genome organization, gene number, GC content and SSRs. While the genomes revealed higher biased codon preferences in Karst habitat than those in Danxia habitats. Eighteen and 11 divergent hotpots were identified at interspecific and intrageneric levels for species identification and further phylogenetic studies. Seven genes (clpP, accD, ccsA, ndhH, rpl20, rpoC2, and rps4) were under positive selection and may be related to adaptation. Phylogenetic analysis revealed that F. danxiaensis is sister to F. major and F. simplex. However, the interspecific relationships are not consistent with the habitat types. CONCLUSIONS: The characteristics and interspecific relationship of F. danxiaensis plastomes provide new insights into further integration of geographical factors, environmental factors, and genetic variations on the genomic study of F. danxiaensis. Together, our study will contribute to the study of species identification, population genetics, and conservation biology of F. danxiaensis.

High-Pressure Synthesis, Crystal Structure, and Physical Properties of a Spinel Compound Co0.7Al2S4.

In this paper, we report on the discovery of a spinel compound, Co0.7Al2S4, which was synthesized at high-pressure. The systematic characterizations were carried out by structural, magnetic, and heat capacity measurements. The compound crystallizes into a cubic structure with the space group Fd3̅m (no. 227) and the lattice constant a = 9.9580(1) Å. Magnetic susceptibility measurements suggest that Co0.7Al2S4 exhibits a spin glass ground state, freezing at Tf ∼ 7.2 K with a Weiss temperature Tθ ∼ -115.9 K, which is verified by ac magnetic susceptibility and heat capacity measurements. The frustration parameter f for Co0.7Al2S4 is calculated to be about 16.6, based on the formula f = | Tθ/Tf |, indicating that Co0.7Al2S4 is a high-frustration magnet. Specific heat data displays a T2 dependence below the freezing temperature, which is different from the linear dependence observed in a common spin glass system. Compared with the similar compound CoAl2O4, it is suggested that the vacancies in the Co sites should be responsible for the occurrence of the spin glass behavior of Co0.7Al2S4.

Cross-view contrastive representation learning approach to predicting DTIs via integrating multi-source information.

Drug-target interaction (DTI) prediction serves as the foundation of new drug findings and drug repositioning. For drugs/targets, the sequence data contains the biological structural information, while the heterogeneous network contains the biochemical functional information. These two types of information describe different aspects of drugs and targets. Due to the complexity of DTI machinery, it is necessary to learn the representation from multiple perspectives. We hereby try to design a way to leverage information from multi-source data to the maximum extent and find a strategy to fuse them. To address the above challenges, we propose a model, named MOVE (short for integrating multi-source information for predicting DTI via cross-view contrastive learning), for learning comprehensive representations of each drug and target from multi-source data. MOVE extracts information from the sequence view and the network view, then utilizes a fusion module with auxiliary contrastive learning to facilitate the fusion of representations. Experimental results on the benchmark dataset demonstrate that MOVE is effective in DTI prediction.

Design, synthesis, and evaluation of antitumor activity of Mobocertinib derivatives, a third-generation EGFR inhibitor.

Mobocertinib, as a structural analog of the third generation TKI Osimertinib, can selectively act on the EGFRex20 mutation. We have structurally modified Mobocertinib to obtain new EGFR inhibitors. In this paper, we chose Mobocertinib as a lead compound for structural modification to investigate the effect of Mobocertinib derivatives on EGFRT790M mutation. We designed and synthesized 63 Mobocertinib derivatives by structural modification using the structural similarity strategy and the bioelectronic isoarrangement principle. Then, we evaluated the in vitro antitumor activity of the 63 Mobocertinib derivatives and found that the IC50 of compound H-13 against EGFRL858R/T790M mutated H1975 cells was 3.91 µM, and in further kinase activity evaluation, the IC50 of H-13 against EGFRL858R/T790M kinase was 395.2 nM. In addition, the preferred compound H-13 was able to promote apoptosis of H1975 tumor cells and block the proliferation of H1975 cells in the G0/G1 phase; meanwhile, it was able to significantly inhibit the migratory ability of H1975 tumor cells and inhibit the growth of H1975 cells in a time-concentration-dependent manner. In the in vivo anti-tumor activity study, the preferred compound H-13 had no obvious toxicity to normal mice, and the tumor inhibition effect on H1975 cell-loaded nude mice was close to that of Mobocertinib. Finally, molecular dynamics simulations showed that the binding energy between compound H-13 and 3IKA protein was calculated to be -162.417 ± 14.559 kJ/mol. In summary, the preferred compound H-13 can be a potential third-generation EGFR inhibitor.

Effect of Ultrasound-Guided Erector Spinae Plane Block on Pain After Laparoscopic Transabdominal Preperitoneal Repair: A Prospective, Double-Blind, Randomized Controlled Study.

Objective: The present study was performed to evaluate the effect of ultrasound-guided erector spinae plane block (ESPB) on pain after laparoscopic transabdominal preperitoneal (TAPP) repair. Therefore, improved postoperative pain management is crucial for enhancing the overall patient experience and recovery. Methods: This prospective, double-blind, randomized controlled trial enrolled 40 male patients with a unilateral inguinal hernia at Xi'an Aerospace General Hospital from November 1, 2020, to February 1, 2021. Participants were assigned through a random number table at a 1:1 ratio to receive either ESPB with 20 ml 0.5% ropivacaine in the experimental group (Group E) or ESPB with 20 ml normal saline in the control group (Group C), with 20 cases in each group. The primary outcome was assessed using visual analogue scale (VAS) scores for exercise pain at 2h, 6h, 12h, 18h, and 24h postoperatively. Secondary outcomes included time lapses before patient-controlled intravenous analgesia (PCIA) use, intraoperative remifentanil usage, additional sufentanil, postoperative nalbuphine consumption, analgesic remedies at 24h postoperatively, and incidence of postoperative adverse events. Results: Group E provided more pain mitigation for patients than Group C, as evidenced by the significantly lower VAS scores during exercise pain at 2h (Group C: 1.95±1.19; Group E:4.00±1.38), 6h (Group C: 2.00±1.12; Group E:3.90±1.37), and 12h (Group C: 2.05±1.05; Group E:3.55±1.36) postoperatively (P < .05), and the pain mitigation for Group C was significant only at 18h and 24h postoperatively compared to at 2h postoperatively (P < .05). Group E resulted in significantly reduced intraoperative use of remifentanil and, additional sufentanil and postoperative nalbuphine consumption versus Group C (P < .05). Group E exhibited a better pain tolerance than Group C, as demonstrated by the longer time lapse before the use of PCIA (RR value=5.709, t=8.446, P < .05). Group C required more analgesic remedies within 24 h after surgery than Group E (P < .05). Group E did not increase the risk of postoperative adverse events, given the absence of statistical significance in the intergroup comparison (P > .05). Conclusion: Ultrasound-guided ESPB demonstrates notable benefits by decreasing intraoperative and postoperative anesthetic drug requirements, enhancing pain management, and elevating postoperative comfort and quality of life for patients. While acknowledging the study's limitations, it is crucial to highlight the potential clinical implications of these findings. The incorporation of ESPB with ropivacaine into postoperative pain management protocols could represent a significant advancement in clinical practice. The observed improvements in pain management and reduced reliance on anesthetic drugs may lead to more tailored and efficient postoperative care, potentially enhancing patient recovery experiences. Further research and practical implementation studies are warranted to fully elucidate the specific impact and optimal integration of ESPB with ropivacaine within broader clinical settings.

Rational design and synthesis of 2,4-dichloro-6-methyl pyrimidine derivatives as potential selective EGFRT790M/L858R inhibitors for the treatment of non-small cell lung cancer.

Many patients with non-small cell lung cancer (NSCLC) initially benefit from epidermal growth factor receptor (EGFR) targeted therapy. Unfortunately, varying degrees of resistance or side effects eventually develop. Overcoming and preventing the resistance and side effects of EGFR inhibitors has become a hot topic of research today. Based on the previous studies on AZD-9291, we designed and synthesized two series of 2,4-dichloro-6-methylpyrimidine derivatives, 19 compounds in total, as potential inhibitors of the EGFR kinase. The most promising compound, L-18, showed better inhibitory activity (81.9%) and selectivity against EGFRT790M/L858R kinase. In addition, L-18 showed strong antiproliferative activity against H1975 cells with an IC50 value of 0.65 ± 0.06 µM and no toxicity to normal cells (LO-2). L-18 was able to dose-dependently induce the apoptosis of H1975 cells and produced a cell-cycle-blocking effect, and it can also dose-dependently inhibit the migration and invasion of H1975 cells. L-18 also showed in vivo anticancer efficacy in H1975 cells xenograft mice. We also performed a series of in vivo and in vitro toxicological evaluations of compound L-18, which did not cause obvious injury in mice during administration. These results suggest that L-18 may be a promising drug candidate that warrants further investigation.

Assessment of the Relationship Between Genetic Determinants of Obesity, Unhealthy Eating Habits and Chronic Obstructive Pulmonary Disease: A Mendelian Randomisation Study.

Background: Clinical studies have shown that the onset and exacerbation of chronic obstructive pulmonary disease (COPD) are related to obesity and dietary behaviours, but the genetic relationship between them is not clear.Aims: To investigate the relationship between the genetic determinants of obesity, dietary habits (alcohol consumption, intake of sweets, salt intake) and COPD.Methods: Exposure and outcome datasets were obtained from the IEU Open GWAS project. The exposure dataset includes dietary habits (Salt added to food, Sweets intake, Alcohol consumption), obesity level (represented by body mass index (BMI) and body fat percentage (BFP) data sets.). The outcome dataset includes COPD and acute COPD admissions. The collected data were imported into the RStudio software and conducted Mendelian randomisation analysis. Additionally, heterogeneity and horizontal pleiotropy tests were conducted on the data to ensure the veracity of the results.Results: The results showed that BMI was positively correlated with the risk of acute COPD admission (OR = 1.74, 95% CI 1.39-2.18) and COPD (OR = 1.81, 95%CI 1.41-2.33). In addition, BFP was also a risk factor for COPD (OR = 1.98, 95% CI 1.42-2.77) and acute exacerbation of COPD admission (OR = 1.99, 95%CI 1.43-2.77). The increase of salt, sugar and alcohol consumption will not increase the risk of COPD and the risk of hospitalisation due to COPD.Conclusion: Therefore, we should strengthen the guidance of diet and living habits of obese patients. For patients with heavier weight and higher body fat rate, they should be instructed to lose weight and fat to prevent the occurrence of COPD. For obese patients with COPD, more attention should be paid to prevent the occurrence of acute exacerbation of COPD in advance.

Multifunctional transmission-type microwave metadevice based on spin-decoupled and linear-to-circular metasurfaces.

Metasurfaces have enabled precise electromagnetic (EM) wave manipulation with strong potential to obtain unprecedented functionalities and multifunctional behavior in flat optical devices. One promising aspect to achieve multifunction is polarization-dependent metadevices enabled by simultaneous phase control over orthogonally polarized waves. Among these, metasurfaces with geometric phase shows their natural and robust phase control ability over different circularly polarized waves. However, the phase responses under the circularly polarized incidence are locked to be opposite with each other, resulting in limited multifunctionality. In this study, we propose what we believe to be a novel transmission-type microwave metadevice constructed by linear-to-circular metasurface and spin-decoupled metasurface. By endowing independent phase adjustment capability to each unit structure in a spin-decoupled metasurface, the metadevice can reconfigure arbitrary phase wavefronts under orthogonal polarization state incidence, thereby achieving flexible multifunctionality. As a proof-of-concept, the feasibility and reliability of proposed metasurfaces were verified by simulating multifunctional directional deflection, off-axis focusing, and focused vortex beam generation. Finally, the multifunctional manipulation capability of the metadevice is successfully demonstrated by actually measuring the generation of orbital angular momentum modes. This work is expected to drive the application development of metasurface devices in wireless communication.

Enterovirus B types cause severe infection in infants aged 0-3 months.

BACKGROUND: Enterovirus (EV) infections are being increasingly seen in younger infants, often being more severe than in older children. The risk factors of EV infection in infants have been inadequately investigated till date. METHODS: We conducted a retrospective study on hospitalized children with laboratory-confirmed EV infection (50 infants aged 0-3 months and 65 older than 3 months) at a tertiary care center in China. Prevalence, clinical characteristics, and genetic features of the virus were analyzed, and independent predictors for severe infection were assessed. RESULTS: Clinical findings showed that severe infection was more common in infants aged 0-3 months than in older children (78.0% vs. 35.4%, p < 0.001), with higher morbidity of pneumonia, meningitis, and sepsis (p < 0.01). EV-B types were detected more frequently in infants aged 0-3 months than in older children (88.0% vs. 7.7%, p < 0.001). Echovirus 11 was the most identified EV-B, and it recombined with E6 in P2 and P3 regions. Risk factors for severe EV infection included EV-B types infection, age less than 3 months, elevated alanine aminotransferase level, abnormal platelet count, and abnormal cerebrospinal fluid characteristics. CONCLUSIONS: Our data indicated that EV-B types mainly cause severe infection in infants aged 0-3 months. Therefore, knowledge about EV-B types could have implications in designing effective intervention and prevention strategies for young infants with severe EV infection.

An exploratory study of delayed flash visual evoked potential P2 wave latency in subcortical arteriosclerotic encephalopathy.

BACKGROUND: Patients with cognitive dysfunction may present with significantly prolonged the P2 wave latency of flash visual evoked potential. However, no studies have been reported on whether the P2 wave latency of flash visual evoked potential is prolonged in patients with subcortical arteriosclerotic encephalopathy (SAE). OBJECTIVE: To examine the relationship between flash visual evoked potential P2 wave latency (FVEP-P2 wave latency) and cognitive impairment in patients with SAE. METHODS: Overall, we recruited 38 SAE patients as the observation cohort (OC) and 34 healthy volunteers as the control cohort (CC). We measured the FVEP-P2 wave latency for both groups. The SAE patients' cognitive abilities were evaluated via mini-mental state examination (MMSE) and the association between the latency of FVEP-P2 and MMSE score was explored by Pearsons´s correlation test. RESULTS: There is no significant difference between OC (21 males and 17 females; 68.6 ± 6.7 years of age and 9.6 ± 2.8 years of education) and CC (19 males and 15 females; 65.3 ± 5.9 years of age and 10.1 ± 2.6 years of education) in gender and age composition and education level. The FVEP-P2 wave latency of the CC group was (108.80 ± 16.70) ms and the OC FVEP-P2 wave latency was (152.31 ± 20.70) ms. The OC FVEP-P2 wave latency was significantly longer than the CC (P < 0.05). In terms of MMSE scores, the MMSE scores of CC was (28.41 ± 2.34), and that of OC was (9.08 ± 4.39). Compared to the CC, the OC MMSE score was significantly lower (P < 0.05). In addition, the FVEP-P2 wave latency was inversely related to the MMSE (r = -0.4465, P < 0.05) in SAE patients. CONCLUSION: The FVEP-P2 wave latency wave latency was significantly prolonged in SAE patients and strongly associated with the degree of cognitive dysfunction.

Carbon Sequestration Potential of Biomass Production along Highways in China.

In response to climate change, China is making great efforts to increase the green area for carbon sequestration. Road verges, as marginal land with favorable conditions for plant growth and ease of transportation, can be used for biomass production, but the biomass production and carbon sequestration potential have not been assessed. Here, we mapped the biomass production potential of road verges in China by combining a biomass model and Geographic Information System and then evaluated the effect of road runoff and CO2 fertilization on the production according to the runoff coefficient and vehicle emission inventory. Nationwide, road verges can produce 15.86 Mt C yr-1 of biomass. Road runoff contributes to a biomass production of 1.26 Mt C yr-1 through increasing soil water availability, which mainly occurs in arid regions. The CO2 fertilization effect by vehicle emission is considerable in Eastern and Southern China, contributing to a production of 0.09 Mt C yr-1. Life cycle assessment shows that major road verges in China have a carbon sequestration potential of 6.87 Mt C yr-1 currently. Our results revealed that road verges can make a significant contribution to carbon neutrality under proper management.

Graph convolutional network approach to discovering disease-related circRNA-miRNA-mRNA axes.

Non-coding RNAs are gaining prominence in biology and medicine, as they play major roles in cellular homeostasis among which the circRNA-miRNA-mRNA axes are involved in a series of disease-related pathways, such as apoptosis, cell invasion and metastasis. Recently, many computational methods have been developed for the prediction of the relationship between ncRNAs and diseases, which can alleviate the time-consuming and labor-intensive exploration involved with biological experiments. However, these methods handle ncRNAs separately, ignoring the impact of the interactions among ncRNAs on the diseases. In this paper we present a novel approach to discovering disease-related circRNA-miRNA-mRNA axes from the disease-RNA information network. Our method, using graph convolutional network, learns the characteristic representation of each biological entity by propagating and aggregating local neighbor information based on the global structure of the network. The approach is evaluated using the real-world datasets and the results show that it outperforms other state-of-the-art baselines on most of the metrics.

Developmental inflection point for the effect of maternal childhood adversity on children's mental health from childhood to adolescence: Time-varying effect of gender differences.

Childhood adversities have a well-established dose-response relationship with later mental health. However, less attention has been given to intergenerational influences. Further, it is unknown how intergenerational influences intersect with children's developmental stages and gender. The current study examined whether a developmental inflection point exists when the intergenerational influences of childhood adversities gain salience and explored differences by children's gender. Data were from the Young Women and Child Development Study (n = 361). Time-varying effect models (TVEMs) and moderation TVEMs by child's gender were evaluated. Our findings reveal that ages 5-8, the period of transition into primary schools, may represent a developmental inflection point when the intergenerational influences of maternal childhood adversity start emerging substantially. The results from gender interaction TVEMs reveal that maternal childhood adversity was a statistically significant predictor of internalizing problems until age 11, regardless of child's gender, and remained statistically significant for girls' internalizing problems until age 16.7. For externalizing problems, maternal childhood adversity was a statistically significant predictor until age 13, regardless of gender.

Comparison of continuous pericapsular nerve group (PENG) block versus continuous fascia iliaca compartment block on pain management and quadriceps muscle strength after total hip arthroplasty: a prospective, randomized controlled study.

BACKGROUND: This investigation aimed to evaluate the impact of continuous pericapsular nerve group (PENG) block and continuous fascia iliac compartment block (FICB) on postoperative pain following total hip arthroplasty (THA). METHODS: This prospective, randomized, and controlled trial recruited a cohort of fifty-seven patients with unilateral femoral neck fractures from Xi'an Aerospace General Hospital in northwest China between July 2020 and November 2021. These patients were randomly assigned to two groups: the continuous PENG block group (PENG group, n = 29) and the continuous FICB group (FICB group, n = 28). Under ultrasound guidance, PENG block and FICB procedures were performed prior to spinal anesthesia, utilizing 20 ml of 0.25% ropivacaine for PENG block and 30 ml of 0.25% ropivacaine for FICB. Subsequently, a catheter was inserted. All study participants received a standardized postoperative multimodal analgesic regimen, including intravenous administration of 30 mg Ketorolac tromethamine every eight hours and patient-controlled neural analgesia (PCNA) after surgery. Numerical rating scale (NRS) scores at rest and during exercise were recorded at various time points: prior to block (T0), 30 min post-blockade (T1), and 6 h (T2), 12 h (T3), 24 h (T4), and 48 h (T5) postoperatively. Additional data collected encompassed postoperative quadriceps muscle strength, the time of initial ambulation after surgery, the number of effective PCNA activations, rescue analgesia requirements, and occurrences of adverse events (such as nausea and vomiting, hematoma, infection, catheter detachment, or displacement) within 48 h following surgery. RESULTS: In the PENG group, the resting NRS pain scores exhibited lower values at T1, T4, and T5 than those at T0. Furthermore, exercise NRS pain scores at T1-T5 were lower in the PENG group than in the FICB group. Similarly, during the same postoperative period, the PENG group demonstrated enhanced quadriceps strength on the affected side compared to the FICB group. Additionally, the PENG group displayed earlier postoperative ambulation and reduced occurrences of effective PCNA activations and rescue analgesia requirements compared to the FICB group. CONCLUSION: Continuous PENG block exhibited superior analgesic efficacy after THA compared to continuous FICB, promoting recovery of quadriceps strength on the affected side and facilitating early postoperative ambulation. TRIAL REGISTRATION: This clinical trial was registered in the China Clinical Trials Center ( http://www.chictr.org.cn ) on 20/07/2020, with the registration number ChiCTR2000034821.

Temporal dynamic of antibiotic resistance genes in the Zaohe-Weihe hyporheic zone: driven by oxygen and bacterial community.

The widespread spread of antibiotic resistance genes (ARGs) in hyporheic zone (HZ) has become an emerging environmental problem due to their potentially harmful nature. In this research, three different oxygen treatment systems were set up to study the effects of oxygen changes on the abundance of ARGs in the HZ. In addition, the effects of temperature and salinity on ARGs were investigated under aerobic and anaerobic systems, respectively. The bacterial community composition of sediment samples and the relationship with ARGs were analyzed. The explanation ratio and causality of the driving factors affecting ARGs were analyzed using variation partitioning analysis (VPA) and structural equation model (SEM). The relative abundance of ARGs and mobile genetic elements (MGEs) in the anaerobic system increased significantly, which was higher than that in the aerobic system and the aerobic-anaerobic interaction system. The experiment of salinity and temperature also further proved this result. There were many bacterial communities that affected tetracycline and sulfonamide ARGs in sediments, and these host bacteria are mainly concentrated in Proteobacteria, Firmicutes and Bacteroidetes. VPA and SEM further revealed that the abundance of ARGs was mainly influenced by changes in bacterial communities and oxygen conditions, and horizontal gene transfer (HGT) of MGEs also had a positive effect on the spread of ARGs. Those findings suggest that complex oxygen conditions in the HZ alter bacterial communities and promote MGEs-mediated horizontal transfer, which together lead to the spread of ARGs. This study has value as a reference for formulating effective strategies to minimize the propagation of ARGs in underground environment.

Maternal childhood adversity and adolescent marijuana use at age 17 years: The role of parental mental health and parenting behaviors.

INTRODUCTION: Children's risk for marijuana use may be linked to their parents' history of childhood adversity, yet little is known about the mechanisms underlying this link. This study examined whether maternal parenting behavior and mental health serve as mechanisms linking maternal childhood adversity to their children's marijuana use at age 17 years, by gender. METHODS: Data were from the Young Women and Child Development Study (59% male), a longitudinal panel study, which began in 1988 and followed mother-child dyads for 17 years (n = 240). Participants were recruited from health and social services agencies located in a metropolitan region of Washington State. Hypotheses were tested using Structural Equation Modeling in Mplus. Multiple-group analysis was conducted to evaluate potential gender differences. RESULTS: Results showed that maternal childhood adversity was associated with their mental health outcomes (ß = .32, p < .001), which in turn was predictive of mothers' harsh parenting (ß = .27, p < .01). Maternal harsh parenting behavior was then associated with their children's marijuana use at age 17 years (ß = .34, p < .001). Multiple group analyses revealed that the path from harsh parenting to adolescent marijuana use differed across genders being only significant for boys (ß = .42, p < .001). CONCLUSIONS: The intergenerational impact of childhood adversity highlights the need for interventions that target both parents and children. This would support teen mothers with a history of childhood adversity to acquire skills and knowledge to help mitigate its impact on their parenting behaviors and offset risks for their children.