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Abstract Clinical trials and studies have implicated that E3 ubiquitin ligase BTBD3 (BTB Domain Containing 3) is a cancer-associated gene. However, the role and underlying mechanism of BTBD3 in colorectal cancer (CRC) is not fully understood yet. Herein, our study demonstrated that the mRNA and protein levels of BTBD3 were decreased in CRC tissues and associated with TYPO3 and Wnt/β-catenin pathway. Our results showed that circRAE1 knockdown and TYRO3 overexpression activated Wnt/β-catenin signaling pathway and the EMT process-associated markers, indicating that circRAE1/miR-388-3p/TYRO3 axis exacerbated tumorigenesis of CRC by activating Wnt/β-catenin signaling pathway. In addition, overexpression of BTBD3 reduced CRC cell migration and invasion in vitro and inhibited tumor growth in vivo. Our data demonstrated that BTBD3 suppressed CRC progression through negative regulation of the circRAE1/miR-388-3p/TYRO3 axis and the Wnt/β-catenin pathway. Our data further confirmed that BTBD3 bound and ubiquitinated β-catenin and led to β-catenin degradation, therefore blocked the Wnt/β-catenin pathway and suppressed the CRC tumorigenesis. This study explored the mechanism of BTBD3 involved in CRC tumorigenesis and provided a new theoretical basis for the prevention and treatment of CRC.

Abstract Background The controversy surrounding Roux-en-Y (R-Y) and Billroth II with Braun (BII + B) reconstruction as an anti-bile reflux procedure after distal gastrectomy has persisted. Recent studies have demonstrated their efficacy, but the long-term outcomes and postoperative quality of life (QoL) among patients have yet to be evaluated. Therefore, we compared the short-term and long-term outcomes of the two procedures as well as QoL. Methods The clinical data of 151 patients who underwent total laparoscopic distal gastrectomy (TLDG) at the Gastrointestinal Surgery Department of the Second Hospital of Fujian Medical University from January 2016 to December 2019 were retrospectively analyzed. Of these, 57 cases with Roux-en-Y procedure (R-Y group) and 94 cases with Billroth II with Braun procedure were included (BII + B group). Operative and postoperative conditions, early and late complications, endoscopic outcomes at year 1 and year 3 after surgery, nutritional indicators, and quality of life scores at year 3 postoperatively were compared between the two groups. Results The R-Y group recorded a significantly longer operative time (194.65 ± 21.52 vs. 183.88 ± 18.02 min) and anastomotic time (36.96 ± 2.43 vs. 27.97 ± 3.74 min) compared to the BII + B group (p 0.05). Both groups showed comparable rates of early and late complications. Endoscopic findings indicated similar food residuals at years 1 and 3 post-surgery for both groups. The R-Y group had a lower occurrence of residual gastritis and bile reflux at year 1 and year 3 after surgery, with a statistically significant difference (p 0.05). Quality of life scores measured by the QLQ-C30 scale were not significantly different between the two groups. However, on the QLQ-STO22 scale, the reflux score was significantly lower in the R-Y group than in the BII + B group (0 [0, 0] vs. 5.56 [0, 11.11]) (p = 0.003). The rest of the scores were not significantly different (p > 0.05). Conclusion Both R-Y and B II + B reconstructions are equally safe and efficient for TLDG. Nevertheless, the R-Y reconstruction reduces the incidence of residual gastritis, bile reflux, and reflux esophagitis, as well as postoperative reflux symptoms, and provides a better quality of life for patients. R-Y reconstruction is superior to BII + B reconstruction for TLDG.

Abstract This paper presents a digital low computation detection method for signal nonlinear distortion. After presetting ADC sampling rate and completing data sampling, the low sampling rate data extracted from the sampling data complete the autocorrelation analysis to correct and calculate the accurate fundamental frequency. According to the relationship between the fundamental frequency and the sampling rate, the complete periodic segment data of the signal cutting out from the sampling data carry out the digital quadrature detection operation to obtain the value of each harmonic component and nonlinear distortion. Experiments show that the calculation of this method is less than that of FFT spectrum analysis method when measuring the THD lower than 15 order. When calculating the 15-order THD at 1024 points, the calculation time is reduced by 44.26%. Moreover, the digital quadrature detection method has high measurement accuracy with less than 0.6% error of detecting 5-order THD.

Context Paeoniflorin (PF) and calycosin-7-glucoside (CG, Paeonia lactiflora Pall. extract) have demonstrated protective effects in ischaemic stroke.Objective To investigate the synergistic effects of PF + CG on ischaemia/reperfusion injury in vivo and in vitro.Materials and methods Male Sprague-Dawley rats were subjected to the middle cerebral artery occlusion/reperfusion (MCAO/R). After MCAO/R for 24 h, rats were randomly subdivided into 5 groups: sham, model (MCAO/R), study treatment (PF + CG, 40 + 20 mg/kg), LY294002 (20 mg/kg), and study treatment + LY294002. Males were given via intragastric administration; the duration of the in vivo experiment was 8 days. Neurologic deficits, cerebral infarction, brain edoema, and protein levels were assessed in vivo. Hippocampal neurons (HT22) were refreshed with glucose-free DMEM and placed in an anaerobic chamber for 8 h. Subsequently, HT22 cells were reoxygenated in a 37 °C incubator with 5% CO2 for 6 h. SOD, MDA, ROS, LDH and protein levels were measured in vitro.Results PF + CG significantly reduced neurobehavioral outcomes (21%), cerebral infarct volume (44%), brain edoema (1.6%) compared with the MCAO/R group. Moreover, PF + CG increased p-PI3K/PI3K (4.69%, 7.4%), p-AKT/AKT (6.25%, 60.6%) and Bcl-2/BAX (33%, 49%) expression in vivo and in vitro, and reduced GSK-3β (10.5%, 9.6%) expression. In vitro, PF + CG suppressed apoptosis in HT22 cells and decreased ROS and MDA levels (20%, 50%, respectively).Conclusions PF + CG showed a synergistic protective effect against ischaemic brain injury, potentially being a future treatment for ischaemic stroke.

ADAR (Adenosine Deaminases Acting on RNA) proteins are a group of enzymes that play a vital role in RNA editing by converting adenosine to inosine in RNAs. This process is a frequent post-transcriptional event observed in metazoan transcripts. Recent studies indicate widespread dysregulation of ADAR-mediated RNA editing across many immune-related diseases, such as human cancer. We comprehensively review ADARs’ function as pattern recognizers and their capability to contribute to mediating immune-related pathways. We also highlight the potential role of site-specific RNA editing in maintaining homeostasis and its relationship to various diseases, such as human cancers. More importantly, we summarize the latest cutting-edge computational approaches and data resources for predicting and analyzing RNA editing sites. Lastly, we cover the recent advancement in site-directed ADAR editing tool development. This review presents an up-to-date overview of ADAR-mediated RNA editing, how site-specific RNA editing could potentially impact disease pathology, and how they could be harnessed for therapeutic applications.

Cannulated screw fixation is widely used in the treatment of femoral neck fractures. During surgery, we often face the situation that a guide wire needs to be adjusted because of poor positioning in the femoral neck. It is difficult to adjust the direction of the guide wire in the neck of the femur due to its elasticity. This study developed a practical technique to adjust the guide wire to the correct position. When the direction of insertion of the guide wire has deviated, first, measure the length of the guide wire. Second, select the appropriate cannulated screw based on the measurement, and screw the cannulated screw in along the direction of the guide wire to Ward's triangle. Then return the guide wire to the front of the cannulated screw. At this time, the cannulated screw can be used as a built‐in guide, and a screwdriver can be used to fine‐tune the position of the screw to the optimal direction under the X‐ray guidance. Finally, the cannulated screw is screwed in in this direction until it passes through the Ward triangle area, and the guide wire is inserted. This technique can help doctors insert a guide wire more quickly and accurately, reducing intraoperative injury and the operation time.

This work deals with energy performance calculate results of new solid composite propellants based on Hexanitroethane (HNE) and Hydrazinium nitroformate (HNF). The energy characteristics of solid propellants with HNE and HNF are estimated using NASA Chemical Equilibrium with Applications (CEA). The effect of HNE and HNF as energetic oxidizers on the energy characteristics of composite modified double-base (CMDB) propellants, hydroxyl-terminated polybutadiene (HTPB) propellants, nitrate ester plasticized polyether (NEPE) propellants, glycidyl azide polymer (GAP) propellants has been carried out. Characteristics of ingredients and propellant formulations with HNE and HNF are presented together with the calculate results which demonstrate the increased performance compared to conventional high-performance propellants based on Ammonium Perchlorate (AP). The results show that HNE and HNF can improve the standard theoretical specific impulse of the four propellants in different degrees, and HTPB propellant has the most significant improvement, which is 12.26 s for HNE-based propellant and 14.12 s for HNF-based propellant. At the same time, both HNE and HNF reduce the infrared emission of propellant exhaust plumes when they replace AP, and reduce or even completely eliminate HCl gas in exhaust products. Therefore, it is expected that HNE-based and HNF-based propellants may provide a promising chlorine-free alternative to existing AP-based formulations.

Abstract Background In tibial plateau fractures, the posterolateral segment of the tibia plateau is frequently affected and challenging to treat. Although there are many surgical approaches and fixation methods for the treatment of these fractures, all of these methods have limitations. We designed a new rotational support plate (RSP) and a special pressurizer that can fix the fracture directly via the anterolateral approach. This method is advantageous because it leads to little trauma, involves a simple operation, and has a reliable fixation effect. This study details the technique of treating these fractures with the RSP and special pressurizer and provides the outcomes. Methods From May 2016 to January 2019, the data of 12 patients with posterolateral tibial plateau fractures treated with the RSP and special pressurizer in our hospital were retrospectively analyzed. Postoperative rehabilitation was advised, knee X-rays were taken at follow-ups, and fracture healing, complications, and knee range of motion were assessed. The Hospital for Special Surgery (HSS) knee score and Knee Injury and Osteoarthritis Outcome Score (KOOS) were used to evaluate knee function at the last follow-up. Results The average follow-up time of all patients was 16.5 months (range, 12–25 months). The average bony union time was 3.2 months (range, 3–4.5 months). At the last follow-up, the average knee range of motion was 138° (range, 107–145°). The average HSS score was 91 (range, 64–98). The average KOOS Symptoms score was 90 (range, 75–96). The average KOOS Pain score was 91 (range, 72–97). The average KOOS ADL score was 91 (range, 74–97). The average KOOS sport/recreation score was 83 (range, 70–90). The average KOOS QOL score was 88 (range, 69–93). Skin necrosis, incision infections, and fixation failure did not occur during the follow-up period. Conclusions With our newly designed RSP and special pressurizer, posterolateral tibial plateau fractures can be easily and effectively reduced and fixed through the anterolateral approach, which serves as a novel treatment for posterolateral tibial plateau fractures.

Background. The enhanced recovery after surgery (ERAS) program is aimed to shorten patients’ recovery process and improve clinical outcomes. This study aimed to compare the outcomes between the ERAS program and the traditional pathway among patients with ankle fracture and distal radius fracture. Methods. This is a multicenter prospective clinical controlled study consisting of 323 consecutive adults with ankle fracture from 12 centers and 323 consecutive adults with distal radial fracture from 13 centers scheduled for open reduction and internal fixation between January 2017 and December 2018. According to the perioperative protocol, patients were divided into two groups: the ERAS group and the traditional group. The primary outcome was the patients’ satisfaction of the whole treatment on discharge and at 6 months postoperatively. The secondary outcomes include delapsed time between admission and surgery, length of hospital stay, postoperative complications, functional score, and the MOS item short form health survey-36. Results. Data describing 772 patients with ankle fracture and 658 patients with distal radius fracture were collected, of which 323 patients with ankle fracture and 323 patients with distal radial fracture were included for analysis. The patients in the ERAS group showed higher satisfaction levels on discharge and at 6 months postoperatively than in the traditional group (P

It remains poorly understood how brain causal connectivity networks change following hearing loss and their effects on cognition. In the current study, we investigated this issue. Twelve patients with long-term bilateral sensorineural hearing loss [mean age, 55.7 ± 2.0; range, 39–63 years; threshold of hearing level (HL): left ear, 49.0 ± 4.1 dB HL, range, 31.25–76.25 dB HL; right ear, 55.1 ± 7.1 dB HL, range, 35–115 dB HL; the duration of hearing loss, 16.67 ± 4.5, range, 3–55 years] and 12 matched normally hearing controls (mean age, 52.3 ± 1.8; range, 42–63 years; threshold of hearing level: left ear, 17.6 ± 1.3 dB HL, range, 11.25–26.25 dB HL; right ear, 19.7 ± 1.3 dB HL, range, 8.75–26.25 dB HL) participated in this experiment. We constructed and analyzed the causal connectivity networks based on functional magnetic resonance imaging data of these participants. Two-sample t-tests revealed significant changes of causal connections and nodal degrees in the right secondary visual cortex, associative visual cortex, right dorsolateral prefrontal cortex, left subgenual cortex, and the left cingulate cortex, as well as the shortest causal connectivity paths from the right secondary visual cortex to Broca’s area in hearing loss patients. Neuropsychological tests indicated that hearing loss patients presented significant cognitive decline. Pearson’s correlation analysis indicated that changes of nodal degrees and the shortest causal connectivity paths were significantly related with poor cognitive performances. We also found a cross-modal reorganization between associative visual cortex and auditory cortex in patients with hearing loss. Additionally, we noted that visual and auditory signals had different effects on neural activities of Broca’s area, respectively. These results suggest that changes in brain causal connectivity network are an important neuroimaging mark of cognitive decline. Our findings provide some implications for rehabilitation of hearing loss patients.

Abstract Background This study aims to investigate the difference in vaginal microecology, local immunity and HPV infection among childbearing-age women with different degrees of cervical lesions. Methods A total of 432 patients were included in this study. Among these patients, 136 patients had LSIL, 263 patients had HSIL and 33 patients had CSCC. These patients were assigned as the research groups. In addition, 100 healthy females were enrolled and assigned as the control group. Results The microbiological indexes of vaginal secretions were evaluated. Furthermore, the concentrations of SIgA, IgG, IL-2 and IL-10 in vaginal lavage fluid, as well as the presence of HPV, mycoplasma and Chlamydia in cervical secretions, were detected. The results is that: (1) Differences in evaluation indexes of vaginal microecology among all research groups and the control group were statistically significant (P

Abstract Background Long noncoding RNAs (lncRNAs) are functionally associated with cancer development and progression. Although gene copy number variation (CNV) is common in hepatocellular carcinoma (HCC), it is not known how CNV in lncRNAs affects HCC progression and recurrence. We aimed to identify a CNV‐related lncRNA involved in HCC progression and recurrence and illustrate its underlying mechanisms and prognostic value. Methods We analyzed the whole genome sequencing (WGS) data of matched cancerous and noncancerous liver samples from 49 patients with HCC to identify lncRNAs with CNV. The results were validated in another cohort of 238 paired HCC and nontumor samples by TaqMan copy number assay. We preformed Kaplan‐Meier analysis and log‐rank test to identify lncRNA CNV with prognostic value. We conducted loss‐ and gain‐of‐function studies to explore the biological functions of LINC01133 in vitro and in vivo. The competing endogenous RNAs (ceRNAs) mechanism was clarified by microRNA sequencing (miR‐seq), quantitative real‐time PCR (qRT‐PCR), western blot, and dual‐luciferase reporter assays. We confirmed the binding mechanism between lncRNA and protein by RNA pull‐down, RNA immunoprecipitation, qRT‐PCR, and western blot analyses. Results Genomic copy numbers of LINC01133 were increased in HCC, which were positively related with the elevated expression of LINC01133. Increased copy number of LINC01133 predicted the poor prognosis in HCC patients. LINC01133 overexpression in HCC cells promoted proliferation and aggressive phenotypes in vitro, and facilitated tumor growth and lung metastasis in vivo, whereas LINC01133 knockdown had the opposite effects. LINC01133 sponged miR‐199a‐5p, resulting in enhanced expression of SNAI1, which induced epithelial‐to‐mesenchymal transition (EMT) in HCC cells. In addition, LINC01133 interacted with Annexin A2 (ANXA2) to activate the ANXA2/STAT3 signaling pathway. Conclusions LINC01133 promotes HCC progression by sponging miR‐199a‐5p and interacting with ANXA2. LINC01133 CNV gain is predictive of poor prognosis in patients with HCC.

Abstract Background Influenza virus is a single-stranded RNA virus that causes influenza in humans and animals. About 600 million people around the world suffer from influenza every year. Upon recognizing viral RNA molecules, TLR7 (Toll-like receptor) initiates corresponding immune responses. Traditional Chinese Medicines (TCMs), including Yinqiao powder, Xinjiaxiangruyin and Guizhi-and-Mahuang decoction, have been extensively applied in clinical treatment of influenza. Although the therapeutic efficacy of TCMs against influenza virus in vivo was reported previously, its underlying mechanisms are not clearly understood. This study aimed to investigate the immunological mechanisms in the treatment of influenza virus infected mice with three Chinese herbal compounds as well as the effect on TLR7/NF-κB signaling pathway during recovery. Methods Wild type and TLR7 KO C57BL/6 mice were infected with influenza virus FM1 and then treated with three TCMs. The physical parameters of mice (body weight and lung index) and the expression levels of components in TLR7/NF-κB signaling pathway were evaluated. Results After viral infection, Guizhi-and-Mahuang decoction and Yinqiao powder showed better anti-viral effect under normal condition. Compared to the viral control group, expression levels of TLR7, MyD88, IRAK4 and NF-κB were significantly reduced in all treatment groups. Furthermore, the three TCM treatment groups showed poor therapeutic efficacy and no difference in viral load compared to the viral control group in TLR7 KO mice. Conclusion Our study indicated that Guizhi-and-Mahuang decoction and Yinqiao powder might play a crucial role of anti-influenza virus by regulating TLR7/NF-κB signal pathway.

Periodontal disease is a chronic inflammatory process that potentially leads to alveolar bone destruction and tooth loss. Tissue engineering combined with stem cell therapy is a potential effective treatment for periodontal bone loss. Amniotic membrane (AM) is a potential scaffold enriched with multiple growth factors. It has the effects of anti-inflammation, antiangiogenesis, and immunosuppression. Herein, we used adipose-derived stem cells (ADSCs) and an AM co-cultured system to study bone regeneration in a rat periodontal defect model in vivo. Methods: Human ADSCs were isolated from the infrapatellar fat pad, and characterized by flow cytometry, reverse transcription-polymerase chain reaction, and multipotent differentiation assays. The co-culture system was applied in the periodontal two-wall osseous defect in a rat model, and computed tomography was used to measure the effect. Results: Human ADSCs isolated from the infrapatellar fat pad showed spindle-like morphology. Flow cytometry results demonstrated that ADSCs expressed a high level of CD90 and CD105, but not CD31, CD34, and CD45. ADSCs strongly expressed stemness genes, including SOX2, OCT4, NANOG, and KLF4 on different passages. Furthermore, ADSCs were able to differentiate into osteogenic, chondrogenic, and adipogenic cells. In the periodontal osseous defect rat model, ADSCs and the AM co-culture system significantly increased bone regeneration. Conclusion: This study provides the basis for using ADSCs with an AM co-culture system as stem cell therapy and scaffold transplantation in clinical periodontology.

Paroxysmal autonomic nerve dysfunction is a relatively rare clinical syndrome, and is clinically diagnosed based on the combined presence of sympathetic hyperactivity and parasympathetic hyperactivity. Early diagnosis of paroxysmal autonomic nerve dysfunction is difficult because its early clinical manifestations are complicated and varied, and it is easily misdiagnosed as central high fever, hospital infection, and so on. The causes and mechanism of the disease are complex, and there is no effective preventive measures. This paper will report 4 cases of patients with severe traumatic brain injury (TBI) who suffered from episodes of this disease. The effective therapies include bromocriptine, propranolol, physical cooling and hyperbaric oxygen therapy. The report also provides review of literature about paroxysmal autonomic nerve dysfunction, in order to improve diagnosis and treatment of the disease. doi: 10.3969/j.issn.1672-6731.2014.07.016

A 66‐year‐old woman had sustained crush injury 3 hours prior to her presentation to our hospital. The diagnosis was defined as lateral tibial plateau fracture of the right knee (Schatzker III). Supine position was set up and a pad was put under the affected hip. After sterilization of the surgical field the sterilized sheets were placed beneath the leg in order to be higher than the other side. A rolled sheet was put under the knee joint so that the knee joint was flexed around 30° to 40°. After the surgical field was draped the skin was incised. Iliotibial band was incised by blade (not by electrotomy) and sharp dissection was performed in the Gerdy's tubercle. Capsulotomy was made by cutting the tibial meniscal ligament. Then the meniscus was tagged superiorly and the articular surface was clearly visualized. A window was made in the lateral cortex beneath the plateau, so the impacted fragment was elevated through the window. The metaphyseal void was filled by bone allograft. The placement of the raft‐screw plate must be ensured that the raft screws passing the plate could purchase the subchondral bone. After perfect placement of the plate was defined, the femoral distractor was removed and the knee joint was relaxed. It was ensured that the alignment of the lower leg was normal, and then the other screws were inserted. Following placing drainage in the wound the iliotibial band was closed and the subcutaneous soft tissue and skin were closed in layer.

Interactive educational videos have grown in popularity in the higher education setting over the last two decades. This exploratory study investigates the mediating and moderating effects of user engagement (UE) on the relationships between the antecedents of UE (i.e., intrinsic load, extraneous load, germane load, and task value) and learning satisfaction. A cross-sectional survey study was conducted in June 2023. We conveniently sampled 49 year-one undergraduate students, who completed a self-report questionnaire consisting of items pertaining to cognitive load, task value, user engagement, and learning satisfaction. Data was analysed using hierarchical linear regression models. Findings revealed that reward fully mediated the relationship between germane load and learning satisfaction. In addition, reward was also found to moderate the relation between (a) germane load and learning satisfaction, and (b) task value and learning satisfaction. These findings highlight the importance of creating rewarding experiences when designing interactive educational videos. [ABSTRACT FROM AUTHOR]

Elastomer sealing performance is of critical importance for downhole tools application including the use of fracturing (Frac) plugs during multi-stage hydraulic fracking. In practice sealing performances of such plugs are normally evaluated through pressure tests, and in numerical simulation studies, maximum contact stress, average contact stress and contact length data are used to determine sealing quality between a packer and casing. In previous studies, the impact of friction forces on sealing performance is often overlooked. This work aims to fill this knowledge gap in determining the influence of friction forces on elastomer packer sealing performances. We first determined the most appropriate constitutive hyperelastic model for the elastomers used in frac plug. Then we compared analytical calculation results with Finite Element Analysis simulation using a simplified tubular geometry and showed the significant influences on interfacial friction on elastomer packer stress distribution, deformation, and contact stress after setting. With the demonstration of validity of FEA method, we conducted systematic numerical simulation studies to show how the interfacial friction coefficients can affect the maximum contact stress, average contact stress, contact stress distribution, and maximum mises stress for an actual packer used in plug products. In addition, we also demonstrated how the groove in a packer can affect packer deformation and evolvement during setting with the consideration of interfacial stress. This study underscores the critical role that friction forces play in Frac plug performance and provides a new dimension for optimizing packer design by controlling interfacial interactions at the packer contact surfaces. [ABSTRACT FROM AUTHOR]

Most viruses and transposons serve as effective carriers for the introduction of foreign DNA up to 11 kb into vertebrate genomes. However, their activity markedly diminishes with payloads exceeding 11 kb. Expanding the payload capacity of transposons could facilitate more sophisticated cargo designs, improving the regulation of expression and minimizing mutagenic risks associated with molecular therapeutics, metabolic engineering, and transgenic animal production. In this study, we improved the Tol2 transposon by increasing protein expression levels using a translational enhancer (QBI SP163, ST) and enhanced the nuclear targeting ability using the nuclear localization protein H2B (SHT). The modified Tol2 and ST transposon efficiently integrated large DNA cargos into human cell cultures (H1299), comparable to the well-established super PiggyBac system. Furthermore, mRNA from ST and SHT showed a significant increase in transgene delivery efficiency of large DNA payloads (8 kb, 14 kb, and 24 kb) into zebrafish (Danio rerio). This study presents a modified Tol2 transposon as an enhanced nonviral vector for the delivery of large DNA payloads in transgenic applications. [ABSTRACT FROM AUTHOR]

The timing of mammalian diversification in relation to the Cretaceous-Paleogene (KPg) mass extinction continues to be a subject of substantial debate. Previous studies have either focused on limited taxonomic samples with available whole-genome data or relied on short sequence alignments coupled with extensive species samples. In the present study, we improved an existing dataset from the landmark study of Meredith et al. (2011) by filling in missing fragments and further generated another dataset containing 120 taxa and 98 exonic markers. Using these two datasets, we then constructed phylogenies for extant mammalian families, providing improved resolution of many conflicting relationships. Moreover, the timetrees generated, which were calibrated using appropriate molecular clock models and multiple fossil records, indicated that the interordinal diversification of placental mammals initiated before the Late Cretaceous period. Additionally, intraordinal diversification of both extant placental and marsupial lineages accelerated after the KPg boundary, supporting the hypothesis that the availability of numerous vacant ecological niches subsequent to the mass extinction event facilitated rapid diversification. Thus, our results support a scenario of placental radiation characterized by both basal cladogenesis and active interordinal divergences spanning from the Late Cretaceous into the Paleogene. [ABSTRACT FROM AUTHOR]