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BACKGROUND: Microglia express phosphatidylinositol 3-kinase (PI3K) has been implicated in the induction and maintenance of long-term potentiation (LTP) and in hippocampal synaptic plasticity. However, there are few studies on the interference of PI3K signal pathway in microglia. OBJECTIVE: The study goal is to gain a better understanding of the mechanism by which EA affects synapses provides insights into how electroacupuncture (EA) modulates synaptic plasticity in learning and memory. METHODS: Rat models of posttraumatic stress disorder (PTSD) were used to explore the effects of EA on microglial PI3K pathway, brain-derived neurotrophic factor (BDNF) and LTP, and the target and mechanism underlying the effects of EA on PI3K from the perspective of protein ubiquitination. RESULTS: EA induced microglial BDNF expression by activating the PI3K-AKT pathway, thereby facilitating LTP and synaptic plasticity. EA inhibited lincRNA 02023 to rescue the binding of WWP2 to PTEN, thereby promoting PTEN ubiquitination and degradation. CONCLUSION: The mechanism of EA improving the learning and memory ability of PTSD rats may be that it can promote the competitive combination of WWP2 and PTEN by inhibiting Linc RNA02023, and then lead to microglial PI3K and its pathway activation, BDNF up-regulation, and finally induce LTP and repair damaged synaptic plasticity.

Among the efforts to reduce mosquito-transmitted diseases, such as malaria and dengue fever, essential oils (EOs) have become increasingly popular as natural replacements for the repellant DEET. In this study, seven commercially available plant EOs against Aedes species mosquitoes were evaluated for their complete protection time (CPT, min) in vivo using human-hand in cage tests (GB2009/China and WHO2009). Among the EOs with the highest efficacy in repelling mosquitoes, Aedes albopictus (Skuse) were clove bud oil and patchouli oil. Both were further assessed according to the in vivo method recommended by the WHO, to determine their minimum effective dose and CPT. A comparison of the ED50 values (dose yielding a 50% repellent response) of these two EOs against Aedes aegypti(L.) showed that the ED50 (2.496 µg/cm2) of patchouli oil was 1248 times higher than that of clove bud oil (0.002 µg/cm2), thus demonstrating them greater efficacy of the latter in repelling Ae. aegypti mosquitoes. For the 2 EOs, eugenol was the major component with higher than 80% in relative amount of the clove bud oil. The patchouli oil had more than 30% of character chemical patchouli alcohol along with α-bulnesene (10.962%), α-guaiene (9.227%), and seychellene (7.566%). Clove bud oil was found to confer longer complete protection than patchouli oil against a common species of mosquito. These results suggest use of EOs as safe, highly potent repellents for use in daily life and against mosquito-transmitted diseases, such as malaria and dengue fever.

In this study, we aimed to analyze the risk factors of bone cement leakage in PKP treatment of OVCFs, and provide suggestions for reducing bone cement leakage.A retrospective study of 517 cases of OVCFs treated with PKP were divided into two groups according to whether they had bone cement leakage or not, leakage group (N=72) and non-leakage group (N=445). The risk factors of leakage were systematically analyzed using clinical baseline data, imaging observation data, and surgical related factors. To select the statistically significant results (p0.05) among the risk factors mentioned above, we used the binary Logistic regression method to identify the main risk factors.The univariate analysis of clinical baseline data，imaging observation data and surgical related factors showed that BMD (p0.001), hypertension (p0.05), injury factors (p0.01), cortical defect (p0.001), grade of vertebral compression (p0.001), surgical approach(p0.05), stage of bone cement injection (p0.01), and balloon pressure (BP) (p0.05) were the risk factors for bone cement leakage. The recovery rate of vertebral height (RRVH), and the Cobb angle correction rate (CACR)were lower in bone cement leakage group (p0.001). The correction effect of kyphosis after operation was limited. Binary Logistic analysis results showed that BMD (OR=5.605), cortical defect (OR=3.115), and stage of bone cement injection (OR=2.385) were bone cement leakage independent risk factors.Impairment of BMD value，defects of cortical bone，and inappropriate stage of bone cement injection will increase the risk of bone cement leakage in PKP treatment，and then limit PKP effects.

Treatment strategies with a strong scientific rationale based on specific biomarkers are needed to improve outcomes in patients with advanced sarcomas. Suppression of cell-cycle progression through reactivation of the tumor suppressor retinoblastoma (Rb) using CDK4/6 inhibitors is a potential avenue for novel targeted therapies in sarcomas that harbor intact Rb signaling. Here, we evaluated combination treatment strategies (sequential and concomitant) with the CDK4/6 inhibitor abemacicib to identify optimal combination strategies. Expression of Rb was examined in 1,043 sarcoma tumor specimens, and 50% were found to be Rb-positive. Using in vitro and in vivo models, an effective two-step sequential combination strategy was developed. Abemaciclib was used first to prime Rb-positive sarcoma cells to reversibly arrest in G1 phase. Upon drug removal, cells synchronously traversed to S phase, where a second treatment with S-phase targeted agents (gemcitabine or Wee1 kinase inhibitor) mediated a synergistic response by inducing DNA damage. The response to treatment could be noninvasively monitored using real-time positron emission tomography imaging and serum thymidine kinase activity. Collectively, these results show that a novel, sequential treatment strategy with a CDK4/6 inhibitor followed by a DNA-damaging agent was effective, resulting in synergistic tumor cell killing. This approach can be readily translated into a clinical trial with noninvasive functional imaging and serum biomarkers as indicators of response and cell cycling.Significance:An innovative sequential therapeutic strategy targeting Rb, followed by treatment with agents that perturb DNA synthesis pathways, results in synergistic killing of Rb-positive sarcomas that can be noninvasively monitored.

Background: Pulmonary hypertension (PH) associated with congenital heart disease (CHD) is the most common type of PH in pediatric patients. The airway microbiome profile in CHD-PH patients remains rarely studied. Methods: A total of 158 children were recruited for collection of oropharyngeal swabs to sequence the 16S ribosomal RNA ( 16S rRNA) V3-V4 region of respiratory microbiome, to establish a correlation between these bacterial groups and echocardiography indicators in CHD-PH patients. Results: Bacterial α- and β-diversity of the airway microbiome indicated a significantly lower richness in the CHD-PH group and compositional differences associated with the specific taxa and their relative abundances in the upper respiratory tract. Principal coordinate analysis showed that the pharynx microbiota composition in the CHD-PH group varied from that in the CHD or control group. The linear discriminant analysis effect size also highlighted an increased presence of Streptococcus and Rothia in pediatric CHD-PH patients. Comparison of microbial composition between pediatric and adult PH patients showed significant differences and separation of microbiota. The correlation between bacterial abundance and transthoracic echocardiography indexes in CHD-associated PH indicated that different groups of microbiomes may be related to different PH grades. Conclusions: In summary, our study reported the systematic definition and divergent profile of the upper respiratory tract microbiota in pediatric PH patients, CHD and reference subjects, as well as between pediatric and adult PH patients.

Anterior cervical discectomy and fusion (ACDF) have a history of more than 60 years to treat cervical spondylotic myelopathy. This study is based on the original classic surgical procedure to remove the bony endplate to expand the range of vertical decompression to analyze and compare the clinical efficacy of two different ACDF in treating cervical spondylotic myelopathy.The inpatients in hospital were randomly divided into two groups A and B. Patients in Group A received ACDF surgery with bony endplates preserved, and patients in group B received ACDF surgery with bony endplates removed. All patients were followed-up for three years, and then compared the clinical efficacy from the following aspects, blood loss statistics during and after the operation, Japanese Orthopedic Association's scoring (JOA) standard for cervical spondylotic myelopathy, Cervical curvature index, cervical flexion and extension range, intervertebral bone graft fusion time and fusion rate.1. The operative time and intraoperative (postoperative) blood loss in group A were significantly better than that in group B, with statistical significance (P 0.05)0.2. There was no significant difference in postoperative neurological function recovery, cervical curvature index, cervical flexion and extension activity, and Intervertebral fusion time between two groups (P 0.05), while group A was superior to group B in terms of bone graft fusion rate (P 0.05). 3. Four patients (6.7%) in group B suffered from dyspnea due to neck hematoma caused by drainage tube blockage, but all of them were cured immediately and no death occurred.During the 3-year follow-up period after the operation, six patients in group B have subsidence and loosening of the internal fixator due to bone subsidence around the implant. Although immediate surgical treatment is not required, renovation surgery is inevitable in the long term.

Astrocyte-specific glutamate transporter subtype 1 (GLT-1) plays an important role in influencing glutamate excitatory toxicity and preventing the death of excitatory toxic neurons. Although the mammalian target of rapamycin (mTOR)/protein kinase B(Akt)/nuclear factor kappa B signaling cascade is involved in the upregulation of astrocytic GLT-1 in oxygen-glucose deprivation (OGD), it is unclear whether the mTOR/Akt pathway is involved in astrocytic GLT-1 upregulation in OGD and reoxygenation (OGD/R). In this study, we found that the treatment of cultured astrocytes with rapamycin and triciribine led to the decreased astrocytes' protrusions, smaller nuclei, and an increased apoptotic rate. The inhibitors of mTOR complex 1 significantly increased the expression levels of phosphorylated Akt-Ser473 (p-Akt), phosphorylated Akt-Thr308(p-Akt), and GLT-1, while Akt-specific inhibitors blocked GLT-1 expression, suggesting that the mTOR/Akt pathway is involved in GLT-1 upregulation. We further demonstrated that astrocytes under OGD/R adapted to environmental changes through the mTOR/Akt pathway, mainly by altering cell morphology and apoptosis and upregulating the expression levels of p-Akt and GLT-1. Our results suggested that astrocytes may adapt to short-term ischemic-reperfusion injury by regulating cell morphology, apoptosis and GLT-1 upregulation.

The k-means algorithm is widely used for clustering, compressing, and summarizing vector data. We present a fast and memory-efficient GPU-based algorithm for exact k-means, Asynchronous Selective Batched K-means (ASB K-means). Unlike most GPU-based k-means algorithms that require loading the whole dataset onto the GPU for clustering, the amount of GPU memory required to run our algorithm can be chosen to be much smaller than the size of the whole dataset. Thus, our algorithm can cluster datasets whose size exceeds the available GPU memory. The algorithm works in a batched fashion and applies the triangle inequality in each k-means iteration to omit a data point if its membership assignment, i.e., the cluster it belongs to, remains unchanged, thus significantly reducing the number of data points that need to be transferred between the CPU’s RAM and the GPU’s global memory and enabling the algorithm to very efficiently process large datasets. Our algorithm can be substantially faster than a GPU-based implementation of standard k-means even in situations when application of the standard algorithm is feasible because the whole dataset fits into GPU memory. Experiments show that ASB K-means can run up to 15x times faster than a standard GPU-based implementation of k-means, and it also outperforms the GPU-based k-means implementation in NVIDIA’s open-source RAPIDS machine learning library on all the datasets used in our experiments.

Objectives To summarize the ultrasonic characteristics of peripheral nerve damage in type 2 diabetes and to verify the diagnostic value of DCEC score for DPN. Methods A total of 289 patients with type 2 diabetes evaluated peripheral neuropathy with neuroultrasound and nerve conduction at the Affiliated Hospital of Guizhou Medical University from June 2016 to June 2020. According to the diagnostic criteria from 2017 guidelines of China, 289 patients with type 2 diabetes were divided into three groups: DPN group: 203 cases; subclinical group: 48 cases; and non-DPN group: 38 cases. Kruskal Wallis test was used to identify the differences and characteristics of ultrasound scores between the all groups. The best cut-off value, sensitivity and specificity of DCEC score were obtained by receiver operator characteristic curve. Taking the diagnostic standard of diabetes peripheral neuropathy as the “gold standard”, the best diagnostic threshold, sensitivity and specificity were obtained by drawing the ROC curve of DCEC score, and then the diagnostic value of DCEC score for DPN was verified Results Compared with non-DPN group, DCEC score in DPN group was significantly higher (P < 0.05). Otherwise,according to the ROC curve, the best cut-off value of DCEC score for DPN diagnosis was 12.5 (sensitivity 69.7%, specificity 71.1%). Conclusions The DCEC score system can effectively diagnose DPN with length-dependence,mainly including the increase of definition score.

Introduction Multiple rib fractures (≥ 3 displaced rib fractures and/or flail chest) are severe chest trauma with high morbidity and mortality. Rib fixation has become the first choice for multiple rib fracture treatment. However, the timing of surgical rib fixation is unclear. Materials and methods The present study explored whether early rib fracture fixation can improve the outcome of multiple rib fractures. The present research included patients who were hospitalized in three Jiangsu hospitals following diagnosis with multiple rib fractures. Patients received early rib fracture fixation (≤ 48 h) or delayed rib fracture fixation (> 48 h) utilizing computer-based random sequencing (in a 1:1 ratio). The primary outcome measures included hospital length of stay, intensive care unit (ICU) stay, mechanical ventilation, inflammatory cytokine levels, infection marker levels, infection, and mortality. Results A total of 403 individuals were classified into two groups, namely, the early group (n = 201) and the delayed group (n = 202). Patients belonging to the two groups had similar baseline clinical data, and there were no statistically significant differences between them. Early rib fracture fixation greatly decreased the length of stay in the ICU (4.63 days vs. 6.72 days, p p p p = 0.008). Early rib fracture fixation can decrease inflammatory cytokine levels and infection marker levels, prevent hyperinflammation and improve infection in patients with multiple rib fractures. The timing of rib fracture fixation does not influence the surgical procedure time, operative blood loss, 30-day all-cause mortality, or surgical site infection. Conclusion The findings from the present research indicated that early rib fracture fixation (≤ 48 h) is a safe, rational, effective and economical strategy and worth clinical promotion.

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Background In addition to providing painless and comfortable treatments to patients, anesthesiologists also ensure the safety of their lives and provide emergency services during public health emergencies, natural disasters, and trauma cases. Globally, the ratio of anesthesiologists to surgeons is 1:2.9, but only 1:7.5 in China, according to a WHO survey. In addition to an urgent need to train more anesthesia professionals, China should also pay attention to their career development and job satisfaction. To identify the relevant factors affecting job satisfaction, we conducted a survey among the graduates majored in anesthesiology at the Naval Medical University. Methods A questionnaire survey was conducted among 595 college graduates majored in anesthesiology who graduated from 1995 to 2021. It contained demographic information, career development status, a job satisfaction scale, work pressure, and turnover intention of the graduates. A multivariate logistic model was used to analyze the influencing factors of satisfaction. Results We received 318 valid questionnaires. According to the survey, 72.96% of respondents were satisfied with their current job, and the overall job satisfaction score was 3.54. According to the results of the logistic regression, age (p = 0.037), level of the medical institution (p < 0.001), and work pressure (p = 0.002) were independent variables associated with graduates' job satisfaction. Conclusion Results indicate that job satisfaction of the graduates is comparable to levels in developed countries, however, the influencing factors are different, leading to different solutions for the improvement. Age, level of the medical institution, and work pressure all play an essential role in predicting job satisfaction. More targeted approaches are needed, for instance, providing more employment guidance for newly graduated trainees, offering more training opportunities for working groups in different positions, and providing clinicians with a better evaluation method. In addition to increasing job satisfaction, these measures may also be helpful to stabilize the anesthesia workforce and improve the attractiveness of the profession.

The depth of electrodes inserted into the charge plays a vital role in controlling the submerged arc furnace. Therefore, we used ultrasound waves reflected from the electrode tip to estimate the depth of electrodes inserted into the charge. However, graphite’s ultrasonic velocity and transmission loss are the basis for establishing an ultrasonic measurement system. Thus, we expected to improve our understanding of them through numerical simulations and experimental measurements. First, we proposed an ultrasonic detection method to estimate the electrode length by embedding graphite rods in Söderberg electrodes. Then, we developed a 3D finite element model in COMSOL for wave transmission in the graphite rod. The wave transmission through 20 and 40 cm graphite rods was simulated using finite element models. The transmission loss, sound pressure, intensity, and displacement distribution of the sound wave passing through the graphite electrode were calculated. To verify the simulation calculation results, we further conducted an acoustic experiment. The results showed that transmission loss varies significantly with frequency. When the frequency was between 25 and 55 kHz, the transmission loss of the graphite rod was slight. At 47 kHz, the transmission loss was 1.837 dB/m.

The construction of the world tourism destination on the Tibetan Plateau is inseparable from the traditional tourist attractions, which are significant landscape ecological units. Based on the data of high-grade tourist attractions on the Tibetan Plateau, the spatial heterogeneity and influence factors are studied employing the Standard Deviation Ellipse (SDE), Kernel Density Estimation (KDE), spatial autocorrelation (SA), and modified tourism gravity model methods. The results show that: (1) the overall spatial distribution characteristic of high-grade tourist attractions is in the direction of northeast-southwest, with solid centripetal force, and the center of gravity of the ellipse is in Yushu City. (2) The spatial heterogeneity of the kernel density distribution is remarkable, clustered in the southeastern half of the plateau, showing a double nucleus-driven and strip-connected pattern. The distribution among cities has a hierarchical heterogeneity, and the two capital cities of Xining and Lhasa play a crucial role. (3) The high-grade tourist attractions are spatially dependent, with evident characteristics of large dispersion and small clustering, and the spatial association type is mainly negative. (4) This paper verifies the significant single-factor mechanism affecting the spatial distribution from supportive and intrinsic dimensions with natural environmental base, tourism resource endowment, socio-economic development, transportation location constraints, and spatial tourism linkages. Finally, the article provides suggestions for the high-quality development of high-grade tourist attractions on the Tibetan Plateau.

We examine the mechanism of warming and tonifying kidney-yang recipe (WTKYR) in treating perimenopausal depression (PMD) using a network pharmacological approach. We identified the active ingredients and targets of WTKYR using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. PMD targets were extracted from the Online Mendelian Inheritance in Man (OMIM), DisGeNET, and GeneCards databases. Venn diagrams were created with Venny to identify common WTKYR and PMD targets. A network diagram of WTKYR targets in PMD was created with Cytoscape to examine its core active ingredients. A protein–protein interaction (PPI) network of WTKYR’s targets was constructed using the STRING database, and its primary targets were evaluated using Network Analyzer and MCODE. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of essential WTKYR target genes were performed with Bioconductor. The LibDock program was applied to molecularly dock the core active ingredients of the WTKYR and the critical targets of PMD. The core WTKYR components for PMD identified were as oleic acid, beta-sitosterol, and phytodolor. The core WTKYR targets identified were the Jun proto-oncogene AP-1 transcription factor subunit (JUN), peroxisome proliferator-activated receptor gamma (PPARG), brain-derived neurotrophic factor (BDNF), caspase 3 (CASP3), and estrogen receptor 1 (ESR1) proteins and the neurotrophin, estrogen, serotonergic synapse, and cyclic adenosine monophosphate (cAMP) signaling pathways. The primary functions of these pathways include extensive neuroprotective and regenerative effects, regulation of 5-hydroxytryptamine (5-HT) metabolism, and participation in regulating the physiological functions of endogenous substances. These improve synaptic sensitivity, promote neuronal cell excitability, and enhance persistent firing in the medial and lateral entorhinal cortex. Molecular docking results show good affinity between the core active ingredients of WTKYR and the critical targets of PMD. This study predicted the essential WTKYR components and its primary targets and pathways for PMD treatment, and found that improving synaptic plasticity, participating in neuroelectrophysiological processes, and regulating related signaling pathways enhance PMD, which require confirmation by future cell or animal validation experiments.

Rotundic acid (RA), an ursane-type pentacyclic triterpene acid isolated from the dried barks of Ilex rotunda Thunb. (Aquifoliaceae), possesses diverse bioactivities. To further study its pharmacokinetics, a simple and sensitive liquid chromatography with triple quadrupole mass spectrometry (LC-QqQ-MS/MS) method was developed and validated to quantify RA concentration in rat plasma and tissue using etofesalamide as an internal standard (IS). Plasma and tissue samples were subjected to one-step protein precipitation. Chromatographic separation was achieved on a ZORBAX Eclipse XDB-C18 column (4.6 mm × 50 mm, 5 μm) under gradient conditions with eluents of methanol:acetonitrile (1:1, V/V) and 5 mM ammonium formate:methanol (9:1, V/V) at 0.5 mL/min. Multiple reaction monitoring transitions were performed at m/z 487.30 → 437.30 for RA and m/z 256.10 → 227.10 for IS in the negative mode. The developed LC-QqQ-MS/MS method exhibited good linearity (2–500 ng/mL) and was fully validated in accordance with U.S. Food and Drug Administration bioanalytical guidelines. Dose proportionality and bioavailability in rats were determined by comparing pharmacokinetic data after single oral (10, 20, and 40 mg/kg) and intravenous (10 mg/kg) administration of RA. Tissue distribution was studied following oral administration at 20 mg/kg. The results showed that the absolute bioavailability of RA after administration at different doses ranged from 16.1% to 19.4%. RA was rapidly absorbed in a dose-dependent manner and highly distributed in the liver. In conclusion, this study is the first to systematically elucidate the absorption and distribution characteristics of RA in rats, which could provide additional information for further development and evaluation of RA in drug metabolism and pharmacokinetic studies.

Low Molecular Weight Cyclin E (LMW-E) are the tumor specific, oncogenic forms of cyclin E that are post translationally generated by neutrophil elastase (NE) mediated cleavage of the 50 KDa full-length cyclin E1 (FL-cycE, encoded by CCNE1 gene). While FL-cycE localizes mainly to the cell nucleus, LMW-E lack the N-terminus nuclear localization signal and are detected in both the nucleus and cytoplasm. Compared to FL-cycE, LMW-E exhibit longer half-life and higher affinity to their kinase partner CDK2 and are resistant to natural CDK inhibitors such as p21 and p27. It is currently assumed that LMW-E drive the tumorigenic process by promoting G1/S cell cycle transition and accelerating mitotic exit. Here we report that LMW-E overexpression also promotes genomic instability by deregulating DNA replication in a CDC6 dependent manner. To this end, we developed an immunohistochemistry (IHC) assay with a cyclin E antibody that can identify LMW-E expressing tumors and examined the association of genetic instability of each tumor with LMW-E status in 2 different cohorts of breast cancer patients. Cohort 1 is a retrospective cohort of 725 patients with stage I-II breast cancer treated at MD Anderson (Houston, TX) between 1985 and 1999. Cohort 2 is a prospective cohort of 85 patients with stage I-II breast cancer who enrolled in our study at MD Anderson between January 2000 and June 2010. Our results show that positive LMW-E status in stage 1 or 2 breast cancer patients correlates with increasing copy number variations, as identified by Molecular Inversion Probe (MIP) in cohort 1 and somatic mutations, as identified by Whole Exome Sequencing (WES) in cohort 2. Second, using immortalized human mammary epithelial cells (hMECs) engineered to express doxycycline inducible LMW-E or FL-cycE in CCNE1 knock-out background, we found that FL-cycE over-expression leads to DNA damage, cell cycle arrest and cell death. LMW-E overexpression, on the other hand, facilitates cell proliferation with damaged DNA, resulting in multi-nuclei and micro-nuclei formation in daughter cells. Third, overexpression of FL-cycE reduces chromatin bound MCM complex, while LMW-E overexpression promotes the chromatin loading of pre-replication complex including MCMs. Lastly, we show that LMW-E but not FL-cycE is the major form of cyclin E that binds to the chromatin. Specifically, in both LMW-Einducible hMECs and LMW-Ehighbreast tumor cell lines, CDC6 is required for the nuclear translocation and chromatin loading of LMW-E. Our findings have revealed the unique oncogenic function of LMW-E in deregulating replication licensing, promoting replication stress tolerance and genomic instability that fuels tumor development. These findings also provide potential novel therapeutic strategies for treating LMW-Ehigh breast tumors, who do not respond to the current standard of care therapies. Citation Format: Mi Li, Kwang Huei Low, Tuyen Bui, Kelly K Hunt, Khandan Keyomarsi. Low molecular weight cyclin E facilitate replication stress tolerance in breast cancer development [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-05-02.

This study assesses the therapeutic effect of propranolol on cervical cancer and its mechanism. Propranolol’s effect on cervical cancer was evaluated by MTT, Western blotting, flow cytometry and colony formation. By searching Drug Bank and String, cGMP/PKG signaling might be downstream targets of propranolol for subsequent analysis. Our results found that propranolol could significantly inhibit Hela and SiHA cell vitality and clone formation in a dose dependent manner. Further, Annexin V-PE/7-AAD Apoptosis Detection assay showed that propranolol could increase Hela and SiHA cell apoptosis. Finally, propranolol attenuated the phosphorylation level of VASP at Ser239 which is critical for PKG activation. In conclusion, propranolol suppressed cervical cancer cell proliferation via inhibition of cGMP/PKG signaling, which provides an affordable and effective method for cervical cancer remedy.

The aerial roots of vanilla plant contain an strikingly high level of tricin in lignin (29.1 mg g−1). It will be a noteworthy feedstock for value-added chemicals and commodities to advance plant bioengineering and lignin valorization.

Fe3O4@SiO2@UiO-66 exhibits excellent adsorption capacity of uranium(vi) and easy separation.

Plant cellulose microfibrils are increasingly employed to produce functional nanofibers and nanocrystals for biomaterials, but their catalytic formation and conversion mechanisms remain elusive. Here, we characterize length-reduced cellulose nanofibers assembly in situ accounting for the high density of amorphous cellulose regions in the natural rice fragile culm 16 (Osfc16) mutant defective in cellulose biosynthesis using both classic and advanced atomic force microscopy (AFM) techniques equipped with a single-molecular recognition system. By employing individual types of cellulases, we observe efficient enzymatic catalysis modes in the mutant, due to amorphous and inner-broken cellulose chains elevated as breakpoints for initiating and completing cellulose hydrolyses into higher-yield fermentable sugars. Furthermore, effective chemical catalysis mode is examined in vitro for cellulose nanofibers conversion into nanocrystals with reduced dimensions. Our study addresses how plant cellulose substrates are digestible and convertible, revealing a strategy for precise engineering of cellulose substrates toward cost-effective biofuels and high-quality bioproducts.

Hybridization is recognized as a major force in species evolution and biodiversity formation, generally leading to the origin and differentiation of new species. Multiple hybridization events cannot easily be reconstructed, yet they offer the potential to study a number of evolutionary processes. Here, we used nuclear expressed sequence tag-simple sequence repeat and large-scale single nucleotide polymorphism variation data, combined with niche analysis, to investigate the putative independent hybridization events in Notopterygium, a group of perennial herb plants endemic to China. Population genomic analysis indicated that the four studied species are genetically well-delimited and that N. forrestii and N. oviforme have originated by hybridization. According to Approximate Bayesian Computation, the best-fit model involved the formation of N. forrestii from the crossing of N. franchetii and N. incisum, with N. forrestii further backcrossing to N. franchetii to form N. oviforme. The niche analyses indicated that niche divergence [likely triggered by the regional climate changes, particularly the intensification of East Asian winter monsoon, and tectonic movements (affecting both Qinghai-Tibetan Plateau and Qinling Mountains)] may have promoted and maintained the reproductive isolation among hybrid species. N. forrestii shows ecological specialization with respect to their parental species, whereas N. oviforme has completely shifted its niche. These results suggested that the climate and environmental factors together triggered the two-step hybridization of the East Asia herb plants. Our study also emphasizes the power of genome-wide SNPs for investigating suspected cases of hybridization, particularly unravelling old hybridization events., This work was financially supported by the National Natural Science Foundation of China (31470400, 32260092), the Key Program of Research and Development of Shaanxi Province (2022ZDLSF06-02) and the Shaanxi Academy of Sciences (2022K-09)., Graphical abstract Keywords 1. Introduction 2. Materials and methods 2.1. Plant material 2.2. Microsatellite data analysis 2.3. Processing of SLAF SNP data 2.4. Complete chloroplast genome analysis 2.5. Testing hybrid origins with ABC program 2.6. Ecological niche comparisons 3. Results 3.1. Population genetic analyses of nuclear EST-SSRs 3.2. Processing of SLAF SNP data 3.3. Nuclear SNP cluster analysis 3.4. Chloroplast genome analysis 3.5. Approximate Bayesian Computation 3.6. Ecological niche modelling 4. Discussion 4.1. Hybrid origins of N. Forrestii and N. Oviforme 4.2. Demographical history of hybrid species 4.3. Ecological isolation among hybrid species Declaration of Competing Interest Acknowledgements Author contributions Appendix A. Supplementary data References