Reduction of Cofed Carbon Dioxide Modifies the Local Coordination Environment of Zeolite-Supported, Atomically Dispersed Chromium to Promote Ethane Dehydrogenation.

The reduction of CO2 is known to promote increased alkene yields from alkane dehydrogenations when the reactions are cocatalyzed. The mechanism of this promotion is not understood in the context of catalyst active-site environments because CO2 is amphoteric, and even general aspects of the chemistry, including the significance of competing side reactions, differ significantly across catalysts. Atomically dispersed chromium cations stabilized in highly siliceous MFI zeolite are shown here to enable the study of the role of parallel CO2 reduction during ethylene-selective ethane dehydrogenation. Based on infrared spectroscopy and X-ray absorption spectroscopy data interpreted through calculations using density functional theory (DFT), the synthesized catalyst contains atomically dispersed Cr cations stabilized by silanol nests in micropores. Reactor studies show that cofeeding CO2 increases stable ethylene-selective ethane dehydrogenation rates over a wide range of partial pressures. Operando X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine-structure (EXAFS) spectra indicate that during reaction at 650 °C the Cr cations maintain a nominal 2+ charge and a total Cr-O coordination number of approximately 2. However, CO2 reduction induces a change, correlated with the CO2 partial pressure, in the population of two distinct Cr-O scattering paths. This indicates that the promotional effect of parallel CO2 reduction can be attributed to a subtle change in Cr-O bond lengths in the local coordination environment of the active site. These insights are made possible by simultaneously fitting multiple EXAFS spectra recorded in different reaction conditions; this novel procedure is expected to be generally applicable for interpreting operando catalysis EXAFS data.

Metabolomics assisted by transcriptomics analysis to reveal metabolic characteristics and potential biomarkers associated with treatment response of neoadjuvant therapy with TCbHP regimen in HER2 + breast cancer.

BACKGROUND: This study aimed to explore potential indicators associated with the neoadjuvant efficacy of TCbHP regimen (taxane, carboplatin, trastuzumab, and pertuzumab) in HER2 + breast cancer (BrCa) patients. METHODS: A total of 120 plasma samples from 40 patients with HER2 + BrCa were prospectively collected at three treatment times of neoadjuvant therapy (NAT) with TCbHP regimen. Serum metabolites were analyzed based on LC-MS and GC-MS data. Random forest was used to establish predictive models based on pre-therapeutic differentially expressed metabolites. Time series analysis was used to obtain potential monitors for treatment response. Transcriptome analysis was performed in nine available pre­therapeutic specimens of core needle biopsies. Integrated analyses of metabolomics and transcriptomics were also performed in these nine patients. qRT-PCR was used to detect altered genes in trastuzumab-sensitive and trastuzumab-resistant cell lines. RESULTS: Twenty-one patients achieved pCR, and 19 patients achieved non-pCR. There were significant differences in plasma metabolic profiles before and during treatment. A total of 100 differential metabolites were identified between pCR patients and non-pCR patients at baseline; these metabolites were markedly enriched in 40 metabolic pathways. The area under the curve (AUC) values for discriminating the pCR and non-PCR groups from the NAT of the single potential metabolite [sophorose, N-(2-acetamido) iminodiacetic acid, taurine and 6-hydroxy-2-aminohexanoic acid] or combined panel of these metabolites were greater than 0.910. Eighteen metabolites exhibited potential for monitoring efficacy. Several validated genes might be associated with trastuzumab resistance. Thirty-nine altered pathways were found to be abnormally expressed at both the transcriptional and metabolic levels. CONCLUSION: Serum-metabolomics could be used as a powerful tool for exploring informative biomarkers for predicting or monitoring treatment efficacy. Metabolomics integrated with transcriptomics analysis could assist in obtaining new insights into biochemical pathophysiology and might facilitate the development of new treatment targets for insensitive patients.

Quantification of Hepatic Steatosis on Dual-Energy CT in Comparison With MRI mDIXON-Quant Sequence in Breast Cancer.

OBJECTIVE: The study aimed to evaluate the correlation and diagnostic value of liver fat quantification in unenhanced dual-energy CT (DECT) using quantitative magnetic resonance imaging (MRI) mDIXON-Quant sequence as reference standard in patients with breast cancer. METHODS: Patients with breast cancer were prospectively recruited between June 2018 and April 2020. Each patient underwent liver DECT and MRI mDIXON-Quant examination. The DECT-fat volume fraction (FVF) and liver-spleen attenuation differences were compared with the MRI-proton density fat fraction using scatterplots, Bland-Altman plots, and concordance correlation coefficient. Receiver operating characteristic curves were established to determine the diagnostic accuracy of hepatic steatosis by DECT. RESULTS: A total of 216 patients with breast cancer (mean age, 50.08 ± 9.33 years) were evaluated. The DECT-FVF correlated well with MRI-proton density fat fraction ( r2 = 0.902; P < 0.001), which was higher than the difference in liver-spleen attenuation ( r2 = 0.728; P < 0.001). Bland-Altman analysis revealed slight positive bias; the mean difference was 3.986. The DECT-FVF yielded an average concordance correlation coefficient of 0.677, which was higher than the difference of liver-spleen attenuation (-0.544). The DECT-FVF and the difference in liver-spleen attenuation both lead to mild overestimation of hepatic steatosis. The areas under the curve of DECT-FVF (0.956) were higher than the difference in liver-spleen attenuation (0.807) in identifying hepatic steatosis ( P < 0.001). CONCLUSIONS: Dual-energy CT-FVF may serve as a reliable screening and quantitative tool for hepatic steatosis in patients with breast cancer.

The photoionization of methoxymethanol: Fingerprinting a reactive C2 oxygenate in a complex reactive mixture.

Methoxymethanol (CH3OCH2OH) is a reactive C2 ether-alcohol that is formed by coupling events in both heterogeneous and homogeneous systems. It is found in complex reactive environments-for example those associated with catalytic reactors, combustion systems, and liquid-phase mixtures of oxygenates. Using tunable synchrotron-generated vacuum-ultraviolet photons between 10.0 and 11.5 eV, we report on the photoionization spectroscopy of methoxymethanol. We determine that the lowest-energy photoionization process is the dissociative ionization of methoxymethanol via H-atom loss to produce [C2H5O2]+, a fragment cation with a mass-to-charge ratio (m/z) = 61.029. We measure the appearance energy of this fragment ion to be 10.24 ± 0.05 eV. The parent cation is not detected in the energy range examined. To elucidate the origin of the m/z = 61.029 (C2H5O2) fragment, we used automated electronic structure calculations to identify key stationary points on the cation potential energy surface and compute conformer-specific microcanonical rate coefficients for the important unimolecular processes. The calculated H-atom dissociation pathway results in a [C2H5O2]+ fragment appearance at 10.21 eV, in excellent agreement with experimental results.

Global Research Trends and Hotspots in Lateral Epicondylitis During the Past 30 Years: A Bibliometric and Visualization Study.

BACKGROUND Lateral epicondylitis is a common clinical disease characterized by lateral elbow pain, seriously affecting patients' daily life and work. There is a lack of comprehensive and systematic visual analysis of the literature in this field. Therefore, we analyzed the literature on lateral epicondylitis in the past 30 years and summarized the hot spots and frontiers of research in this field to provide ideas and references for subsequent researchers. MATERIAL AND METHODS CiteSpace, VOSviewer, and R-Bibliometrix tools were primarily used to collect, visualize, and analyze data from the literature on lateral epicondylitis in the Web of Science database's core dataset from 1990 to 2022. RESULTS There were altogether 1556 items in the literature. Recent years have seen a noticeable development trend in the volume of pertinent literature that is published annually. The United States took first place with 447 papers. Univ Queensland ranked first with 42 papers. Vicenzino B, an academic at the University of Queensland, Australia, ranked first, with 48 papers. CONCLUSIONS Yearly volumes and forecasts suggest the USA will continue to lead the world in publications on lateral epicondylitis, with extensive collaboration among authors. More collaboration is still needed in various nations and organizations, according to an analysis of the research literature from the previous 30 years. The mechanism of action of different injectable preparations, such as corticosteroids for the treatment of LE is still unclear, as well as the cellular transduction pathways through which PRP affects LE.

Home-based exercise program and Health education in patients with patellofemoral pain: a randomized controlled trial.

BACKGROUND: Patellofemoral pain (PFP) is one of the most common disorders of the knee joint. Home-based exercise is an effective intervention to achieve self-management for chronic diseases. This study evaluated the effects of home-based exercise and health education in patients with PFP. METHODS: Patients who had PFP were randomly allocated to an intervention group (IG) or control group (CG). Patients in the IG received a 6-week tailored home-based exercise program with health education via remote support, while patients in the CG group only received health education. Clinical outcomes were compared using the Anterior Knee Pain Scale (AKPS) to measure function and the Visual Analog Scale (VAS) to measure "worst pain" and "pain with daily activity". Muscle strength was measured according to the peak torque of the knee muscles using an isokinetic system. RESULTS: Among a total of 112 participants screened for eligibility, 38 were randomized and analyzed, including 19 participants in the intervention group and 19 participants in the control group. There were no significant differences in baseline characteristics between the groups. At 6-week follow-up, the intervention group showed a greater worst pain reduction (between-group difference, -19.3 [95%CI, -23.2 to -15.5]; P < 0.01) and pain with daily activity (between-group difference, -22.9 [95%CI, -28.3 to -17.4]; P < 0.01) than the control group. Similarly, the intervention group had better improvements in AKPS (between-group difference, 9.0 [95%CI, 4.1 to 13.9]; P < 0.01) and knee extensor strength (between-group difference, 20.1 [95%CI, 14.5 to 25.8]; P < 0.01), compared to the control group. No adverse events were reported. CONCLUSION: Home-based exercise and health education resulted in less pain, better function, and higher knee muscle strength compared with no exercise in patients with PFP. A large randomized controlled trial with long-term follow-up is required to confirm these findings. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200056224 ( https://www.chictr.org.cn/showproj.aspx?proj=135506 ). Registered on February 1, 2022.

Effects of biochar and freeze‒thaw cycles on the bacterial community and multifunctionality in a cold black soil area.

Global climate change has altered soil freeze‒thaw cycle events, and little is known about soil microbe response to and multifunctionality regarding freeze‒thaw cycles. Therefore, in this study, biochar was used as a material to place under seasonal freeze-thaw cycling conditions. The purpose of this study was to explore the ability of biochar to regulate the function of freeze-thaw soil cycles to ensure spring sowing and food production. The results showed that biochar significantly increased the richness and diversity of soil bacteria before and after freezing-thawing. In the freezing period, the B50 treatment had the greatest improvement effect (2.6% and 5.5%, respectively), while in the thawing period, the B75 treatment had the best improvement effect. Biochar changed the composition and distribution characteristics of the bacterial structure and enhanced the multifunctionality of freeze-thaw soil and the stability of the bacterial symbiotic network. Compared with the CK treatment, the topological characteristics of the bacterial ecological network of the B50 treatment increased the most. They were 0.89 (Avg.degree), 9.79 (Modularity), 9 (Nodes), and 255 (Links). The freeze-thaw cycle decreased the richness and diversity of the bacterial community and changed the composition and distribution of the bacterial community, and the total bacterial population decreased by 658 (CK), 394 (B25), 644 (B50) and 86 (B75) during the thawing period compared with the freezing period. The soil multifunctionality in the freezing period was higher than that during the thawing period, indicating that the freeze-thaw cycle reduced soil ecological function. From the perspective of abiotic analysis, the decrease in soil multifunctionality was due to the decrease in soil nutrients, enzyme activities, soil basic respiration and other singular functions. From the perspective of bacteria, the decrease in soil multifunctionality was mainly due to the change in the Actinobacteriota group. This work expands the understanding of biochar ecology in cold black soil. These results are conducive to the sustainable development of soil ecological function in cold regions and ultimately ensure crop growth and food productivity.

Molecular mechanisms of mesocotyl elongation induced by brassinosteroid in maize under deep-seeding stress by RNA-sequencing, microstructure observation, and physiological metabolism.

Deep-seeding is an important way to improve maize drought resistance, mesocotyl elongation can significantly enhance its seedling germination. To improve our understanding of transcription-mediated maize mesocotyl elongation under deep-seeding stress. RNA-sequencing was used to identify differentially expressed genes (DEGs) in both deep-seeding tolerant W64A and intolerant K12 mesocotyls following culture for 10 days after 2.0 mg·L-1 24-epibrassinolide (EBR) induced stress at the depths of 3 and 20 cm. Phenotypically, the mesocotyl length of both maize significantly increased under 20 cm stress and in the presence of EBR. Microstructure observations revealed that the mesocotyls underwent programmed cell death under deep-seeding stress, which was alleviated by EBR. This was found to be regulated by multiple DEGs encoding cysteine protease/senescence-specific cysteine protease, aspartic protease family protein, phospholipase D, etc. and transcription factors (TFs; MYB, NAC). Additionally, some DEGs associated with cell wall components, i.e., cellulose synthase/cellulose synthase like protein (CESA/CSL), fasciclin-like arabinogalactan (APG), leucine-rich repeat protein (LRR) and lignin biosynthesis enzymes including phenylalanine ammonia-lyase, S-adenosyl-L-methionine-dependent methyltransferases, 4-coumarate-CoA ligase, cinnamoyl CoA reductase, cinnamyl alcohol dehydrogenase, catalase, peroxiredoxin/peroxidase were found to control cell wall sclerosis. Moreover, in auxin, ethylene, brassinosteriod, cytokinin, zeatin, abscisic acid, gibberellin, jasmonic acid, and salicylic acid signaling transduction pathways, the corresponding DEGs were activated/inhibited by TFs (ARF, BZR1/2, B-ARR, A-ARR, MYC2, ABF, TGA) and synthesis of phytohormones-related metabolites. These findings provide information on the molecular mechanisms controlling maize deep-seeding tolerance and will aid in the breeding of deep-seeding maize varieties.

Additional adjuvant capecitabine in early breast cancer patients: a meta-analysis of randomized controlled trials.

Aims: To assess the efficacy and safety of adjuvant capecitabine in early breast cancer patients. Methods: A literature search of databases was conducted to identify randomized controlled trials reporting the efficacy and toxicity of capecitabine as adjuvant therapy in early breast cancer patients. Results: Six studies were eligible and included a total of 6941 patients. Disease-free survival (hazard ratio = 0.79; 95% CI = 0.71-0.88; p < 0.0001) was significantly improved with additional capecitabine, whereas improvement in overall survival (OS) was not significant. The more pronounced benefits in both disease-free survival and OS were observed among triple-negative breast cancer patients. Conclusion: Additional capecitabine in the adjuvant setting conferred substantial disease-free survival benefit and a tendency toward improved OS. Triple-negative breast cancer patients can benefit from capecitabine irrespective of the administration sequence. Capecitabine may be considered a preferred additional treatment for early-stage triple-negative breast cancer patients, and sequential capecitabine can serve as an alternative choice for patients with poor tolerance.

Lay abstract The authors' meta-analysis focused on the adjuvant role of capecitabine in early-stage breast cancer patients. The authors combined data from different studies to show that disease-free survival was significantly improved with additional capecitabine as adjuvant chemotherapy. The more pronounced survival benefits were observed among triple-negative breast cancer patients irrespective of the administration sequence (concurrent/sequential). Capecitabine may be considered a preferred additional treatment for early-stage triple-negative breast cancer patients, and sequential capecitabine can serve as an alternative choice for patients with poor tolerance.

HOXC10 Regulates Osteogenesis of Mesenchymal Stromal Cells Through Interaction with Its Natural Antisense Transcript lncHOXC-AS3.

The characteristics of mesenchymal stromal cells (MSCs) which derived from multiple myeloma (MM) patients are typically impaired in osteogenic differentiation. However, the underlying molecular mechanisms need to be further investigated. lncRNAs are emerging as critical regulation molecules in oncogenic pathways. In this study, we identified that bioactive lncRNA HOXC-AS3, which is transcribed in opposite to HOXC10, was presented in MSCs derived from bone marrow (BM) of MM patients (MM-MSCs). HOXC-AS3 was able to interact with HOXC10 at the overlapping parts and this interaction increased HOXC10 stability, then promoted its expression, conferring osteogenesis repression to MM-MSCs. In mouse models, intravenously administered siHOXC-AS3 was proven to be effective in prevention of bone loss, sustained by both anticatabolic activities and bone-forming. These data showed that lncHOXC-AS3 was required for osteogenesis in BM-MSCs by enhancing HOXC10 expression. Our finding thus unveils a novel insight for the potential clinical significance of lncRNA HOXC-AS3 as a therapeutic target for bone disease in MM. Stem Cells 2019;37:247-256.

ZmSRL5 is involved in drought tolerance by maintaining cuticular wax structure in maize.

Cuticular wax is a natural barrier on terrestrial plant organs, which protects plants from damages caused by a variety of stresses. Here, we report the identification and functional characterization of a cuticular-wax-related gene, Zea mays L. SEMI-ROLLED LEAF 5 (ZmSRL5). The loss-of-function mutant srl5, which was created by a 3,745 bp insertion in the first intron that led to the premature transcript, exhibited abnormal wax crystal morphology and distribution, which, in turn, caused the pleiotropic phenotypes including increased chlorophyll leaching and water loss rate, decreased leaf temperature, sensitivity to drought, as well as semi-rolled mature leaves. However, total wax amounts showed no significant difference between wild type and semi-rolled leaf5 (srl5) mutant. The phenotype of srl5 was confirmed through the generation of two allelic mutants using CRISPR/Cas9. ZmSRL5 encodes a CASPARIAN-STRIP-MEMBRANE-DOMAIN-LIKE (CASPL) protein located in plasma membrane, and highly expressed in developing leaves. Further analysis showed that the expressions of the most wax related genes were not affected or slightly altered in srl5. This study, thus, primarily uncovers that ZmSRL5 is required for the structure formation of the cuticular wax and could increase the drought tolerance by maintaining the proper cuticular wax structure in maize.

Multiple transcriptional factors control stomata development in rice.

Grass stomata can balance gas exchange and evaporation effectively in rapidly changing environments via their unique anatomical features. Although the key components of stomatal development in Arabidopsis have been largely elucidated over the past decade, the molecular mechanisms that govern stomatal development in grasses are poorly understood. Via the genome editing system and T-DNA insertion lines, the key transcriptional factors (TFs) regulating stomatal development in rice (Oryza sativa) were knocked out. A combination of genetic and biochemical assays subsequently revealed the functions of these TFs. OsSPCH/OsICE is essential for the initiation of stomatal lineage. OsMUTE/OsICE determines meristemoid to guard mother cell (GMC) transition. OsFAMA/OsICE influences subsidiary mother cell asymmetric division and mature stoma differentiation. OsFLP regulates the orientation of GMC symmetrical division. More importantly, we found that OsSCR/OsSHR controls the initiation of stomatal lineage cells and the formation of subsidiary cells. The transcription of OsSCR is activated by OsSPCH and OsMUTE. This study characterised the functions of master regulatory TFs that control each stomatal developmental stage in rice. Our findings are helpful for elucidating how various species reprogramme the molecular mechanisms to generate different stomatal types during evolution.

Enantioselective liquid-liquid extraction of DL-mandelic acid using chiral diphosphine ligands as extractants.

In order to expand the application range of chiral diphosphine ligands, (S)-BINAP, (S)-SEGPHOS, and (S)-MeO-BIPHEP were employed as extractants to recognize DL-mandelic acid. The results indicated that (S)-SEGPHOS-Cu exhibited considerable ability to recognize DL-mandelic acid with operational enantioselectivity (α) of 2.677. The process of extraction of DL-mandelic acid using (S)-SEGPHOS-Cu as extractant was systematically investigated. Performance factor (pf) was adopted to comprehensively evaluate the extraction. After optimization by response surface methodology (RSM), the optimal extraction condition is temperature of 5.5°C, (S)-SEGPHOS-Cu concentration of 3.0 mmol/L, and pH of 8.0. And the predicted and experimental maximum values of pf were 0.26374 and 0.26839, respectively.

The BET Bromodomain Inhibitor OTX015 Synergizes with Targeted Agents in Multiple Myeloma.

Treatment failure remains a main challenge in the management of high-risk multiple myeloma (MM) even with the expanding repertoire of new drugs. Combinatorial therapy is considered an encouraging strategy that can overcome the compensatory mechanisms and undesirable off-target effects that limit the benefits of many prospective agents. Preliminary results of a current phase I trial have indicated that the new BET bromodomain inhibitor OTX015 has favorable activity and tolerability. However, OTX015 is not efficacious enough as a monotherapy. Here, we provide evidence that synergistic drug combinations with OTX015 were generally more specific to particular cellular contexts than single agent activities. In addition, pairing OTX015 with three classes of drugs dramatically enhanced the antitumor activity in mouse models of disseminated human myeloma. Our studies further underscored that the BET inhibitor OTX015 sensitized MM cells by interrupting several pathways and genes critical for MM cell proliferation and drug response, which provided the rationale for multiple myeloma therapy with OTX015 combined with conventional chemotherapeutic drugs. Thus, the context specificity of synergistic combinations not only provide profound insights into therapeutically relevant selectivity but also improve control of complex biological systems.

Survival benefit of pure dose-dense chemotherapy in breast cancer: a meta-analysis of randomized controlled trials.

BACKGROUND: Dose-dense chemotherapy is a widely accepted regimen for high-risk breast cancer patients. However, conflicting survival benefits of pure dose-dense chemotherapy have been reported in different randomized controlled trials (RCTs). This meta-analysis aimed to further assess the efficacy and safety of pure dose-dense chemotherapy in breast cancer. METHODS: A literature search of electronic databases and websites was performed to identify phase III RCTs reporting the efficacy and toxicity of pure dose-dense chemotherapy. The endpoints of interest were overall survival (OS), disease-free survival (DFS), and toxicities. The hazard ratios (HRs) of death and recurrence and the odds ratios (ORs) of adverse events were estimated and pooled. RESULTS: Seven studies (five trials) were eligible, encompassing a total of 9851 patients. Patients treated with dose-dense chemotherapy obtained better DFS (HR = 0.83; 95% CI 0.75-0.91; p = 0.0001) than those treated with the conventional schedule, while OS benefit of dose-dense chemotherapy was less impressive (HR = 0.86; 95% CI 0.73-1.02; p = 0.08). However, significant OS benefit was observed in node-positive patients (HR = 0.77; 95% CI 0.66-0.90; p = 0.001). The incidence of anemia, pain, and transaminase elevation was higher in the dose-dense chemotherapy arm. CONCLUSIONS: Dose-dense chemotherapy leads to better prognosis; these findings suggest that it may be a potentially preferred treatment for breast cancer patients, particularly for women with lymph node involvement. However, more RCTs are warranted to better define the best candidates for dose-dense chemotherapy.

Synthesis of CuPF6 -(S)-BINAP loaded resin and its enantioselectivity toward phenylalanine enantiomers.

A type of resin-anchored CuPF6 -(S)-BINAP was synthesized and identified. The PS-CuPF6 -(S)-BINAP resin was used to adsorb the phenylalanine enantiomers. The results showed that the adsorption capacity of PS-CuPF6 -(S)-BINAP resin toward L-phenylalanine was higher than that of resin toward D-phenylalanine. PS-CuPF6 -(S)-BINAP resin exhibited good enantioselectivity toward L-phenylalanine and D-phenylalanine. The influence of phenylalanine concentration, pH, adsorption time, and temperature on the enantioselectivity of the resin were investigated. The results showed that the enantioselectivity of the resin increased with increasing the phenylalanine concentration, pH, and adsorption time, while it decreased with an increase in temperature. The causes for these influences are discussed. The highest enantioselectivity (α = 2.81) was obtained when the condition of phenylalanine concentration was 0.05 mmol/mL, pH was 8, adsorption time was 12 h, and temperature 5°C. The desorption test for removing D/L-phenylalanine on PS-CuPF6 -(S)-BINAP resin was also investigated. The desorption ratios of D-phenylalanine and L-phenylalanine at pH of 1 were 95.7% and 94.3%, respectively. This result indicated that the PS-CuPF6 -(S)-BINAP resin could be regenerated by shaking with an acidic solution. The reusability of the PS-CuPF6 -(S)-BINAP resin was also assessed and the resin exhibited considerable reusability.

Homologs of SCAR/WAVE complex components are required for epidermal cell morphogenesis in rice.

Filamentous actins (F-actins) play a vital role in epidermal cell morphogenesis. However, a limited number of studies have examined actin-dependent leaf epidermal cell morphogenesis events in rice. In this study, two recessive mutants were isolated: less pronounced lobe epidermal cell2-1 (lpl2-1) and lpl3-1, whose leaf and stem epidermis developed a smooth surface, with fewer serrated pavement cell (PC) lobes, and decreased papillae. The lpl2-1 also exhibited irregular stomata patterns, reduced plant height, and short panicles and roots. Molecular genetic studies demonstrated that LPL2 and LPL3 encode the PIROGI/Specifically Rac1-associated protein 1 (PIR/SRA1)-like and NCK-associated protein 1 (NAP1)-like proteins, respectively, two components of the suppressor of cAMP receptor/Wiskott-Aldrich syndrome protein-family verprolin-homologous protein (SCAR/WAVE) regulatory complex involved in actin nucleation and function. Epidermal cells exhibited abnormal arrangement of F-actins in both lpl2 and lpl3 expanding leaves. Moreover, the distorted trichomes of Arabidopsis pir could be partially restored by an overexpression of LPL2 A yeast two-hybrid assay revealed that LPL2 can directly interact with LPL3 in vitro Collectively, the results indicate that LPL2 and LPL3 are two functionally conserved homologs of the SCAR/WAVE complex components, and that they play an important role in controlling epidermal cell morphogenesis in rice by organising F-actin.

Efficacy and Mechanism of Action of Yiru Tiaojing Granule Against Hyperprolactinemia In Vitro and In Vivo.

Yiru Tiaojing Granule, a traditional Chinese medicine formula, is used to treat hyperprolactinemia. This study was conducted to evaluate the mechanism of action and pharmacological activity of Yiru Tiaojing Granule on prolactin secretion. The animal model of hyperprolactinemia was induced by metoclopramide. The dopamine D2 receptor in hyperprolactinemia rat models was analyzed by immunohistochemistry. The biochemical parameters, including a follicle-stimulating hormone, luteinizing hormone, estradiol, progesterone, testosterone, and prolactin, were measured by an enzyme-linked immunosorbent assay. Furthermore, the expression of prolactin and the dopamine D2 receptor was analyzed by Western blotting. The components in the Yiru Tiaojing Granule-medicated serum were assayed by liquid chromatography-tandem mass spectrometry. The Yiru Tiaojing Granule significantly decreased the prolactin level in the hyperprolactinemia rat model, and increased the estradiol, luteinizing hormone, and progesterone levels. The high and medium doses of Yiru Tiaojing Granule reduced dopamine D2 receptor expression in the brain (p < 0.001) and produced a similar effect on bromocriptine (p < 0.001). Yiru Tiaojing Granule-medicated serum reduced (p < 0.001) prolactin expression in MMQ cells in a concentration-dependent manner, but had no effects on GH3 cells. The level of the dopamine D2 receptor in MMQ cells was also increased dose-dependently (p < 0.05). In addition, the protein kinase A and cyclic adenosine monophosphate in MMQ cells were significantly attenuated dose-dependently by treatment with a high and medium dose of Yiru Tiaojing Granule-medicated serum (p < 0.05) and bromocriptine-medicated serum (p < 0.01). The results suggested that Yiru Tiaojing Granule was effective against hyperprolactinemia, and the activation of the dopamine D2 receptor, which was related to the second messenger cyclic adenosine monophosphate and protein kinase A, might be the potential mechanism.

The role of locoregional surgery in de novo stage IV breast cancer: A meta-analysis of randomized controlled trials.

BACKGROUND: We performed an updated meta-analysis to explore the value of locoregional surgery in de novo stage IV breast cancer patients. METHODS: A literature search was conducted to identify randomized controlled trials comparing primary tumor resection with systemic therapy in de novo stage IV breast cancer. The hazard ratio (HR) of overall survival (OS), local relapse-free survival (LRFS), and distant relapse-free survival (DRFS) were estimated and pooled. RESULTS: Six studies were eligible, including a total of 1368 patients. Both OS (HR = 0.86; 95 %CI: 0.77-0.96; p = 0.01; I2 = 45 %) and LRFS (HR = 0.35; 95 %CI: 0.20-0.62; p = 0.0003; I2 = 83 %) were significantly improved with locoregional surgery compared with systemic therapy alone. There was no significant difference in terms of DRFS (HR = 0.96; 95 %CI: 0.41-2.22; p = 0.92; I2 = 86 %). The OS benefit was more pronounced in hormone receptor-positive patients (HR = 0.79; p = 0.003) and HER2-negative patients (HR = 0.80; p = 0.003). CONCLUSIONS: This study demonstrated that locoregional surgery conferred significant OS and LRFS benefits in de novo stage IV breast cancer patients and may serve as an alternative choice for selected patients.

Deep learning-based automatic pipeline for 3D needle localization on intra-procedural 3D MRI.

PURPOSE: Accurate and rapid needle localization on 3D magnetic resonance imaging (MRI) is critical for MRI-guided percutaneous interventions. The current workflow requires manual needle localization on 3D MRI, which is time-consuming and cumbersome. Automatic methods using 2D deep learning networks for needle segmentation require manual image plane localization, while 3D networks are challenged by the need for sufficient training datasets. This work aimed to develop an automatic deep learning-based pipeline for accurate and rapid 3D needle localization on in vivo intra-procedural 3D MRI using a limited training dataset. METHODS: The proposed automatic pipeline adopted Shifted Window (Swin) Transformers and employed a coarse-to-fine segmentation strategy: (1) initial 3D needle feature segmentation with 3D Swin UNEt TRansfomer (UNETR); (2) generation of a 2D reformatted image containing the needle feature; (3) fine 2D needle feature segmentation with 2D Swin Transformer and calculation of 3D needle tip position and axis orientation. Pre-training and data augmentation were performed to improve network training. The pipeline was evaluated via cross-validation with 49 in vivo intra-procedural 3D MR images from preclinical pig experiments. The needle tip and axis localization errors were compared with human intra-reader variation using the Wilcoxon signed rank test, with p < 0.05 considered significant. RESULTS: The average end-to-end computational time for the pipeline was 6 s per 3D volume. The median Dice scores of the 3D Swin UNETR and 2D Swin Transformer in the pipeline were 0.80 and 0.93, respectively. The median 3D needle tip and axis localization errors were 1.48 mm (1.09 pixels) and 0.98°, respectively. Needle tip localization errors were significantly smaller than human intra-reader variation (median 1.70 mm; p < 0.01). CONCLUSION: The proposed automatic pipeline achieved rapid pixel-level 3D needle localization on intra-procedural 3D MRI without requiring a large 3D training dataset and has the potential to assist MRI-guided percutaneous interventions.