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In this study, a vitellogenin like1 gene (SfVg-like1) in Sogatella furcifera was identified. The open reading frame (ORF) encoded 1,321 amino acid sequence. Structure analysis reveals that the amino acid sequence of SfVg-like1 has 3 conserved LPD_N, DUF1943 and VWFD domains. Phylogenetic analyses showed that SfVg-like1 was clustered in the same branch with the Vg-like1 of Nilaparvata lugens (100% bootstrap value) compared with other Hemiptera insects Vgs associated with vitellogenesis. Temporo-spatial expression analyses showed that SfVg-like1 expressed during all stages, and in both genders. The relative expression levels of SfVg-like1 mRNA were higher in adults than in nymph developmental stages. The knockdown of SfVg-like1 gene resulted in the inhibition of the ovarian development in female adults, whereas the morphology of the testis in male adults was not been affected. The silence of SfVg-like1 could decrease the relative expression levels of target of rapamycin (SfTOR, GenBank MW193765) and vitellogenin (SfVg, GenBank MH271114) genes significantly in female adults. However, the knockdown of SfTOR or SfVg genes in female adults did not affect the transcript level of SfVg-like1. Therefore, it demonstrated that SfVg-like1 might locate on the upstream signaling pathways of SfTOR and SfVg. These results demonstrate that SfVg-like1 is essential for S. furcifera reproduction, and it could be the potential target for the control of this pest.
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Hemípteros , Vitelogeninas , Feminino , Masculino , Animais , Vitelogeninas/genética , Vitelogeninas/metabolismo , Filogenia , Sequência de Aminoácidos , ReproduçãoRESUMO
Transition-metal catalyzed intermolecular 1,2-diarylation of electronically unactivated alkenes has emerged as an extensive research topic in organic synthesis. However, most examples are mainly limited to terminal alkenes. Furthermore, transition-metal catalyzed asymmetric 1,2-diarylation of unactivated alkenes still remains unsolved and is a formidable challenge. Herein, we describe a highly efficient directed nickel-catalyzed reductive 1,2-diarylation of unactivated internal alkenes with high diastereoselectivities. More importantly, our further effort towards enantioselective 1,2-diarylation of the unactivated terminal and challenging internal alkenes is achieved, furnishing various polyarylalkanes featuring benzylic stereocenters in high yields and with good to high enantioselectivities and high diastereoselectivities. Interestingly, the generation of cationic Ni-catalyst by adding alkali metal fluoride is the key to increased efficiency of this enantioselective reaction.
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Miniature robots are untethered actuators, which have great prospects to transform targeted drug delivery because they can potentially deliver high concentrations of medicine to the disease site(s) with minimal complications. However, existing miniature robots cannot perform advanced targeted combination therapy; majority of them can at most transport one type of drug, while those that can carry multiple drugs are unable to change their drug-dispensing sequence and dosage. Furthermore, the latter robots cannot transport more than three types of drugs, selectively dispense their drugs, maintain their mobility, or release their drugs at multiple sites. Here, a millimeter-scale soft robot is proposed, which can be actuated by alternating magnetic fields to dispense four types of drugs with reprogrammable drug-dispensing sequence and dosage (dispensing rates: 0.0992-0.231 µL h-1). This robot has six degrees-of-freedom motions, and it can deliver its drugs to multiple desired sites by rolling and two-anchor crawling across unstructured environments with negligible drug leakage. Such dexterity is highly desirable and unprecedented for miniature robots with drug-dispensing capabilities. The soft robot therefore has great potential to enable advanced targeted combination therapy, where four types of drugs must be delivered to various disease sites, each with a specific sequence and dosage of drugs.
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Browning of white adipose tissue is a novel approach for the management of obesity and obesity-related metabolic disorders. Kaempferol (KPF) is a common dietary nutrient found abundantly in many fruits and vegetables and has been shown to have the potential to regulate lipid metabolism. However, the detailed mechanism by which it affects the browning of white adipose tissue remains unclear. In the present study, we sought to determine how KPF induces adipocytes to undergo a browning transformation by establishing a primary adipocyte model and an obese mouse model. Our results showed that KPF-treated mice were rescued from diet-induced obesity, glucose tolerance and insulin resistance, associated with increased expression of adaptive thermogenesis-related proteins. KPF-promoted white adipose browning correlated with the AMPK/SIRT1/PGC-1α pathway, as the use of an AMPK inhibitor in preadipocytes partially reversed the observed browning phenotype of KPF-treated cells. Taken together, these data suggest that KPF promotes browning of white adipose tissue through activation of the AMPK/SIRT1/PGC-1α pathway. This study demonstrates that KPF is a promising natural product for the treatment of obesity by promoting white fat browning.
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There is a correlation between IBD and breast cancer according to previous observational studies. However, so far there is no evidence to support if there is a causal relationship between these 2 diseases. We acquired comprehensive Genome-Wide Association Study (GWAS) summary data on IBD (including ulcerative colitis [UC] and Crohn disease [CD]) as well as breast cancer of completely European descent from the IEU GWAS database. The estimation of bidirectional causality between IBD (including UC and CD) and breast cancer was achieved through the utilization of 2-sample Mendelian randomization (MR). The MR results were also assessed for any potential bias caused by heterogeneity and pleiotropy through sensitivity analyses. Our study found a bidirectional causal effect between IBD and breast cancer. Genetic susceptibility to IBD was associated with an increased risk of breast cancer (ORâ =â 1.053, 95% CI: 1.016-1.090, Pâ =â .004). Similarly, the presence of breast cancer may increase the risk of IBD (ORâ =â 1.111, 95% CI: 1.035-1.194, Pâ =â .004). Moreover, the bidirectional causal effect between IBD and breast cancer can be confirmed by another GWAS of IBD. Subtype analysis showed that CD was associated with breast cancer (ORâ =â 1.050, 95% CI: 1.020-1.080, Pâ <â .001), but not UC and breast cancer. There was a suggestive association between breast cancer and UC (ORâ =â 1.106, 95% CI: 1.011-1.209, Pâ =â .028), but not with CD. This study supports a bidirectional causal effect between IBD and breast cancer. There appear to be considerable differences in the specific associations of UC and CD with AD. Understanding that IBD including its specific subtypes and breast cancer constitute common risk factors can contribute to the clinical management of both diseases.
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Neoplasias da Mama , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Humanos , Análise da Randomização Mendeliana/métodos , Neoplasias da Mama/genética , Neoplasias da Mama/epidemiologia , Feminino , Doença de Crohn/genética , Doença de Crohn/epidemiologia , Doenças Inflamatórias Intestinais/genética , Colite Ulcerativa/genética , Colite Ulcerativa/epidemiologia , Fatores de Risco , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVE: To compare the diagnostic value of microvascular flow imaging (MVFI) with that of contrast-enhanced ultrasound (CEUS) for the analysis of blood flow in benign and malignant cervical lymph nodes. MATERIAL AND METHODS: As a prospective study, 95 cervical enlarged lymph nodes (43 benign and 52 malignant) were observed in 95 patients using conventional ultrasonography (including gray and Color Doppler Flow Imaging), CEUS, and MVFI. Two researchers evaluated vascular parameters of MVFI (vascular distribution, internal vascular features, vascular index) and CEUS (enhancement mode, enhancement type) and compared the diagnostic effects of MVFI and CEUS.All results were compared with pathological findings. RESULTS: There were significant differences in the vascular distribution and internal vascular features of benign and malignant lymph nodes on MVFI (Pâ<â0.05). The vascular distribution of benign lymph nodes was mainly of the central and avascular types, the internal blood vessels were mostly normal, the vascular distribution of malignant lymph nodes was mainly mixed, the internal vessels were mainly tortuous and displaced. The optimal cut-off value of the benign and malignant lymph node vascular index (VI) was 15.55%, and the area under the receiver operating characteristic curve (AUC) of the VI was 0.876. There were also significant differences in the enhancement mode and types of benign and malignant lymph nodes in CEUS (Pâ<â0.05). The benign lymph nodes showed centrifugal perfusion, and the enhancement types were mostly type I and type II. Most malignant lymph nodes showed centripetal or mixed perfusion, and the enhancement types were usually type III and type IV. The accuracy, sensitivity, and specificity of CEUS in the diagnosis of lymph node lesions were 84.2%, 84.6% and 83.7%, respectively, and the AUC was 0.845. The accuracy, sensitivity, and specificity of MVFI in the diagnosis of lymph node lesions were 85.3%, 84.6%, and 86.0%, respectively, and the AUC was 0.886. CONCLUSION: Both CEUS and MVFI are valuable in differentiating benign and malignant lesions of lymph nodes and have a similar diagnostic performance; however, MVFI is less invasive and simpler than CEUS. Therefore it is preferred for auxiliary examination of enlarged lymph nodes that are difficult to diagnose by conventional ultrasound.
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Meios de Contraste , Linfonodos , Humanos , Estudos Prospectivos , Sensibilidade e Especificidade , Ultrassonografia/métodos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Diagnóstico DiferencialRESUMO
Background: Based on the ovarian-adnexal reporting and data system (O-RADS), we constructed a nomogram model to predict the malignancy potential of adnexal masses with sophisticated ultrasound morphology. Methods: In a multicenter retrospective study, a total of 430 subjects with masses were collected in the adnexal region through an electronic medical record system at the Fourth Hospital of Harbin Medical University during the period of January 2019-April 2023. A total of 157 subjects were included in the exception validation cohort from Harbin Medical University Tumor Hospital. The pathological tumor findings were invoked as the gold standard to classify the subjects into benign and malignant groups. All patients were randomly allocated to the validation set and training set in a ratio of 7:3. A stepwise regression analysis was utilized for filtering variables. Logistic regression was conducted to construct a nomogram prediction model, which was further validated in the training set. The forest plot, C-index, calibration curve, and clinical decision curve were utilized to verify the model and assess its accuracy and validity, which were further compared with existing adnexal lesion models (O-RADS US) and assessments of different types of neoplasia in the adnexa (ADNEX). Results: Four predictors as independent risk factors for malignancy were followed in the preparation of the diagnostic model: O-RADS classification, HE4 level, acoustic shadow, and protrusion blood flow score (all p < 0.05). The model showed moderate predictive power in the training set with a C-index of 0.959 (95%CI: 0.940-0.977), 0.929 (95%CI: 0.884-0.974) in the validation set, and 0.892 (95%CI: 0.843-0.940) in the external validation set. It showed that the predicted consequences of the nomogram agreed well with the actual results of the calibration curve, and the novel nomogram was clinically beneficial in decision curve analysis. Conclusion: The risk of the nomogram of adnexal masses with complex ultrasound morphology contained four characteristics that showed a suitable predictive ability and provided better risk stratification. Its diagnostic performance significantly exceeded that of the ADNEX model and O-RADS US, and its screening performance was essentially equivalent to that of the ADNEX model and O-RADS US classification.
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Acute gouty arthritis (AGA) is an acute inflammatory disease, whose occurrence and development mechanism are associated with inflammatory reaction of joint tissue. This study investigated the role of neoisoastilbin (NIA) in the treatment of AGA and explored the underlying mechanisms. C57BL/6 mice underwent intraarticular injection of monosodium urate (MSU) to establish an AGA model in vivo. Enzyme-linked immunosorbent assay, histopathological hematoxylin-eosin staining, western blotting, and other methods were used to observe the therapeutic effects of NIA on AGA and investigate the role of the NF-κB/NLRP3 pathway in the treatment. We found that NIA effectively reduced MSU-induced joint swelling and inflammatory cell infiltration in a concentration-dependent manner. NIA also significantly reduced interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels as compared with the respective values in the model mice group. In addition, administration of NIA significantly mitigated the phosphorylation of NF-κB-related proteins (IKKα, NF-κB, and IκBα) and the expression of NLRP3-related proteins (NLRP3, caspase-1, and ASC) in MSU-induced joint tissues. In conclusion, our research indicated that NIA significantly improved AGA, and its underlying mechanism was achieved by simultaneously inhibiting the NF-κB/NLRP3 pathway and the expression of inflammatory factors. This research preliminarily suggested the potential role of NIA in the treatment of AGA.
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Activation of adipose tissue thermogenesis is a promising strategy in the treatment of obesity and obesity-related metabolic disorders. Kaempferol (KPF) is a predominant dietary flavonoid with multiple pharmacological properties, such as anti-inflammatory and antioxidant activities. In this study, we sought to characterize the role of KPF in adipocyte thermogenesis. We demonstrated that KPF-treated mice were protected from diet-induced obesity, glucose tolerance, and insulin resistance, accompanied by markedly increased energy expenditure, ex vivo oxygen consumption of white fat, and increased expression of proteins related to adaptive thermogenesis. KPF-promoted beige cell formation is a cell-autonomous effect, since the overexpression of cyclin-dependent kinase 6 (CDK6) in preadipocytes partially reversed browning phenotypes observed in KPF-treated cells. Overall, these data implicate that KPF is involved in promoting beige cell formation by suppressing CDK6 protein expression. This study provides evidence that KPF is a promising natural product for obesity treatment by boosting energy expenditure.
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Subunidade alfa 2 de Fator de Ligação ao Core , Quinase 6 Dependente de Ciclina , Animais , Camundongos , Quinase 6 Dependente de Ciclina/metabolismo , Quinase 6 Dependente de Ciclina/farmacologia , Quinase 6 Dependente de Ciclina/uso terapêutico , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Subunidade alfa 2 de Fator de Ligação ao Core/farmacologia , Subunidade alfa 2 de Fator de Ligação ao Core/uso terapêutico , Tecido Adiposo Marrom/metabolismo , Quempferóis/farmacologia , Adipócitos , Obesidade/tratamento farmacológico , Obesidade/genética , Obesidade/metabolismo , Tecido Adiposo Branco/metabolismo , Dieta Hiperlipídica/efeitos adversos , Transdução de Sinais , Termogênese , Camundongos Endogâmicos C57BL , Metabolismo EnergéticoRESUMO
3D printing via vat photopolymerization (VP) is a highly promising approach for fabricating magnetic soft millirobots (MSMRs) with accurate miniature 3D structures; however, magnetic filler materials added to resin either strongly interfere with the photon energy source or sediment too fast, resulting in the nonuniformity of the filler distribution or failed prints, which limits the application of VP. To this end, a circulating vat photopolymerization (CVP) platform that can print MSMRs with high uniformity, high particle loading, and strong magnetic response is presented. After extensive characterization of materials and 3D printed parts, it is found that SrFe12 O19 is an ideal magnetic filler for CVP and can be printed with 30% particle loading and high uniformity. By using CVP, various tethered and untethered MSMRs are 3D printed monolithically and demonstrate the capability of reversible 3D-to-3D transformation and liquid droplet manipulation in 3D, an important task for in vitro diagnostics that are not shown with conventional MSMRs. A fully automated liquid droplet handling platform that manipulates droplets with MSMR is presented for detecting carbapenem antibiotic resistance in hazardous biosamples as a proof of concept, and the results agree with the benchmark.
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Fenômenos Magnéticos , Impressão Tridimensional , Fenômenos FísicosRESUMO
Magnetic miniature robots (MMRs) are small-scale, untethered actuators which can be controlled by magnetic fields. As these actuators can non-invasively access highly confined and enclosed spaces; they have great potential to revolutionize numerous applications in robotics, materials science, and biomedicine. While the creation of MMRs with six-degrees-of-freedom (six-DOF) represents a major advancement for this class of actuators, these robots are not widely adopted due to two critical limitations: i) under precise orientation control, these MMRs have slow sixth-DOF angular velocities (4 degree s-1 ) and it is difficult to apply desired magnetic forces on them; ii) such MMRs cannot perform soft-bodied functionalities. Here a fabrication method that can magnetize optimal MMRs to produce 51-297-fold larger sixth-DOF torque than existing small-scale, magnetic actuators is introduced. A universal actuation method that is applicable for rigid and soft MMRs with six-DOF is also proposed. Under precise orientation control, the optimal MMRs can execute full six-DOF motions reliably and achieve sixth-DOF angular velocities of 173 degree s-1 . The soft MMRs can display unprecedented functionalities; the six-DOF jellyfish-like robot can swim across barriers impassable by existing similar devices and the six-DOF gripper is 20-folds quicker than its five-DOF predecessor in completing a complicated, small-scale assembly.
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Vitellogenin (Vg) and the target of rapamycin (TOR) are important genes involved in insect reproduction regulation. In this work, the full lengths of the Vg (SfVg) and TOR (SfTOR) genes of the white-backed planthopper Sogatella furcifera were cloned. The expression pattern in females showed that SfVg was highly expressed in fat bodies, and SfTOR was highly expressed in Malpighian tubules. After silencing SfVg or SfTOR, female adults did not deposit eggs. Their ovarian development was delayed, and yolk protein deposition in the oocytes was reduced. However, wild-type females mated with SfTOR-silenced males could lay eggs and produce offsprings normally. The dissections of testes and accessory glands of males with SfTOR knockdown showed that their development was not affected. Therefore, the silencing of the SfVg or SfTOR genes can effectively inhibit female reproduction, but SfTOR knockdown has no significant effect on male reproductive capacity. Furthermore, silencing SfTOR can cause SfVg expression to decrease significantly. All of the above results revealed that SfVg and SfTOR are essential for white-backed planthopper reproduction and may provide a potential target for pest control.
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Hemípteros , Animais , Feminino , Hemípteros/genética , Masculino , Controle de Pragas , Reprodução , Sirolimo , Vitelogeninas/genéticaRESUMO
Miniature soft robots are mobile devices, which are made of smart materials that can be actuated by external stimuli to realize their desired functionalities. Here, the key advancements and challenges of the locomotion producible by miniature soft robots in micro- to centimeter length scales are highlighted. It is highly desirable to endow these small machines with dexterous locomotive gaits as it enables them to easily access highly confined and enclosed spaces via a noninvasive manner. If miniature soft robots are able to capitalize this unique ability, they will have the potential to transform a vast range of applications, including but not limited to, minimally invasive medical treatments, lab-on-chip applications, and search-and-rescue missions. The gaits of miniature soft robots are categorized into terrestrial, aquatic, and aerial locomotion. Except for the centimeter-scale robots that can perform aerial locomotion, the discussions in this report are centered around soft robots that are in the micro- to millimeter length scales. Under each category of locomotion, prospective methods and strategies that can improve their gait performances are also discussed. This report provides critical analyses and discussions that can inspire future strategies to make miniature soft robots significantly more agile.