Drivers and suppressors of triple-negative breast cancer.

To identify regulators of triple-negative breast cancer (TNBC), gene expression profiles of malignant parts of TNBC (mTNBC) and normal adjacent (nadj) parts of the same breasts have been compared. We are interested in the roles of estrogen receptor ß (ERß) and the cytochrome P450 family (CYPs) as drivers of TNBC. We examined by RNA sequencing the mTNBC and nadj parts of five women. We found more than a fivefold elevation in mTNBC of genes already known to be expressed in TNBC: BIRC5/survivin, Wnt-10A and -7B, matrix metalloproteinases (MMPs), chemokines, anterior gradient proteins, and lysophosphatidic acid receptor and the known basal characteristics of TNBC, sox10, ROPN1B, and Col9a3. There were two unexpected findings: 1) a strong induction of CYPs involved in activation of fatty acids (CYP4), and in inactivation of calcitriol (CYP24A1) and retinoic acid (CYP26A1); and 2) a marked down-regulation of FOS, FRA1, and JUN, known tethering partners of ERß. ERß is expressed in 20 to 30% of TNBCs and is being evaluated as a target for treating TNBC. We used ERß+ TNBC patient-derived xenografts in mice and found that the ERß agonist LY500703 had no effect on growth or proliferation. Expression of CYPs was confirmed by immunohistochemistry in formalin-fixed and paraffin-embedded (FFPE) TNBC. In TNBC cell lines, the CYP4Z1-catalyzed fatty acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) increased proliferation, while calcitriol decreased proliferation but only after inhibition of CYP24A1. We conclude that CYP-mediated pathways can be drivers of TNBC but that ERß is unlikely to be a tumor suppressor because the absence of its main tethering partners renders ERß functionless on genes involved in proliferation and inflammation.

[Retrospective Analysis of Neurological Symptoms of Severe/Critical COVID-19 Patients in Sichuan Province].

OBJECTIVE: To retrospectively analyze the symptoms and characteristics of nervous system damage in severe/critically severe patients with coronavirus disease 2019 (COVID-19) in Sichuan province, with a view to providing basic references for the prevention and treatment of COVID-19. METHODS: A total of 90 patients with severe/critically severe COVID-19 were included, who were diagnosed and treated in COVID-19 designated hospital of Sichuan province from 11 January 2020 to 20 March 2020. Clinical features, test results, treatment options and clinical outcomes were analyzed retrospectively. RESULTS: Of 90 patients, there were 54 males and 36 females, with an average age of (53.90±16.92) years. In addition to the classic symptoms such as fever and/or respiratory symptoms, 53 patients also had various degrees of neurologic manifestations, including 33 cases of fatigue, 21 muscle soreness, 12 dizziness, 8 headaches, 3 mental disorders, and 1 consciousness disorders and 1 case of neck pain. Compared with the patients without neurologic manifestations, those with neurologic manifestations took a longer time from admission to diagnosis of COVID-19 ( P<0.05), and received more antifungal treatment ( P<0.05). CONCLUSIONS: Neurological symptoms are not uncommon in severe/critically severe patients with COVID-19, and it's relatively difficult in the treatment. It should be paid attention in order to avoid misdiagnosis.

Specific K+ Binding Sites as CO2 Traps in a Porous MOF for Enhanced CO2 Selective Sorption.

Metal-organic frameworks (MOFs) can be fine-tuned to boost sorbent-sorbate interactions in order to improve gas sorption and separation performance, but the design of MOFs with ideal structural features for gas separation applications remains a challenge. Herein it is reported that unsaturated alkali metal sites can be immobilized in MOFs through a tetrazole based motif and that gas affinity can thereby be boosted. In the prototypal MOF of this type-NKU-521 (NKU denotes Nankai University), K+ cations are effectively embedded in a trinuclear Co2+ -tetrazole coordination motif. The embedded K+ sites are exposed to the pores of NKU-521 through water removal, and the isosteric heat (Qst ) for CO2 is boosted to 41 kJ mol-1 . The nature of the binding site is validated by molecular simulations and structural characterization. The K+ cations in effect serve as gas traps and boost the CO2 -framework affinity, as measured by the Qst , by 24%. In addition, the impact of unsaturated alkali metal sites upon the separation of hydrocarbons is evaluated for the first time in MOFs using ideal adsorbed solution theory (IAST) calculations and column breakthrough experiments. The results reveal that the presence of exposed K+ sites benefits gas sorption and hydrocarbon separation performances of this MOF.

[Remote sensing extraction method of Codonopsis pilosula planting area in Weiyuan county].

Due to the large amount of Codonopsis pilosula planted in Weiyuan county,and the arable land area,the local medicinal materials office uses a large amount of manpower,financial resources and material resources to estimate its area every year. In order to extract the information of local Chinese medicinal materials more quickly and simply,we try to apply remote sensing technology to the extraction of Chinese medicinal materials. This paper will use Weiyuan county of Gansu province as the research area,and use the domestic ZY-3 Satellite multi-spectral remote sensing image as the data source to find out the spectral characteristics of the party's participation in other remote sensing images. The visual interpretation method was used to extract the planting area of the C. pilosula in Weiyuan county. The estimated value of the planting area of C. pilosula using satellite remote sensing technology was 75 965 mu( 1 mu≈667 m2),which was basically consistent with the field survey data of the local medicinal materials office. After the accuracy verification,it was found that the precision of C. pilosula planted by visual interpretation was more than 70%. It is concluded that the satellite remote sensing technology can be used to extract the information of C. pilosula and it can provide the relevant information of the planting area of Chinese medicinal materials quickly and accurately.

[Extraction of distribution information of Angelicae sinensis plants in Weiyuan county based on remote sensing technology].

Due to the large amount of nutrients required during the cultivation of Angelica sinensis and in order to prevent the occurrence of pests and diseases,and the annual reduction of the planting area of Angelica and the balance of supply and demand of A. sinensis,the A. sinensis plantation adopts the rotation mode. This paper takes Wuyuan county of Gansu province as the research scope and use GF-1 Satellite data as the data source,using remote sensing technology combined with field survey results,to explore the effective method of visual interpretation for the extraction of A. sinensis planting area. A sample was selected to generate a spectrum according to different feature types. The different characteristics of A. sinensis and other features were analyzed and distinguished in remote sensing images,so that the A. sinensis planting plots were extracted and verified in remote sensing images. The results showed that the accuracy verification value of the visual interpretation method was 95. 85%. It is determined that the visual interpretation method can effectively extract the A. sinensis planting plots within the research scope and realize the comprehensive grasp of the spatial distribution information of A. sinensis.

Metal-Organic Framework Derived Core-Shell Co/Co3O4@N-C Nanocomposites as High Performance Anode Materials for Lithium Ion Batteries.

Metal-organic frameworks (MOFs) with diverse structures, adjustable pore sizes, and high surface areas have exhibited awesome potential in many fields. Here we report a simple carbonization strategy to obtain a series of core-shell structured Co/Co3O4 nanoparticles encapsulated into nitrogen-doped carbon shells from cobalt-based metal-organic framework precursors at different carbonization temperatures. When it is applied as an anodes for lithium ion batteries, the Co/Co3O4@N-C-700 electrode delivers a maximum initial discharge capacity of 1535 mAh g-1, the highest reversible capacity (903 mAh g-1 at a current density of 100 mA g-1 after 100 cycles), and the best rate performance (i.e., 774 mAh g-1 at a current density of 1.0 A g-1 after 100 cycles) in comparison with those of Co/Co3O4@N-C-600 and Co/Co3O4@N-C-800 electrodes. The excellent electrochemical performance could be mainly attributed to the unique core-shell structure, abundant graphited carbon, and the well-dispersed Co/Co3O4 nanoparticles which can promote the specific capacity through conversion reactions.

Is Adductor Canal Block Better Than Femoral Nerve Block in Primary Total Knee Arthroplasty? A GRADE Analysis of the Evidence Through a Systematic Review and Meta-Analysis.

BACKGROUND: Total knee arthroplasty (TKA) is associated with intense postoperative pain with a need for early ambulation to gain function and prevent postoperative complications. Compared with femoral nerve block (FNB), adductor canal block (ACB) can relieve postoperative pain and preserve quadriceps muscle strength. This meta-analysis was conducted to investigate which analgesic method provides better pain relief and functional recovery after TKA. METHOD: We conducted a meta-analysis to identify relevant randomized controlled trials involving ACB and FNB after TKA in electronic databases, including Web of Science, Embase, PubMed, and the Cochrane Library, up to November 2016. Finally, 9 randomized controlled trials involving 609 patients (668 knees) were included in our study. Review Manager Software and Grading of Recommendations Assessment, Development, and Evaluation profiler were used to perform the meta-analysis. RESULTS: Compared with FNB, ACB resulted in better quadriceps muscle strength and mobilization ability. There were no significant differences in the visual analog scale at rest, visual analog scale with mobilization, rescue opioid consumption, patient satisfaction, and length of hospital stay. CONCLUSION: Compared with FNB, ACB shows similar pain control after TKA. However, ACB can better preserve quadriceps muscle strength and improve mobilization ability. In conclusion, ACB showed better functional recovery after TKA without compromising pain control. Therefore, ACB is recommended as an alternative analgesic method for early ambulation after TKA.

[Effects of Effective Fractions of Panax Notoginseng on the Expression of TF and TFPI-2 in Rat En- dometrium with Whole Cycle Exogenous Estrogen Intervention].

Objective To observe the effects of notoginsenoside, Panax notoginseng flavonoids (PNF) , Panax notoginseng acid (PNA) , and their mixtures on the expressions of tissue factor (TF) and tissue factor pathway inhibitor 2 (TFPI-2) in rat endometriaum with whole cycle exogenous estrogen inter- vention. Methods Totally 160 female impuberty rats were randomly divided into the blank group (n =40) and the model group (n =120). Rats in the blank group were administered with normal saline by gastroga- vage for 3 weeks, while those in the model group were administered with estradiol valerate suspension. The two interventions lasted for 3 consecutive weeks. After 3 weeks of intervention, rats with asexual cycle were randomly divided into six groups, i.e., the model group, the continuous estrogen group, the No- toginsenoside group, the PNF group, the PNA group, the mixture group. Rats in the model group, the continuous estrogen group, the Notoginsenoside group, the PNF group, the PNA group, the mixture group were respectively administered with normal saline, estrogen, notoginsenoside, PNF, PNA, and mixture of effective Panax notoginseng fractions by gastrogavage for 2 successive weeks. Expression levels of TF, TFPI-2, TF mRNA, and TFPI-2 mRNA in the endometrium were detected 2 weeks later. Re-sults Compared with the blank group, positive expressions of TF and TF mRNA increased, and positive expressions of TFPI-2 and TFPI-2 mRNA decreased in the model group (P <0. 05, P <0. 01). Compared with the model group, the expressions of TF and TF mRNA significantly increased, the expressions of TF- PI-2 and TFPI-2 mRNA significantly decreased in the estrogen group at the end of the 5th week (P < 0. 01). Compared with the model group and the estrogen group, positive expressions of TF and TF mRNA significantly decreased, positive expressions of TFPI-2 and TFPI-2 mRNA significantly increased in the Notoginsenoside group, the PNF group, the PNA group, the mixture group (P <0. 05, P <0. 01). Com- pared with the Notoginsenoside group, positive expressions of TFPI-2 and TFPI-2 mRNA significantly in- creased in the mixture group (P <0. 05). Compared with the PNF group, the expressions of TF and TF mRNA significantly decreased in the Notoginsenoside group and the mixture group (P <0. 01) ; positive expressions of TFPI-2 increased in the mixture group (P <0. 05, P <0. 01). Conclusions The effective fractions of Panax notoginseng could decrease the-expression of TF and increase the expression of TFPI- 2 in rat endometrium with whole cycle exogenous estrogen intervention. They activated blood circulation and arrested bleeding possibly through inhibiting TF, blocking activation of coagulation system, and re- ducing inflammatory response. Meanwhile, it also could strengthen endometrial extracellular matrix, maintain the endometrial stability, thereby reducing endometrial disintegration and bleeding, and being beneficial for endometrium repairing and remodeling.

Asymmetric Construction of Spirooxindoles by Organocatalytic Multicomponent Reactions Using Diazooxindoles.

The first highly diastereo- and enantioselective multicomponent reaction of diazooxindoles, nitrosoarenes, and nitroalkenes using a newly developed hydrogen-bond catalyst has been successfully developed for the efficient construction of a series of spirooxindole derivatives with excellent functional-group tolerance. Spirooxindoles are formed in excellent yields and stereoselectivities, and the method represents an unprecedented approach for trapping the active intermediate with a nitroalkene to form biologically important compounds having three contiguous stereogenic centers with excellent asymmetric induction.

The impact of city size on income inclusive growth: A human capital perspective and evidence from China.

This paper methodically investigates the influence of inclusive income growth on city size, examining it through the dual lenses of "income" and "distribution." The analysis leverages meticulously collected panel data encompassing 276 Chinese cities at the prefecture level and above, spanning the period from 2005 to 2019. Theoretical analysis indicates that the effect of city size expansion on per capita income adheres to a 'U'-shaped trajectory, while its influence on the urban-rural income gap manifests an 'inverted U' pattern. Moreover, the inclusive income growth stemming from city size demonstrates notable heterogeneity across various geographic locations and city hierarchies. The findings reveal that human capital serves as the primary mechanism through which city size influences inclusive income growth. After decomposing the income inclusiveness index, it becomes evident that the expansion of city size exerts a more potent direct driving effect on the income of urban residents. On the one hand, city size expansion directly increases rural residents' income levels by improving labor productivity. On the other hand, it facilitates leapfrog income development by inducing the rural labor force to move to cities.

Ascorbic acid-mediated reduction of arabinoxylan viscosity through free radical reactions.

Arabinoxylan (AX) is a potential natural food additive that can enhance the textural properties of food. However, the addition of ascorbic acid (AA) can easily lead to a decrease in the viscosity of AX, which poses a challenge in the development of AX-rich foods. Therefore, the purpose of this study is to elucidate the mechanisms behind the reduction in AX viscosity in the presence of AA. The results indicated that AA could reduce the apparent viscosity and molecular weight of AX without significantly affecting the monosaccharide composition, suggesting a potential mechanism related to the cleavage of AX glycosidic bonds. Interestingly, free radicals were present in the reaction system, and the generation of free radicals under different conditions was consistent with the reduction in apparent viscosity of AX. Furthermore, the reduction in AX apparent viscosity by AA was influenced by various factors including AA concentration, reaction time, temperature, pH, and metal ions. These findings suggested that the mechanism of AX degradation may be due to AA-induced free radical generation, leading to non-selective attacks on glycosidic bonds. Therefore, this study revealed that the potential mechanism behind the reduction in AX viscosity induced by AA involved the generation of ascorbic acid radicals.

Dynamics of α-glucan from Agrocybe cylindracea water extract at different developmental stages and its structure characteristics.

Polysaccharides are the important bioactive macromolecules in Agrocybe cylindracea, but their changes are as yet elusive during developmental process. This study investigated the dynamic changes of polysaccharides from A. cylindracea fruiting body water extract at four developmental stages and its structure characteristics. Results revealed that the polysaccharides from A. cylindracea water extract significantly increased at the pileus expansion stage and the increased fraction could be α-glucan. The further purification and identification indicated that this α-glucan was a glycogen. It had typical morphology of ß particles with a molecular weight of 1375 kDa. Its backbone comprised α-D-(1 â†’ 4)-Glcp and α-D-(1 â†’ 4,6)-Glcp residues at a ratio of 5:1, terminated by α-D-Glcp residue. Rheological behavior suggested that it was a Newtonian fluid at the concentration of 1 %. In addition, despite both the glycogen and natural starch were composed of D-glucose, they exhibited the entirely distinct Maltese cross characteristic and unique crystalline structure. This study is the first to demonstrate the presence of abundant glycogen in the pileus expansion stage of A. cylindracea, which provides new insights on the change patterns of fungal polysaccharides.

Changes of the Physicochemical Properties and Structural Characteristics of Alkali-Extracted Polysaccharides from Agrocybe cylindracea Across the Growth Process.

Polysaccharides derived from Agrocybe cylindracea have been demonstrated to exhibit various bioactivities. However, studies on their structural characteristics during the growth process are limited. This study aimed to compare the physicochemical properties and structural characteristics of alkali-extracted polysaccharides from A. cylindracea fruiting bodies (JACP) across four growth stages. Results showed that the extraction yields and protein levels of JACP declined along with the growth of A. cylindracea, while the contents of neutral sugar and glucose increased significantly. However, JACP exhibited structural characteristics similar to those across the four stages. Four polysaccharide subfractions were isolated from each growth stage, including JACP-Et30, JACP-Et50, JACP-Et60, and JACP-Et70. JACP-Et30 from the four stages and JACP-Et50 from the initial three stages were identified as heteroglucans with ß-1,3-d-Glcp and ß-1,6-d-Glcp residues as main chains, respectively. However, other subfractions were considered as ß-1,6-d-glucans containing minor glucuronic acid. These subfractions were predominantly replaced by Glcp residues at the O-3 and O-6 positions. Overall, while JACP exhibited variable physicochemical properties, its structural characteristics remained stable during the growth process, offering new insights into its potential applications in the food and medicinal industries.

Insights into dynamic evolution of glucuronofucogalactoglucan from water extract of Agrocybe cylindracea during maturation.

This study explored the physicochemical properties and structural characteristics of Agrocybe cylindracea polysaccharides at four developmental stages, as well as their dynamic evolution during maturation. Results showed that the polysaccharides from A. cylindracea water extract exhibited similar structural characteristics across all four maturity stages, despite a significant reduction in yields. Four water-soluble heteroglycans, including one high molecular weight (ACPM-Et50-I) and three low molecular weight (ACPM-Et50-II, ACPM-Et60, ACPM-Et80), were isolated from A. cylindracea at each maturity stage. ACPM-Et50-I was identified as branched heterogalactans, while ACPM-Et60 and ACPM-Et80 were branched heteroglucans. However, ACPM-Et50-II was characterized as a branched glucuronofucogalactoglucan at the tide-turning stage but a glucuronofucoglucogalactan at the pileus expansion stage due to the increase of its α-(1 â†’ 6)-D-Galp. In general, although the structural skeletons of most A. cylindracea heteroglycans were similar during maturation as shown by their highly consistent glycosyl linkages, there were still differences in the distribution of some heteroglucans. This work has for the first time reported a glucuronofucogalactoglucan in A. cylindracea and its dynamic evolution during maturation, which may facilitate the potential application of A. cylindracea in food and biomedicine industries.

Factors associated with heterochronic gastric cancer development post-endoscopic mucosal dissection in early gastric cancer patients.

BACKGROUND: Endoscopic mucosal resection is an innovative method for treating early gastric cancer and has been widely used in clinical practice. AIM: To analyze the factors associated with the development of heterochronic gastric cancer in patients with early gastric cancer who had undergone endoscopic mucosal dissection (EMD). METHODS: A cohort of patients with early gastric cancer treated using EMD was retrospectively analyzed, and patients who developed heterochronic gastric cancer after the surgery were compared with those who did not. The effects of patient age, sex, tumor size, pathological type, and surgical technique on the development of heterochronic gastric cancer were assessed using statistical analysis. RESULTS: Of the 300 patients with early gastric cancer, 150 patients developed heterochronic gastric cancer after EMD. Statistical analysis revealed that patient age (P value = XX), sex (P value = XX), tumor size (P value = XX), pathological type (P value = XX), and surgical technique (P value = XX) were significantly associated with the occurrence of heterochronic gastric cancer. CONCLUSION: Age, sex, tumor size, pathological type, and surgical technique are key factors influencing the occurrence of heterochronic gastric cancer after EMD in patients with early gastric cancer. To address these factors, postoperative follow-up and management should be strengthened to improve the prognosis and survival rate of patients.

[Effect of miR-199a regulating IGF1 expression on differentiation of osteoblasts under mechanical stimulation].

PURPOSE: To investigate the expression change of microRNA (miR) - 199a in MC3T3-E1 cells stimulated by mechanical stretch and its mechanism of osteogenic differentiation. METHODS: MC3T3-E1 cells cultured in vitro were loaded with 12% stretch for 0, 3, 6, 12 and 24 hours, alkaline phosphatase (ALP) activity was detected by ALP activity test kit, the expressions of osteocalcin (OCN), osteoblast specific transcription factor osterix (OSX), Runt related transcription factor 2 (Runx2) mRNA and miR-199a were detected by real-time fluorescence quantitative PCR. MC3T3-E1 cells were divided into control group, stretch group, stretch + miR-NC group and stretch + miR-199a group, and the expressions of miR-199a, OCN, OSX, Runx2 mRNA and protein and ALP activity were observed after 12% stretch and transfection of miR-199a. Alizarin red S (ARS) staining was used to observe calcium nodule formation ability. The target relationship between miR-199a and insulin like growth factor-1 (IGF1) was detected by double luciferase reporter gene assay; in addition, the effect of miR-199a mimic on IGF1 mRNA and protein expression was detected by real-time fluorescent quantitative PCR and Western blot. SPSS 24.0 software package was used to analyze the data. RESULTS: Compared with those at the time point of 0 h, ALP activity and expression level of OCN, OSX and Runx2 mRNA of MC3T3-E1 cells at 3, 6, 12 and 24 hours after mechanical stretch stimulation were significantly higher, while the expression level of miR-199a was significantly lower(P＜0.05), and the change was most significant at 12 h. Compared with those in the control group, the expression level of miR-199a was significantly lower in the stretch group, while ALP activity, the expression level of OCN, OSX and Runx2 mRNA and protein, calcium nodule formation level were significantly high in the stretch group(P＜0.05); there was no significant difference in the above indexes between the stretch group and stretch + miR-NC group(P＞0.05). Compared with stretch + miR-NC group, the expression level of miR-199a in stretch + miR-199a group was significantly higher; while ALP activity, OCN, OSX, Runx2 mRNA and protein expression level, calcium nodule formation level were significantly lower(P＜0.05). miR-199a could targetedly bind to IGF1, and the expression level of IGF1 mRNA and protein in MC3T3-E1 cells was significantly reduced by miR-199a mimic(P＜0.05). CONCLUSIONS: MiR-199a can inhibit the osteogenic differentiation of MC3T3-E1 cells induced by mechanical stretch stimulation, and its mechanism may be related to the targeted regulation of IGF1 expression.

Solitary primary pulmonary synovial sarcoma: A case report.

BACKGROUND: Synovial sarcoma (SS) is an uncommon and highly malignant soft tissue sarcoma in the clinic, with primary pulmonary SS (PPSS) being extremely rare. Here, we describe the clinical characteristics, diagnosis, and treatment of a solitary PPSS case confirmed via surgical resection and fluorescence in situ hybridization (FISH). CASE SUMMARY: A 33-year-old man was admitted because of intermittent coughing and hemoptysis for one month, with lung shadows observed for two years. Whole-body positron emission tomography-computed tomography (PET-CT) revealed a solitary mass in the upper lobe of the right lung, with uneven radioactivity uptake and a maximum standardized uptake value of 5.6. The greyish-yellow specimen obtained following thoracoscopic resection was covered with small multi-nodulated structures and consisted of soft tissue. Hematoxylin and eosin staining revealed spindle-shaped malignant tumor cells. Immunohistochemistry indicated these tumor cells were CD99 and BCL-2-positive. Furthermore, the FISH test revealed synovial sarcoma translocation genetic reassortment, which confirmed the diagnosis of SS. CONCLUSION: PPSS is extremely rare and tends to be misdiagnosed as many primary pulmonary diseases. PET-CT, histologic analysis, and FISH tests can be used to differentiate PPSS from other diseases. Surgical resection is regularly recommended for the treatment of solitary PPSS and is helpful for improving the prognosis.

Enhanced Degradation of Juvenile Hormone Promotes Reproductive Diapause in the Predatory Ladybeetle Coccinella Septempunctata.

Improved knowledge on the regulation of reproductive diapause in Coccinella septempunctata, an important predator of aphids, is crucial for improving shelf-life and mass production of the ladybeetles. In many insects, the absence of juvenile hormone (JH) is a central regulator of reproductive diapause. JH is principally degraded by JH esterase (JHE) and JH epoxide hydrolase (JHEH). Previous studies have shown that genes encoding these enzymes were upregulated in early diapause of C. septempunctata, but whether increased JH degradation contributes to the reduction of JH levels and facilitates reproductive diapause remains unknown. Here, we investigate the role of JH and JH degradation genes during reproductive diapause in C. septempunctata females. Applying methoprene, a JH analogue, to the diapause preparation females clearly elevated JH signaling and reversed diapause program, suggesting that a lower level of JH is critical for the induction of reproductive diapause in the ladybeetle. Full-length cDNA sequences of JHE and JHEH were cloned and characterized, and their deduced proteins contain all the conserved active domains and typical motifs as identified in other insects. The expressions of JHE and JHEH were both significantly increased in diapause preparation and remained at a high level for a period throughout diapause, and then decreased after the termination of diapause. Knocking down these JH degradation genes clearly increased the expression levels of JH-inducible genes Krüppel-homolog 1 (Kr-h1) and vitellogenin (Vg), indicating an elevated JH level. Simultaneously, silencing JH degradation genes distinctly reduced diapause-related features and promotes reproduction, indicated by accelerated ovary growth, yolk deposition, and suppressed lipid accumulation. These results indicate that the enhanced JH degradation plays a critical role in regulating reproductive diapause of C. septempunctata.

Intranasal insulin ameliorates neurological impairment after intracerebral hemorrhage in mice.

In Alzheimer's disease and ischemic stroke, intranasal insulin can act as a neuroprotective agent. However, whether intranasal insulin has a neuroprotective effect in intracerebral hemorrhage and its potential mechanisms remain poorly understood. In this study, a mouse model of autologous blood-induced intracerebral hemorrhage was treated with 0.5, 1, or 2 IU insulin via intranasal delivery, twice per day, until 24 or 72 hours after surgery. Compared with saline treatment, 1 IU intranasal insulin treatment significantly reduced hematoma volume and brain edema after cerebral hemorrhage, decreased blood-brain barrier permeability and neuronal degeneration damage, reduced neurobehavioral deficits, and improved the survival rate of mice. Expression levels of p-AKT and p-GSK3ß were significantly increased in the perihematoma tissues after intranasal insulin therapy. Our findings suggest that intranasal insulin therapy can protect the neurological function of mice after intracerebral hemorrhage through the AKT/GSK3ß signaling pathway. The study was approved by the Ethics Committee of the North Sichuan Medical College of China (approval No. NSMC(A)2019(01)) on January 7, 2019.

Structural insights into the substrate tunnel of Saccharomyces cerevisiae carbonic anhydrase Nce103.

BACKGROUND: The carbonic anhydrases (CAs) are involved in inorganic carbon utilization. They have been classified into six evolutionary and structural families: alpha-, beta-, gamma-, delta-, epsilon-, zeta- CAs, with beta-CAs present in higher plants, algae and prokaryotes. The yeast Saccharomyces cerevisiae encodes a single copy of beta-CA Nce103/YNL036W. RESULTS: We determined the crystal structure of Nce103 in complex with a substrate analog at 2.04 A resolution. It assembles as a homodimer, with the active site located at the interface between two monomers. At the bottom of the substrate pocket, a zinc ion is coordinated by the three highly conserved residues Cys57, His112 and Cys115 in addition to a water molecule. Residues Asp59, Arg61, Gly111, Leu102, Val80, Phe75 and Phe97 form a tunnel to the bottom of the active site which is occupied by a molecule of the substrate analog acetate. Activity assays of full length and two truncated versions of Nce103 indicated that the N-terminal arm is indispensable. CONCLUSION: The quaternary structure of Nce103 resembles the typical plant type beta-CAs of known structure, with an N-terminal arm indispensable for the enzymatic activity. Comparative structure analysis enables us to draw a possible tunnel for the substrate to access the active site which is located at the bottom of a funnel-shaped substrate pocket.