Real-time continuous glucose monitoring-guided glucose management in inpatients with diabetes receiving short-term continuous subcutaneous insulin infusion: a randomized clinical trial.

Background: The use of real-time continuous glucose monitoring (rtCGM) technology remains largely investigational in the hospital setting. The current study aimed to evaluate the effectiveness of rtCGM in inpatients with diabetes who were treated with short-term continuous subcutaneous insulin infusion (CSII). Methods: In this randomized, parallel controlled trial conducted on the endocrinology wards in a tertiary hospital located in Shanghai, adults with type 1 and type 2 diabetes who required short-term CSII during hospitalization were randomly assigned (1:1) to receive either rtCGM-based glucose monitoring and management program or point-of-care (POC) standard of care (8 times/day) with blinded CGM. Primary outcome measure was the difference in the percentage of time within the target glucose range of 3.9-10 mmol/L (TIR, %). This study was registered at www.chictr.org.cn (ChiCTR2300068933). Findings: Among the 475 randomized participants (237 in the rtCGM group and 238 in the POC group), the mean age of was 60 ± 13 years, and the mean baseline glycated hemoglobin level was 9.4 ± 1.8%. The CGM-recorded mean TIR was 71.1 ± 15.8% in the rtCGM group and 62.9 ± 18.9% in the POC group, with a mean difference of 8.2% (95% confidence interval [CI]: 5.1-11.4%, P < 0.001). The mean time above range >10 mmol/L was significantly lower in the rtCGM group than in the POC group (28.3 ± 15.8% vs. 36.6 ± 19.0%, P < 0.001), whereas there was no significant between-group difference in the time below range <3.9 mmol/L (P = 0.11). Moreover, the time to reach target glucose was significantly shorter in the rtCGM group than in the POC group (2.0 [1.0-4.0] days vs. 4.0 [2.0-5.0] days, P < 0.001). There were no serious adverse events in both groups. Interpretation: In patients with diabetes who received short-term CSII during hospitalization, the rtCGM program resulted in better glucose control than the POC standard of care, without increasing the risk of hypoglycemia. Funding: The Program of Shanghai Academic Research Leader (22XD1402300), Shanghai Oriental Talent Program (Youth Project) (No. NA), the Shanghai "Rising Stars of Medical Talent" Youth Development Program-Outstanding Youth Medical Talents (SHWSRS(2021)_099), and the Shanghai Research Center for Endocrine and Metabolic Diseases (2022ZZ01002).

Dual-site molecular glues for enhancing protein-protein interactions of the CDK12-DDB1 complex.

Protein-protein interactions (PPIs) stabilization with molecular glues plays a crucial role in drug discovery, albeit with significant challenges. In this study, we propose a dual-site approach, targeting the PPI region and its dynamic surroundings. We conduct molecular dynamics simulations to identify critical sites on the PPI that stabilize the cyclin-dependent kinase 12 - DNA damage-binding protein 1 (CDK12-DDB1) complex, resulting in further cyclin K degradation. This exploration leads to the creation of LL-K12-18, a dual-site molecular glue, which enhances the glue properties to augment degradation kinetics and efficiency. Notably, LL-K12-18 demonstrates strong inhibition of gene transcription and anti-proliferative effects in tumor cells, showing significant potency improvements in MDA-MB-231 (88-fold) and MDA-MB-468 cells (307-fold) when compared to its precursor compound SR-4835. These findings underscore the potential of dual-site approaches in disrupting CDK12 function and offer a structural insight-based framework for the design of cyclin K molecular glues.

PD-1 inhibitor combined with SBRT, GM-CSF, and thymosin alpha-1 in metastatic breast cancer: A case report and literature review.

RATIONALE: Triple-negative breast cancer is characterized by a worse prognosis compared with other breast cancer subtypes, especially in the case of pretreated metastatic triple-negative breast cancer (mTNBC). Because of the limited treatment options and suboptimal response rates, there is a pressing need to explore novel treatment protocols. PATIENT CONCERNS: A 48-year-old female patient diagnosed with mTNBC who had not responded to multiple lines of therapy (including surgery, chemotherapy, and radiotherapy) but demonstrated significant efficacy and abscopal effects after enrolling in our clinical trial. DIAGNOSES: Triple-negative breast cancer with lung metastases. INTERVENTIONS: The clinical trial combined stereotactic body radiotherapy, immunotherapy, granulocyte-macrophage colony-stimulating factor, and thymosin alpha-1 to treat previously treated metastatic solid cancers. OUTCOMES: This combined treatment regimen implemented in this clinical trial yielded the patient's notable efficacy, accompanied by abscopal effects. The target lesion and the 3 observed lesions achieved a partial response according to the RECIST v1.1 criteria. reevaluation scans after 2 cycles of immunotherapy indicated a regression rate of -78.97% for the target lesion and -56.73% for the observed lesions. Hematological indexes were stable, and there was no apparent myelosuppression. Also, the tumor marker CA-199 exhibited a downward trend. During the course of treatment, the patient experienced a grade 2 skin reaction, which improved after receiving antiallergic treatment. No further adverse effects were observed. LESSONS: This treatment regimen may offer a promising treatment strategy for patients with mTNBC and other metastatic solid cancers.

A Super-Adhesive 2D Diamond Smart Nanofluid with Self-Healing Properties and Multifunctional Applications.

Smart responsive materials are capable of responding to external stimuli and, compared to traditional materials, can be effectively reused and reduce usage costs in applications. However, smart responsive materials often face challenges such as the inability to repair extensive damage, instability in long-term performance, and inapplicability in extreme environments. This study combines 2D diamond nanosheets with organic fluorinated molecules to prepare a smart nanofluid (fluorinated diamond nanosheets, F-DN) with self-healing and self-adhesion properties. This smart nanofluid can be used to design various coatings for different applications. For example, coatings prepared on textured steel plates using the drop-casting method have excellent superhydrophobic and high oleophobic properties; coatings on titanium alloy plates achieve low friction and wear in the presence of lubricating additives of F-DN in perfluoropolyether (PFPE). Most impressively, coatings on steel plates not only provide effective corrosion resistance but also have the ability to self-heal significant damage (approximately 2 mm in width), withstand extremely low temperatures (-64 °C), and resist long-term corrosion factors (immersion in 3.5 wt % NaCl solution for 35 days). Additionally, it can act as a "coating glue" to repair extensive damage to other corrosion-resistant organic coatings and recover their original protective properties. Therefore, the smart nanofluid developed in this study offers diverse applications and presents new materials system for the future development of smart responsive materials.

Doping Engineering in Manganese Oxides for Aqueous Zinc-Ion Batteries.

Manganese oxides (MnxOy) are considered a promising cathode material for aqueous zinc-ion batteries (AZIBs) due to their high theoretical specific capacity, various oxidation states and crystal phases, and environmental friendliness. Nevertheless, their practical application is limited by their intrinsic poor conductivity, structural deterioration, and manganese dissolution resulting from Jahn-Teller distortion. To address these problems, doping engineering is thought to be a favorable modification strategy to optimize the structure, chemistry, and composition of the material and boost the electrochemical performance. In this review, the latest progress on doped MnxOy-based cathodes for AZIBs has been systematically summarized. The contents of this review are as follows: (1) the classification of MnxOy-based cathodes; (2) the energy storage mechanisms of MnxOy-based cathodes; (3) the synthesis route and role of doping engineering in MnxOy-based cathodes; and (4) the doped MnxOy-based cathodes for AZIBs. Finally, the development trends of MnxOy-based cathodes and AZIBs are described.

Multi-metabolomics and intestine microbiome analysis: YZC extract ameliorates septic-ALI by modulating intestine microbiota to reduce TMAO/NLRP3 signaling.

BACKGROUND: Sepsis causes inflammation in response to infection, often leading to acute lung injury (ALI). Yazhicao (Commelina communis L., YZC) is widely distributed in the global tropics and has good anti-respiratory inflammatory activity; however, the protection of YZC against septic-ALI has not been established. PURPOSE: The role of YZC in septic-ALI will be investigated in this study. METHODS AND RESULTS: In this study, YZC was shown to inhibit excessive inflammation and alleviate septic-ALI. Network pharmacology predicts that Quercetin, Acacetin and Diosmetin have the potential to serve as the pharmacological substance basis of YZC in alleviating septic-ALI. The metabolomics results indicated that YZC could improve the metabolic disorders caused by septic-ALI, which were mostly concerned with energy metabolism and amino acid metabolism, with Trimethylamine (TMA)/Trimethylamine N-oxide (TMAO) being potential small molecule metabolic markers for the clinical diagnosis and treatment of septic-ALI. YZC inhibits the initiation and progression of septic-ALI by controlling the TMA/TMAO metabolites. Our results also suggest that YZC protects the intestinal barrier from damage. Furthermore, our research indicated that YZC reduces TMAO synthesis by inhibiting TMA production through remodeling the intestine microbiota. We investigated the mechanism of YZC-mediated protection against septic-ALI and showed that YZC reduced the expression of proteins associated with NLRP3 inflammatory vesicles in the lung by inhibiting the expression of NF-κB. CONCLUSION: These results show that YZC inhibits the NF-κB/NLRP3 signaling pathway by regulating metabolic and intestinal flora disorders in septic-ALI mice to reduce TMAO synthesis. This study presents a theoretical groundwork for the advancement of novel medications and clinical use of YZC to enhance septic-ALI and furnishes a theoretical rationale for regulating intestinal microbiota as a therapeutic instrument to treat sepsis and septic-ALI.

Research on traditional Chinese medicine as an effective drug for promoting wound healing.

ETHNOPHARMACOLOGICAL RELEVANCE: The incidence of skin trauma is high and the repair process is complex, often leading to poor healing and other issues, which can result in significant economic and social burdens. Traditional Chinese medicine (TCM) is a valuable resource with proven effectiveness and safety in wound repair, widely utilized in clinical practice. A systematic analysis of wound healing with a focus on TCM research progress holds both academic and clinical importance. AIM OF THE REVIEW: This article reviews the research progress of TCM in promoting wound healing, and provides basic data for the development of innovative drugs that promote wound healing. MATERIALS AND METHODS: This article provides a review of the literature from the past decade and conducts a thorough analysis of various databases that contain reports on the use of TCM for wound repair. The data for this systematic research was gathered from electronic databases including CNKI, SciFinder, and PubMed. The study explores and summarizes the research findings and patterns by creating relevant charts. RESULTS: This study reviewed the mechanism of wound healing, experimental TCM methods to promote wound healing, the theory and mode of action of TCM to promote wound healing, the active ingredients of TCM that promote wound healing, the efficacy of TCM formulae to promote wound healing, and the potential toxicity of TCM and its antidotes. This study enriched the theory of TCM in promoting wound healing. CONCLUSION: Skin wound healing is a complex process that can be influenced by various internal and external factors. This article offers a theoretical foundation for exploring and utilizing TCM resources that enhance wound repair. By analyzing a range of TCM that promote wound healing, the article highlights the clinical importance and future potential of these medicines in promoting wound healing.

Effects of ambient temperature, relative humidity and absolute humidity on risk of nasopharyngeal carcinoma in China.

Nasopharyngeal carcinoma (NPC) has a unique geographic distribution. It is unknown whether meteorological factors are related to the incidence of NPC. To investigate the effect of ambient temperature, relative humidity (RH), and absolute humidity (AH) on the incidence of NPC, we collected the incidence rate of NPC in 2016 and meteorological data from 2006 to 2016 from 484 cities and counties across 31 provinces in China. Generalized additive models with quasi-Poisson regression and generalized linear models with natural cubic splines were employed respectively to elucidate the nonlinear relationships and specify the partial linear relationships. Subgroup and interactive analysis were also conducted. Temperature (R2 = 0.68, p < .001), RH (R2 = 0.47, p < .001), and AH (R2 = 0.70, p < .001) exhibited nonlinear correlations with NPC incidence rate. The risk of NPC incidence increased by 20.3% (95% confidence intervals [CI]: [18.9%, 21.7%]) per 1°C increase in temperature, by 6.3% (95% CI: [5.3%, 7.2%]) per 1% increase in RH, and by 32.2% (95% CI: [30.7%, 33.7%]) per 1 g/m3 increase in AH, between their the 25th and the 99th percentiles. In addition, the combination of low temperature and low RH was also related to increased risk (relative risk: 1.60, 95% CI: [1.18, 2.17]). Males and eastern or rural populations tended to be more vulnerable. In summary, this study suggests that ambient temperature, RH, and particularly AH are associated with the risk of NPC incidence.

Stable composition of gut microbiome in the Asian ladybeetle Coccinella septempunctata reared on natural and artificial diets.

The Asian ladybeetle, Coccinella septempunctata, is an important insect of predatory natural enemy, which has a strong control effect and application prospects for aphids, whiteflies, mealybugs, and other small-sized pests of agriculture and forestry crops. Gut microbiota composition posed impacts on development of insects. In order to clarify the effect of artificial feed feeding on the intestinal microbial species and structure of C. septempunctata, we compared the intestinal microbial flora of C. septempunctata reared on bean aphids and artificial food for 15 days. Results show that Proteobacteria was the dominant component in all groups at phylum level, Rhodobacter, Methylovigula, Burkholderia, and Bradyrhizobium were the dominant bacteria among all groups at genus level. As to the differences in bacterial community structure and diversity, there is no significant difference between Shannon index and Simpson index, the principal components analysis of the bacterial communities, and the samples were roughly distributed in different regions. After 15 days of feeding, artificial diet did not significantly reduce the microbial diversity of the gut of C. septempunctata compared to the aphid group, and there was no significant effect on the abundance of dominant flora in the gut of C. septempunctata, C. septempunctata gut has a similar core microbiota. This study clarifies the effects in intestinal microbial diversity and composition structure of the C. septempunctata with artificial diet, and provides a theoretical basis for understanding the intestinal microorganisms and optimizating the artificial diet of C. septempunctata.

Genus Physalis L.: A review of resources and cultivation, chemical composition, pharmacological effects and applications.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Physalis L. (Solanaceae) is commonly used in the treatment of dermatitis, leprosy, bronchitis, pneumonia, hepatitis and rheumatism in China and other Asian countries. AIM OF THE REVIEW: This article reviews the resources, cultivation, phytochemistry, pharmacological properties, and applications of Physalis L., and proposes further research strategies to enhance its therapeutic potential in treating various human diseases. MATERIALS AND METHODS: We conducted a systematic search of electronic databases, including CNKI, SciFinder and PubMed, using the term "Physalis L." to collect information on the resources, phytochemistry, pharmacological activities, and applications of Physalis L. in China during the past ten years (2013.1-2023.1). RESULTS: So far, a variety of chemical constituents have been isolated and identified from Physalis L. mainly including steroids, flavonoids, and so on. Various pharmacological activities were evaluated by studying different extracts of Physalis L., these activities include anti-inflammatory, antibacterial, antioxidant, antiviral, antineoplastic, and other aspects. CONCLUSION: Physalis L. occupies an important position in the traditional medical system. It is cost-effective and is a significant plant with therapeutic applications in modern medicine. However, further in-depth studies are needed to determine the medical use of this plant resources and cultivation, chemical composition, pharmacological effects and applications.

Unclassified glutathione-S-transferase AiGSTu1 confers chlorantraniliprole tolerance in Agrotis ipsilon.

BACKGROUND: Chlorantraniliprole (CAP) is a diamide insecticide with high efficacy against many pest insects, including the black cutworm, Agrotis ipsilon. Agrotis ipsilon is a serious pest causing significant yield losses in crops. Glutathione-S-transferases (GSTs) belong to a family of metabolic enzymes that can detoxify a wide range of pesticides. However, little is known about the functions of GSTs in CAP tolerance in A. ipsilon. RESULTS: A cDNA sequence (designated AiGSTu1) encoding an unclassified GST was identified from A. ipsilon. AiGSTu1 is highly expressed during the 3rd -instar larval and the pupal stages. Most of the mRNA transcripts were found in larval Malpighian tubules. Exposure to CAP strongly enhanced AiGSTu1 expression, GST activity, hydrogen peroxide (H2 O2 ) and malondialdehyde levels in larvae. H2 O2 treatment upregulated the transcription level of AiGSTu1, suggesting that CAP-induced oxidative stress may activate AiGSTu1 expression. The activity of recombinant AiGSTu1 was inhibited by CAP in a dose-dependent manner. Metabolism assay results demonstrated that AiGSTu1 is capable of depleting CAP. Overexpression of AiGSTu1 enhanced the tolerance of Escherichia coli cells to H2 O2 and the oxidative stress inducer, cumene hydroperoxide. Silencing of AiGSTu1 by RNA interference increased the susceptibility of A. ipsilon larvae to CAP. CONCLUSION: The findings of this study provide valuable insights into the potential role of AiGSTu1 in CAP detoxification and will improve our understanding of CAP tolerance in A. ipsilon. © 2023 Society of Chemical Industry.

A metabolism-based study of the mechanism of action of Scrophularia ningpoensis Hemsl. on nephrogenic edema.

Nephrogenic edema (NE) is a type of edema with hypoproteinemia and water and sodium retention as a result of renal injury. Traditional Chinese medicine has proved that Scrophularia ningpoensis Hemsl. has an effect on NE, but its mechanism is not clear. In this study, the main components and blood components of S. ningpoensis were identified using ultra-high-performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry (UPLC-Q-TOF-MS). Pathological section and blood biochemical analysis were used to estimate the therapeutic effect of S. ningpoensis on NE. Network pharmacology was used to predict the potential pathways of S. ningpoensis. The metabolomics method was used to study the changes in small-molecule metabolites in the body. The results showed that S. ningpoensis could relieve NE by regulating relative to renal function and body edema, and its mechanism may be related to the regulation of energy metabolism, recovery of renal injury, and reduction in inflammation. The active component harpagoside may be one of the important compounds of S. ningpoensis in the treatment of NE. We confirmed that S. ningpoensis has a therapeutic effect on NE, which provides a solid scientific research basis for the clinical application of S. ningpoensis.

Anemarrhena asphodeloides Bunge total saponins ameliorate diabetic cardiomyopathy by modifying the PI3K/AKT/HIF-1α pathway to restore glycolytic metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Based on the theory of traditional Chinese medicine (TCM), diabetic cardiomyopathy (DCM) belongs to the category of "Xiaoke disease" according to the symptoms, and "stasis-heat" is the main pathogenesis of DCM. The Chinese medicine Anemarrhena asphodeloides Bunge (AAB), as a representative of heat-clearing and engendering fluid, is often used clinically in the treatment of DCM. Anemarrhena asphodeloides Bunge total saponins (RATS) are the main bioactive components of AAB, the modern pharmacologic effects of RATS are anti-inflammatory, hypoglycemic, and cardioprotective. However, the potential protective mechanisms of RATS against DCM remain largely undiscovered. AIM OF THE STUDY: The primary goal of this study was to explore the effect of RATS on DCM and its mechanism of action. MATERIALS AND METHODS: Streptozotocin and a high-fat diet were used to induce DCM in rats. UHPLC/Q-TOF-MS was used to determine the chemical components of RATS. The degenerative alterations and apoptotic cells in the heart were assessed by HE staining and TUNEL. Network pharmacology was used to anticipate the probable targets and important pathways of RATS. The alterations in metabolites and main metabolic pathways in heart tissue were discovered using 1 H-NMR metabolomics. Ultimately, immunohistochemistry was used to find critical pathway protein expression. RESULTS: First of all, UHPLC/Q-TOF-MS analysis showed that RATS contained 11 active ingredients. In animal experiments, we found that RATS lowered blood glucose and lipid levels in DCM rats, and alleviated cardiac pathological damage, and decreased cardiomyocyte apoptosis. Furthermore, the study found that RATS effectively reduced inflammatory factor release and the level of oxidative stress. Mechanistically, RATS downregulated the expression levels of PI3K, AKT, HIF-1α, LDHA, and GLUT4 proteins. Additionally, glycolysis was discovered to be a crucial pathway for RATS in the therapy of DCM. CONCLUSIONS: Our findings suggest that the protective effect of RATS on DCM may be attributed to the inhibition of the PI3K/AKT/HIF-1α pathway and the correction of glycolytic metabolism.

Epsilon Class Glutathione S-Transferase Confers Phoxim Tolerance in the Black Cutworm Agrotis ipsilon (Lepidoptera: Noctuidae).

The black cutworm Agrotis ipsilon is a serious crop pest. Phoxim, an organophosphorus insecticide, has been widely used to control A. ipsilon. When phoxim is extensively applied, the susceptibility of A. ipsilon to insecticide is reduced. However, the mechanisms of tolerance of A. ipsilon to phoxim remain unclear. Herein, we report that an epsilon class glutathione S-transferase, AiGSTE1, confers phoxim tolerance in A. ipsilon. Exposure to a sublethal concentration (LC50) of phoxim caused oxidative stress and activated the transcription of AiGSTe1 genes in A. ipsilon larvae. Recombinant AiGSTE1 expressed in Escherichia coli could metabolize phoxim. Furthermore, E. coli cells overexpressing AiGSTE1 displayed significant tolerance to oxidative stress. Knockdown of AiGSTe1 by RNA interference significantly increased the mortality of A. ipsilon larvae to phoxim. These results demonstrate that AiGSTE1 confers phoxim tolerance in A. ipsilon by metabolizing the insecticide and preventing phoxim-induced oxidative stress.

Condensed tannin accretions specifically distributed in mesophyll cells of non-salt secretor mangroves help in salt tolerance.

MAIN CONCLUSION: Auto-fluorescent condensed tannins specifically accumulated in mesophyll cells of non-salt secretor mangroves are involved in the compartmentation of Na+ and osmotic regulation, contributing to their salt tolerance. Salinity is a major abiotic stress affecting the distribution and growth of mangrove plants. The salt exclusion mechanism from salt secretor mangrove leaves is quite known; however, salt management strategies in non-salt secretor leaves remain unclear. In this study, we reported the auto-fluorescent inclusions (AFIs) specifically accumulated in mesophyll cells (MCs) of four non-salt secretor mangroves but absent in three salt secretors. The AFIs increased with the leaf development under natural condition, and applied NaCl concentrations applied in the lab. The AFIs in MCs were isolated and identified as condensed tannin accretions (CTAs) using the dye dimethyl-amino-cinnamaldehyde (DMACA), specific for condensed tannin (CT), both in situ leaf cross sections and in the purified AFIs. Fluorescence microscopy and transmission electron microscope (TEM) analysis indicated that the CTAs originated from the inflated chloroplasts. The CTAs had an obvious membrane and could induce changes in shape and fluorescence intensity in hypotonic and hypertonic NaCl solutions, suggesting CTAs might have osmotic regulation ability and play an important role in the osmotic regulation in MCs. The purified CTAs were labeled by the fluorescent sodium-binding benzofuran isophthalate acetoxymethyl ester (SBFI-AM), confirming they were involved in the compartmentation of excess Na+ in MCs. This study provided a new view on the salt resistance-associated strategies in mangroves.

High-Performance Vertical Light-Emitting Transistors Based on ZnO Transistor/Quantum-Dot Light-Emitting Diode Integration and Electron Injection Layer Modification.

Vertical light-emitting transistors (VLETs) consisting of vertically stacked unipolar transistors and organic light-emitting diodes (OLEDs) have been proposed as a prospective building block for display technologies. In addition to OLEDs, quantum-dot (QD) LEDs (QLEDs) with high brightness and high color purity have also become attractive light-emitting devices for display applications. However, few studies have attempted to integrate QLEDs into VLETs, as this not only involves technical issues such as compatible solution process of QDs and fine patterning of electrodes in multilayer stacked geometries but also requires a high driving current that is demanding on transistor design. Here we show that these integration issues of QLEDs can be addressed by using inorganic transistors with robust processability and high mobility, such as the studied ZnO transistor, which facilitates simple fabrication of QD VLETs (QVLETs) with efficient emission in the patterned channel area, suitable for high-resolution display applications. We perform a detailed optimization of QVLET by modifying ZnO:polyethylenimine nanocomposite as the electron injection layer (EIL) between the integrated ZnO transistor/QLED, and achieve the highest external quantum efficiency of ~3% and uniform emission in the patterned transistor channel. Furthermore, combined with a systematic study of corresponding QLEDs, electron-only diodes, and electroluminescence images, we provide a deeper understanding of the effect of EIL modification on current balance and distribution, and thus on QVLET performance.

Identification of ZmBK2 Gene Variation Involved in Regulating Maize Brittleness.

Maize stalk strength is a crucial agronomic trait that affects lodging resistance. We used map-based cloning and allelic tests to identify a maize mutant associated with decreased stalk strength and confirmed that the mutated gene, ZmBK2, is a homolog of Arabidopsis AtCOBL4, which encodes a COBRA-like glycosylphosphatidylinositol (GPI)-anchored protein. The bk2 mutant exhibited lower cellulose content and whole-plant brittleness. Microscopic observations showed that sclerenchymatous cells were reduced in number and had thinner cell walls, suggesting that ZmBK2 affects the development of cell walls. Transcriptome sequencing of differentially expressed genes in the leaves and stalks revealed substantial changes in the genes associated with cell wall development. We constructed a cell wall regulatory network using these differentially expressed genes, which revealed that abnormal cellulose synthesis may be a reason for brittleness. These results reinforce our understanding of cell wall development and provide a foundation for studying the mechanisms underlying maize lodging resistance.

Influence of Top Seal Damage on Contact Seal in Ram Blowout Preventer.

Top seal failure of ram blowout preventer (BOP) is one of the main factors leading to well control risk. The constitutive model and parameters of nitrile butadiene rubber (NBR) were optimized by compression and tensile tests, and the failure analysis model of the contact seal of the ram BOP top seal was built. The nonlinear contact mechanical behavior of the connection part of the BOP top seal was analyzed by the finite element method. Then, the influence of corrosion and wear defects at the top seal position of the 2FZ35-70 BOP under rated working pressure on the contact seal were studied, and the results showed that the overall contact pressure distribution of the top seal corrosion defects was uniform, the local contact pressure of the corrosion pit edge increased, and the top contact pressure decreased. The overall contact pressure of the wear defect of the top seal decreased linearly, the contact pressure at the maximum depth of the wear defect was the smallest, and the contact pressure gradually decreased to both sides. Ultimately, to guarantee the safety and reliability of the ram BOP, it is suggested that the acceptable depths of the seal corrosion pit and the wear at the top of the ram BOP are 4.0 mm and 0.2 mm, respectively, thus the reliability evaluation problem of the quantitative seal of the ram BOP top seal is solved.

Black carp RNF5 inhibits STING/IFN signaling through promoting K48-linked ubiquitination and degradation of STING.

Ubiquitination is one of the important post-translational modifications (PTMs) of proteins that plays a vital role in regulating substrate degradation to ensure cellular homeostasis. Ring finger protein 5 (RNF5) is an essential E3 ubiquitin ligase for inhibiting STING-mediated interferon (IFN) signaling in mammals. Nevertheless, the function of RNF5 in STING/IFN pathway remains obscure in teleost. Here, we reported that over-expression of black carp RNF5 (bcRNF5) inhibited STING-mediated transcription activity of bcIFNa, DrIFNφ1, NF-κB and ISRE promoters and antiviral activity against SVCV. Moreover, knockdown of bcRNF5 increased the expression of host genes, including bcIFNa, bcIFNb, bcILß, bcMX1 and bcViperin, and also enhanced the antiviral capability of host cells. Immunofluorescence (IF) and Co-immunoprecipitation (Co-IP) assay confirmed that bcRNF5 was mainly localized in the cytoplasm and interacted with bcSTING. The expression level of bcSTING protein was attenuated by co-expressed bcRNF5 and MG132 treatment rescued this attenuating effect, suggesting that bcRNF5-mediated bcSTING degradation was dependent on the proteasome pathway. Subsequent, Co-IP and immunoblot (IB) experiments identified that bcRNF5 triggered the K48-linked but not K63-linked ubiquitination of bcSTING. Altogether, above results conclude that RNF5 suppresses STING/IFN signaling by enhancing K48-linked ubiquitination and protease degradation of STING in black carp.

ATG16L1 negatively regulates MAVS-mediated antiviral signaling in black carp Mylopharyngodon piceus.

Autophagy related 16 like 1 (ATG16L1) is a crucial component of autophagy that regulates the formation of the autophagosome. In mammals, ATG16L1 also performs important roles in immunity, including controlling viral replication and regulating innate immune signaling; however, investigation on the role of piscine ATG16L1 in immunity is rare. In this report, the ATG16L1 homolog of black carp Mylopharyngodon piceus (bcATG16L1) was cloned and identified, and its negative regulatory role in mitochondrial antiviral signaling protein (MAVS)-mediated antiviral signaling was described. The coding region of bcATG16L1 consists of 1830 nucleotides and encodes 609 amino acids, including one coiled-coil domain at the N-terminus, three low complexity region domains in the middle, and seven WD40 domains at the C-terminus. By immunofluorescence assay and immunoblotting, we found that bcATG16L1 is a cytosolic protein with a molecular weight of ∼74 kDa. In addition, over-expression of bcATG16L1 suppressed bcMAVS-mediated bcIFNa and DrIFNφ1 promoters transcriptional activity and inhibited bcMAVS-mediated antiviral activity. We further confirmed the co-localization of bcATG16L1 and bcMAVS by immunofluorescence assay and verified the protein interaction between bcATG16L1 and bcMAVS by immunoprecipitation assay. Our results report for the first time that black carp ATG16L1 suppresses MAVS-mediated antiviral signaling in teleost fish.