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Human immunodeficiency virus (HIV) continues to be a significant global health challenge despite decades of research and advances in treatment. Substantial gaps in our understanding of the mechanisms of HIV pathogenesis and the host immune responses still exist. The interaction between HIV and these immune responses is pivotal in the disease progression to acquired immunodeficiency syndrome (AIDS). Recently, the caspase recruitment domain-containing protein 8 (CARD8) inflammasome has emerged as a crucial factor in orchestrating innate immune responses to HIV infection and exerting a substantial impact on viral pathogenesis. CARD8 restricts viral replication by detecting the activity of HIV protease. Conversely, it also contributes to the depletion of CD4+ T cells, a key feature of disease progression towards AIDS. The purpose of this review is to summarize the role of the CARD8 inflammasome in HIV pathogenesis, delving into its mechanisms of action and potential implications for the development of therapeutic strategies.

Permanent magnet synchronous motor (PMSM) speed control systems with conventional linear active disturbance rejection control (CLADRC) strategy encounter issues regarding the coupling between dynamic response and disturbance suppression and have poor performance in suppressing complex nonlinear disturbances. In order to address these issues, this paper proposes an improved two-degree-of-freedom LADRC (TDOF-LADRC) strategy, which can enhance the disturbance rejection performance of the system while decoupling entirely the system's dynamic and anti-disturbance performance to boost the system robustness and simplify controller parameter tuning. PMSM models that consider total disturbances are developed to design the TDOF-LADRC speed controller accurately. Moreover, to evaluate the control performance of the TDOF-LADRC strategy, its stability is proven, and the influence of each controller parameter on the system control performance is analyzed. Based on it, a comparison is made between the disturbance observation ability and anti-disturbance performance of TDOF-LADRC and CLADRC to prove the superiority of TDOF-LADRC in rejecting disturbances. Finally, experiments are performed on a 750 W PMSM experimental platform, and the results demonstrate that the proposed TDOF-LADRC exhibits the properties of two degrees of freedom and improves the disturbance rejection performance of the PMSM system.

Abstract Purpose To compare the safety and efficacy of CPG in the rectus abdominis and intercostal regions. Materials and methods This retrospective study included 226 patients who underwent CPG at a single center, with the stoma placed in the rectus abdominis or intercostal region. Surgical outcomes and complications, such as pain and infection within 6 months postoperatively, were recorded. Results The surgical success rate was 100%, and the all-cause mortality rate within 1 month was 0%. An intercostal stoma was placed in 56 patients; a rectus abdominis stoma was placed in 170 patients. The duration of surgery was longer for intercostal stoma placement (37.66 ± 14.63 min) than for rectus abdominis stoma placement (30.26 ± 12.40 min) (P = 0.000). At 1 month postsurgery, the rate of stoma infection was greater in the intercostal group (32.1%) than in the rectus abdominis group (20.6%), but the difference was not significant (P = 0.077). No significant difference was observed in the infection rate between the two groups at 3 or 6 months postsurgery (P > 0.05). Intercostal stoma patients reported higher pain scores during the perioperative period and at 1 month postsurgery (P = 0.000), but pain scores were similar between the two groups at 3 and 6 months postsurgery. The perioperative complication rates for intercostal and rectus abdominis surgery were 1.8% and 5.3%, respectively (P = 0.464), with no significant difference in the incidence of tube dislodgement (P = 0.514). Patient weight improved significantly at 3 and 6 months postoperatively compared to preoperatively (P

Deformation control of deep roadways is a major challenge for mine safety production. Taking a deep roadway with a burial depth of 965 m in a mine in North China as the engineering background, on-site investigation found that significant creep deformation occurred in the surrounding rock of the roadway. The original supporting U-shaped steel support failed due to insufficient supporting strength. The rock mass near the roadway experienced a transition from triaxial stress conditions to biaxial and even uniaxial stress states as a result of excavation and unloading, leading to a gradient stress distribution in the surrounding rock. From the perspective of the roadway's deviatoric stress field distribution, we investigated the gradient failure mechanism of the roadway and validated it through theoretical analysis and numerical simulations. The study found that the ratio of horizontal principal stress and vertical principal stress determines the distribution shape of the surrounding rock deviatoric stress field. The gradient distribution of the stress field in the roadway will cause time-related deformation of the roadway, which will lead to large deformation and failure of the roadway. Based on this, the control mechanism of roadway gradient failure was studied, and then a combined support technology of CFST supports with high bearing capacity was proposed.

ABSTRACTA critical determinant for early post-entry events, the HIV-1 capsid (CA) protein forms the conical core when it rearranges around the dimeric RNA genome and associated viral proteins. Although mutations in CA have been reported to alter innate immune sensing of HIV-1, a direct link between core stability and sensing of HIV-1 nucleic acids has not been established. Herein, we assessed how manipulating the stability of the CA lattice through chemical and genetic approaches affects innate immune recognition of HIV-1. We found that destabilization of the CA lattice resulted in potent sensing of reverse transcription products when destabilization per se does not completely block reverse transcription. Surprisingly, due to the combined effects of enhanced reverse transcription and defects in nuclear entry, two separate CA mutants that form hyperstable cores induced innate immune sensing more potently than destabilizing CA mutations. At low concentrations that allowed the accumulation of reverse transcription products, CA-targeting compounds GS-CA1 and lenacapavir measurably impacted CA lattice stability in cells and modestly enhanced innate immune sensing of HIV. Interestingly, innate immune activation observed with viruses containing unstable cores was abolished by low doses of lenacapavir. Innate immune activation observed with both hyperstable and unstable CA mutants was dependent on the cGAS-STING DNA-sensing pathway and reverse transcription. Overall, our findings demonstrate that CA lattice stability and reverse transcription are finely balanced to support reverse transcription and minimize cGAS-STING-mediated sensing of the resulting viral DNA.IMPORTANCEIn HIV-1 particles, the dimeric RNA genome and associated viral proteins and enzymes are encased in a proteinaceous lattice composed of the viral capsid protein. Herein, we assessed how altering the stability of this capsid lattice through orthogonal genetic and chemical approaches impacts the induction of innate immune responses. Specifically, we found that decreasing capsid lattice stability results in more potent sensing of viral reverse transcription products, but not the genomic RNA, in a cGAS-STING-dependent manner. The recently developed capsid inhibitors lenacapavir and GS-CA1 enhanced the innate immune sensing of HIV-1. Unexpectedly, due to increased levels of reverse transcription and cytosolic accumulation of the resulting viral cDNA, capsid mutants with hyperstable cores also resulted in the potent induction of type I interferon-mediated innate immunity. Our findings suggest that HIV-1 capsid lattice stability and reverse transcription are finely balanced to minimize exposure of reverse transcription products in the cytosol of host cells.

Abstract Outdated coal mining technologies involve considerable mine water resource waste. For coal mines located in water-starved western regions of China, this jeopardizes the sustainable coal mining development, local eco-environment, and agricultural production. Coal mine underground reservoirs furnish conservation and cyclic utilization of water resources in the coal mining process. The weakest links of underground reservoirs are artificial dams that are prone to frequent occurrence of water seepage and instability failures. Aiming to explore the deformation rules of artificial dams under fluid–solid coupling action, this study developed a nested multi-coupling test system comprising a model shelf, a mine pressure simulation device, a water pressure simulation device, and a monitoring system, The maximum size of the model shelf is 1400 mm * 1300 mm * 200 mm. The mine pressure simulation device was composed of static-load and vibration-load oil cylinders of various sizes. A servo motor mainly controlled the water pressure device; with a water pressure sensor and high-precision flowmeter, water pressure could be accurately adjusted. By taking the underground reservoir in the Wulanmulun Coal Mine as an example, the deformation failure characteristics of the MB-1 dam under fluid–solid coupling conditions were simulated to validate the reasonability and feasibility of the developed system. The obtained experimental results indicated that the artificial dam damage was induced by increased mine pressure, leading to shear compression failure. The artificial dam underwent plastic deformation at a water pressure of 11.43 kPa, accompanied with the generation of microfractures, which rapid propagation under vibration loading violated the dam’s stability.

Abstract Background Cleft palate repair surgery may result in severe pain in the immediate postoperative period. The aim of this study is to compare the effects of different doses of nalbuphine for postoperative analgesia in children with cleft palate. Methods From November 2019 to June 2021, 90 children (45 males and 45 females, age 9–20 months old, ASA class I—II) were selected for palatoplasty. They were randomly divided into three groups: the control group (Group C), the N1 group (postoperative analgesia with 0.05 mg/kg/h nalbuphine) and the N2 group (postoperative analgesia with 0.075 mg/kg/h nalbuphine). Each group had 30 cases. Nalbuphine was not continuously infused in Group C but was continuously infused in Groups N1 and N2 at rates of 0.05 mg/kg/h and 0.075 mg/kg/h, respectively, for 24 h for postoperative analgesia. The FLACC analgesia score and Ramsay Sedation score were recorded at 10 min (T1), 30 min (T2), 2 h (T3), 12 h (T4) and 24 h (T5) after the operation. Adverse reactions such as nausea, vomiting and respiratory depression were observed and recorded. Results Compared with those in Group C, the FLACC scores in the N1 and N2 groups decreased significantly at T1-T5 (p

Abstract Detecting exosomal markers using laser desorption/ionization time‐of‐flight mass spectrometry (LDI‐TOF MS) is a novel approach for examining liquid biopsies of non‐small cell lung cancer (NSCLC) samples. However, LDI‐TOF MS is limited by low sensitivity and poor reproducibility when analyzing intact proteins directly. In this report, gold nanoparticles/cellulose nanocrystals (AuNPs/CNC) is introduced as the matrix for direct analysis of intact proteins in NSCLC serum exosomes. AuNPs/CNC with “dual dispersion” effects dispersed and stabilized AuNPs and improved ion inhibition effects caused by protein aggregation. These features increased the signal‐to‐noise ratio of [M+H]+ peaks by two orders of magnitude and lowered the detection limit of intact proteins to 0.01 mg mL–1. The coefficient of variation with or without AuNPs/CNC is measured as 10.2% and 32.5%, respectively. The excellent reproducibility yielded a linear relationship (y = 15.41x – 7.983, R2 = 0.989) over the protein concentration range of 0.01 to 20 mg mL–1. Finally, AuNPs/CNC‐assisted LDI‐TOF MS provides clinically relevant fingerprint information of exosomal proteins in NSCLC serum, and characteristic proteins S100 calcium‐binding protein A10, Urokinase plasminogen activator surface receptor, Plasma protease C1 inhibitor, Tyrosine‐protein kinase Fgr and Mannose‐binding lectin associated serine protease 2 represented excellent predictive biomarkers of NSCLC risk.

Under the trend in climate change, global warming, and the increasingly serious urban heat island effect, promoting urban wind corridor planning to reduce urban temperature and mitigate the effect of urban heat islands has received widespread attention in many cities. With emerging awareness of the need to explicitly incorporate climate considerations into urban planning and design, integrating current spatial analysis and simulation tools to enhance urban wind corridor planning to obtain the best urban ventilation effect has become an increasingly important research topic in green city development. However, how to systematically carry out urban wind corridor planning by employing related technology and simulation tools is a topic that needs to be explored urgently in both theory and practice. Taking Zhumadian City in China as an example, this study proposes a method and planning approach that uses remote sensing (RS), geographic information system (GIS), and computational fluid dynamics (CFD) in an integrated way to understand urban landscape and to conduct urban wind corridor planning. The research results reveal that the urban form of Zhumadian City favors the development of urban wind corridors, and that the railway lines and some major roads in the city have the potential to be developed as the city’s main wind corridors. However, there are still ventilation barriers resulting from the existing land use model and building layout patterns that need to be adjusted. In terms of local-level analysis, the CFD simulation analysis also reveals that some common building layout patterns may result in environments with poor ventilation. Finally, based on the results of our empirical analysis and local planning environment, specific suggestions are provided on how to develop appropriate strategies for urban wind corridor planning and adjustments related to land use planning and building layout patterns in order to mitigate the impact of the urban heat island effect.

Seed size/weight plays an important role in determining crop yield, yet only few genes controlling seed size have been characterized in soybean. Here, we perform a genome-wide association study and identify a major quantitative trait locus (QTL), named GmSW17 (Seed Width 17), on chromosome 17 that determine soybean seed width/weight in natural population. GmSW17 encodes a ubiquitin-specific protease, an ortholog to UBP22, belonging to the ubiquitin-specific protease (USPs/UBPs) family. Further functional investigations reveal that GmSW17 interacts with GmSGF11 and GmENY2 to form a deubiquitinase (DUB) module, which influences H2Bub levels and negatively regulates the expression of GmDP-E2F-1, thereby inhibiting the G1-to-S transition. Population analysis demonstrates that GmSW17 undergo artificial selection during soybean domestication but has not been fixed in modern breeding. In summary, our study identifies a predominant gene related to soybean seed weight, providing potential advantages for high-yield breeding in soybean. Seed size plays an important role in determining soybean yield. Here, the authors report GmSW17, encoding a homolog of Arabidopsis UBP22 that plays a role in deubiquitination, as a positive regulator of soybean seed width and seed weight through inhibition of the G1-to-S transition by interacting with GmSGF11 and GmENY2. [ABSTRACT FROM AUTHOR]

The energy sector, serving as a pivotal propellant within the macroeconomic framework, finds its production, distribution, and consumption aspects considerably influenced by climatic variations. In this study, a two-tier Stackelberg model for the green energy supply chain is developed, which is employed to analyze the profit disparities between suppliers and retailers both in the absence and presence of meteorological disasters. Furthermore, the research delves into the optimal supply chain strategies under three distinct scenarios in the context of meteorological disasters. A comparative analysis is conducted to examine the decision-making variances and the shifts in the interests of each supply chain participant under these scenarios. The findings reveal two critical insights: First, meteorological disasters detrimentally affect the environmental friendliness of energy products, as well as the profits of both retailers and suppliers. Second, the selection of the optimal strategy varies depending on the evaluation criterion used. When product greenness is the metric, subsidies aimed at promoting sales costs emerge as the superior strategy. Conversely, for retailers and suppliers, subsidies that target the environmental friendliness of energy products prove to be the most effective. Based on the conclusions, the paper also makes recommendations for governments and companies. [ABSTRACT FROM AUTHOR]