The role of metabolic memory in diabetic kidney disease: identification of key genes and therapeutic targets.

Diabetic kidney disease (DKD) is characterized by complex pathogenesis and poor prognosis; therefore, an exploration of novel etiological factors may be beneficial. Despite glycemic control, the persistence of transient hyperglycemia still induces vascular complications due to metabolic memory. However, its contribution to DKD remains unclear. Using single-cell RNA sequencing data from the Gene Expression Omnibus (GEO) database, we clustered 12 cell types and employed enrichment analysis and a cell‒cell communication network. Fibrosis, a characteristic of DKD, was found to be associated with metabolic memory. To further identify genes related to metabolic memory and fibrosis in DKD, we combined the above datasets from humans with a rat renal fibrosis model and mouse models of metabolic memory. After overlapping, NDRG1, NR4A1, KCNC4 and ZFP36 were selected. Pharmacology analysis and molecular docking revealed that pioglitazone and resveratrol were possible agents affecting these hub genes. Based on the ex vivo results, NDRG1 was selected for further study. Knockdown of NDRG1 reduced TGF-ß expression in human kidney-2 cells (HK-2 cells). Compared to that in patients who had diabetes for more than 10 years but not DKD, NDRG1 expression in blood samples was upregulated in DKD patients. In summary, NDRG1 is a key gene involved in regulating fibrosis in DKD from a metabolic memory perspective. Bioinformatics analysis combined with experimental validation provided reliable evidence for identifying metabolic memory in DKD patients.

Facile synthesis of hierarchical core-shell carbon@ZnIn2S4 composite for boosted photothermal-assisted photocatalytic H2 production.

Against the backdrop of energy shortage, hydrogen energy has attracted much attention as a green and clean energy source. In order to explore efficient hydrogen production pathways, we designed a composite photocatalyst with carbon-based core-shell photothermal-assisted photocatalytic system (Carbon@ZnIn2S4, denoted as C@ZIS). The well-designed catalyst C@ZIS composites demonstrated a photocatalytic hydrogen precipitation rate of 2.97 mmol g-1 h-1 even in the absence of the noble metal Pt co-catalyst. The incorporation of carbon-based core-shell photocatalysts into a photocatalytic reaction significantly affects the activity of the reaction by triggering a photothermal effect in the reaction solution. The results of the physicochemical experiments demonstrated that the carbon spheres in C@ZIS composite system could provide a greater number of active sites, thereby accelerating the electron transfer and separation efficiency, and thus enhancing the photocatalytic activity. The study presents an efficacious design concept for the development of efficacious carbon-based core-shell photothermal-assisted photocatalysts, which is anticipated to facilitate the efficient conversion of solar energy to hydrogen energy.

Early Radiographic and Clinical Outcomes of Robotic-arm-assisted versus Conventional Total Knee Arthroplasty: A Multicenter Randomized Controlled Trial.

OBJECTIVE: A robotic system was recently introduced to improve prosthetic alignment during total knee arthroplasty (TKA). The purpose of this multicenter, prospective, randomized controlled trial (RCT) was to determine whether robotic-arm-assisted TKA improves clinical and radiological outcomes when compared to conventional TKA. METHODS: One hundred and thirty patients who underwent primary TKA were enrolled in this prospective, randomized controlled trial, which was conducted at three hospitals. Five patients were lost to follow-up 6 weeks after surgery. Therefore, 125 participants (63 in the intervention group and 62 in the control group) remained in the final analysis. The primary outcome was the rate at which the mechanical axis of the femur deviated by less than 3° from the mechanical axis of the tibia. This was evaluated by full-length weight-bearing X-rays of the lower limb 6 weeks postoperatively. Secondary outcomes included operation times, 6-week postoperative functional outcomes evaluated by the American Knee Society score (KSS) and the Western Ontario and McMaster Universities osteoarthritis index (WOMAC), short form-36 (SF-36) health survey results, and the occurrence of adverse events (AEs) and serious adverse events (SAEs). RESULTS: At 6 weeks postoperatively, we found that the rate of radiographic inliers was significantly higher in the intervention group (78.7% vs 51.6%; p = 0.00; 95% confidence interval, 10.9% to 43.2%). The operation was significantly longer in the intervention group than in the control group (119.5 vs 85.0 min; p = 0.00). There were no significant differences in the 6-week postoperative functional outcomes, SF-36, AEs, and SAEs between the two groups. There were no AEs or SAEs that were determined to be "positively related" to the robotic system. CONCLUSION: Robotic-arm-assisted TKA is safe and effective, as demonstrated in this trial.

Human brain organoids for understanding substance use disorders.

Substance use disorders (SUDs) are complex mental health conditions involving a problematic pattern of substance use. Challenges remain in understanding their neural mechanisms, which are likely to lead to improved SUD treatments. Human brain organoids, brain-like 3D in vitro cultures derived from human stem cells, show unique potential in recapitulating the response of a developing human brain to substances. Here, we review the recent progress in understanding SUDs using human brain organoid models focusing on neurodevelopmental perspectives. We first summarize the background of SUDs in humans. Moreover, we introduce the development of various human brain organoid models and then discuss current progress and findings underlying the abuse of substances like nicotine, alcohol, and other addictive drugs using organoid models. Furthermore, we review efforts to develop organ chips and microphysiological systems to engineer better human brain organoids for advancing SUD studies. Lastly, we conclude by elaborating on the current challenges and future directions of SUD studies using human brain organoids.

Successful treatment of hemophagocytic intravascular large B-cell lymphoma with CNS involvement with BTK inhibitor combined with rituximab and high-dose methotrexate.

This is a case of hemophagocytic intravascular large B-cell lymphoma (IVLBCL) with central nervous system (CNS) involvement. Although R-CHOP chemotherapy regimen has been shown significant improvement in survival rate. The prognosis and outcomes remain unsatisfactory, which is identified as outstanding challenges and need solutions. Gene and molecular profiling studies may provide new therapeutic strategies, especially the BCR/TLR/IL-1R/NF-κB signaling pathway in IVLBCL. Here, we treated the hemophagocytic IVLBCL CNS-involved patient with the Bruton tyrosine kinase inhibitor (BTKi) to block NF-κB pathway, and indicated that the second-generation BTKi zanubrutinib-based treatment was feasible and efficient.

Clinical efficacy of Gamma Knife® combined with transarterial chemoembolization and immunotherapy in the treatment of primary liver cancer.

BACKGROUND: This study was designed to investigate the clinical efficacy and safety of Gamma Knife® combined with transarterial chemoembolization (TACE) and immunotherapy in the treatment of primary liver cancer. AIM: To investigate the clinical efficacy and safety of Gamma Knife® combined with TACE and immune-targeted therapy in the treatment of primary liver cancer. METHODS: Clinical data from 51 patients with primary liver cancer admitted to our hospital between May 2018 and October 2022 were retrospectively collected. All patients underwent Gamma Knife® treatment combined with TACE and immunotherapy. The clinical efficacy, changes in liver function, overall survival (OS), and progression-free survival (PFS) of patients with different treatment responses were evaluated, and adverse reactions were recorded. RESULTS: The last follow-up for this study was conducted on October 31, 2023. Clinical evaluation of the 51 patients with primary liver cancer revealed a partial response (PR) in 27 patients, accounting for 52.94% (27/51); stable disease (SD) in 16 patients, accounting for 31.37% (16/51); and progressive disease (PD) in 8 patients, accounting for 15.69% (8/51). The objective response rate was 52.94%, and the disease control rate was 84.31%. Alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and alpha-fetoprotein isoform levels decreased after treatment compared with pretreatment (all P = 0.000). The median OS was 26 months [95% confidence interval (95%CI): 19.946-32.054] in the PR group and 19 months (95%CI: 14.156-23.125) in the SD + PD group, with a statistically significant difference (P = 0.015). The median PFS was 20 months (95%CI: 18.441-34.559) in the PR group and 12 months (95%CI: 8.745-13.425) in the SD + PD group, with a statistically significant difference (P = 0.002). Common adverse reactions during treatment included nausea and vomiting (39.22%), thrombocytopenia (27.45%), and leukopenia (25.49%), with no treatment-related deaths reported. CONCLUSION: Gamma Knife® combined with TACE and immune-targeted therapy is safe and effective in the treatment of primary liver cancer and has a good effect on improving the clinical benefit rate and liver function of patients.

Strong Vertical Piezoelectricity and Broad-pH-Value Photocatalyst in Ferroelastic Y2Se2BrF Monolayer.

With the development of miniaturized devices, there is an increasing demand for 2D multifunctional materials. Six ferroelastic semiconductors, Y2Se2XX' (X, X' = I, Br, Cl, or F; X ≠ X') monolayers, are theoretically predicted here. Their in-plane anisotropic band structure, elastic and piezoelectric properties can be switched by ferroelastic strain. Moderate energy barriers can prevent the undesired ferroelastic switching that minor interferences produce. These monolayers exhibit high carrier mobilities (up to 104 cm2 V-1 s-1) with strong in-plane anisotropy. Furthermore, their wide bandgaps and high potential differences make them broad-pH-value and high-performance photocatalysts at pH value of 0-14. Strikingly, Y2Se2BrF possesses outstanding d33 (d33 = -405.97 pm/V), greatly outperforming CuInP2S6 by 4.26 times. Overall, the nano Y2Se2BrF is a hopeful candidate for multifunctional devices to generate a direct current and achieve solar-free photocatalysis. This work provides a new paradigm for the design of multifunctional energy materials.

Metabolism and distribution of two major constituents of 'Xing-Nao-Jing Injection'-germacrone and curdione in rats.

Germacrone and curdione are germacrane-type sesquiterpenoids that are widely distributed and have extensive pharmacological activities; they are the main constituents of 'Xing-Nao-Jing Injection' (XNJ). Studies on the metabolic features of germacrane-type sesquiterpenoids are limited. In this study, the metabolites of germacrone and curdione were characterized by UHPLC-Q-Exactive Oribitrap mass spectrometry after they were orally administered to rats. In total, 60 and 76 metabolites were found and preliminarily identified in rats administered germacrone and curdione, respectively, among which at least 123 potential new compounds were included. New metabolic reactions of germacrane-type sesquiterpenoids were identified, which included oxidation (+4 O and +5 O), ethylation, methyl-sulfinylation, vitamin C conjugation, and cysteine conjugation reactions. Among the 136 metabolites (including 113 oxidation metabolites, two glucuronidation, two methylation, nine methyl-sulfinylation, three ethylation, six cysteine conjugation, and one Vitamin C conjugation metabolites), 32 metabolites were detected in nine organs, and the stomach, intestine, liver, kidneys, and small intestine were the main organs for the distribution of these metabolites. All 136 metabolites were detected in urine and 64 of them were found in feces. The results of this study not only contribute to research on in vivo processes related to germacrane-type sesquiterpenoids but also provide a strong foundation for a better understanding of in vivo processes and the effective forms of germacrone, curdione, and XNJ.

Analysis of the associations between moderate-to-vigorous physical activity and screen time on psychological symptoms among university students: a cross-sectional survey based on six geographic regions in China.

BACKGROUND: Declining physical activity and increasing screen time (ST) among Chinese adolescents have become major concerns shared by scholars, while mental health issues are also on the rise. Previous studies have confirmed the association between physical activity and screen time and psychological symptoms, but it is unclear how their psychological symptoms, especially for Chinese university students who have a high proportion of psychological symptoms, and no research evidence has been found. METHODS: This study investigated physical activity, screen time, and psychological symptoms in 11,173 university students aged 19-22 years in six regions of China. A binary logistic regression analysis was used to analyze the association between moderate-to-vigorous physical activity (MVPA) and screen time and psychological symptoms. And the generalize linear model (GLM) analysis was used to further analyze the association between MVPA and screen time and psychological symptoms. RESULTS: The detection rate of psychological symptoms among Chinese university students was 16.3%, with a higher percentage of female students (17.5%) than male students (14.7%). The proportion of male students (8.2%) with MVPA > 60 min/d was higher than that of female students (2.3%), and the proportion of male students (33.8%) and female students (34.5%) with screen time > 2 h/d was basically the same. The generalize linear model (GLM) analysis showed that university students with MVPA < 30 min/d and screen time > 2 h/d (OR = 1.59, 95% CI: 1.10-2.31) had the highest risk of psychological symptoms (OR = 1.59, 95% CI: 1.10-2.31) compared to university students with MVPA > 60 min/d and screen time < 1 h/d as the reference group. The risk of psychological symptoms was the highest among those with MVPA < 30 min/d and screen time > 2 h/d (OR = 1.59,95% CI: 1.10-2.31). In addition, university students with MVPA > 60 min/d and a screen time of 1-2 h/d (OR = 0.09, 95% CI: 0.03-0.25) had the lowest risk of psychological symptoms (P < 0.001). The same trend was observed for both male and female students. CONCLUSION: Chinese university students have a certain proportion of psychological symptom problems, and there is a significant between MVPA and screen time and psychological symptoms, and the same trend exists for both male and female students. Chinese university students should perform MVPA for not less than 60 min a day, and at the same time control the duration of screen time, and screen time should be controlled between 1 and 2 h a day, which has a better promotion effect on psychological health.

Gut Microbiome Dysbiosis in Patients with Pemphigus and Correlation with Pathogenic Autoantibodies.

BACKGROUND: Pemphigus is a group of potentially life-threatening autoimmune bullous diseases induced by pathogenic autoantibodies binding to the surface of epidermal cells. The role of the gut microbiota (GM) has been described in various autoimmune diseases. However, the impact of the GM on pemphigus is less understood. This study aimed to investigate whether there was alterations in the composition and function of the GM in pemphigus patients compared to healthy controls (HCs). METHODS: Fecal samples were collected from 20 patients with active pemphigus (AP), 11 patients with remission pemphigus (PR), and 47 HCs. To sequence the fecal samples, 16S rRNA was applied, and bioinformatic analyses were performed. RESULTS: We found differences in the abundance of certain bacterial taxa among the three groups. At the family level, the abundance of Prevotellaceae and Coriobacteriaceae positively correlated with pathogenic autoantibodies. At the genus level, the abundance of Klebsiella, Akkermansia, Bifidobacterium, Collinsella, Gemmiger, and Prevotella positively correlated with pathogenic autoantibodies. Meanwhile, the abundance of Veillonella and Clostridium_XlVa negatively correlated with pathogenic autoantibodies. A BugBase analysis revealed that the sum of potentially pathogenic bacteria was elevated in the AP group in comparison to the PR group. Additionally, the proportion of Gram-negative bacteria in the PR group was statistically significantly lower in comparison to the HC group. CONCLUSION: The differences in GM composition among the three groups, and the correlation between certain bacterial taxa and pathogenic autoantibodies of pemphigus, support a linkage between the GM and pemphigus.

Investigation on the molecular mechanism of SPA interference with osteogenic differentiation of bone marrow mesenchymal stem cells.

Binding of Staphylococcus aureus protein A (SPA) to osteoblasts induces apoptosis and inhibits bone formation. Bone marrow-derived mesenchymal stem cells (BMSCs) have the ability to differentiate into bone, fat and cartilage. Therefore, it was important to analyze the molecular mechanism of SPA on osteogenic differentiation. We introduced transcript sequence data to screen out differentially expressed genes (DEGs) related to SPA-interfered BMSC. Protein-protein interaction (PPI) network of DEGs was established to screen biomarkers associated with SPA-interfered BMSC. Receiver operating characteristic (ROC) curve was plotted to evaluate the ability of biomarkers to discriminate between two groups of samples. Finally, we performed GSEA and regulatory analysis based on biomarkers. We identified 321 DEGs. Subsequently, 6 biomarkers (Cenpf, Kntc1, Nek2, Asf1b, Troap and Kif14) were identified by hubba algorithm in PPI. ROC analysis showed that six biomarkers could clearly discriminate between normal differentiated and SPA-interfered BMSC. Moreover, we found that these biomarkers were mainly enriched in the pyrimidine metabolism pathway. We also constructed '71 circRNAs-14 miRNAs-5 mRNAs' and '10 lncRNAs-5 miRNAs-2 mRNAs' networks. Kntc1 and Asf1b genes were associated with rno-miR-3571. Nek2 and Asf1b genes were associated with rno-miR-497-5p. Finally, we found significantly lower expression of six biomarkers in the SPA-interfered group compared to the normal group by RT-qPCR. Overall, we obtained 6 biomarkers (Cenpf, Kntc1, Nek2, Asf1b, Troap, and Kif14) related to SPA-interfered BMSC, which provided a theoretical basis to explore the key factors of SPA affecting osteogenic differentiation.

Fangchinoline protects hepatic ischemia/reperfusion liver injury in rats through anti-oxidative stress and anti-inflammation properties: an in silico study.

Liver ischemia-reperfusion (I/R) injury is a common cause of organ failure, developed by a sudden block in the blood and oxygen supply and subsequent restoration. I/R damage is responsible for acute and chronic rejection after organ transplantation, accounting for 10% of early graft failure. The study investigated the therapeutic properties of fangchinoline in liver injury-induced rats. The rats were divided into three groups: Sham, I/R without pretreatment, and I/R + 10 mg/kg fangchinoline pretreatment. Blood and liver samples were collected for assays, and an in silico docking analysis was conducted to determine fangchinoline's inhibitory effect. The pretreatment with 10 mg/kg of fangchinoline effectively reduced hepatic marker enzymes such as AST, LDH, and ALT in the serum of rats with liver I/R damage. Fangchinoline treatment significantly reduced interleukin-8 (IL-8), IL-6, and tumor necrosis factor-α (TNF-α) in I/R-induced rats, boosting antioxidants and decreasing MDA. Histopathological studies showed liver injury protection, and fangchinoline inhibited TNF-α and IL-6 with improved binding affinity. Fangchinoline has hepatoprotective properties by reducing inflammation in rats with liver I/R damage, as demonstrated in the current study. Hence, it can be an effective salutary agent in preventing liver damage caused by I/R.

Structural characteristics of sulfated xylogalactomannan isolated from Caulerpa okamurae and its anticoagulant activity.

Due to wonderful taste, rich nutrition and biological functions, many marine green algae in the genus Caulerpa have been recently developed as candidates for green caviar. A novel water-soluble sulfated xylogalactomannan CO-0-1 was obtained from the green algae Caulerpa okamurae. CO-0-1 was mainly composed of mannose (Man), galactose (Gal), and xylose (Xyl) at the ratio of 4.4:4.0:1.4 with the molecular weight at 470 kDa and the sulfate content at 12.78 %. The sulfated xylogalactomannan had Man at the backbone with →4)-ß-D-Manp-(1→ and →2)-ß-D-Manp-(1→ as the main chain and branches at O-3 position. The side chains contained →3)-ß-D-Galp-(1→ and minor →2)-ß-D-Xylp(1→. The sulfate groups only distributed at the side chains and at O-6 position of →3)-ß-D-Galp-(1→ and O-4 position of (1→2)-ß-D-Xylp. The anticoagulant activity indicated that CO-0-1 displayed intrinsic anticoagulant and specific anti-thrombin activities. The investigation expanded the utilization and development scene and scope of the green algae Caulerpa okamurae.

Precise maxillofacial soft tissue reconstruction: A combination of cone beam computed tomography and 3dMD photogrammetry system.

Introduction: The reconstruction of both extra- and intra-oral soft tissue defects, particularly in restoring the morphology of the lip and the corners of the mouth, has posed a significant challenge for surgeons. Inappropriate methods often lead to maxillofacial deformity which then causes psychological and functional problems. This study aimed to address the challenge of reconstructing extensive and complex maxillofacial soft tissue defects, mainly focusing on the lip, the corners of the mouth, and the surrounding areas. Materials and methods: We developed a reconstruction approach by combining the 3dMDface System (3dMD) with the cone beam computed tomography (CBCT). Firstly, with the extra-oral incision line, we evaluated the shape and the size of the extra-oral defect with 3dMD digitally. Then we used the corresponding maxillary and mandible tooth positions to record the intra-oral defect, which was then converted to digital images by combining 3dMD and CBCT. The islands of the anterolateral thigh perforator flap were then designed after the locations of the perforators were detected with Doppler ultrasonography. Results: A clinical case diagnosed as dermatofibrosarcoma protuberans was presented to illustrate the approach. The patient's tumor resection and the size of multiple defects were measured and simulated via the virtual surgery system. A three-island perforator flap from the descending branch of the lateral femoral circumflex artery was designed accurately. Two weeks postoperatively, the flap was healed as anticipated and the patient was satisfied with the profile. Conclusion: The combination of the 3dMD and CBCT technologies improves the accuracy and fitness of extra- and intra-oral soft tissue reconstruction.

Copper ion-doped multifunctional hydrogel with mild photothermal enhancement promotes vascularized bone regeneration.

The design and construction of a new and excellent synthetic graft is of great significance in the field of bone defect repair and reconstruction. In this study, a dopamine modified chitosan hydrogel doped with Cu ions with a mild photothermal effect was designed to provide a better microenvironment to advance the bone repair via promote the angiogenesis and osteogenesis. Characterizations showed the successful synthesis of the material while it also presented excellent biocompatibility and mild photothermal effect under the irradiation of near-infrared light. Further, it could enhance the angiogenesis of HUVECs cells through promoting the ability of migration and tube formation and enhance the osteogenic differentiation of MC3T3-E1 cells via increasing the content of vital osteogenic factors including Runx2, Col-1, OPN, OCN, OSX, etc. The in vivo experiment also testified that it could promote the bone defect repair in rat models. These results indicate the multifunctional hydrogel is an ideal material for the treatment of bone defects and has good clinical application potential.

Engineering human midbrain organoid microphysiological systems to model prenatal PFOS exposure.

Perfluorooctane sulfonate (PFOS), a class of synthetic chemicals detected in various environmental compartments, has been associated with dysfunctions of the human central nervous system (CNS). However, the underlying neurotoxicology of PFOS exposure is largely understudied due to the lack of relevant human models. Here, we report bioengineered human midbrain organoid microphysiological systems (hMO-MPSs) to recapitulate the response of a fetal human brain to multiple concurrent PFOS exposure conditions. Each hMO-MPS consists of an hMO on a fully 3D printed holder device with a perfusable organoid adhesion layer for enhancing air-liquid interface culturing. Leveraging the unique, simply-fabricated holder devices, hMO-MPSs are scalable, easy to use, and compatible with conventional well-plates, and allow easy transfer onto a multiple-electrode array (MEA) system for plug-and-play measurement of neural activity. Interestingly, the neural activity of hMO-MPSs initially increased and subsequently decreased by exposure to a concentration range of 0, 30, 100, to 300 µM of PFOS. Furthermore, PFOS exposure impaired neural development and promoted neuroinflammation in the engineered hMO-MPSs. Along with PFOS, our platform is broadly applicable for studies toxicology of various other environmental pollutants.

ACLS4 could be a potential therapeutic target for severe acute pancreatitis.

Acute pancreatitis (AP) is currently among the most prevalent digestive diseases. The pathogenesis of AP remains elusive, and there is no specific treatment. Therefore, identifying novel therapeutic targets is imperative for effective management and prevention of AP. In this study, we conducted a comprehensive transcriptomic analysis of peripheral blood from patients with AP and the pancreatic tissue from a mouse model of AP. Our analyses revealed that mouse model of AP exhibited a higher enrichment of mitogen-activated protein kinase signaling, endocytosis, apoptosis and tight junction pathways than the control. Subsequent weighted gene co-expression network analysis identified 15 gene modules, containing between 50 and 1000 genes each, which demonstrated significant correlations within samples from patients with AP. Further screening identified four genes (ACSL4, GALNT3, WSB1, and IL1R1) that were significantly upregulated in severe acute pancreatitis (SAP) in both human and mouse samples. In mouse models of SAP, ACSL4 was significantly upregulated in the pancreas, whereas GALNT3, WSB1, and IL1R1 were not. Lastly, we found that a commercially available ACSL4 inhibitor, PRGL493, markedly reduced IL-6 and TNFα expression, alleviated pancreatic edema and necrosis, and diminished the infiltration of inflammatory cells. In conclusion, this study comprehensively depicts the key genes and signaling pathways implicated in AP and suggests the potential of ACSL4 as a novel therapeutic target for SAP. These findings provide valuable insights for further exploration of therapeutic strategies for SAP.

Mechanical Properties of Carbon Fiber-Reinforced Plastic with Two Types of Bolted Connections at Low Temperatures.

Carbon fiber-reinforced plastic (CFRP) is frequently utilized as a bolted joint material in aircraft applications because of its high specific strength and specific modulus. Therefore, the performance of CFRP under -50° is significant. Here, we discuss the specimens of two bolted connections (single-nailed and double-nailed) used for static load tensile and tensile fatigue tests. We obtained the failure curves and fatigue life relationships of the specimens with two different connection methods at different tightening torques (2 N/m, 4 N/m, and 6 N/m) and low room temperatures. Our analysis reveals the effect of the bolt tightening torque and temperature on the structural mechanical properties of a CFRP bolted joint. It provides a data reference for researchers to design a composite bolted joint structure in an airplane flight environment.

An updated patent review of stimulator of interferon genes agonists (2021 - present).

INTRODUCTION: Stimulator of Interferon Genes (STING) is an innate immune sensor. Activation of STING triggers a downstream response that results in the expression of proinflammatory cytokines (TNF-α, IL-1ß) via nuclear factor kappa-B (NF-κB) or the expression of type I interferons (IFNs) via an interferon regulatory factor 3 (IRF3). IFNs can eventually result in promotion of the adaptive immune response including activation of tumor-specific CD8+ T cells to abolish the tumor. Consequently, activation of STING has been considered as a potential strategy for cancer treatment. AREAS COVERED: This article provides an overview on structures and pharmacological data of CDN-like and non-nucleotide STING agonists acting as anticancer agents (January 2021 to October 2023) from a medicinal chemistry perspective. The data in this review come from EPO, WIPO, RCSB PDB, CDDI. EXPERT OPINION: In recent years, several structurally diverse STING agonists have been identified. As an immune enhancer, they are used in the treatment of tumors, which has received extensive attention from scientific community and pharmaceutical companies. Despite the multiple challenges that have appeared, STING agonists may offer opportunities for immunotherapy.

Limited effects of xylem anatomy on embolism resistance in cycad leaves.

Drought-induced xylem embolism is a primary cause of plant mortality. Although c. 70% of cycads are threatened by extinction and extant cycads diversified during a period of increasing aridification, the vulnerability of cycads to embolism spread has been overlooked. We quantified the vulnerability to drought-induced embolism, pressure-volume curves, in situ water potentials, and a suite of xylem anatomical traits of leaf pinnae and rachises for 20 cycad species. We tested whether anatomical traits were linked to hydraulic safety in cycads. Compared with other major vascular plant clades, cycads exhibited similar embolism resistance to angiosperms and pteridophytes but were more vulnerable to embolism than noncycad gymnosperms. All 20 cycads had both tracheids and vessels, the proportions of which were unrelated to embolism resistance. Only vessel pit membrane fraction was positively correlated to embolism resistance, contrary to angiosperms. Water potential at turgor loss was significantly correlated to embolism resistance among cycads. Our results show that cycads exhibit low resistance to xylem embolism and that xylem anatomical traits - particularly vessels - may influence embolism resistance together with tracheids. This study highlights the importance of understanding the mechanisms of drought resistance in evolutionarily unique and threatened lineages like the cycads.