SR9009 attenuates inflammation-related NPMSC pyroptosis and IVDD through NR1D1/NLRP3/IL-1ß pathway.

Intervertebral disc is a highly rhythmical tissue. As a key factor linking biorhythm and inflammatory response, the shielding effect of NR1D1 in the process of intervertebral disc degeneration remains unclear. Here, we first confirmed that NR1D1 in the nucleus pulposus tissue presents periodic rhythmic changes and decreases in expression with intervertebral disc degeneration. Second, when NR1D1 was activated by SR9009 in vitro, NLRP3 inflammasome assembly and IL-1ß production were inhibited, while ECM synthesis was increased. Finally, the vivo experiments further confirmed that the activation of NR1D1 can delay the process of disc degeneration to a certain extent. Mechanistically, we demonstrate that NR1D1 can bind to IL-1ß and NLRP3 promoters, and that the NR1D1/NLRP3/IL-1ß pathway is involved in this process. Our results demonstrate that the activation of NR1D1 can effectively reduce IL-1ß secretion, alleviate LPS-induced NPMSC pyroptosis, and protect ECM degeneration.

A Paternò-Büchi Reaction of Aromatics with Quinones under Visible Light Irradiation.

Reported herein is a Paternò-Büchi reaction of aromatic double bonds with quinones under visible light irradiation. The reactions of aromatics with quinones exposed to blue LED irradiation yielded oxetanes at -78 °C, which was attributed to both the activation of double bonds in aromatics and the stabilization of oxetanes by thiadiazole, oxadiazole, or selenadiazole groups. The addition of Cu(OTf)2 to the reaction system at room temperature resulted in the formation of diaryl ethers via the copper-catalyzed ring opening of oxetanes in situ. Notably, the substrate scope was extended to general aromatics.

Novel subtype of obesity influencing the outcomes of sleeve gastrectomy: Familial aggregation of obesity.

BACKGROUND: Differences in the preoperative characteristics and weight loss outcomes after sleeve gastrectomy (SG) between patients with familial aggregation of obesity (FAO) and patients with sporadic obesity (SO) have not been elucidated. AIM: To explore the impact of SG on weight loss and the alleviation of obesity-related comorbidities in individuals with FAO. METHODS: A total of 193 patients with obesity who underwent SG were selected. Patients with FAO/SO were matched 1:1 by propensity score matching and were categorized into 4 groups based on the number of first-degree relatives with obesity (1SO vs 1FAO, 2SO vs 2FAO). The baseline characteristics, weight loss outcomes, prevalence of obesity-related comorbidities and incidence of major surgery-related complications were compared between groups. RESULTS: We defined FAO as the presence of two or more first-degree relatives with obesity. Patients with FAO did not initially show significant differences in baseline data, short-term postoperative weight loss, or obesity-related comorbidities when compared to patients with SO preoperatively. However, distinctions between the two groups became evident at the two-year mark, with statistically significant differences in both percentage of total weight loss (P = 0.006) and percentage of excess weight loss (P < 0.001). The FAO group exhibited weaker remission of type 2 diabetes mellitus (T2DM) (P = 0.031), hyperlipidemia (P = 0.012), and non-alcoholic fatty liver disease (NAFLD) (P = 0.003) as well as a lower incidence of acid reflux (P = 0.038). CONCLUSION: FAO patients is associated with decreased mid-to-long-term weight loss outcomes; the alleviation of T2DM, hyperlipidemia and NAFLD; and decreased incidence of acid reflux postoperatively.

A TGF-ß signaling-related lncRNA signature for prediction of glioma prognosis, immune microenvironment, and immunotherapy response.

AIMS: The dysregulation of TGF-ß signaling is a crucial pathophysiological process in tumorigenesis and progression. LncRNAs have diverse biological functions and are significant participants in the regulation of tumor signaling pathways. However, the clinical value of lncRNAs related to TGF-ß signaling in glioma is currently unclear. METHODS: Data on glioma's RNA-seq transcriptome, somatic mutation, DNA methylation data, and clinicopathological information were derived from the CGGA and TCGA databases. A prognostic lncRNA signature was constructed by Cox and LASSO regression analyses. TIMER2.0 database was utilized to deduce immune infiltration characteristics. "ELMER v.2" was used to reconstruct TF-methylation-gene regulatory network. Immunotherapy and chemotherapy response predictions were implemented by the TIDE algorithm and GDSC database, respectively. In vitro and in vivo experiments were conducted to verify the results and clarify the regulatory mechanism of lncRNA. RESULTS: In glioma, a TGF-ß signaling-related 15-lncRNA signature was constructed, including AC010173.1, HOXA-AS2, AC074286.1, AL592424.1, DRAIC, HOXC13-AS, AC007938.1, AC010729.1, AC013472.3, AC093895.1, AC131097.4, AL606970.4, HOXC-AS1, AGAP2-AS1, and AC002456.1. This signature proved to be a reliable prognostic tool, with high risk indicating an unfavorable prognosis and being linked to malignant clinicopathological and genomic mutation traits. Risk levels were associated with different immune infiltration landscapes, where high risk was indicative of high levels of macrophage infiltration. In addition, high risk also suggested better immunotherapy and chemotherapy response. cg05987823 was an important methylation site in glioma progression, and AP-1 transcription factor family participated in the regulation of signature lncRNA expression. AGAP2-AS1 knockdown in in vitro and in vivo experiments inhibited the proliferation, migration, and invasion of glioma cells, as well as the growth of glioma, by downregulating the expression levels of NF-κB and ERK 1/2 in the TGF-ß signaling pathway. CONCLUSIONS: A prognostic lncRNA signature of TGF-ß signaling was established in glioma, which can be used for prognostic judgment, immune infiltration status inference, and immunotherapy response prediction. AGAP2-AS1 plays an important role in glioma progression.

Melatonin alleviates oxidative stress-induced injury to nucleus pulposus-derived mesenchymal stem cells through activating PI3K/Akt pathway.

Background: The changes in the microenvironment of degenerative intervertebral discs cause oxidative stress injury and excessive apoptosis of intervertebral disc endogenous stem cells. The purpose of this study was to explore the possible mechanism of the protective effect of melatonin on oxidative stress injury in NPMSCs induced by H2O2. Methods: The Cell Counting Kit-8 assay was used to evaluate the cytotoxicity of hydrogen peroxide and the protective effects of melatonin. ROS content was detected by 2'7'-dichlorofluorescin diacetate (DCFH-DA). Mitochondrial membrane potential (MMP) was detected by the JC-1assay. Transferase mediated d-UTP Nick end labeling (TUNEL) and Annexin V/PI double staining were used to determine the apoptosis rate. Additionally, apoptosis-associated proteins and PI3K/Akt signaling pathway-related proteins were evaluated by immunofluorescence, immunoblotting and PCR. ECMs were evaluated by RT‒PCR and immunofluorescence. In vivo, X-ray, Magnetic resonance imaging (MRI) and Histological analyses were used to evaluate the protective effect of melatonin. Results: Melatonin had an obvious protective effect on NPMSCs treated with 0-10 µM melatonin for 24 h. In addition, melatonin also had obvious protective effects on mitochondrial dysfunction, decreased membrane potential and cell senescence induced by H2O2. More importantly, melatonin could significantly reduce the apoptosis of nucleus pulposus mesenchymal stem cells induced by H2O2 by regulating the expression of apoptosis-related proteins and decreasing the rate of apoptosis. After treatment with melatonin, the PI3K/Akt pathway was significantly activated in nucleus pulposus mesenchymal stem cells, while the protective effect was significantly weakened after PI3K-IN-1 treatment. In vivo, the results of X-ray, MRI and histological analyses showed that therapy with melatonin could partially reduce the degree of intervertebral disc degeneration. Conclusion: Our research demonstrated that melatonin can effectively alleviate the excessive apoptosis and mitochondrial dysfunction of nucleus pulposus mesenchymal stem cells induced by oxidative stress via the PI3K/Akt pathway, which provides a novel idea for the therapy of intervertebral disc degeneration. The translational potential of this article: This study indicates that melatonin can effectively alleviate the excessive apoptosis and mitochondrial dysfunction of NPMSCs through activating the PI3K/Akt pathway. Melatonin might serve as a promising candidate for the prevention and treatment of Intervertebral disc degeneration disease (IVDD) in the future.

Polyhydroxyalkanoates: the natural biopolyester for future medical innovations.

Polyhydroxyalkanoates (PHAs) are a family of natural microbial biopolyesters with the same basic chemical structure and diverse side chain groups. Based on their excellent biodegradability, biocompatibility, thermoplastic properties and diversity, PHAs are highly promising medical biomaterials and elements of medical devices for applications in tissue engineering and drug delivery. However, due to the high cost of biotechnological production, most PHAs have yet to be applied in the clinic and have only been studied at laboratory scale. This review focuses on the biosynthesis, diversity, physical properties, biodegradability and biosafety of PHAs. We also discuss optimization strategies for improved microbial production of commercial PHAs via novel synthetic biology tools. Moreover, we also systematically summarize various medical devices based on PHAs and related design approaches for medical applications, including tissue repair and drug delivery. The main degradation product of PHAs, 3-hydroxybutyrate (3HB), is recognized as a new functional molecule for cancer therapy and immune regulation. Although PHAs still account for only a small percentage of medical polymers, up-and-coming novel medical PHA devices will enter the clinical translation stage in the next few years.

Expanding potential targets of herbal chemicals by node2vec based on herb-drug interactions.

BACKGROUND: The identification of chemical-target interaction is key to pharmaceutical research and development, but the unclear materials basis and complex mechanisms of traditional medicine (TM) make it difficult, especially for low-content chemicals which are hard to test in experiments. In this research, we aim to apply the node2vec algorithm in the context of drug-herb interactions for expanding potential targets and taking advantage of molecular docking and experiments for verification. METHODS: Regarding the widely reported risks between cardiovascular drugs and herbs, Salvia miltiorrhiza (Danshen, DS) and Ligusticum chuanxiong (Chuanxiong, CX), which are widely used in the treatment of cardiovascular disease (CVD), and approved drugs for CVD form the new dataset as an example. Three data groups DS-drug, CX-drug, and DS-CX-drug were applied to serve as the context of drug-herb interactions for link prediction. Three types of datasets were set under three groups, containing information from chemical-target connection (CTC), chemical-chemical connection (CCC) and protein-protein interaction (PPI) in increasing steps. Five algorithms, including node2vec, were applied as comparisons. Molecular docking and pharmacological experiments were used for verification. RESULTS: Node2vec represented the best performance with average AUROC and AP values of 0.91 on the datasets "CTC, CCC, PPI". Targets of 32 herbal chemicals were identified within 43 predicted edges of herbal chemicals and drug targets. Among them, 11 potential chemical-drug target interactions showed better binding affinity by molecular docking. Further pharmacological experiments indicated caffeic acid increased the thermal stability of the protein GGT1 and ligustilide and low-content chemical neocryptotanshinone induced mRNA change of FGF2 and MTNR1A, respectively. CONCLUSIONS: The analytical framework and methods established in the study provide an important reference for researchers in discovering herb-drug interactions, alerting clinical risks, and understanding complex mechanisms of TM.

Patient-related factors related to prolonged preparation-to-colonoscopy interval and insufficient purgative intake before colonoscopy: A post-hoc observational study.

OBJECTIVES: Prolonged preparation-to-colonoscopy (PC) interval and insufficient purgative intake (PI) are two important indicators for quality of bowel preparation for colonoscopy. We aimed to investigate patient-related factors associated with increased PC interval or insufficient PI. METHODS: The post-hoc regression analyses were performed using the data from two prospective studies (NCT04434625 and NCT04101097). Patients receiving reinforced instructions for bowel preparation were recruited. The co-primary outcomes included prolonged PC interval or insufficient PI. RESULTS: Altogether 1806 patients from five endoscopic centers underwent bowel preparation from September 2019 to March 2021. The cut-off values were 6 h for PC interval and 80% for PI. In all, 116 (6.4%) and 73 (4.0%) presented an extended PC interval and insufficient PI, respectively. Multivariate logistic regression analysis showed that a low education level was significantly associated with PC interval ≥6 h. Female sex, body mass index (BMI), and coronary artery disease (CAD) were found to be significantly correlated with insufficient PI in univariate analysis, while multivariate analysis demonstrated BMI <20 kg/m2 (odds ratio [OR] 4.14, 95% confidence interval [CI] 1.92-8.94, P < 0.001) and 20-25 kg/m2 (OR 2.23, 95% CI 1.33-3.73, P = 0.002) and CAD (OR 3.23, 95% CI 1.22-8.53, P = 0.018) were identified as independent risk factors for PI <80%. CONCLUSIONS: In spite of reinforced education, a number of patients did not follow the instructions for bowel preparation. The factors for a prolonged PC interval did not overlap with those for insufficient PI. Individualized interference may be considered in different subpopulations.

Mechanically robust bamboo node and its hierarchically fibrous structural design.

Although short bamboo nodes function in mechanical support and fluid exchange for bamboo survival, their structures are not fully understood compared to unidirectional fibrous internodes. Here, we identify the spatial heterostructure of the bamboo node via multiscale imaging strategies and investigate its mechanical properties by multimodal mechanical tests. We find three kinds of hierarchical fiber reinforcement schemes that originate from the bamboo node, including spatially tightened interlocking, triaxial interconnected scaffolding and isotropic intertwining. These reinforcement schemes, built on porous vascular bundles, microfibers and more-refined twist-aligned nanofibers, govern the structural stability of the bamboo via hierarchical toughening. In addition, the spatial liquid transport associated with these multiscale fibers within the bamboo node is experimentally verified, which gives perceptible evidence for life-indispensable multidirectional fluid exchange. The functional integration of mechanical reinforcement and liquid transport reflects the fact that the bamboo node has opted for elaborate structural optimization rather than ingredient richness. This study will advance our understanding of biological materials and provide insight into the design of fiber-reinforced structures and biomass utilization.

Scalable Manufacturing of Mechanical Robust Bioinspired Ceramic-Resin Composites with Locally Tunable Heterogeneous Structures.

Lightweight structural materials with a unique combination of high stiffness, strength, toughness, and hardness, are highly desired yet challenging to be artificially fabricated. Biological structural materials, on the other hand, ingeniously integrate multiple mutually exclusive mechanical properties together relying on their hierarchically heterogeneous structures bonded with gradient interfaces. Here, a scalable bottom-up approach combining continuous nanofiber-assisted evaporation-induced self-assembly with laminating, pressure-less sintering and resin infiltration is reported to fabricate bioinspired heterogeneous ceramic-resin composites with locally tunable microstructure to fulfill specific properties. A gradient interlayer is introduced to provide a gradual transition between adjacent heterogeneous layers, effectively alleviating their property mismatch. The optimized heterogeneous nacre-like composite, as a demonstration, exhibits an attractive combination of low density (≈2.8 g cm-3 ), high strength (≈292 MPa), toughness (≈6.4 MPa m1/2 ), surface hardness (≈1144 kgf mm-2 ) and impact-resistance, surpassing the overall performance of engineering alumina. This material-independent approach paves the way for designing advanced bioinspired heterogeneous materials for diverse structural and functional applications.

Controlled Desiccation of Preprinted Hydrogel Scaffolds Toward Complex 3D Microarchitectures.

Additive manufacturing (AM) is the key to creating a wide variety of 3D structures with unique and programmable functionalities. Direct ink writing is one of the widely used AM technologies with numerous printable materials. However, the extrude-based method is limited by low fabrication resolution, which is confined to printing macrostructures. Herein, a new AM strategy is reported, using a low-cost extrusion 3D printer, to create 3D microarchitectures at the macroscopic level through controlled desiccation of preprinted hydrogel scaffolds followed by infilling objective components. A printable hydrogel with a high-water content ensures maximum shrinkage (≈99.5% in volume) of the printed scaffolds to achieve high resolution. Stable covalent cross-linking and a suitable drying rate enable uniform shrinkage of the scaffolds to retain their original architectures. Particularly, this method can be adapted to produce liquid-metal-based 3D circuits and nanocomposite-based microrobots, indicating its capability to fabricate functional and complex 3D architectures with micron-level resolution from different material systems.

Comparison of the long-term outcomes of patients with hepatocellular carcinoma within the Milan criteria treated by ablation, resection, or transplantation.

BACKGROUND: Liver transplantation (LT), resection (LR), and ablation (LA) are three curative-intent treatment options for patients with early hepatocellular carcinoma (HCC). We aimed to develop a prognostic calculator to compare the long-term outcomes following each of these therapies. METHODS: A total of 976 patients with HCC within the Milan criteria who underwent LT, LR, and LA between 2009 and 2019 from four institutions were evaluated. Multistate competing risks prediction models for recurrence-free survival (RFS), recurrence within the Milan criteria (RWM), and HCC-specific survival (HSS) were derived to develop a prognostic calculator. RESULTS: During a median follow-up of 51 months, 420 (43%) patients developed recurrence. In the multivariate analysis, larger tumor size, multinodularity, older age, male, higher alpha-fetoprotein (AFP), higher albumin-bilirubin (ALBI) grade, and the presence of portal hypertension were significantly associated with higher recurrence and decreased survival rates. The RFS and HSS were both significantly higher among patients treated by LT than by LR or LA and significantly higher between patients treated by LR than by LA (all p < 0.001). For multinodular HCC ≤3 cm, although LT had better RFS and HSS than LR or LA, LA was noninferior to LR. An online prognostic calculator was then developed based on the preoperative clinical factors that were independently associated with outcomes to evaluate RFS, RWM, and HSS at different time intervals for all three treatment options. CONCLUSIONS: Although LT resulted in the best recurrence and survival outcomes, LR and LA also offered durable long-term alternatives. This prognostic calculator is a useful tool for clinicians to guide an informed and personalized discussion with patients based on their tumor biology and liver function.

Global Research Trends on Smart Homes for Older Adults: Bibliometric and Scientometric Analyses.

A growing aging population across the world signifies the importance of smart homes equipped with appropriate technology for the safety and health of older adults. Well-designed smart homes can increase the desire of older adults' aging-in-place and bring economic benefits to the country by reducing budgets for care providers. To obtain a structural overview and provide significant insights into the characteristics of smart homes for older adults, this study conducted bibliometric and scientometric analyses. We used the Web of Science Core Collection database, searching for keywords "smart home*", "home automation", or "domotics" with terms related to older adults, resulting in a total of 1408 documents. VOSviewer software was used to map and visualize the documents. The results showed that research on smart homes for older adults began appearing from 1997 and increased steadily, peaking from 2015. The main research areas were technical engineering fields, such as computer science and engineering, telecommunications with minimal research in humanities, social sciences, and design, indicating the necessity to expand research toward a human-centered perspective, age-friendly technology, and convergence study.

Older Adults' Response to Color Visibility in Indoor Residential Environment Using Eye-Tracking Technology.

Older adults spend relatively more time in indoor residential environments than young people. As their visual and cognitive abilities decline, they experience a high risk of accidents in indoor environments; thus, understanding their gaze behavior while considering cognitive capacity is essential in preventing potential accidents and planning for aging-friendly environments. The purpose of this study was to examine whether the use of color in living environments affects the visual attention of older adults. The following two experiments were conducted using eye-tracking technology: Experiment 1: Older adults' gaze behaviors were measured while viewing four images consisting of nine sets of door-door frames with different color combinations of safety colors, black and white; and Experiment 2: Based on results from Experiment 1, images of simulated living environments were created, and older adults' gaze behaviors were measured while viewing eight images in which two door colors were applied to verify spatial color visibility. Their cognitive state represented by the Mini-Mental State Examination (MMSE) was then compared with their gaze behavior. The results show that: (a) participants paid more attention to doors with color combinations including red (red-black and white-red) and remained longer on the red-black combination; (b) older adults looked at red-black doors faster than white doors in the same position; (c) the dwell time on a red-black door was longer than on that of the corresponding position of a white door; and (d) based on participants' MMSE values, the gaze behaviors of the group with low cognition were less focused and observable than those of the group with normal cognition. The results of this study are significant in that they reveal that indoor color can improve the visibility of elements that can impact safety in the living environments of older adults and enhance their quality of life.

Self-assembled liquid crystal architectures for soft matter photonics.

Self-assembled architectures of soft matter have fascinated scientists for centuries due to their unique physical properties originated from controllable orientational and/or positional orders, and diverse optic and photonic applications. If one could know how to design, fabricate, and manipulate these optical microstructures in soft matter systems, such as liquid crystals (LCs), that would open new opportunities in both scientific research and practical applications, such as the interaction between light and soft matter, the intrinsic assembly of the topological patterns, and the multidimensional control of the light (polarization, phase, spatial distribution, propagation direction). Here, we summarize recent progresses in self-assembled optical architectures in typical thermotropic LCs and bio-based lyotropic LCs. After briefly introducing the basic definitions and properties of the materials, we present the manipulation schemes of various LC microstructures, especially the topological and topographic configurations. This work further illustrates external-stimuli-enabled dynamic controllability of self-assembled optical structures of these soft materials, and demonstrates several emerging applications. Lastly, we discuss the challenges and opportunities of these materials towards soft matter photonics, and envision future perspectives in this field.

The Diagnostic Values of Peptidoglycan, Lipopolysaccharide, and (1,3)-Beta-D-Glucan in Patients with Suspected Bloodstream Infection: A Single Center, Prospective Study.

This study aimed to assess the diagnostic values of peptidoglycan (PGN), lipopolysaccharide (LPS) and (1,3)-Beta-D-Glucan (BDG) in patients with suspected bloodstream infection. We collected 493 heparin anticoagulant samples from patients undergoing blood culture in Peking Union Medical College Hospital from November 2020 to March 2021. The PGN, LPS, and BDG in the plasma were detected using an automatic enzyme labeling analyzer, GLP-F300. The diagnostic efficacy for PGN, LPS, and BDG were assessed by calculating the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). This study validated that not only common bacteria and fungi, but also some rare bacteria and fungi, could be detected by testing the PGN, LPS, and BDG, in the plasma. The sensitivity, specificity, and total coincidence rate were 83.3%, 95.6%, and 94.5% for PGN; 77.9%, 95.1%, and 92.1% for LPS; and 83.8%, 96.9%, and 95.9% for BDG, respectively, which were consistent with the clinical diagnosis. The positive rates for PGN, LPS, and BDG and the multi-marker detection approach for PGN, LPS, and BDG individually were 11.16%, 17.65%, and 9.13%, and 32.86% significantly higher than that of the blood culture (p < 0.05). The AUC values for PGN, LPS, and BDG were 0.881 (0.814−0.948), 0.871 (0.816−0.925), and 0.897 (0.825−0.969), separately, which were higher than that of C-reactive protein (0.594 [0.530−0.659]) and procalcitonin (0.648 [0.587−0.708]). Plasma PGN, LPS, and BDG performs well in the early diagnosis of bloodstream infections caused by Gram-positive and Gram-negative bacterial and fungal pathogens.

Overexpression of Pennisetum purpureum CCoAOMT Contributes to Lignin Deposition and Drought Tolerance by Promoting the Accumulation of Flavonoids in Transgenic Tobacco.

Elephant grass (Pennisetum purpureum) is a fast-growing and low-nutrient demand plant that is widely used as a forage grass and potential energy crop in tropical and subtropical regions of Asia, Africa, and the United States. Transgenic tobacco with the PpCCoAOMT gene from Pennisetum purpureum produces high lignin content that is associated with drought tolerance in relation to lower accumulation of reactive oxygen species (ROS), along with higher antioxidant enzyme activities and osmotic adjustment. In this study, transgenic tobacco plants revealed no obvious cost to plant growth when expressing the PpCCoAOMT gene. Metabolomic studies demonstrated that tobacco plants tolerant to drought stress accumulated flavonoids under normal and drought conditions, which likely explains the observed tolerance phenotype in wild-type tobacco. Our results suggest that plants overexpressing PpCCoAOMT were better able to cope with water deficit than were wild-type controls; metabolic flux was redirected within primary and specialized metabolism to induce metabolites related to defense to drought stress. These results could help to develop drought-resistant plants for agriculture in the future.

Advances in modified hyaluronic acid-based hydrogels for skin wound healing.

Hyaluronic acid (HA) is a natural linear anionic polysaccharide with many unique characteristics such as excellent biocompatibility and biodegradability, native biofunctionality, hydrophilicity, and non-immunoreactivity. HA plays crucial roles in numerous biological processes, including the inflammatory response, cell adhesion, migration, proliferation, differentiation, angiogenesis, and tissue regeneration. All these properties and biological functions of HA make it an appealing material for the synthesis of biomedical hydrogels for skin wound healing. Since HA is not able to be gelate alone, it must be processed and functionalized through chemical modifications and crosslinking to generate versatile HA-based hydrogels. In recent years, different physical and chemical crosslinking strategies for HA-based hydrogels have been developed and designed, such as radical polymerization, Schiff-base crosslinking, enzymatic crosslinking, and dynamic covalent crosslinking, and they have broad and promising applications in skin wound healing and tissue engineering. In this review, we focus on chemical modification and crosslinking strategies for HA-based hydrogels, aiming to provide an overview of the latest advances in the development of HA-based hydrogels for skin wound healing. We summarize and propose feasible measures for the application of HA-based hydrogels for skin treatment, and discuss future application trends, which may ultimately promote HA-based hydrogels as a promising biomaterial for clinical applications.

Knockin of the G275E mutation of the nicotinic acetylcholine receptor (nAChR) α6 confers high levels of resistance to spinosyns in Spodoptera exigua.

Spinosyns, including spinosad and spinetoram, act on the insect central nervous system, gradually paralyzing or destroying the target insect. Spinosad resistance is associated with loss-of-function mutations in the nicotinic acetylcholine receptor (nAChR) α6 subunit in a number of agricultural pests. Using gene editing, nAChR α6 has been verified as a target for spinosyns in five insect species. Recently, a point mutation (G275E) in exon 9 of nAChR α6 was identified in spinosad-resistant strains of Thrips palmi and Tuta absoluta. To date, no in vivo functional evidence has been obtained to support that this mutation is involved in spinosyn resistance in lepidopteran pests. In this study, the G275E mutation was introduced into the nAChR of Spodoptera exigua using clustered regularly interspaced short palindromic repeats (CRISPR) / CRISPR-associated protein 9 (Cas9) gene-editing technology. Reverse transcriptase-polymerase chain reaction and sequencing confirmed that this mutation was present in exon 9 of the nAChR transcripts in the edited 275E strain. The results of bioassays showed that the 275E strain was highly resistant to spinosad (230-fold) and spinetoram (792-fold) compared to the unedited background strain, directly confirming that the G275E mutation of the nAChR α6 subunit confers high levels of spinosyn resistance in S. exigua. Inheritance analysis showed that the resistance trait is autosomal and incompletely recessive. This study employs a reverse genetics approach to validate the functional role played by the G275E mutation in nAChR α6 of S. exigua in spinosyns resistance and provides another example of the use of CRISPR/Cas9 gene-editing technology to confirm the role played by candidate target site mutations in insecticide resistance.

New polymerized sesquiterpene lactones from Ainsliaea yunnanensis and their activity evaluation.

Two new dimeric and trimeric sesquiterpene lactones (1-2), and nine known sesquiterpene lactones (3-11) were isolated from the EtOAc phase of the ethanolic extract of Ainsliaea yunnanensis. Their structures were identified by NMR, IR and HR-ESIMS spectroscopic methods, and compound 1 was confirmed by single crystal X-ray diffraction experiment. All the compounds were tested for their cytotoxic, anti-microbial and anti-inflammatory activities. Compounds 1, 2, 3, 5, 7, 9 and 11 showed very significant selective cytotoxic activities on MDA-MB-468, PANC-1, HEPG2 or A549 cells. Compounds 6 and 11 showed very significant inhibiting effect on Epicoccum sp. (CPCC 400307), Fusarium solani (CPCC 800013) or Bacillus subtilis. Meanwhile, compounds 6 and 7 can inhibit the NLRP3 inflammasome's activation at the concentration of 10 µM.