S-Nitrosylation Targets GSNO Reductase for Selective Autophagy during Hypoxia Responses in Plants.

Nitric oxide (NO) regulates diverse cellular signaling through S-nitrosylation of specific Cys residues of target proteins. The intracellular level of S-nitrosoglutathione (GSNO), a major bioactive NO species, is regulated by GSNO reductase (GSNOR), a highly conserved master regulator of NO signaling. However, little is known about how the activity of GSNOR is regulated. Here, we show that S-nitrosylation induces selective autophagy of Arabidopsis GSNOR1 during hypoxia responses. S-nitrosylation of GSNOR1 at Cys-10 induces conformational changes, exposing its AUTOPHAGY-RELATED8 (ATG8)-interacting motif (AIM) accessible by autophagy machinery. Upon binding by ATG8, GSNOR1 is recruited into the autophagosome and degraded in an AIM-dependent manner. Physiologically, the S-nitrosylation-induced selective autophagy of GSNOR1 is relevant to hypoxia responses. Our discovery reveals a unique mechanism by which S-nitrosylation mediates selective autophagy of GSNOR1, thereby establishing a molecular link between NO signaling and autophagy.

Comprehensive analysis of bulk and single-cell transcriptomic data reveals a novel signature associated with endoplasmic reticulum stress, lipid metabolism, and liver metastasis in pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with high probability of recurrence and distant metastasis. Liver metastasis is the predominant metastatic mode developed in most pancreatic cancer cases, which seriously affects the overall survival rate of patients. Abnormally activated endoplasmic reticulum stress and lipid metabolism reprogramming are closely related to tumor growth and metastasis. This study aims to construct a prognostic model based on endoplasmic reticulum stress and lipid metabolism for pancreatic cancer, and further explore its correlation with tumor immunity and the possibility of immunotherapy. METHODS: Transcriptomic and clinical data are acquired from TCGA, ICGC, and GEO databases. Potential prognostic genes were screened by consistent clustering and WGCNA methods, and the whole cohort was randomly divided into training and testing groups. The prognostic model was constructed by machine learning method in the training cohort and verified in the test, TCGA and ICGC cohorts. The clinical application of this model and its relationship with tumor immunity were analyzed, and the relationship between endoplasmic reticulum stress and intercellular communication was further explored. RESULTS: A total of 92 characteristic genes related to endoplasmic reticulum stress, lipid metabolism and liver metastasis were identified in pancreatic cancer. We established and validated a prognostic model for pancreatic cancer with 7 signatures, including ADH1C, APOE, RAP1GAP, NPC1L1, P4HB, SOD2, and TNFSF10. This model is considered to be an independent prognosticator and is a more accurate predictor of overall survival than age, gender, and stage. TIDE score was increased in high-risk group, while the infiltration levels of CD8+ T cells and M1 macrophages were decreased. The number and intensity of intercellular communication were increased in the high ER stress group. CONCLUSIONS: We constructed and validated a novel prognostic model for pancreatic cancer, which can also be used as an instrumental variable to predict the prognosis and immune microenvironment. In addition, this study revealed the effect of ER stress on cell-cell communication in the tumor microenvironment.

Current research progress, opportunities, and challenges of Limosillactobacillus reuteri-based probiotic dietary strategies.

Limosillactobacillus reuteri (L. reuteri), a type of Lactobacillus spp., stands out as the most extensively researched probiotic. Its remarkable intestinal adhesion has led to widespread applications in both the food and medical sectors. Notably, recent research highlights the probiotic efficacy of L. reuteri sourced from breast milk, particularly in influencing social behavior and mitigating atopic dermatitis. In this review, our emphasis is on surveying recent literature regarding the promotion of host's health by L. reuteri. We aim to provide a concise summary of the latest regulatory effects and potential mechanisms attributed to L. reuteri in the realms of metabolism, brain- and immune-related functions. The mechanism through which L. reuteri promotes host health by modulating the intestinal microenvironment primarily involves promoting intestinal epithelial renewal, bolstering intestinal barrier function, regulating gut microbiota and its metabolites, and suppressing inflammation and immune responses. Additionally, this review delves into new technologies, identifies shortcomings, and addresses challenges in current L. reuteri research. Finally, the application prospects of L. reuteri are provided. Therefore, a better understanding of the role and mechanisms of L. reuteri will contribute significantly to the development of new probiotic functional foods and enable precise, targeted interventions for various diseases.

Pd(II)-Catalyzed ß-C(sp3)-H Alkynylation of Alanine in Di- and Tripeptides with Asn as an Endogenous Directing Group.

The introduction of alkyne moieties into peptides remains in demand as it represents a promising approach for further structural diversification of peptides. Herein, we describe the Pd(II)-catalyzed C(sp3)-H alkynylation of Ala-Asn-embedded di- and tripeptides using Asn as the endogenous lead group. In addition, a key building block for the glycopeptide Tyc4PG-14 and Tyc4PG-15 was produced by our methodology.

Visible-light-driven photocatalytic carboxylation to aromatic carboxylic acids with CO2.

(Hetero)aromatic carboxylic acids and their derivatives attract attention due to their role in the synthesis of several biologically active molecules, active pharmaceutical ingredients, polymers, etc. Carbon dioxide (CO2) is a prime C1 source for the synthesis of aromatic carboxylic acids because of its nontoxicity, nonflammability, abundance and renewability. Owing to the thermodynamic and chemical inertness of CO2, traditional carboxylation to aromatic carboxylic acids with CO2 is always performed under harsh reaction conditions or using stoichiometric metallic reductants. Visible-light-driven carboxylation with CO2 provides an environmentally benign, mild, and high-efficiency route for the production of aromatic carboxylic acids. This review comprehensively introduces the visible-light-driven preparation of aromatic carboxylic acids through a visible-light-driven oxidative addition and reductive elimination mechanism, binding of aryl (radical) anions which are produced by photoinduced electron transfer (PET) to CO2, binding of carbon dioxide anion radicals (CO2˙-) which are formed by PET to aryl compounds, radical coupling between CO2˙- and aryl radicals, and other mechanisms. Finally, this review provides a summary and the future work direction. This article offers a theoretical guidance for efficient synthesis of aromatic carboxylic acids via photocatalysis.

Novel sulfonyl-substituted tetrandrine derivatives for colon cancer treatment by inducing mitochondrial apoptosis and inhibiting PI3K/AKT/mTOR pathway.

Tetrandrine (TET) possesses multiple pharmacological activities and could suppress tumor proliferation via PI3K pathway inhibition. However, inferior antitumor activity and potential toxicity limit its clinical application. In the present study, a series of 14-sulfonamide and sulfonate TET derivatives were designed, synthesized, and evaluated for biological activities. Through structural-activity relationship studies, compound 3c with α, ß-unsaturated carbonyl group exhibited the most potent activity against all tested tumor cell lines (including Hela, HCT116, HepG2, MCF-7, and SHSY5Y), as well as negligible toxicity against normal cell lines LO2 and HEK293. Additionally, compound 3c effectively inhibited HCT116 and CT26 cell proliferation in vitro with increased cell proportion in the G2/M phase, activated the mitochondrial apoptosis pathway, and induced colon cancer cell apoptosis by suppressing the PI3K/AKT/mTOR pathway. The further molecular docking results confirmed that compound 3c is potentially bound to multiple residues in PI3K with a stronger binding affinity than TET. Ultimately, compound 3c dramatically suppressed tumor growth in the CT26 xenograft tumor model, without noticeable visceral toxicity detected in the high-dose group. In summary, compound 3c might present new insights for designing new PI3K inhibitors and be a potential candidate for colon cancer treatment.

αO-Conotoxin GeXIVA[1,2] Suppresses In Vivo Tumor Growth of Triple-Negative Breast Cancer by Inhibiting AKT-mTOR, STAT3 and NF-κB Signaling Mediated Proliferation and Inducing Apoptosis.

Breast cancer is one of the leading causes of cancer mortality worldwide, and triple-negative breast cancer (TNBC) is the most problematic subtype. There is an urgent need to develop novel drug candidates for TNBC. Marine toxins are a valuable source for drug discovery. We previously identified αO-conotoxin GeXIVA[1,2] from Conus generalis, which is a selective antagonist of α9 nicotinic acetylcholine receptors (nAChRs). Recent studies indicated that α9 nAChR expression is positively correlated with breast cancer development; thus, α9 nAChR could serve as a therapeutic target for breast cancer. In this study, we aimed to investigate the in vivo antitumor effects of GeXIVA[1,2] on TNBC and to elucidate its underlying anticancer mechanism. Our data showed that GeXIVA[1,2] effectively suppressed 4T1 tumor growth in vivo at a very low dose of 0.1 nmol per mouse. Our results uncovered that the antitumor mechanism of GeXIVA[1,2] simultaneously induced apoptosis and blocked proliferation. Further investigations revealed that GeXIVA[1,2]-induced Caspase-3-dependent apoptosis was achieved through regulating Bax/Bcl-2 balance, and GeXIVA[1,2]-inhibited proliferation was mediated by the downregulation of the AKT-mTOR, STAT3 and NF-κB signaling pathways. Our study provides valuable arguments to demonstrate the potential of GeXIVA[1,2] as a novel marine-derived anticancer drug candidate for the treatment of TNBC.

Combined toxic effects of polyethylene microplastics and lambda-cyhalothrin on gut of zebrafish (Danio rerio).

Microplastics (MPs), which are prevalent and increasingly accumulating in aquatic environments. Other pollutants coexist with MPs in the water, such as pesticides, and may be carried or transferred to aquatic organisms, posing unpredictable ecological risks. This study sought to assess the adsorption of lambda-cyhalothrin (LCT) by virgin and aged polyethylene MPs (VPE and APE, respectively), and to examine their influence on LCT's toxicity in zebrafish, specifically regarding acute toxicity, oxidative stress, gut microbiota and immunity. The adsorption results showed that VPE and APE could adsorb LCT, with adsorption capacities of 34.4 mg∙g-1 and 39.0 mg∙g-1, respectively. Compared with LCT exposure alone, VPE and APE increased the acute toxicity of LCT to zebrafish. Additionally, exposure to LCT and PE-MPs alone can induce oxidative stress in the zebrafish gut, while combined exposure can exacerbate the oxidative stress response and intensify intestinal lipid peroxidation. Moreover, exposure to LCT or PE-MPs alone promotes inflammation, and combined exposure leads to downregulation of the myd88-nf-κb related gene expression, thus impacting intestinal immunity. Furthermore, exposure to APE increased LCT toxicity to zebrafish more than VPE. Meanwhile, exposure to PE-MPs and LCT alone or in combination has the potential to affect gut microbiota function and alter the abundance and diversity of the zebrafish gut flora. Collectively, the presence of PE-MPs may affect the toxicity of pesticides in zebrafish. The findings emphasize the importance of studying the interaction between MPs and pesticides in the aquatic environment.

Nervogenic Acid Derivatives and Phenanthrenes from Liparis nervosa and Their Antimicrobial and Immunosuppressive Activities.

Two new nervogenic acid derivatives liparisnervosides Q (1) and R (5), as well as five known nervogenic acid derivatives (2-4, 6, 7) and four phenanthrenes (8-11) were isolated from the whole plant of Liparis nervosa (Thunb. ex A. Murray) Lindl.. Their structures were detremined using extensive spectroscopic techniques, including 1D, 2D NMR, and HR-ESI-MS, and acid hydrolysis. Furthermore, their antimicrobial and immunosuppressive activities were evaluated. Nervosine VII (3) exhibited antimicrobial activity against Staphylococcus aureus with an MIC of 62.5 µg/mL and inhibited the proliferation of human T cells with an IC50 value of 9.67±0.96 µM. These findings contribute to our understanding of the potential pharmacological properties of these compounds.

Metabolite profiling and antioxidant capacity of natural Ophiocordyceps gracilis and its cultures using LC-MS/MS-based metabolomics: Comparison with Ophiocordyceps sinensis.

INTRODUCTION: Ophiocordyceps gracilis is an entomopathogenic fungus and a precious traditional Chinese medicine with similar medicinal properties to Ophiocordyceps sinensis. However, information on the metabolite profiles of natural O. gracilis and its cultures is lacking, which limits their utilization. OBJECTIVE: The metabolic variations and antioxidant activities of O. gracilis cultures and natural O. gracilis were analyzed to evaluate the nutritional and medicinal value of O. gracilis and its cultures. METHOD: The metabolite profiles of O. gracilis cultures (fruiting bodies and aerial mycelia), natural O. gracilis, and natural O. sinensis were compared by LC-MS/MS coupled with multivariate data analysis. Furthermore, their antioxidant activities were evaluated based on their DPPH• , ABTS•+ , and • OH scavenging abilities. RESULTS: A total of 612 metabolites were identified, and the metabolic compositions of the four Cordyceps samples were similar, with differences observed in the levels of some metabolites. There were 126 differential metabolites between natural O. gracilis and natural O. sinensis, among which fatty acids, carbohydrates, and secondary metabolites are predominant in natural O. gracilis. Furthermore, 116 differential metabolites between O. gracilis cultures and natural Cordyceps were identified, with generally higher levels in O. gracilis cultures than in natural Cordyceps. O. gracilis cultivated fruiting bodies exhibited the strongest antioxidant capacity among Cordyceps samples. Additionally, 46 primary and 24 secondary differential metabolites contribute to antioxidant activities. CONCLUSION: This study provides a reference for the application of natural O. gracilis and its cultures in functional food and medicine from the perspective of metabolites and antioxidant capacity.

Tortuosity and Proximal-Specific Hemodynamics Associated with Plaque Location in the Carotid Bulb Stenosis.

BACKGROUND: Atherosclerotic plaque locations in the carotid bulb increasingly have been found to be associated with patterns of ischemic lesions and plaque progression. However, the occurrence of carotid bulb plaque is a complex process. We aimed to investigate plaque characteristics and geometric and hemodynamic parameters among patients with body and apical plaques of the carotid bulb and to identify the mechanism of bulb plaque formation and location. METHODS: Consecutive patients with single carotid bulb stenosis (50-99%) were enrolled retrospectively. Patients were divided into body and apical plaque groups based on plaque location. Plaque location and characteristics were identified and measured on high-resolution vessel wall magnetic resonance imaging. Geometric parameters were derived from time-of-flight magnetic resonance imaging. Computational fluid dynamics simulations were performed to quantify wall shear stress (WSS) and four associated WSS-based metrics on the plaque side, on the non-plaque side, and in different parts of the lesion. Plaque characteristics and geometric and hemodynamic parameters were compared, and their associations with the plaque location were determined. RESULTS: Seventy patients were recruited (41 body plaques and 29 apical plaques). WSSplaque values were lower than WSSnon-plaque values for all plaques (median [interquartile range], 12.59 [9.83-22.14] vs. 17.27 [11.63-27.63] Pa, p = 0.001). In a multivariate binary logistic regression, the tortuosity of the stenosed region, the magnitudes of the mean relative residence time, and the minimum transverse WSS in the proximal part of the lesion were the key factors independently associated with plaque location (p = 0.022, 0.013, and 0.012, respectively). CONCLUSIONS: Plaque formation was associated with the local flow pattern, and the tortuosity and proximal-specific hemodynamics were significantly associated with plaque location in the carotid bulb.

The clinicopathological significance of thymic epithelial markers expression in thymoma and thymic carcinoma.

BACKGROUND: The classification of thymomas is based on the morphology of epithelial tumor cells and the proportion of lymphocytes. Type A thymomas are composed of the spindle or oval tumor epithelial cells. Tumor cells of B thymomas are epithelioid-shaped with increasing atypia. Type AB thymomas have the features of epithelial tumor cells of A and B thymomas. The diagnosis can be difficult because of the complex morphology. Some novel thymic epithelial markers have been reported in several preclinical studies, but they have not been applied to clinical practice. Here, we investigated the expression of 3 cortical and 3 medullary markers, which are thymoproteasome-specific subunit ß5t (ß5t), thymus-specific serine protease 16 (PRSS16), cathepsin V, autoimmune regulator (AIRE), CD40 and claudin-4. METHODS: Immunohistochemistry was used to analyze 53 cases of thymomas and thymic squamous cell carcinomas (TSCC), aiming to explore the expression of cortical and medullary epithelial markers and their correlation with histological classification, Masaoka-Koga stage, and prognosis. RESULTS: Our results found that for cortical epithelial markers the expression of ß5t, PRSS16, and cathepsin V was higher in type AB and B thymomas than in micronodular thymoma with lymphoid stroma (MNT), and we observed a dramatic increase of ß5t and PRSS16 expression in type AB compared to type A thymomas. In medullary epithelial markers, the expression of AIRE was higher in type A than in B3 thymomas. CD40 and ß5t expression were associated with the Masaoka-Koga stage. High cathepsin V expression was related to a good prognosis and a longer progression-free survival. CONCLUSION: This is the first comprehensive analysis of the role of thymic cortical and medullary epithelial markers as biomarkers for differential diagnosis and prognosis in thymic tumors. Thymic medullary epithelial immunophenotype was found to exhibit in type A, MNT, and TSCC. Type B thymomas primarily exhibited a cortical epithelial immunophenotype. Type AB thymomas showed cortical, medullary, or mixed corticomedullary epithelial immunophenotype. Our results demonstrated that thymic cortical and medullary epithelial markers including ß5t, PRSS16, cathepsin V, and AIRE could be used as ancillary markers in the diagnosis and prognosis of thymic epithelial tumors.

A nexus of dietary restriction and gut microbiota: Recent insights into metabolic health.

In recent times, dietary restriction (DR) has received considerable attention for its promising effects on metabolism and longevity. Previous studies on DR have mainly focused on the health benefits produced by different restriction patterns, whereas comprehensive reviews of the role of gut microbiota during DR are limited. In this review, we discuss the effects of caloric restriction, fasting, protein restriction, and amino acid restriction from a microbiome perspective. Furthermore, the underlying mechanisms by which DR affects metabolic health by regulating intestinal homeostasis are summarized. Specifically, we reviewed the impacts of different DRs on specific gut microbiota. Additionally, we put forward the limitations of the current research and suggest the development of personalized microbes-directed DR for different populations and corresponding next-generation sequencing technologies for accurate microbiological analysis. DR effectively modulates the composition of the gut microbiota and microbial metabolites. In particular, DR markedly affects the rhythmic oscillation of microbes which may be related to the circadian clock system. Moreover, increasing evidence supports that DR profoundly improves metabolic syndrome, inflammatory bowel disease, and cognitive impairment. To summarize, DR may be an effective and executable dietary manipulation strategy for maintaining metabolic health, however, further investigation is needed to elucidate the underlying mechanisms.

How Eutrophication Promotes Exotic Aquatic Plant Invasion in the Lake Littoral Zone?

Eutrophication and exotic species invasion are key drivers of the global loss of biodiversity and ecosystem functions in lakes. We selected two exotic plants (Alternanthera philoxeroides and Myriophyllum aquaticum) and two native plants (Myriophyllum spicatum and Vallisneria spinulosa) to elucidate the effect of eutrophication on exotic plant invasiveness. We found that (1) elevated nutrient favored invasion of exotic species and inhibited growth of native plants. Species combinations and plant densities of native plants had limited effects on the resistance to invasion of the exotics. (2) A. philoxeroides featured the tightest connectivity among traits, which is consistent with its high competitive ability. Although eutrophication caused physiological stress to A. philoxeroides, it could effectively regulate enzyme activity and alleviate the stress. (3) M. aquaticum possessed strong tolerance to habitat disturbance and was highly disruptive to the surrounding plants. Eutrophication will exacerbate the adverse effects of M. aquaticum on the littoral ecosystem. (4) Nutrient enrichment reduced the biomass and relative growth rates of V. spinulosa and lowered phenolics and starch contents of M. spicatum, thereby making them more susceptible to habitat fluctuations. Overall, our study highlights how eutrophication alters the invasiveness of exotic plants and the resistance of native plants in the littoral zone, which is of relevance in a world with intensified human activities.

Eradication and graft retention can be achieved in the treatment for acute septic arthritis after primary posterior cruciate ligament reconstruction: analysis of 1561 reconstructions.

PURPOSE: Acute septic arthritis after arthroscopic posterior cruciate ligament (PCL) reconstruction is a rare but severe complication. Optimal management has not been established. The purposes of this study were to analyze clinical findings and to retrospectively evaluate the graft-retaining treatment regimen. METHODS: From 2010 to 2021, a total of 1561 primary PCL reconstructions were performed at our institution. Seven patients with septic arthritis were identified and retrospectively analyzed with regard to incidence, clinical manifestations, treatment, postoperative clinical course and follow-up results. RESULTS: The mean interval from PCL reconstruction to the onset of symptoms was 11.0 ± 4.0 days. Staphylococcus aureus was the most commonly found pathogen. Eradication was achieved in all patients after a mean of 1.1 ± 0.4 procedures, with graft retention in all patients. The mean duration of antibiotic treatment was 5.7 ± 1.5 weeks. At the last follow-up, there was no recurrence, graft insufficiency or osteoarthritis. CONCLUSION: Arthroscopic graft-retaining treatment combined with individual antibiotic therapy, eradication and good to excellent functional results can be achieved, which might encourage surgeons to try to retain the graft as much as possible. LEVEL OF EVIDENCE: Level IV.

Comparative metabolic profiling of mycelia, fermentation broth, spore powder and fruiting bodies of Ophiocordyceps gracilis by LC-MS/MS.

INTRODUCTION: Ophiocordyceps gracilis, a type of edible and medicinal fungus, exhibits multiple health-promoting effects. Due to the scarcity of natural O. gracilis, artificial cultures have been developed as its substitutes. However, lacking comprehension of the metabolite composition of cultures limits its utilisation. OBJECTIVE: This research aimed to evaluate the nutritional and medicinal value of four cultures of O. gracilis by analysing their metabolite composition. In addition, metabolic pathways in mycelia and fruiting bodies were analysed to explore fruiting body formation mechanism at metabolic level. METHOD: The mycelia, fermentation broth, spore powder and fruiting bodies of O. gracilis were cultivated in this study. Their metabolite composition was compared using an untargeted metabolomics approach based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Principal component analysis (PCA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA) showed that the four cultures have noticeable differences in metabolite composition. A total of 612 metabolites were identified, among which 159 metabolites showed significant differences, and these differential metabolites were classified into 13 categories. The metabolites in the fruiting bodies were the most abundant compared with other cultures. However, each culture had its own advantages and significantly accumulates some active metabolites respectively. Pearson's correlation analysed the mutual relationship among metabolites. In addition, seven metabolic pathways were closely related to fruiting body formation, such as "Biosynthesis of plant secondary metabolites", "amino acids metabolism", "tricarboxylic acid (TCA) cycle". CONCLUSION: This study offered a reference to mycelia, fermentation broth, spore powder and fruiting bodies of O. gracilis as health-promoting functional foods and medicine.

Research on an Intelligent Mining Complete System of a Fully Mechanized Mining Face in Thin Coal Seam.

The mining environment of thin coal seam working faces is generally harsh, the labor intensity is high, and the production efficiency is low. Previous studies have shown that thin coal seam mining finds it difficult to follow machines, does not have complete sets of equipment, has a low degree of automation, and has difficult system co-control, which easily causes production safety accidents. In order to effectively solve the problems existing in thin coal seam mining, Binhu Coal Mine has established intelligent fully mechanized mining and actively explored automatic coal cutting, automatic support following, and intelligent control. The combination of an SAC electro-hydraulic control system and SAP pumping station control system has been applied in 16,108 intelligent fully mechanized coal mining faces, which realizes the automatic following of underground support and the control of adjacent support, partition support, and group operation; the automatic coal cutting of the shearer is realized by editing the automatic coal-cutting state of the shearer and adjusting the automatic parameters. A centralized control center is set up, which realizes the remote control and one-button start-stop of working face equipment. Through a comparative analysis of 16,108 intelligent fully mechanized mining faces and traditional fully mechanized mining faces, it is found that intelligent fully mechanized mining faces have obvious advantages in terms of equipment maintenance, equipment operation mode, and working face efficiency, which improve the equipment and technical mining level of thin coal seam. The application of intelligent mining in Binhu Coal Mine has a great and far-reaching impact on the development of thin coal seam mining technology in China.

Robot-assisted all-epiphyseal anterior cruciate ligament reconstruction in skeletally immature patients: a retrospective study.

PURPOSE: To review a series of adolescent patients with anterior cruciate ligament (ACL) injuries surgically treated with robot-assisted all-epiphyseal ACL reconstruction (ACLR), and to compare with the traditional freehand group. METHODS: This retrospective clinical study included 16 patients with ACL injuries who underwent ACLR by robot-assisted technique or traditional freehand method from June 2018 to March 2020. All patients were divided into the robot-assisted group (6 patients) or the traditional surgery group (10 patients). The number of intra-operative fluoroscopies, operation time, accuracy of bone tunnel insertions, International Knee Documentation Committee (IKDC) subjective score and ligament laxity testing were recorded in the two groups. RESULTS: All patients returned for follow-up, at a mean of 31.6 ± 4.5 months after surgery. The average age of the robot-assisted group was 12.2 ± 1.3 years. The number of intra-operative fluoroscopies was 10.9 ± 2.8 in the traditional freehand group, whereas it was only 3.0 ± 0.6 in the robot-assisted group, which was significantly lower (P < 0.05). The operative time in the robot-assisted group was shorter than that in the traditional freehand group (87 ± 10.7 min vs. 126 ± 12.1 min, P < 0.05). The distance between the center of actual insertion and the center of the idea insertion on both femoral and tibial intra-articular bone tunnel were 1.5 ± 0.3 mm and 1.6 ± 0.3 mm for the robot-assisted group and 2.7 mm ± 0.4 mm and 2.4 ± 0.4 mm for the traditional freehand group (P < 0.05). There were no significant differences between the two groups in function recovery at the last follow-up. CONCLUSIONS: All-epiphyseal ACLR is a technically demanding procedure with a small margin of error. Robot-assisted treatment of ACL injuries in skeletally immature patients is more accurate than traditional freehand method, with shorter operation time and fewer intra-operative fluoroscopies.

A Neutral Polysaccharide from Spores of Ophiocordyceps gracilis Regulates Oxidative Stress via NRF2/FNIP1 Pathway.

Ophiocordyceps gracilis (O. gracilis) is a parasitic fungus used in traditional Chinese medicine and functional foods. In this study, a neutral heteropolysaccharide (GSP-1a) was isolated from spores of O. gracilis, and its structure and antioxidant capacities were investigated. GSP-1a was found to have a molecular weight of 72.8 kDa and primarily consisted of mannose (42.28%), galactose (35.7%), and glucose (22.02%). The backbone of GSP-1a was composed of various sugar residues, including →6)-α-D-Manp-(1→, →2,6)-α-D-Manp-(1→, →2,4,6)-α-D-Manp-(1→, →6)-α-D-Glcp-(1→, and →3,6)-α-D-Glcp-(1→, with some branches consisting of →6)-α-D-Manp-(1→ and α-D-Gal-(1→. In vitro, antioxidant activity assays demonstrated that GSP-1a exhibited scavenging effects on hydroxyl radical (•OH), 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical cation (ABTS•+), and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•). Moreover, GSP-1a was found to alleviate H2O2-induced oxidative stress in HepG2 cells by reducing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), while enhancing the activities of superoxide dismutase (SOD). Furthermore, GSP-1a upregulated the mRNA expression of antioxidant enzymes such as Ho-1, Gclm, and Nqo1, and regulated the NRF2/KEAP1 and FNIP1/FEM1B pathways. The findings elucidated the structural types of GSP-1a and provided a reliable theoretical basis for its usage as a natural antioxidant in functional foods or medicine.

Impaired T1 mapping and Tmax during the first 7 days after ischemic stroke. A retrospective observational study.

OBJECTIVE: To measure the relative T1 (rT1) value in different hypo-perfused regions after ischemic stroke using T1 mapping derived by Strategically Acquired Gradient Echo (STAGE) and assess its relationship with onset time and severity of ischemia. MATERIALS AND METHODS: Sixty-three patients with acute anterior circulation ischemic stroke from 2017 to 2022 who underwent STAGE, diffusion weighted imaging (DWI) and dynamic susceptibility contrast perfusion weighted imaging (DSC-PWI) within 7 days were retrospectively enrolled. The areas with reduced diffusion and hypo-perfusion were segmented based on apparent diffusion coefficient (ADC) value < 0.62 × 10-3mm2/s and time-to-maximum (Tmax) thresholds (4, 6, 8, and 10 seconds). We measured the T1 value in the diffusion reduced and every 2 s Tmax strata regions and calculated rT1 (T1ipsi/T1contra) to explore the relationship between rT1 value, Tmax, and onset time. RESULTS: rT1 value was increased in diffusion reduced (1.42) and hypo-perfused regions (1.02, 1.06, 1.12, 1.27, Tmax 4-6 s, 6-8 s, 8-10 s, > 10 s, respectively; all different from 1, P < 0.001). rT1 value was positively correlated with Tmax (rs = 0.61, P < 0.001) and onset time in area with reduced diffusion (rs = 0.39, P = 0.014). CONCLUSIONS: Increased rT1 value in different hypo-perfused brain regions using T1 mapping derived by STAGE may reflect the edema; it was associated with the severity of Tmax and showed a weak correlation with the onset time in diffusion reduced areas.