Tanshinone IIA suppresses ferroptosis to attenuate renal podocyte injury in diabetic nephropathy through the embryonic lethal abnormal visual-like protein 1 and acyl-coenzyme A synthetase long-chain family member 4 signaling pathway.

AIMS/INTRODUCTION: Tanshinone IIA (TIIA) is one of the main components of the root of the red-rooted Salvia miltiorrhiza Bunge. However, the molecular mechanisms underlying TIIA-mediated protective effects in diabetic nephropathy (DN) are still unclear. MATERIALS AND METHODS: High glucose (HG)-induced mouse podocyte cell line (MPC5) cells were used as the in vitro model of DN and treated with TIIA. Cell viability, proliferation and apoptosis were detected using 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide, 5-ethynyl-2'-deoxyuridine and flow cytometry assays. The protein levels were assessed using western blot assay. The levels of inflammatory factors were deleted by enzyme-linked immunoassay. Fe+ level, reactive oxygen species, malondialdehyde and glutathione products were detected using special assay kits. After ENCORI prediction, the interaction between embryonic lethal abnormal visual-like protein 1 (ELAVL1) and acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) was verified using co-immunoprecipitation assay and dual-luciferase reporter assays. ACSL4 messenger ribonucleic acid expression was measured using real-time quantitative polymerase chain reaction. RESULTS: TIIA repressed HG-induced MPC5 cell apoptosis, inflammatory response and ferroptosis. ACSL4 upregulation relieved the repression of TIIA on HG-mediated MPC5 cell injury and ferroptosis. ELAVL1 is bound with ACSL4 to positively regulate the stability of ACSL4 messenger ribonucleic acid. TIIA hindered HG-triggered MPC5 cell injury and ferroptosis by regulating the ELAVL1-ACSL4 pathway. TIIA blocked DN progression in in vivo research. CONCLUSION: TIIA treatment restrained HG-caused MPC5 cell injury and ferroptosis partly through targeting the ELAVL1-ACSL4 axis, providing a promising therapeutic target for DN treatment.

ALKBH5 suppresses autophagic flux via N6-methyladenosine demethylation of ZKSCAN3 mRNA in acute pancreatitis.

BACKGROUND: Increasing evidence has demonstrated that N6-methyladenosine (m6A) RNA modification plays an essential role in a wide range of pathological conditions. Impaired autophagy is a critical hallmark of acute pancreatitis (AP). AIM: To explore the role of the m6A modification of ZKSCAN3 in the regulation of autophagy in AP. METHODS: The AP mouse cell model was established by cerulein-treated mouse pancreatic acinar cells (MPC-83), and the results were confirmed by the levels of amylase and inflammatory factors. Autophagy activity was evaluated by specific identification of the autophagy-related microstructure and the expression of autophagy-related genes. ZKSCAN3 and ALKBH5 were knocked down to study the function in AP. A m6A RNA binding protein immunoprecipitation assay was used to study how the m6A modification of ZKSCAN3 mRNA is regulated by ALKBH. RESULTS: The increased expression of amylase and inflammatory factors in the supernatant and the accumulation of autophagic vacuoles verified that the AP mouse cell model was established. The downregulation of LAMP2 and upregulation of LC3-II/I and SQSTM1 demonstrated that autophagy was impaired in AP. The expression of ZKSCAN3 was upregulated in AP. Inhibition of ZKSCAN3 increased the expression of LAMP2 and decreased the expression of the inflammatory factors, LC3-II/I and SQSTM1. Furthermore, ALKBH5 was upregulated in AP. Knockdown of ALKBH5 downregulated ZKSCAN3 expression and restored decreased autophagic flux in AP. Notably, the bioinformatic analysis revealed 23 potential m6A modification sites on ZKSCAN3 mRNA. The m6A modification of ZKSCAN3 mRNA was significantly decreased in AP. Knockdown of ALKBH5 increased the modification of ZKSCAN3 mRNA, which confirmed that ALKBH5 upregulated ZKSCAN3 expression in a m6A-dependent manner. CONCLUSION: ALKBH5 inhibits autophagic flux through m6A demethylation of ZKSCAN3 mRNA in AP, thereby aggravating the severity of the disease.

Characterization of metabolic patterns in porcine cumulus cells during meiotic maturation.

Metabolic coupling between oocytes and the surrounding somatic cells allows for normal two-way communication, and their interactions is necessary for generating developmentally competent eggs. However, the metabolic framework that support oocyte maturation in surrounding cumulus cells is still lacking. Herin, we established a temporal metabolome profile of porcine cumulus cells at three key stages during oocyte maturation, illustrating the picture of global metabolic network in cumulus cells. Importantly, we discovered the novel metabolic signature in cumulus cells during meiotic maturation, in specific, significant consumption of fatty acids, elevated activity of hexosamine biosynthetic pathway (HBP), and enhanced polyamine biosynthesis. Meanwhile, we observed the different utilization of tryptophan, active biosynthesis of progesterone, and progressive decrease in purine and pyrimidine metabolism as the oocytes progress through meiosis. Collectively, our metabolomic data serves an entree to elaborate on the dynamic changes in these metabolic pathways, which not only reveals the metabolic networks controlling oocyte development, but also lays a foundation for the discovery of biomarkers in the improvement in porcine oocyte culture system.

The Microtubule End Binding Protein Mal3 Is Essential for the Dynamic Assembly of Microtubules during Magnaporthe oryzae Growth and Pathogenesis.

Cytoskeletal microtubules (MTs) play crucial roles in many aspects of life processes in eukaryotic organisms. They dynamically assemble physiologically important MT arrays under different cell conditions. Currently, aspects of MT assembly underlying the development and pathogenesis of the model plant pathogenic fungus Magnaporthe oryzae (M. oryzae) are unclear. In this study, we characterized the MT plus end binding protein MoMal3 in M. oryzae. We found that knockout of MoMal3 results in defects in hyphal polar growth, appressorium-mediated host penetration and nucleus division. Using high-resolution live-cell imaging, we further found that the MoMal3 mutant assembled a rigid MT in parallel with the MT during hyphal polar growth, the cage-like network in the appressorium and the stick-like spindle in nuclear division. These aberrant MT organization patterns in the MoMal3 mutant impaired actin-based cell growth and host infection. Taken together, these findings showed that M. oryzae relies on MoMal3 to assemble elaborate MT arrays for growth and infection. The results also revealed the assembly mode of MTs in M. oryzae, indicating that MTs are pivotal for M. oryzae growth and host infection and may be new targets for devastating fungus control.

An Anti-Oxidative Bioink for Cartilage Tissue Engineering Applications.

Since chondrocytes are highly vulnerable to oxidative stress, an anti-oxidative bioink combined with 3D bioprinting may facilitate its applications in cartilage tissue engineering. We developed an anti-oxidative bioink with methacrylate-modified rutin (RTMA) as an additional bioactive component and glycidyl methacrylate silk fibroin as a biomaterial component. Bioink containing 0% RTMA was used as the control sample. Compared with hydrogel samples produced with the control bioink, solidified anti-oxidative bioinks displayed a similar porous microstructure, which is suitable for cell adhesion and migration, and the transportation of nutrients and wastes. Among photo-cured samples prepared with anti-oxidative bioinks and the control bioink, the sample containing 1 mg/mL of RTMA (RTMA-1) showed good degradation, promising mechanical properties, and the best cytocompatibility, and it was selected for further investigation. Based on the results of 3D bioprinting tests, the RTMA-1 bioink exhibited good printability and high shape fidelity. The results demonstrated that RTMA-1 reduced intracellular oxidative stress in encapsulated chondrocytes under H2O2 stimulation, which results from upregulation of COLII and AGG and downregulation of MMP13 and MMP1. By using in vitro and in vivo tests, our data suggest that the RTMA-1 bioink significantly enhanced the regeneration and maturation of cartilage tissue compared to the control bioink, indicating that this anti-oxidative bioink can be used for 3D bioprinting and cartilage tissue engineering applications in the future.

Functional outcomes of different surgical treatments for common peroneal nerve injuries: a retrospective comparative study.

BACKGROUND: This study aims to assess the recovery patterns and factors influencing outcomes in patients with common peroneal nerve (CPN) injury. METHODS: This retrospective study included 45 patients with CPN injuries treated between 2009 and 2019 in Jing'an District Central Hospital. The surgical interventions were categorized into three groups: neurolysis (group A; n = 34 patients), nerve repair (group B; n = 5 patients) and tendon transfer (group C; n = 6 patients). Preoperative and postoperative sensorimotor functions were evaluated using the British Medical Research Council grading system. The outcome of measures included the numeric rating scale, walking ability, numbness and satisfaction. Receiver operating characteristic (ROC) curve analysis was utilized to determine the optimal time interval between injury and surgery for predicting postoperative foot dorsiflexion function, toe dorsiflexion function, and sensory function. RESULTS: Surgical interventions led to improvements in foot dorsiflexion strength in all patient groups, enabling most to regain independent walking ability. Group A (underwent neurolysis) had significant sensory function restoration (P < 0.001), and three patients in Group B (underwent nerve repair) had sensory improvements. ROC analysis revealed that the optimal time interval for achieving M3 foot dorsiflexion recovery was 9.5 months, with an area under the curve (AUC) of 0.871 (95% CI = 0.661-1.000, P = 0.040). For M4 foot dorsiflexion recovery, the optimal cut-off was 5.5 months, with an AUC of 0.785 (95% CI = 0.575-0.995, P = 0.020). When using M3 toe dorsiflexion recovery or S4 sensory function recovery as the gold standard, the optimal cut-off remained at 5.5 months, with AUCs of 0.768 (95% CI = 0.582-0.953, P = 0.025) and 0.853 (95% CI = 0.693-1.000, P = 0.001), respectively. CONCLUSIONS: Our study highlights the importance of early surgical intervention in CPN injury recovery, with optimal outcomes achieved when surgery is performed within 5.5 to 9.5 months post-injury. These findings provide guidance for clinicians in tailoring treatment plans to the specific characteristics and requirements of CPN injury patients.

Metagenomic next-generation sequencing, instead of procalcitonin, could guide antibiotic usage in patients with febrile acute necrotizing pancreatitis: a multicenter, prospective cohort study.

BACKGROUNDS: The effectiveness of procalcitonin-based algorithms in guiding antibiotic usage for febrile acute necrotizing pancreatitis (ANP) remains controversial. Metagenomic next-generation sequencing (mNGS) has been applied to diagnose infectious diseases. We aimed to evaluate the effectiveness of blood mNGS in guiding antibiotic stewardship for febrile ANP. MATERIALS AND METHODS: The prospective multicenter clinical trial was conducted at seven hospitals in China. Blood samples were collected during fever (T ≥38.5°C) from ANP patients. The effectiveness of blood mNGS, procalcitonin, and blood culture in diagnosing pancreatic infection was evaluated and compared. Additionally, the real-world utilization of antibiotics and the potential mNGS-guided antimicrobial strategy in febrile ANP were also analyzed. RESULTS: From May 2023 to October 2023, a total of 78 patients with febrile ANP were enrolled and 30 patients (38.5%) were confirmed infected pancreatic necrosis (IPN). Compared with procalcitonin and blood culture, mNGS showed a significantly higher sensitivity rate (86.7% vs. 56.7% vs. 26.7%, P<0.001). Moreover, mNGS outperformed procalcitonin (89.5% vs. 61.4%, P<0.01) and blood culture (89.5% vs. 69.0%, P<0.01) in terms of negative predictive value. Blood mNGS exhibited the highest accuracy (85.7%) in diagnosing IPN and sterile pancreatic necrosis (SPN), significantly superior to both procalcitonin (65.7%) and blood culture (61.4%). In the multivariate analysis, positive blood mNGS (OR=60.2, P<0.001) and lower fibrinogen level (OR=2.0, P<0.05) were identified as independent predictors associated with IPN, whereas procalcitonin was not associated with IPN, but with increased mortality (OR=11.7, P=0.006). Overall, the rate of correct use of antibiotics in the cohort was only 18.6% (13/70) and would be improved to 81.4% (57/70) if adjusted according to the mNGS results. CONCLUSION: Blood mNGS represents important progress in the early diagnosis of IPN, with particular importance in guiding antibiotic usage for patients with febrile ANP.

Injectable Nanocomposite Immune Hydrogel Dressings: Prevention of Tumor Recurrence and Anti-Infection after Melanoma Resection.

Complex wound repair due to tumor recurrence and infection following tumor resection presents significant clinical challenges. In this study, a bifunctional nanocomposite immune hydrogel dressing, SerMA-LJC, is developed to address the issues associated with repairing infected damaged tissues and preventing tumor recurrence. Specifically, the immune dressing is composed of methacrylic anhydride-modified sericin (SerMA) and self-assembled nanoparticles (LJC) containing lonidamine (Lon), JQ1, and chlorine e6 (Ce6). In vitro and in vivo experiments demonstrate that the nanocomposite hydrogel dressing can trigger immunogenic cell death (ICD) and has a potent anti-tumor effect. Moreover, this dressing can mitigate the acidic microenvironment of tumor cells and suppress the overexpression of PD-L1 on the tumor cell surface, thereby altering the immunosuppressive tumor microenvironment and augmenting the anti-tumor immune response. Further, the RNA sequencing analysis revealed that the hydrogel dressing significantly impacts pathways associated with positive regulation of immune response, apoptotic process, and other relevant pathways, thus triggering a potent anti-tumor immune response. More importantly, the dressing generates a substantial amount of reactive oxygen species (ROS), which can effectively kill Staphylococcus aureus and promote infectious wound healing. In conclusion, this dual-function nanocomposite immune hydrogel dressing exhibits promise in preventing tumor recurrence and promoting infectious wound healing.

Association between social isolation and depression: Evidence from longitudinal and Mendelian randomization analyses.

BACKGROUND: Increasing evidence shows that social isolation and depression are likely to interact with each other, yet the direction and causality of the association are not clear. This study aims to examine the possible reciprocity in the relationship between social isolation and depression. METHODS: This study fitted a cross-lagged panel model (CLPM) by using data from the English Longitudinal Study of Aging (ELSA, 2014-2019, n = 6787) to examine the temporal relationship between social isolation and depressive symptoms in older adults. We then conducted two-sample bidirectional Mendelian randomization (MR) analyses by using independent genetic variants associated with multiple social isolation phenotypes (n = 448,858-487,647) and with depression (n = 215,644-2,113,907) as genetic instruments from genome-wide association studies to assess the causality between social isolation and onset of depression. RESULTS: The CLPM in the ELSA cohort showed a significant and positive lagged effect of social isolation on depressive symptoms (ß = 0.037, P < .001). The reverse cross-lagged path from depressive symptoms to social isolation was also statistically significant (ß = 0.039, P < .001). In two-sample bidirectional MR, the genetically predicted loneliness and social isolation combined phenotype (LNL-ISO) was positively associated with occurrence of depression (OR = 1.88, 95 % CI: 1.41-2.50, P < .001), vice versa (OR = 1.16, 95 % CI:1.13-1.20, P < .001). LIMITATIONS: The self-report nature of the assessments and missing data are study limitations. CONCLUSIONS: These findings suggest a bidirectional relationship between social isolation and depression. It is important to develop interventions that highlight the reciprocal consequences of improving either mental health or social connection in older adults.

Fimbrin associated with Pmk1 to regulate the actin assembly during Magnaporthe oryzae hyphal growth and infection.

The dynamic assembly of the actin cytoskeleton is vital for Magnaporthe oryzae development and host infection. The actin-related protein MoFim1 is a key factor for organizing the M. oryzae actin cytoskeleton. Currently, how MoFim1 is regulated in M. oryzae to precisely rearrange the actin cytoskeleton is unclear. In this study, we found that MoFim1 associates with the M. oryzae mitogen-activated protein (MAP) kinase Pmk1 to regulate actin assembly. MoFim1 directly interacted with Pmk1, and the phosphorylation level of MoFim1 was decreased in Δpmk1, which led to a change in the subcellular distribution of MoFim1 in the hyphae of Δpmk1. Moreover, the actin cytoskeleton was aberrantly organized at the hyphal tip in the Δpmk1, which was similar to what was observed in the Δmofim1 during hyphal growth. Furthermore, phosphorylation analysis revealed that Pmk1 could phosphorylate MoFim1 at serine 94. Loss of phosphorylation of MoFim1 at serine 94 decreased actin bundling activity. Additionally, the expression of the site mutant of MoFim1 S94D (in which serine 94 was replaced with aspartate to mimic phosphorylation) in Δpmk1 could reverse the defects in actin organization and hyphal growth in Δpmk1. It also partially rescues the formation of appressorium failure in Δpmk1. Taken together, these findings suggest a regulatory mechanism in which Pmk1 phosphorylates MoFim1 to regulate the assembly of the actin cytoskeleton during hyphal development and pathogenesis.

KAS-seq profiling captures transcription dynamics during oocyte maturation.

In fully grown oocytes, the genome is considered to be globally transcriptionally silenced. However, this conclusion is primarily derived from the results obtained through immunofluorescence staining or inferred from the highly condensed state of chromosomes, lacking more direct evidence. Here, by using a kethoxal-assisted single-stranded DNA sequencing (KAS-seq) approach, we investigated the landscape of single-strand DNA (ssDNA) throughout the genome and provided a readout of the activity and dynamics of transcription during oocyte meiotic maturation. In non-surrounded nucleolus (NSN) oocytes, we observed a robust KAS-seq signal, indicating the high transcriptional activity. In surrounded nucleolus (SN) oocytes, the presence of ssDNA still persists although the KAS-seq signal was relatively weak, suggesting the presence of transcription. Accompanying with the meiotic resumption, the transcriptional activity gradually decreased, and global repression was detected in matured oocytes. Moreover, we preformed the integrative genomics analysis to dissect the transcriptional dynamics during mouse oocyte maturation. In sum, the present study delineates the detailed transcriptional activity during mammalian oocyte maturation.

Rational Design of CoOOH/α-Fe2O3/SnO2 for Boosted Photoelectrochemical Water Oxidation: The Roles of Underneath SnO2 and Surface CoOOH.

Hematite (α-Fe2O3) photoanode is a promising candidate for efficient PEC solar energy conversion. However, the serious charge recombination together with the sluggish water oxidation kinetics of α-Fe2O3 still restricts its practical application in renewable energy systems. In this work, a CoOOH/α-Fe2O3/SnO2 photoanode was fabricated, in which the ultrathin SnO2 underlayer is deposited on the fluorine-doped tin oxide (FTO) substrate, α-Fe2O3 nanorod array is the absorber layer, and CoOOH nanosheet is the surface modifier, respectively. The resulting CoOOH/α-Fe2O3/SnO2 exhibited excellent PEC water splitting with a high photocurrent density of 2.05 mA cm-2 at 1.23 V vs RHE in the alkaline electrolyte, which is ca. 3.25 times that of bare α-Fe2O3. PEC characterizations demonstrated that SnO2 not only could block hole transport from α-Fe2O3 to FTO substrate but also could efficiently enhance the light-harvesting property and reduce the surface states by controlling the growth process of α-Fe2O3, while the CoOOH overlayer as cocatalysts could rapidly extract the photogenerated holes and provide catalytic active sites for water oxidation. Benefiting from the synergistic effects of SnO2 and CoOOH, the efficiency of the charge recombination and the overpotential for water oxidation of α-Fe2O3 are obviously decreased, resulting in the boosted PEC efficiency for water oxidation. The rational design and simple fabrication strategy display great potentials to be used for other PEC systems with excellent efficiency.

Integrated genetic and epigenetic analyses uncovered GLP1R association with metabolically healthy obesity.

BACKGROUND: Both genetic and epigenetic variations of GLP1R influence the development and progression of obesity. However, the underlying mechanism remains elusive. This study aims to explore the mediation roles of obesity-related methylation sites in GLP1R gene variants-obesity association. METHODS: A total of 300 Chinese adult participants were included in this study and classified into two groups: 180 metabolically healthy obesity (MHO) cases and 120 metabolically healthy normal-weight (MHNW) controls. Questionnaire investigation, physical measurement and laboratory examination were assessed in all participants. 18 single nucleotide polymorphisms (SNPs) and 31 CpG sites were selected for genotype and methylation assays. Causal inference test (CIT) was performed to evaluate the associations between GLP1R genetic variation, DNA methylation and MHO. RESULTS: The study found that rs4714211 polymorphism of GLP1R gene was significantly associated with MHO. Additionally, methylation sites in the intronic region of GLP1R (GLP1R-68-CpG 7.8.9; GLP1R-68-CpG 12.13; GLP1R-68-CpG 17; GLP1R-68-CpG 21) were associated with MHO, and two of these methylation sites (GLP1R-68-CpG 7.8.9; GLP1R-68-CpG 17) partially mediated the association between genotypes and MHO. CONCLUSIONS: Not only the gene polymorphism, but also the DNA methylation of GLP1R was associated with MHO. Epigenetic changes in the methylome may in part explain the relationship between genetic variants and MHO.

Association of Abnormal Sleep Duration and Sleep Disturbance with Physical Activity in Older Adults: Between- and within-Person Effects.

OBJECTIVES: Sleep is associated with physical activity (PA), yet the nature and directions of this association are less understood. This study aimed to disentangle the long-term temporal sequences between sleep duration/disturbance and PA in older adults, distinguishing between- and within-person effects. DESIGN: Longitudinal panel study. SETTING AND PARTICIPANTS: We conducted a longitudinal study using 3 waves of data collected in 2008/09 (T1), 2012/13 (T2), and 2016/17(T3) from adults aged ≥50 years in the English Longitudinal Study of Ageing (N = 10,749 individuals). MEASURES: Sleep duration, sleep disturbance, and PA were assessed by self-reported questionnaires. We used cross-lagged panel models (CLPMs) to examine between-person effects and random intercept cross-lagged panel models (RI-CLPMs) to examine within-person effects. RESULTS: Our analyses revealed a reciprocal relationship between abnormal sleep duration and low PA levels at between-person level (abnormal sleep duration to PA: ßT1-T2 = -0.053, ßT2-T3 = -0.058, all P < .001; PA to abnormal sleep duration: ßT1-T2 = -0.040, ßT2-T3 = -0.045, all P < .05), with abnormal sleep duration being the driving force in the dynamic association. In addition, there was a unidirectional effect of more severe sleep disturbance on lower levels of PA at both between- and within-person levels (between-person level: ßT1-T2 = -0.032, ßT2-T3 = -0.028, all P < .001; within-person level: ßT1-T2 and T2-T3 = -0.031, all P = .011). CONCLUSIONS AND IMPLICATIONS: This study adds novel insights into the temporal directionality of sleep and PA among community-dwelling older adults and highlights poor sleep as a potential risk factor for PA. Intervention strategies should aim to improve sleep to promote PA levels and successful aging.

A finite element method study of the effect of vibration on the dynamic biomechanical response of the lumbar spine.

BACKGROUND: Studies focusing on lumbar spine biomechanics are very limited, and the mechanism of the effect of vibration on lumbar spine biodynamics is unclear. To provide guidance and reference for lumbar spine biodynamics research and vibration safety assessment, this study aims to investigate the effects of different vibrations on lumbar spine biodynamics. METHODS: A validated finite element model of the lumbosacral spine was utilized. The model incorporated a 40 kg mass on the upper side and a 400 N follower preload. As a comparison, another model without a coupled mass was also employed. A sinusoidal acceleration with an amplitude of 1 m/s2 and a frequency of 5 Hz was applied to the upper and lower sides of the model respectively. FINDINGS: When the coupled mass point is not introduced: in the case of upper-side excitation, the lumbar spine shows a significantly larger response in the x-direction than in the z-direction, while in the case of lower-side excitation, the lumbar spine experiences rigid body displacement in the z-direction without any movement, deformation, rotation, or stress changes in the x-direction. When the coupled mass point is introduced: both upper and lower-side excitations result in significant differences in z-directional displacement, with relatively small differences in vertebral rotation angle, disc deformation, and stress. Under upper excitation, low-frequency oscillations occur in the x-direction. In both types of excitations, the anterior-posterior deformation of the L2-L3 and L4-L5 intervertebral discs is greater than the vertical deformation. The peak (maximum) disc stress exceeds the average stress and stress amplitude across the entire disc. Regardless of the excitation type, the stress distribution within the disc at the moment of peak displacement remains nearly identical, with the maximum stress consistently localized on the anterior side of the L4-L5 disc. INTERPRETATION: Accurately simulating lumbar spine biodynamics requires the inclusion of the upper body mass in the lumbosacral spine model. The physiological curvature of the lumbar spine could escalate the risk of lumbar spine vibration injuries. It is more instructive to apply local high stress in the disc as a lumbar spine vibration safety evaluation parameter.

Sesquiterpenoid derivatives isolated from a liquid culture of Hypholoma capnoides 819.

Nine previously undescribed sesquiterpenoids, named as capnoidones A-G (1-6 and 8) and capnoidols A and B (7 and 9), along with three known sesquiterpenoids, fascicularones A, B, and G (12, 11 and 10), were isolated from the fermentation products of the mushroom Hypholoma capnoides 819 (Strophariace). The structures of these compounds were determined through MS and NMR experiments along with electronic circular dichroism analysis. Optical rotation calculations and X-ray diffraction experiments were also conducted for confirmation of the structures. Compounds 1 and 4 displayed mild cytotoxicity towards BV2 microglial cells in mice, while compound 4 exhibited mild cytotoxicity against breast cancer MCF-7 cells. However, none of the compounds demonstrated antibacterial activity against Staphylococcus aureus or Escherichia coli.

Dynamic perturbation analysis of fractional order differential quasiperiodic Mathieu equation.

The paper investigates the influence of parameters on the stability of fractional order differential quasiperiodic Mathieu equations. First, we use the perturbation method to obtain approximate expressions (i.e., transition curves) for the stability and unstable region boundaries of the equation. After obtaining the approximate expression of the transition curve, we use Lyapunov's first method to analyze the stability of the fractional order differential quasiperiodic Mathieu system, thereby obtaining the conditions for the stability of the fractional order differential quasiperiodic Mathieu equation system. Second, by comparing the approximate expressions of the transition curve of the steady-state periodic solution of the quasiperiodic Mathieu oscillator under different parameter conditions, we obtained the conclusion that the fractional order differential term exists in the form of equivalent stiffness and equivalent damping in the fractional order differential quasiperiodic Mathieu system. By comparison, we have summarized the general forms of equivalent linear damping and equivalent stiffness of the system. Through this general form, we can define an approximate expression for the thickness of unstable regions to better study the characteristics of fractional order differential quasiperiodic Mathieu systems. Finally, the influence of the parameters of the fractional order differential quasiperiodic Mathieu equation on the transition curve of the equation was intuitively analyzed through numerical simulation, to analyze the stability changes in the equation.

Mechanistic study on the side arm effect in a palladium/Xu-Phos-catalyzed enantioselective alkoxyalkenylation of γ-hydroxyalkenes.

Recently, the asymmetric bifunctionalization of alkenes has received much attention. However, the development of enantioselective alkoxyalkenylation has posed a considerable challenge and has lagged largely behind. Herein, we report a new palladium-catalyzed enantioselective alkoxyalkenylation reaction, using a range of primary, secondary, and tertiary γ-hydroxy-alkenes with alkenyl halides. By employing newly identified Xu-Phos (Xu8 and Xu9) with a suitable side-arm adjacent to the PCy2 motif, a series of allyl-substituted tetrahydrofurans were obtained in good yields with up to 95% ee. Besides (E)-alkenyl halides, (Z)-alkenyl halide was also examined and provided the corresponding (Z)-product as a single diastereomer, supporting a stereospecific oxidative addition and reductive elimination step. Moreover, deuterium labeling and VCD experiments were employed to determine a cis-oxypalladation mechanism. DFT calculations helped us gain deeper insight into the side-arm effect on the chiral ligand. Finally, the practicability of this method is further demonstrated through a gram-scale synthesis and versatile transformations of the products.

Cadaveric feasibility study of modified contralateral C7 nerve transfer for targeted functional recovery in hemiplegic upper extremity.

BACKGROUND: Contralateral cervical seventh (cC7) nerve to C7 transfer has been proven effective for treating spastic upper limb. However, for those whose major impairment is not in the C7 area, cC7 nerve transfer to other nerve(s) may achieve a better outcome. The aim of this study was to explore the optimal surgical approach for transferring cC7 to one or two nerves by cadaveric study and to discuss the possible applications for hemiplegic patients. METHODS: Modified cC7 transfer to one (five procedures) or two nonadjacent (three procedures) nerve roots was proposed, and success rates of direct coaptation through two surgical approaches were compared: the superficial surface of longus colli (sLC) and the deep surface of longus colli (dLC) approaches. The length, diameter and distance of relevant nerves were also measured in 25 cadavers. RESULTS: Compared with the sLC approach, the distance of the dLC approach was 1.1 ± 0.3 cm shorter. The success rates for the sLC and dLC approaches were as follows, respectively: cC7-C5 surgery, 94% and reached 98%; cC7-C6 surgery, 54% and 96%; cC7-C7 surgery, 42% and 94%; cC7-C8 surgery, 34% and 94%; cC7-T1 surgery, 24% and 62%; cC7-C5C7 surgery, 74% and 98%; cC7-C6C8 surgery, 54% and 98%. cC7-C7T1 surgery, 42% and 88%. CONCLUSIONS: The dLC approach greatly improved direct coaptation rate for cC7 nerve transfer. The modified cC7 nerve transfer procedures are technically feasible for further application in clinic.

Hsa_circ_0009092/miR-665/NLK signaling axis suppresses colorectal cancer progression via recruiting TAMs in the tumor microenvironment.

BACKGROUND: It has been demonstrated that circularRNA (circRNAs) plays a critical role in various cancers. While the potential molecular mechanism of circRNAs in the progression of colorectal cancer (CRC) remains uncertain. METHODS: Differentially expressed circRNAs were identified by RNA sequencing. RT-qPCR detected the expression of circ_0009092, miR-665, and NLK in CRC tissues and cells. Functions of circ_0009092 on tumor cell proliferation, migration, and invasion were investigated by a series of in vitro assays. The underlying mechanism of circ_0009092 was explored by bioinformatics analysis, RNA immunoprecipitation (RIP) and luciferase assays. A co-culture assay in vitro was performed to detect the affection of circ_0009092 on macrophage recruitment in the tumor microenvironment (TME). A xenograft mouse model was used to explore the effect of circ_0009092 on tumor growth. RESULTS: Circ_0009092 was downregulated in CRCand predicted a good prognosis. Overexpression of circ_0009092 reduced tumor cell EMT, proliferation, migration, and invasion in vitro and in vivo. Mechanistically, circ_0009092 elevated the NLK expression via sponging miR-665 and suppressed the Wnt/ß-catenin signaling pathway. EIF4EA3 induced circ_0009092 expression in CRC cells. In addition, NLK regulates phosphorylation and O-GlcNAcylation of STAT3 by binding to STAT3, thereby inhibiting CCL2 expression, in which it inhibits macrophage recruitment in the tumor microenvironment (TME). CONCLUSION: EIF4A3 suppressed circ_0009092 biogenesis, whichinhibits CRC progression by sponging miR-665 to downregulate NLK. Circ_0009092/miR-665/NLK suppressed tumor EMT, proliferation, migration, and invasion by acting on the Wnt/ß-catenin signaling pathway. NLK directly interacted with STAT3 and decreased the CCL2 expression, inhibiting the recruitment of tumor-associated macrophages (TAMs) in the TME. Our study provided novel insights into the roles of circ_0009092 as a novel promising prognostic and therapeutic target in CRC.