The influence of electrode types to the visually induced gamma oscillations in mouse primary visual cortex.

The local field potential (LFP) is an extracellular electrical signal associated with neural ensemble input and dendritic signaling. Previous studies have linked gamma band oscillations of the LFP in cortical circuits to sensory stimuli encoding, attention, memory, and perception. Inconsistent results regarding gamma tuning for visual features were reported, but it remains unclear whether these discrepancies are due to variations in electrode properties. Specifically, the surface area and impedance of the electrode are important characteristics in LFP recording. To comprehensively address these issues, we conducted an electrophysiological study in the V1 region of lightly anesthetized mice using two types of electrodes: one with higher impedance (1 MΩ) and a sharp tip (10 µm), while the other had lower impedance (100 KΩ) but a thicker tip (200 µm). Our findings demonstrate that gamma oscillations acquired by sharp-tip electrodes were significantly stronger than those obtained from thick-tip electrodes. Regarding size tuning, most gamma power exhibited surround suppression at larger gratings when recorded from sharp-tip electrodes. However, the majority showed enhanced gamma power at larger gratings when recorded from thick-tip electrodes. Therefore, our study suggests that microelectrode parameters play a significant role in accurately recording gamma oscillations and responsive tuning to sensory stimuli.

Change in oral health-related behaviours of children before and after dental treatments under general anaesthesia.

This study evaluated the behavioural changes pertaining to children's oral health before and after the dental general anaesthesia (DGA), with particular focus on the factors associated with these changes. The records were collected for the children who received DGA from July 2015 to November 2016, and relevant questionnaires were obtained from their parents/guardians for the information prior to and after the DGA. The questionnaire included Early Childhood Oral Health Impact Scale (ECOHIS) and Dental Subscale of Children's Fear Survey Schedule (CFSS-DS) to investigate the changes in Oral Health-related Quality of Life (OHRQoL) and dental fear. The DGA impact on children's oral hygiene habits and oral health-related behaviours was assessed by analysing the data. The chi-square test and Mann-Whitney test were employed to evaluate the differences. Total of 141 patients (89 before DGA and 77 after DGA, 25 being common) participated in this study. There were 60 children below 5 years and 29 over 5 years before DGA, while 41 children below 5 years and 36 over 5 years after DGA. Most parents/guardians were educated above undergraduate level (59.6% before DGA, 55.8% after DGA). More children lived with grandparents (61.8% before DGA, 54.5% after DGA) than only with parents (20.2% before DGA, 26.0% after DGA). In total, 73.0% (65/89) children before DGA brushed teeth more than twice a day. This proportion increased to 90.9% after DGA (70/77, p = 0.03). The eating difficulty decreased after DGA according to ECOHIS (p = 0.01). CFSS-DS score also decreased after DGA (p < 0.05). After DGA, children's oral hygiene habits and oral health-related quality of life (OHRQoL) improved, children fear for dental treatment decreased, and parents became more attentive towards children oral health.

Injectable hydrogels activated with copper sulfide nanoparticles for enhancing spatiotemporal sterilization and osteogenesis in periodontal therapy.

Developing biomaterials capable of promoting bone regeneration in bacteria-infected sites is of utmost urgency for periodontal disease therapies. Here we produce a hybrid hydrogel by integrating CuS nanoparticles (CuSNPs), which could kill bacteria through photothermal therapy (PTT) triggered by a near infrared (NIR) light, and a gelatin methacryloyl (GelMA) hydrogel, which is injectable and biocompatible. Specifically, CuSNPs were precipitated by chitosan (CS) firstly, then grafted with methacrylic anhydride (MA) to form CuSNP@CS-MA, which was photo-crosslinked with GelMA to synthesize hybrid hydrogels (GelMA/CuSNP). The hybrid hydrogels exhibited a broad-spectrum antibacterial property that could be spatiotemprorally manipulated through applying a NIR light. Their mechanical properties were adjustable by controlling the concentration of CuSNPs, enabling the hydrogels to become more adapted to the oral diseases. Meanwhile, the hybrid hydrogels showed good cytocompatibility in vitro and improved hemostasis in vivo. Moreover, they accelerated alveolar osteogenesis and vascular genesis, successfully treating periodontis in four weeks in a rat model. GelMA/CuSNP hydrogels showed a broad-spectrum sterilization ability via PTT in vitro and outstanding antibacterial property in vivo, suggesting that the hybrid hydrogels could function in the challenging, bacteria-rich, oral environment. Such injectable hybrid hydrogels, capable of achieving both facilitated osteogenesis and NIR-inducible sterilization, represent a new biomaterial for treating periodontitis.

Impact of tumour stroma-immune interactions on survival prognosis and response to neoadjuvant chemotherapy in bladder cancer.

BACKGROUND: The tumour stroma is associated with unfavourable prognosis in diverse solid tumours, but its prognostic and predictive value in bladder cancer (BCa) is unclear. METHODS: In this multicentre, retrospective study, we included 830 patients with BCa from six independent cohorts. Differences in overall survival (OS) and cancer-specific survival (CSS) were investigated between high-tumour stroma ratio (TSR) and low-TSR groups. Multi-omics analyses, including RNA sequencing, immunohistochemistry, and single-cell RNA sequencing, were performed to study stroma-immune interactions. TSR prediction models were developed based on pelvic CT scans, and the best performing model was selected based on receiver operator characteristic analysis. FINDINGS: Compared to low-TSR tumours, high-TSR tumours were significantly associated with worse OS (HR = 1.193, 95% CI: 1.046-1.361, P = 0.008) and CSS (HR = 1.337, 95% CI: 1.139-1.569, P < 0.001), and lower rate of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). High-TSR tumours exhibited higher infiltration of immunosuppressive cells, including Tregs and tumour-associated neutrophils, while low-TSR tumours exhibited higher infiltration of immune-activating cells such as CD8+ Teff and XCR1+ dendritic cells. The TSR prediction model was developed by combining the intra-tumour and tumour base radiomics features, and showed good performance to predict high-TSR, as indicted by area under the curve of 0.871 (95% CI: 0.821-0.921), 0.821 (95% CI: 0.731-0.911), and 0.801 (95% CI: 0.737-0.865) in the training, internal validation, and external validation cohorts, respectively. In patients with low predicted TSR, 92.3% (12/13) achieved pCR, while only 35.3% (6/17) of patients with high predicted TSR achieved pCR. INTERPRETATION: The tumour stroma was found to be significantly associated with clinical outcomes in patients with BCa as a result of tumour stroma-immune interactions. The radiomics prediction model provided non-invasive evaluation of TSR and was able to predict pCR in patients receiving NAC for BCa. FUNDING: This work was supported by National Natural Science Foundation of China (Grant No. 82373254 and 81961128027), Guangdong Provincial Natural Science Foundation (Grant No. 2023A1515010258), Science and Technology Planning Project of Guangdong Province (Grant No. 2023B1212060013). Science and Technology Program of Guangzhou (SL2022A04J01754), Sun Yat-Sen Memorial Hospital Clinical Research 5010 Program (Grant No. SYS-5010Z-202401).

Ginseng-DF ameliorates intestinal mucosal barrier injury and enhances immunity in immunosuppressed mice by regulating MAPK/NF-κB signaling pathways.

PURPOSE: Dietary fiber (DF) has a good application prospect in effectively restoring the integrity of the intestinal mucosal barrier. Ginseng-DF has good physicochemical properties and physiological activity and shows positive effects in enhancing immunity. The aim of this study was to investigate the protective effect of Ginseng-DF on intestinal mucosal barrier injury induced by cyclophosphamide (CTX) in immunosuppressed mice and its possible mechanism. METHODS: The effects of Gginseng-DF on immune function in mice were studied by delayed-type hypersensitivy, lymphocyte proliferation assay and NK cytotoxicity assay, the T lymphocyte differentiation and intestinal barrier integrity were analyzed by flow cytometry and western blot. RESULTS: Ginseng-DF (2.5% and 5%) could attenuate the inhibition of DTH response by CTX, promote the transformation and proliferation of lymphocytes, and stimulate NK effector cell activity. At the same time, Ginseng-DF could restore the proportion of CD4+/CD8+ T lymphocytes induced by CTX to different extents, improved spleen tissue damage, promoted the secretion of immunoglobulin IgG, and enhanced body immunity. More importantly, Ginseng-DF could up-regulate the contents of TNF-α, IFN-γ, IL-6 and IL-1ß in serum and intestine of immunosuppressed mice to maintain the balance between Th1/Th2 cytokines, and improve the permeability of intestinal mucosal barrier. Meanwhile, Ginseng-DF could reduce intestinal epithelial cell apoptosis and improve intestinal adaptive immunity in CTX-induced immunosuppressed mice by regulating MAPK/NF-κB signaling pathway. CONCLUSION: Ginseng-DF can be used as a safe dietary supplement to enhance body immunity and reduce intestinal mucosal injury caused by CTX.

Genomic analyses reveal the stepwise domestication and genetic mechanism of curd biogenesis in cauliflower.

Cauliflower (Brassica oleracea L. var. botrytis) is a distinctive vegetable that supplies a nutrient-rich edible inflorescence meristem for the human diet. However, the genomic bases of its selective breeding have not been studied extensively. Herein, we present a high-quality reference genome assembly C-8 (V2) and a comprehensive genomic variation map consisting of 971 diverse accessions of cauliflower and its relatives. Genomic selection analysis and deep-mined divergences were used to explore a stepwise domestication process for cauliflower that initially evolved from broccoli (Curd-emergence and Curd-improvement), revealing that three MADS-box genes, CAULIFLOWER1 (CAL1), CAL2 and FRUITFULL (FUL2), could have essential roles during curd formation. Genome-wide association studies identified nine loci significantly associated with morphological and biological characters and demonstrated that a zinc-finger protein (BOB06G135460) positively regulates stem height in cauliflower. This study offers valuable genomic resources for better understanding the genetic bases of curd biogenesis and florescent development in crops.

Atractylenolide II regulates the proliferation, ferroptosis, and immune escape of hepatocellular carcinoma cells by inactivating the TRAF6/NF-κB pathway.

Hepatocellular carcinoma (HCC) is a common and lethal tumor worldwide. Atractylenolide II (AT-II) is a natural sesquiterpenoid monomer, with anti-tumor effect. To address the effect and mechanisms of AT-II on HCC. The role and mechanisms of AT-II were assessed through cell counting kit-8, flow cytometry, enzyme-linked immunosorbent assay, immunofluorescence, and western blot experiments in Hep3B and Huh7 cells. In vivo experiments were conducted in BALB/c nude mice using immunohistochemistry and western blot assays. AT-II decreased the cell viability of Hep3B and Huh7 cells with a IC50 of 96.43 µM and 118.38 µM, respectively. AT-II increased relative Fe2+ level, which was further promoted with the incubation of erastin and declined with the ferrostatin-1 in Hep3B and Huh7 cells. AT-II enhanced the level of ROS and MDA, but reduced the GSH level, and the expression of xCT and GPX4. AT-II elevated the percent of CD8+ T cells and the IFN-γ contents, and declined the IL-10 concentrations and the expression of PD-L1 in Hep3B and Huh7 cells. AT-II downregulated the relative protein level of TRAF6, p-p65/p-65, and p-IkBα/IkBα, which was rescued with overexpression of TRAF6. Upregulation of TRAF6 also reversed the effect of AT-II on proliferation, ferroptosis, and immune escape in Hep3B cells. In vivo, AT-II reduced tumor volume and weight, the level of GPX4, xCT, and PD-L1, and the expression of TRAF6, p-p65/p-65, and p-IkBα/IkBα, with the increased expression of CD8. AT-II modulated the proliferation, ferroptosis, and immune escape of HCC cells by downregulating the TRAF6/NF-κB pathway.

Modelling lung infection with Klebsiella pneumoniae after murine traumatic brain injury.

Pneumonia is a common comorbidity in patients with severe traumatic brain injury (TBI), and is associated with increased morbidity and mortality. In this study, we established a model of intratracheal Klebsiella pneumoniae administration in young adult male and female mice, at 4 days following an experimental TBI, to investigate how K. pneumoniae infection influences acute post-TBI outcomes. A dose-response curve determined the optimal dose of K. pneumoniae for inoculation (1 x 10^6 colony forming units), and administration at 4 days post-TBI resulted in transient body weight loss and sickness behaviors (hypoactivity and acute dyspnea). K. pneumoniae infection led to an increase in pro-inflammatory cytokines in serum and bronchoalveolar lavage fluid at 24 h post-infection, in both TBI and sham (uninjured) mice. By 7 days, when myeloperoxidase + neutrophil numbers had returned to baseline in all groups, lung histopathology was observed with an increase in airspace size in TBI + K. pneumoniae mice compared to TBI + vehicle mice. In the brain, increased neuroinflammatory gene expression was observed acutely in response to TBI, with an exacerbated increase in Ccl2 and Hmox1 in TBI + K. pneumoniae mice compared to either TBI or K. pneumoniae alone. However, the presence of neuroinflammatory immune cells in the injured brain, and the extent of damage to cortical and hippocampal brain tissue, was comparable between K. pneumoniae and vehicle-treated mice by 7 days. Examination of the fecal microbiome across a time course did not reveal any pronounced effects of either injury or K. pneumoniae on bacterial diversity or abundance. Together, these findings demonstrate that K. pneumoniae lung infection after TBI induces an acute and transient inflammatory response, primarily localized to the lungs with some systemic effects. However, this infection had minimal impact on secondary injury processes in the brain following TBI. Future studies are needed to evaluate the potential longer-term consequences of this dual-hit insult.

SOS1 tonoplast neo-localization and the RGG protein SALTY are important in the extreme salinity tolerance of Salicornia bigelovii.

The identification of genes involved in salinity tolerance has primarily focused on model plants and crops. However, plants naturally adapted to highly saline environments offer valuable insights into tolerance to extreme salinity. Salicornia plants grow in coastal salt marshes, stimulated by NaCl. To understand this tolerance, we generated genome sequences of two Salicornia species and analyzed the transcriptomic and proteomic responses of Salicornia bigelovii to NaCl. Subcellular membrane proteomes reveal that SbiSOS1, a homolog of the well-known SALT-OVERLY-SENSITIVE 1 (SOS1) protein, appears to localize to the tonoplast, consistent with subcellular localization assays in tobacco. This neo-localized protein can pump Na+ into the vacuole, preventing toxicity in the cytosol. We further identify 11 proteins of interest, of which SbiSALTY, substantially improves yeast growth on saline media. Structural characterization using NMR identified it as an intrinsically disordered protein, localizing to the endoplasmic reticulum in planta, where it can interact with ribosomes and RNA, stabilizing or protecting them during salt stress.

Association of exposure to ambient air pollutants with cognitive performance and dementia risk and the mediating role of pulmonary function: Evidence from the UK Biobank.

BACKGROUND: The pathways by which air pollution affects cognition remain to be explored. This study aimed to explore how single air pollutants [including nitrogen oxide (NOX), nitrogen dioxide (NO2), particulate matter with a diameter of 2.5 micrometers (PM2.5), PM10, and PM2.5-10], and air pollution mixture could affect cognitive function and the incidence of dementia, and determine whether pulmonary function (PF) could play a mediating role in the relationship. METHODS: Multiple statistical methods were employed to evaluate association of five air pollutants (NOX, NO2, PM2.5, PM10, and PM2.5-10) with cognitive function. Bootstrap method was used to estimate mediating role of PF in the association of air pollutants with cognition or the incidence of dementia. RESULTS: A mixture of air pollutants was associated with performance on five cognitive tests, and global cognition (P < 0.05). Significantly negative association was also identified between mixture of air pollutants and PF (ß= -0.020, 95% confidence interval (CI)= -0.029 to -0.011). In addition, as PF scores increase, performance on all cognitive tests significantly improve, while the risk of dementia correspondingly decreases. It was noted that PF was shown to mediate the effects of air pollution mixtures on all cognitive tests as well as global cognition. For global cognition, PF mediated 6.08% of the association. PF was also found to have a mediating role in the association between NOX, NO2, PM2.5, and the risk of dementia. CONCLUSION: Mixed air pollution may impact cognitive function, with PF potentially mediating this relationship.

Leaching behaviour of 226Ra from uranium tailings and adsorption behaviour in geotechnical medias.

The leaching process of uranium tailings is a typical water-rock interaction. The release of 226Ra from uranium tailings depends on the nuclides outside the intrinsic properties of uranium tailings on the one hand, and is influenced by the water medium on the other. In this paper, a uranium tailings repository in southern China was used as a research object, and uranium tailings at different depths were collected by drilling samples and mixed to analyze the 226Ra occurrence states. Static dissolution leaching experiments of 226Ra under different pH conditions, solid-liquid ratio conditions, and ionic strength conditions were carried out, and the adsorption and desorption behaviours of 226Ra in five representative stratigraphic media were investigated. The results show that 226Ra has a strong adsorption capacity in representative strata, with adsorption distribution coefficient Kd values ranging from 1.07E+02 to 1.29E+03 (mL/g) and desorption distribution coefficients ranging from 4.97E+02 to 2.71E+03 (mL/g), but the adsorption is reversible. The 226Ra in uranium tailings exists mainly in the residual and water-soluble states, and the release of 226Ra from uranium tailings under different conditions is mainly from the water-soluble and exchangeable state fractions. Low pH conditions, low solid-liquid ratio conditions and high ionic strength conditions are favourable to the release of 226Ra from uranium tailings, so the release of 226Ra from uranium tailings can be reduced by means of adjusting the pH in the tailings and setting up a water barrier. The results of this research have important guiding significance for the management of existing uranium tailings ponds and the control of 226Ra migration in groundwater, which is conducive to guaranteeing the long-term safety, stability and sustainability of uranium mining sites.

Revealing the impact of thermal annealing on the perovskite/organic bulk heterojunction interface in photovoltaic devices.

Perovskite/organic bulk heterojunction (BHJ) integrated solar cells have tremendous development potential to exceed the Shockley-Queisser limit efficiency of single-junction photovoltaics, due to the merits of spectra response extension. However, the presence of energy level barriers and severe non-radiative recombination at the interface between perovskite and BHJ greatly hindered the transport and collection of charge carriers, usually leading to large Voc and photocurrent loss, as well as the stability degradation of integrated devices. Therefore, investigating the interface properties of perovskite/BHJ is crucial for understanding the charge transport process and enhancing device performance. In this study, we effectively regulated the interface properties and charge transport in perovskite/BHJ integrated devices using a thermal annealing process. Using Kelvin probe microscopy, photoluminescence, and transient absorption spectroscopy, we revealed that moderate annealing treatment would contribute to forming close interface contact and provide more channels or pathways for charge transfer, which is advantageous for the interface charge collection and device performance. In addition, the lone pair electrons of acyl, thiophene and pyrrole function groups in polymer PDPP3T and PCBM can act as the Lewis base and provide electrons to the under-coordinated lead atoms or clusters in the perovskite, effectively passivating traps on the surface and grain boundaries of the perovskite through Lewis acid-base coordination. Finally, we improved the photovoltaic conversion efficiency of the device to 21.57% with enhanced stability using an optimized thermal annealing process. This study provides a comprehensive understanding of the integrated perovskite/BHJ interface properties, which could be extended to other optoelectronic devices based on a similar integrated structure.

Toxicity and fate of cadmium in hydroponically cultivated lettuce (Lactuca sativa L.) influenced by microplastics.

Although more attention has been paid to microplastics (MPs) pollution in environment, research on the synthetic influence of microplastic and heavy metals remains limited. To help fill this information gap, we investigated the adsorption behavior of virgin polyvinyl chloride microplastics (PVCMPs) (≤450 µm white spherical powder) on cadmium (II). The effects on seed germination, seedling growth, photosynthetic system, oxidative stress indicators of lettuce, and changes in Cd bioavailability were evaluated under Cd2+ (25 µmol/L), PVCMPs (200 mg/L), and PVCMP-Cd combined (200 mg/L + 25 µmol/L) exposures in hydroponic system. The results demonstrated that the PVCMPs effectively adsorbed Cd ions, which validated by the pseudo-second-order kinetic and the Langmuir isotherm models, indicating the sorption of Cd2+ on the PVCMPs was primary chemisorption and approximates monomolecular layer sorption. Compared to MPs, Cd significantly inhibits plant seed germination and seedling growth and development. However, Surprising improvement in seed germination under PVCMPs-Cd exposure was observed. Moreover, Cd2+ and MPs alone or combined stress caused oxidative stress with reactive oxygen species (ROS) including H2O2, O2- and Malondialdehyde (MDA) accumulation in plants, and substantially damaged to photosynthesis. With the addition of PVCMPs, the content of Cd in the leaves significantly (P<0.01) decreased by 1.76-fold, and the translocation factor and Cd2+removal rate in the water substantially (P<0.01) decreased by 6.73-fold and 1.67-fold, respectively in contrast to Cd2+ stress alone. Therefore, it is concluded the PVCMP was capable of reducing Cd contents in leaves, alleviating Cd toxicity in lettuce. Notably, this study provides a scientific foundation and reference for comprehending the toxicological interactions between microplastics and heavy metals in the environment.

Sr-Incorporated Bioactive Glass Remodels the Immunological Microenvironment by Enhancing the Mitochondrial Function of Macrophage via the PI3K/AKT/mTOR Signaling Pathway.

The repair of critical-sized bone defects continues to pose a challenge in clinics. Strontium (Sr), recognized for its function in bone metabolism regulation, has shown potential in bone repair. However, the underlying mechanism through which Sr2+ guided favorable osteogenesis by modulating macrophages remains unclear, limiting their application in the design of bone biomaterials. Herein, Sr-incorporated bioactive glass (SrBG) was synthesized for further investigation. The release of Sr ions enhanced the immunomodulatory properties and osteogenic potential by modulating the polarization of macrophages toward the M2 phenotype. In vivo, a 3D-printed SrBG scaffold was fabricated and showed consistently improved bone regeneration by creating a prohealing immunological microenvironment. RNA sequencing was performed to explore the underlying mechanisms. It was found that Sr ions might enhance the mitochondrial function of macrophage by activating PI3K/AKT/mTOR signaling, thereby favoring osteogenesis. Our findings demonstrate the relationship between the immunomodulatory role of Sr ions and the mitochondrial function of macrophages. By focusing on the mitochondrial function of macrophages, Sr2+-mediated immunomodulation sheds light on the future design of biomaterials for tissue regenerative engineering.

Transcriptomic and metabolomic insights into the antimony stress response of tall fescue (Festuca arundinacea).

Antimony (Sb) is a toxic heavy metal that severely inhibits plant growth and development and threatens human health. Tall fescue, one of the most widely used grasses, has been reported to tolerate heavy metal stress. However, the adaptive mechanisms of Sb stress in tall fescue remain largely unknown. In this study, transcriptomic and metabolomic techniques were applied to elucidate the molecular mechanism of the Sb stress response in tall fescue. These results showed that the defense process in tall fescue was rapidly triggered during the early stages of Sb stress. Sb stress had toxic effects on tall fescue, and the cell wall and voltage-gated channels are crucial for regulating Sb permeation into the cells. In addition, the pathway of glycine, serine and threonine metabolism may play key roles in the Sb stress response of tall fescue. Genes such as ALDH7A1 and AGXT2 and metabolites such as aspartic acid, pyruvic acid, and biuret, which are related to biological processes and pathways, were key genes and compounds in the Sb stress response of tall fescue. Therefore, the regulatory mechanisms of specific genes and pathways should be investigated further to improve Sb stress tolerance.

Safety and clinical efficacy of double posterolateral coaxial portals for endoscopic management of posterior ankle impingement syndrome.

Background: This study aims to analyze the safety and clinical efficacy of using double posterolateral coaxial portals for endoscopic treatment of posterior ankle impingement syndrome (PAIS), a procedure that has gained popularity in recent times. Methods: Six fresh foot samples were randomly selected to measure the distances of two posterolateral portals to the sural nerve in different positions (plantar flexion 10°, dorsiflexion 30°, and plantar flexion 30°) for safety evaluation. A prospective analysis was conducted on the clinical efficacy of the operative approach for endoscopic management of posterior ankle impingement syndrome, including evaluation of effectiveness and complications. Results: In this study, the mean distances of the first and second portals to the sural nerve were measured in different ankle positions. The distances were found to be 2.26 ± 0.22 cm and 1.59 ± 0.12 cm in the plantar flexion 10° position, 2.21 ± 0.21 cm and 1.55 ± 0.12 cm in the dorsiflexion 30° position, and 2.46 ± 0.29 cm and 1.73 ± 0.19 cm in the plantar flexion 30° position, demonstrating a significant safety margin from the nerve. A total of 38 patients underwent endoscopic treatment for posterior ankle impingement syndrome using double posterolateral coaxial portals between January 2012 and December 2017. This surgical approach provided access to the subtalar joint and posterior ankle region. The patients were followed up for an average of 38.2 months (24-72 months), with a satisfaction rate of 94.7%. There were no reported complications, and significant improvements were observed in both visual analogue scale (VAS) and The American Orthopedic Foot and Ankle Society Score (AOFAS) scores postoperatively. The VAS score decreased from 5.68 to 0.51 (P < 0.001), while the AOFAS score increased from 71.68 to 92.34 (P < 0.001), resulting in an excellent/good rate of 97.3%. Conclusion: The use of double posterolateral coaxial portals in the treatment of posterior ankle impingement syndrome offers several advantages, including improved safety, reduced risk of nerve injury, enhanced visualization of the posterior ankle and subtalar joint, favorable clinical outcomes, and minimal complications.

Gut microbiota induced abnormal amino acids and their correlation with diabetic retinopathy.

AIM: To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy (DR) and provide a novel strategy to elucidate the pathological mechanism of DR. METHODS: The fecal samples from 32 type 2 diabetes patients with proliferative retinopathy (PDR), 23 with non-proliferative retinopathy (NPDR), 27 without retinopathy (DM), and 29 from the sex-, age- and BMI- matched healthy controls (29 HC) were analyzed by 16S rDNA gene sequencing. Sixty fecal samples from PDR, DM, and HC groups were assayed by untargeted metabolomics. Fecal metabolites were measured using liquid chromatography-mass spectrometry (LC-MS) analysis. Associations between gut microbiota and fecal metabolites were analyzed. RESULTS: A cluster of 2 microbiome and 12 metabolites accompanied with the severity of DR, and the close correlation of the disease progression with PDR-related microbiome and metabolites were found. To be specific, the structure of gut microbiota differed in four groups. Diversity and richness of gut microbiota were significantly lower in PDR and NPDR groups, than those in DM and HC groups. A cluster of microbiome enriched in PDR group, including Pseudomonas, Ruminococcaceae-UCG-002, Ruminococcaceae-UCG-005, Christensenellaceae-R-7, was observed. Functional analysis showed that the glucose and nicotinate degradations were significantly higher in PDR group than those in HC group. Arginine, serine, ornithine, and arachidonic acid were significantly enriched in PDR group, while proline was enriched in HC group. Functional analysis illustrated that arginine biosynthesis, lysine degradation, histidine catabolism, central carbon catabolism in cancer, D-arginine and D-ornithine catabolism were elevated in PDR group. Correlation analysis revealed that Ruminococcaceae-UCG-002 and Christensenellaceae-R-7 were positively associated with L-arginine, ornithine levels in fecal samples. CONCLUSION: This study elaborates the different microbiota structure in the gut from four groups. The relative abundance of Ruminococcaceae-UCG-002 and Parabacteroides are associated with the severity of DR. Amino acid and fatty acid catabolism is especially disordered in PDR group. This may help provide a novel diagnostic parameter for DR, especially PDR.

PD-L1 blockade in mitigating severe acute pancreatitis induced pancreatic damage through modulation of immune cell apoptosis.

Acute pancreatitis (AP) is a prevalent gastrointestinal disorder. The immune response plays a crucial role in AP progression. However, the impact of immune regulatory checkpoint PD-L1 on severe acute pancreatitis (SAP) remains uncertain. Hence, this study aimed to examine the influence of PD-L1 on SAP. We assessed PD-L1 expression in neutrophils and monocytes obtained from SAP patients. We induced SAP in C57BL/6J mice, PD-L1 gene-deficient mice, and PD-L1 humanized mice using intraperitoneal injections of cerulein plus lipopolysaccharide. Prior to the initial cerulein injection, a PD-L1 inhibitor was administered. Pancreatic tissues were collected for morphological and immunohistochemical evaluation, and serum levels of amylase, lipase, and cytokines were measured. Flow cytometry analysis was performed using peripheral blood cells. The expression of PD-L1 in neutrophils and monocytes was significantly higher in SAP patients compared to healthy individuals. Likewise, the expression of PD-L1 in inflammatory cells in the peripheral blood of SAP-induced C57BL/6J mice was notably higher than in the control group. In mice with PD-L1 deficiency, SAP model exhibited lower pancreatic pathology scores, amylase, lipase, and cytokine levels compared to wild-type mice. PD-L1 deletion resulted in reduced neutrophil apoptosis, leading to an earlier peak in neutrophil apoptosis. Furthermore, it decreased early monocyte apoptosis and diminished the peak of T lymphocyte apoptosis. Within the SAP model, administration of a PD-L1 inhibitor reduced pancreatic pathology scores, amylase, lipase, and cytokine levels in both C57BL/6J mice and PD-L1 humanized mice. These findings suggest that inhibiting PD-L1 expression can alleviate the severity of SAP.

Asp-tRNAAsn/Glu-tRNAGln amidotransferase A subunit-like amidase mediates the degradation of insecticide flonicamid by Variovorax boronicumulans CGMCC 4969.

The main metabolic product of the pyridinecarboxamide insecticide flonicamid, N-(4-trifluoromethylnicotinyl)glycinamide (TFNG-AM), has been shown to have very high mobility in soil, leading to its accumulation in the environment. Catabolic pathways of flonicamid have been widely reported, but few studies have focused on the metabolism of TFNG-AM. Here, the rapid transformation of TFNG-AM and production of the corresponding acid product N-(4-trifluoromethylnicotinoyl) glycine (TFNG) by the plant growth-promoting bacterium Variovorax boronicumulans CGMCC 4969 were investigated. With TFNG-AM at an initial concentration of 0.86 mmol/L, 90.70 % was transformed by V. boronicumulans CGMCC 4969 resting cells within 20 d, with a degradation half-life of 4.82 d. A novel amidase that potentially mediated this transformation process, called AmiD, was identified by bioinformatic analyses. The gene encoding amiD was cloned and expressed recombinantly in Escherichia coli, and the enzyme AmiD was characterized. Key amino acid residue Val154, which is associated with the catalytic activity and substrate specificity of signature family amidases, was identified for the first time by homology modeling, structural alignment, and site-directed mutagenesis analyses. When compared to wild-type recombinant AmiD, the mutant AmiD V154G demonstrated a 3.08-fold increase in activity toward TFNG-AM. The activity of AmiD V154G was greatly increased toward aromatic L-phenylalanine amides, heterocyclic TFNG-AM and IAM, and aliphatic asparagine, whereas it was dramatically lowered toward benzamide, phenylacetamide, nicotinamide, acetamide, acrylamide, and hexanamid. Quantitative PCR analysis revealed that AmiD may be a substrate-inducible enzyme in V. boronicumulans CGMCC 4969. The mechanism of transcriptional regulation of AmiD by a member of the AraC family of regulators encoded upstream of the amiD gene was preliminarily investigated. This study deepens our understanding of the mechanisms of metabolism of toxic amides in the environment, providing new ideas for microbial bioremediation.