Enhancing m6A modification in the motor cortex facilitates corticospinal tract remodeling after spinal cord injury.

JOURNAL/nrgr/04.03/01300535-202506000-00026/figure1/v/2024-08-05T133530Z/r/image-tiff Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine (m6A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m6A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein (METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m6A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m6A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m6A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.

Clinical characteristics and therapeutic outcomes after endoscopic endonasal surgery for craniopharyngioma in the elderly.

OBJECTIVE: Craniopharyngiomas (CPs) in adults are rare benign epithelial tumors, and few contemporary studies have explored outcomes after surgical treatment in elderly patients, especially with regard to endoscopic endonasal surgery (EES). METHODS: A retrospective cohort study was conducted on patients aged ≥ 18 years with CP who were treated with EES from 2013 to 2022. The cohort was divided into nonelderly (18-64 years) and elderly (≥ 65 years) groups based on age. Various parameters, including patient and tumor characteristics, surgical outcomes, complications, and follow-up, were compared between the two age groups. RESULTS: A total of 193 patients met the inclusion criteria, with 161 (83.4%) patients in the nonelderly group and 32 (16.6%) patients in the elderly group. Preoperatively, older patients were more likely to have memory impairment (4.3% vs 18.8%, p = 0.010), fatigue or decreased energy (9.3% vs 34.4%, p = 0.001), hypopituitarism (68.7% vs 90.6%, p = 0.012), or hydrocephalus (18% vs 40.6%, p = 0.005), and they were more likely asymptomatic (1.2% vs 9.4%, p = 0.033) and less likely to experience headache (57.8% vs 31.3%, p = 0.006). Patients in the elderly group had a longer symptom duration (median [IQR] 5 [10] months vs 9.5 [13] months, p = 0.001) and higher comorbidity scores (p < 0.001). Postoperatively, gross-total resection was achieved in 145 (90.1%) and 28 (87.5%) patients in the nonelderly and elderly groups, respectively. Older patients were more likely to develop pneumonia (5% vs 21.9%, p = 0.004). There were no significant differences in the extent of resection (p = 0.541), pathological subtypes (88.2% vs 75.0% adamantinomatous, p = 0.089), operation time (mean ± SD 307.8 ± 68.3 minutes vs 323.5 ± 86.0 minutes, p = 0.257), estimated blood loss (median [IQR] 300 [200] ml vs 300 [238] ml, p = 0.594), length of stay (median [IQR] 15 [8] days vs 15 [22] days, p = 0.964), perioperative mortality (2.5% vs 3.1%, p > 0.99), or postoperative severe hypothalamic dysfunction (37.9% vs 50.0%, p = 0.237) between the groups. Multivariate Cox regression analysis demonstrated that tumor calcification (HR 3.406, 95% CI 1.859-27.233, p = 0.038) and preoperative hydrocephalus (HR 3.688, 95% CI 1.310-10.386, p = 0.013) were independently associated with decreased survival. The median follow-up period in the elderly group was shorter (71 months vs 44 months, p = 0.001), and no recurrence was observed (7.1% vs 0%, p = 0.132). CONCLUSIONS: This study demonstrates that EES is a viable treatment option for older CP patients. With appropriate perioperative management, EES does not significantly increase mortality and, in selected populations, is well tolerated by patients.

Effect of polishing process on torque loss ratio and microgap of selective laser melting abutment: an in vitro study.

BACKGROUND: The purpose of this in vitro study was to investigate the effect of polishing post-treatment process on the torque loss ratio and microgap of Selective Laser Melting (SLM) abutments before and after mechanical cycling test through improving the surface roughness of the implant-abutment interface. MATERIALS AND METHODS: Forty SLM abutments were fabricated, with 20 underwent minor back-cutting, designated as polishing, in the implant-abutment interface. The abutments were divided into three groups: SLM abutments (group A), original abutments (group B), and polished SLM abutments (group C), each containing 20 abutments. Surface roughness was evaluated using a laser microscope. Implant-abutment specimens were subjected to mechanical cycling test, and disassembly torque values were measured before and after. Scanning electron microscope (SEM) was used to measure microgap after longitudinal sectioning of specimens. Correlation between surface roughness, torque loss ratio, and microgap were evaluated. LSD's test and Tamhane's T2 comparison were used to analyze the data (α = 0.05). RESULTS: The Sz value of polished SLM abutments (6.86 ± 0.64 µm) demonstrated a significant reduction compared to SLM abutments (26.52 ± 7.12 µm). The torque loss ratio of polished SLM abutments (24.16%) was significantly lower than SLM abutments (58.26%), while no statistically significant difference that original abutments (18.23%). The implant-abutment microgap of polished SLM abutments (2.38 ± 1.39 µm) was significantly lower than SLM abutments (8.69 ± 5.30 µm), and this difference was not statistically significant with original abutments (1.87 ± 0.81 µm). A significant positive correlation was identified between Sz values and the ratio of torque loss after cycling test (r = 0.903, P < 0.01), as well as Sz values and the microgap for all specimens in SLM abutments and polished SLM abutments (r = 0.800, P < 0.01). CONCLUSION: The findings of this study indicated that the polishing step of minor back-cutting can lead to a notable improvement in the roughness of SLM abutments interface, which subsequently optimized the implant-abutment fit. It can be seen that the application of minor back-cutting method has advanced the clinical use of SLM abutments.

Cerebral hypoperfusion resulting from improper cannulation positioning during aortic dissection surgery: a case report.

BACKGROUND: Selective antegrade cerebral perfusion (sACP) is a crucial cerebral protection technique employed during aortic dissection surgeries involving cardiopulmonary bypass. However, postoperative neurological complications, particularly those related to cannulation issues and perfusion problems, remain a significant concern. CASE PRESENTATION: This case report details an unusual instance where a 38-year-old male patient with Marfan syndrome experienced cerebral hypoperfusion during emergency surgery for Stanford Type A aortic dissection. Despite following standard protocols, a significant drop in regional cerebral oxygen saturation (rSO2) and abnormal blood pressure fluctuations were observed shortly after initiating sACP via the innominate artery. After initial attempts to optimize perfusion flow proved ineffective, the cannulation position was adjusted, leading to improvements. Nevertheless, the patient subsequently exhibited signs of cerebral hypoperfusion and was found to have suffered a new cerebral infarction. CONCLUSIONS: This case report underscores the importance of precise cannula placement during sACP procedures and the dire consequences that can arise from improper positioning. It emphasizes the need for continuous monitoring and prompt intervention in cases of abnormal cerebral oxygenation and blood pressure, as well as the value of considering cannulation-related issues as potential causes of postoperative neurological complications.

Expression and biological significance of topoisomerase II α (TOP2A) in oral squamous cell carcinoma.

BACKGROUND: Topoisomerase II α(TOP2A) is usually highly expressed in rapidly proliferating cells, and its expression is regulated by cell cycle. The relationship between TOP2A and oral squamous cell carcinoma (OSCC) needs further study. METHODS: TOP2A immunoreactivity was analyzed using immunohistochemical (IHC) staining analysis in specimens from 20 OSCC patients. Based on the high-throughput sequencing and gene microarray database, the expression of TOP2A mRNA in OSCC was calculated and its ability to identify OSCC tissues was evaluated by diagnostic analysis. CRISPR screen was used to select the genes necessary for OSCC cell growth, and the gene set was analyzed for function enrichment. Single-cell RNA sequencing analysis was conducted to evaluate the expression level of TOP2A mRNA in OSCC cells. RESULTS: Compared with normal oral tissues, the expression of TOP2A protein was up-regulated in OSCC tissues. A total of 1240 OSCC and 428 non-OSCC oral tissue samples were included based on high-throughput dataset retrieval, and it was confirmed that TOP2A mRNA was highly expressed in OSCC tissues [SMD = 1.51 (95% CI 0.94-2.07), sROC AUC = 0.96 (95% CI 0.94-0.98)]. As an essential gene for OSCC cell growth, single-cell RNA sequencing data also confirmed that TOP2A mRNA expression was up-regulated in OSCC cells. CONCLUSION: The up-regulation of TOP2A may play a pivotal role in OSCC.

Physiological evaluation and transcriptomic and proteomic analyses to reveal the anti-aging and reproduction-promoting mechanisms of glycitein in Caenorhabditis elegans.

Soy isoflavones from soy sauce residues have important biological activities. However, the anti-aging and reproduction-promoting effects of glycitein are still rarely reported. Here, we systematically evaluated and explored the anti-aging and reproduction-promoting effects of glycitein in Caenorhabditis elegans (C. elegans). Firstly, we analyzed the effects of glycitein on the lifespan under normal and heat stress, reproduction, locomotion, and reactive oxygen species (ROS) levels of C. elegans. The results showed that 100 µmol L-1 glycitein increased the anti-stress ability of nematodes and activated the antioxidant defense system. Secondly, transcriptomic and proteomic technologies were further used to explore in-depth the anti-aging and reproduction-promoting mechanisms of glycitein in C. elegans. The results showed that both differentially expressed proteins (DEPs) including PDE-2 and MSRA-1 and differentially expressed genes (DEGs) including skpo-2 and cytochrome P450 (cyp-35A3, cyp-35A5, cyp-35C1, cyp-35D1) were associated with the extension of the lifespan and the exertion of antioxidant capacity. VIT-1, plx-2, and Y73F8A.35 were related to promoting reproduction. ASP-1, DNJ-10, and abu-1 were related to the anti-stress ability of glycitein. Pathway analysis revealed that the longevity regulation pathway and FOXO signaling pathway were regulated by the changes in genes and proteins to improve the lifespan of the nematode. Moreover, hydrogenase regulation, longevity regulation, and lipid metabolism were regulated by the changes in genes and proteins to promote the reproduction of nematodes. This study not only demonstrates a viable strategy for utilizing soy sauce residues, but also provides a theoretical foundation and developmental insights for the future application of glycitein.

A Multifunctional Nanoparticle Dual Loading with Chlorin e6 and STING Agonist for Combinatorial Therapy of Melanoma.

Photodynamic therapy (PDT) is a noninvasive therapeutic approach that is effective in killing primary tumors with minimal surgical trauma, but its usage in metastatic lesions of melanoma is restricted by spatial limitations. Recently, stimulator of interferon genes (STING) agoinst-mediated innate immunity can activate the STING pathway and further promote dendritic cell (DC) maturation, tumor-specific cytotoxic T lymphocyte, and natural killer cell infiltration and has emerged as a promising approach for cancer therapy. Herein, the authors intriduce facile nanoparticles named HTCS, which can co-deliver STING agonist (2'3'-cGAMP) and a mitochondrial targeting modified photosensitizer (TPP-PEI-Ce6). While HTCS were intravenously injected to mice, they were endocytosed into tumor cells through hyaluronic acid-mediated active targeting. Thereafter, TPP-PEI-Ce6 was delivered to mitochondria to generate a large variety of reactive oxygen species and killed tumor cells effectively. Then the tumor cell debris further gave rise to immunogenic cell death, which played a role in immunosuppression. Furthermore, 2'3'-cGAMP contained in cell debris activated the STING pathway to promote the release of inflammatory cytokines and the maturation of DCs. As a consequence, the HTCS could achieve photodynamic multiple immunotherapy for melanoma. This work demonstrates multifunctional nanoparticles that efficiently inhibit tumors by PDT and reversing their immunosuppression to realize a versatile therapeutic strategy.

Designing a Novel C3-Fe-N Interface Local Coordination Microenvironment for Efficient Electrocatalytic Water Splitting.

Developing single-atomic electrocatalysts (SACs) with high activity and stability for electrocatalytic water-splitting has been challenging. Moreover, the practical utilization of SACs is still far from meeting the the theoretical prediction. Herein a facile and easy scale-up fabrication method is proposed for designing a novel carbon-iron-nitrogen (C-Fe-N) electrocatalyst with a single atom electron bridge (C-Fe-N SAEBs), which exhibits lower overpotential and impedance than previously reported electrocatalysts. 0.8-C-Fe-N SAEBs exhibits significant activity and excellent stability in the bi-functional decomposition of water. The excellent performance of the C-Fe-N SAEBs electrocatalyst can be attributed to the strong coupling effect at the interface owing to the formation of a single atom C3-Fe-N local coordination microenvironment at the interface, which enhance the exposure of active sites and charge transfer, and reduced the adsorption energy barrier of intermediates. Theoretical calculation and synchrotron radiation analysis are performed to understand the mechanistic insights behind the experimental results. The results reveal that the active C3-Fe-N local coordination microenvironment at the interface not only improves water-splitting behavior but also provides a deeper understanding of local-interface geometry/electronic structure for improving the electrocatalytic activity. Thus, the proposed electrocatalyst, as well as the mechanistic insights into its properties, presents a significant stride toward practical application.

Correction: Physiological evaluation and transcriptomic and proteomic analyses to reveal the anti-aging and reproduction-promoting mechanisms of glycitein in Caenorhabditis elegans.

Correction for 'Physiological evaluation and transcriptomic and proteomic analyses to reveal the anti-aging and reproduction-promoting mechanisms of glycitein in Caenorhabditis elegans' by Jianping Lei et al., Food Funct., 2024, https://doi.org/10.1039/D4FO02271H.

In-situ electrospinning PVB/Camellia oil/ZnO-TiO2 nanofibrous membranes with synergistic antibacterial and degradation of ethylene applied in fruit preservation.

This work utilizes a handheld electrospinning device to prepare a novel nanofibrous composite membrane in situ for packaging freshness. It can realize pick-and-pack and is easy to operate. The nanofibrous membrane is based on PVB as the matrix material, adding Camellia oil (CO) and ZnO-TiO2 composite nanoparticles (ZT) as the active material. The antimicrobial property of the CO and the photocatalytic activity of the nanoparticles give the material good antimicrobial and ethylene degradation functions. Meanwhile, this nanofibrous membrane has good mechanical properties, suitable moisture permeability and good optical properties. The nanofibrous membrane are suitable for both climacteric and non- climacteric fruits. Its use as a cling film extends the shelf life of strawberries by 4 days and significantly slows the ripening of small tomatoes. Therefore, this nanofibrous membrane has great potential for application in the field of fruit preservation.

Bibliometric Analysis of Forensic Human Remains Identification Literature from 1991 to 2022.

OBJECTIVES: To describe the current state of research and future research hotspots through a metrological analysis of the literature in the field of forensic anthropological remains identification research. METHODS: The data retrieved and extracted from the Web of Science Core Collection (WoSCC), the core database of the Web of Science information service platform (hereinafter referred to as "WoS"), was used to analyze the trends and topic changes in research on forensic identification of human remains from 1991 to 2022. Network visualisation of publication trends, countries (regions), institutions, authors and topics related to the identification of remains in forensic anthropology was analysed using python 3.9.2 and Gephi 0.10. RESULTS: A total of 873 papers written in English in the field of forensic anthropological remains identification research were obtained. The journal with the largest number of publications was Forensic Science International (164 articles). The country (region) with the largest number of published papers was China (90 articles). Katholieke Univ Leuven (Netherlands, 21 articles) was the institution with the largest number of publications. Topic analysis revealed that the focus of forensic anthropological remains identification research was sex estimation and age estimation, and the most commonly studied remains were teeth. CONCLUSIONS: The volume of publications in the field of forensic anthropological remains identification research has a distinct phasing. However, the scope of both international and domestic collaborations remains limited. Traditionally, human remains identification has primarily relied on key areas such as the pelvis, skull, and teeth. Looking ahead, future research will likely focus on the more accurate and efficient identification of multiple skeletal remains through the use of machine learning and deep learning techniques.

Genome-Wide Analyses of CCHC Family Genes and Their Expression Profiles under Drought Stress in Rose (Rosa chinensis).

CCHC-type zinc finger proteins (CCHC-ZFPs), ubiquitous across plant species, are integral to their growth, development, hormonal regulation, and stress adaptation. Roses (Rosa sp.), as one of the most significant and extensively cultivated ornamentals, account for more than 30% of the global cut-flower market. Despite its significance, the CCHC gene family in roses (Rosa sp.) remains unexplored. This investigation identified and categorized 41 CCHC gene members located on seven chromosomes of rose into 14 subfamilies through motif distribution and phylogenetic analyses involving ten additional plant species, including Ginkgo biloba, Ostreococcus lucimarinus, Arabidopsis thaliana, and others. This study revealed that dispersed duplication likely plays a crucial role in the diversification of the CCHC genes, with the Ka/Ks ratio suggesting a history of strong purifying selection. Promoter analysis highlighted a rich presence of cis-acting regulatory elements linked to both abiotic and biotic stress responses. Differential expression analysis under drought conditions grouped the 41 CCHC gene members into five distinct clusters, with those in group 4 exhibiting pronounced regulation in roots and leaves under severe drought. Furthermore, virus-induced gene silencing (VIGS) of the RcCCHC25 member from group 4 compromised drought resilience in rose foliage. This comprehensive analysis lays the groundwork for further investigations into the functional dynamics of the CCHC gene family in rose physiology and stress responses.

Monocyte/macrophage-mediated venous thrombus resolution.

Venous thromboembolism (VTE) poses a notable risk of morbidity and mortality. The natural resolution of the venous thrombus might be a potential alternative treatment strategy for VTE. Monocytes/macrophages merge as pivotal cell types in the gradual resolution of the thrombus. In this review, the vital role of macrophages in inducing inflammatory response, augmenting neovascularization, and facilitating the degradation of fibrin and collagen during thrombus resolution was described. The two phenotypes of macrophages involved in thrombus resolution and their dual functions were discussed. Macrophages expressing various factors, including cytokines and their receptors, adhesion molecules, chemokine receptors, vascular endothelial growth factor receptors, profibrinolytic- or antifibrinolytic-related enzymes, and other elements, are explored for their potential to promote or attenuate thrombus resolution. Furthermore, this review provides a comprehensive summary of new and promising therapeutic candidate drugs associated with monocytes/macrophages that have been demonstrated to promote or impair thrombus resolution. However, further clinical trials are essential to validate their efficacy in VTE therapy.

Varying concentrations of tyrosine kinase inhibitors in chronic myeloid leukemia patients following bariatric surgery: a case series.

Bariatric surgery is increasingly performed to treat severe obesity. As a result of anatomical and physiological changes in the gastrointestinal tract, the pharmacokinetics (PK) of oral drugs can be altered, affecting their efficacy and safety. This includes the class of tyrosine kinase inhibitors (TKIs) which are used to treat chronic myeloid leukemia (CML). This case series describes the clinical course of four CML cases with a history of bariatric surgery. The patients used various TKIs (nilotinib, dasatinib, bosutinib, ponatinib, and imatinib) for which 15 drug levels were measured. The measured TKI concentrations were in part subtherapeutic, and highly variable when compared to mean levels measured in the general population. Multiple drug levels were measured in these patients, as the clinicians were aware of the possible impact of bariatric surgery. The drug levels were used as additional input for clinical decision-making. All four patients required TKI switches and/or dose modifications to achieve an effective and tolerable treatment. Eventually, adequate clinical and molecular remissions were achieved in all cases. In summary, TKI concentrations of patients undergoing bariatric surgery may be subtherapeutic. Moreover, there is substantial interindividual and intraindividual variation, which may be explained by the complex interference of bariatric surgery and associated weight loss. For clinical practice, therapeutic drug monitoring is advised in patients with a history of bariatric surgery in case of suboptimal response or loss of response.

Unveiling the role of gut microbiota in curcumin metabolism using antibiotic-treated mice.

Curcumin might exert its therapeutic effects by interacting with gut microbiota. However, the role of gut microbiota in curcumin metabolism in vivo remains poorly understood. To address this, we used antibiotics to deplete gut microbiota and compared curcumin metabolism in control and antibiotic-treated mice. Using Q-TOF and triple quadrupole mass spectrometry, we identified and quantified curcumin metabolites, revealing distinct metabolic pathways in these two mice groups. The novel metabolites, hexahydro-dimethyl-curcumin and hexahydro-didemethyl-curcumin were exclusively derived from gut microbiota. Additionally, gut bacteria deconjugated curcumin metabolites back into their bioactive forms. Moreover, control mice exhibited significantly lower curcumin degradation, suggesting a protective role of gut microbiota against degradation. In conclusion, our results indicated that gut microbiota might enhance the effectiveness of curcumin by deconjugation, production of active metabolites, and protection against degradation in the large intestine. This study enhances our understanding of the interactions between curcumin and gut microbiota.

Does the presence of blind-ended vas deferens and spermatic vessels in laparoscopic exploration of non-palpable testes conclusively indicate testicular absence?

Objective: The purpose of this study was to determine whether the presence of blind-ended vas deferens and spermatic vessels (VDSV) during laparoscopic exploration of non-palpable testes (NPT) indicates testicular absence or atrophy. Materials and methods: A retrospective analysis was conducted on clinical data of patients diagnosed with NPT and treated with surgical intervention at our center from April 2013-April 2023. The dataset encompassed information such as the children's age, affected side, size of the contralateral testis, surgical procedures employed, outcomes, and histopathological examination results. All patients underwent physical examination and ultrasonography preoperatively, followed by a combination of laparoscopic exploration and exploration through inguinal or scrotal incisions during surgery. Long-term follow-up was conducted postoperatively. Results: A total of 476 cases comprising 504 NPT were included in this study: 302 cases on the left side, 146 cases on the right side, and 28 cases bilaterally. All patients underwent surgical treatment within 6-126 months (median 13 months). During laparoscopic exploration, blind-ended VDSV were found in 90 testes (72 on the left side, 18 on the right side), while exploration through inguinal or scrotal incisions revealed 52 (57.8%) testicular nodules with atrophy, which were excised, leaving 38 (42.2%) without any findings. Histopathological examination of atrophic nodules revealed fibrosis as the most common finding in 41 cases (78.8%), followed by involvement of the vas deferens in 33 cases (63.5%), calcification in 24 cases (46.2%), epididymis in 23 cases (44.2%), and hemosiderin deposition in 7 cases (13.6%). Fibrosis, calcification, hemosiderin deposition, involvement of the vas deferens, and epididymis were found in combination in 47 specimens (90.4%). Seminiferous tubules (SNT) were found in 3 specimens (5.7%), and germ cells (GC) were found in 1 specimen (1.9%). Conclusion: The presence of blind-ended VDSV during laparoscopic exploration of NPT does not necessarily indicate testicular absence or disappearance. It is possible that atrophic testicular nodules are located within the inguinal canal or scrotum. This understanding contributes to the management of non-palpable testes. Considering their unpredictable malignant potential, we recommend excision.

Aneuploidy underlies brefeldin A-induced antifungal drug resistance in Cryptococcus neoformans.

Cryptococcus neoformans is at the top of the list of "most wanted" human pathogens. Only three classes of antifungal drugs are available for the treatment of cryptococcosis. Studies on antifungal resistance mechanisms are limited to the investigation of how a particular antifungal drug induces resistance to a particular drug, and the impact of stresses other than antifungals on the development of antifungal resistance and even cross-resistance is largely unexplored. The endoplasmic reticulum (ER) is a ubiquitous subcellular organelle of eukaryotic cells. Brefeldin A (BFA) is a widely used chemical inducer of ER stress. Here, we found that both weak and strong selection by BFA caused aneuploidy formation in C. neoformans, mainly disomy of chromosome 1, chromosome 3, and chromosome 7. Disomy of chromosome 1 conferred cross-resistance to two classes of antifungal drugs: fluconazole and 5-flucytosine, as well as hypersensitivity to amphotericin B. However, drug resistance was unstable, due to the intrinsic instability of aneuploidy. We found overexpression of AFR1 on Chr1 and GEA2 on Chr3 phenocopied BFA resistance conferred by chromosome disomy. Overexpression of AFR1 also caused resistance to fluconazole and hypersensitivity to amphotericin B. Furthermore, a strain with a deletion of AFR1 failed to form chromosome 1 disomy upon BFA treatment. Transcriptome analysis indicated that chromosome 1 disomy simultaneously upregulated AFR1, ERG11, and other efflux and ERG genes. Thus, we posit that BFA has the potential to drive the rapid development of drug resistance and even cross-resistance in C. neoformans, with genome plasticity as the accomplice.

Influence of the examination position and distension medium on the rectal sensory test in patients with functional constipation.

PURPOSE: To evaluate the impact of two different parameters (body position and distension medium) on the rectal sensory test in patients with functional constipation and provide data support for the development of standardized operating procedures in clinical practice. METHODS: Based on a single-center process of the rectal sensory test, 39 patients with functional constipation were recruited for rectal sensory test under different body positions and distension mediums. RESULTS: Among the items of the Constipation Scoring System, the score of frequency of bowel movements showed a negative correlation with the first constant sensation volume (r = -0.323, P = 0.045). Conversely, the score of painful evacuation effort showed a positive correlation with the desire to defecate volume (r = 0.343, P = 0.033). There was a statistically significant difference in the first constant sensation volume (when the distension medium was gas) measured in different body positions (left lateral position, sitting position, squatting position), and the data measured in the squatting position were significantly higher than those in left lateral position (P < 0.05). In terms of research on distension medium, it was found that the first constant sensation volume measured in the squatting position (when the distension medium was water) was significantly lower than that of gas (P < 0.05). CONCLUSION: For patients with functional constipation, there are differences in the results of rectal sensory tests between body positions and distension mediums. When conducting multicenter studies, it is necessary to unify the standard operating procedure (SOP) for operational details to ensure consistency and reliability of the test results.

Anti-inflammation mechanisms of a homogeneous polysaccharide from Phyllanthus emblica L. on DSS induced colitis mice via the gut microbiota and metabolites alteration.

Phyllanthus emblica L. offers promising therapeutic potential for inflammatory diseases. This study revealed the molecular structure of a homogeneous polysaccharide purified from Phyllanthus emblica L. (PEP-1) and evaluated its anti-inflammatory effects on ulcerative colitis (UC) in mice. In the in vivo experiment, administered in varying dosages to dextran sulfate sodium (DSS)-induced UC models, PEP-1 significantly alleviated colonic symptoms, histological damages and reshaped the gut microbiota. Notably, it adjusted the Firmicutes/Bacteroidetes ratio and reduced pro-inflammatory species, closely aligning with shifts in the fecal metabolites and metabolic pathways such as the metabolism of pyrimidine, beta-alanine, and purine. These findings underscore the potential of PEP-1 as a therapeutic agent for UC, providing insights into the mechanisms through gut microbiota and metabolic modulation.