Amoenucles A-F (1-6), six previously undescribed nucleoside derivatives, and two known analogs (7 and 8) were isolated from the culture of Aspergillus amoenus TJ507. Their structures were elucidated through spectroscopic analysis, single-crystal X-ray crystallography, and chemical reactions. Notably, 3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety. Of particular significance, the absolute configuration of the sugar moiety of 1-4 was determined using nuclear magnetic resonance (NMR), electric circular dichroism (ECD) calculations, and a hydrolysis reaction, presenting a potentially valuable method for confirming nucleoside structures. Furthermore, 1, 2, and 5-8 exhibited potential tumor necrosis factor α (TNF-α) inhibitory activities, which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.
Aspergillus/chemistry* ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Molecular Structure ; Nucleosides/isolation & purification* ; Crystallography, X-Ray ; Animals ; Humans ; Mice ; Magnetic Resonance Spectroscopy

Closed-loop neuromodulation, especially using the phase of the electroencephalography (EEG) rhythm to assess the real-time brain state and optimize the brain stimulation process, is becoming a hot research topic. Because the EEG signal is non-stationary, the commonly used EEG phase-based prediction methods have large variances, which may reduce the accuracy of the phase prediction. In this study, we proposed a machine learning-based EEG phase prediction network, which we call EEG phase prediction network (EPN), to capture the overall rhythm distribution pattern of subjects and map the instantaneous phase directly from the narrow-band EEG data. We verified the performance of EPN on pre-recorded data, simulated EEG data, and a real-time experiment. Compared with widely used state-of-the-art models (optimized multi-layer filter architecture, auto-regress, and educated temporal prediction), EPN achieved the lowest variance and the greatest accuracy. Thus, the EPN model will provide broader applications for EEG phase-based closed-loop neuromodulation.
Humans ; Electroencephalography/methods* ; Brain/physiology* ; Machine Learning ; Signal Processing, Computer-Assisted ; Male ; Adult ; Neural Networks, Computer ; Brain Waves/physiology*

OBJECTIVE: To summarize the clinical characteristics of foot and ankle deformities combined with knee and lower limb deformities and evaluate the advantages, clinical outcomes, and considerations of QIN Sihe's surgical strategy for treating such complex deformities. METHODS: Between January 2022 and December 2024, 32 patients with foot and ankle deformities combined with knee and lower limb deformities were enrolled. The cohort included 23 males and 9 females, aged 10-67 years (mean, 41.1 years). The main etiologies included post-polio sequelae (20 cases) and congenital limb deformities (3 cases). Deformities were categorized as follows: equinovarus foot (12 cases), equinus foot (2 cases), equinovalgus foot (3 cases), equinus foot with swan-neck deformity (2 cases), calcaneus foot (5 cases), foot valgus (2 cases), knee flexion deformity (14 cases), genu recurvatum (4 cases), genu varum (3 cases), genu valgum (3 cases), lower limb shortening (3 cases), and lower limb external rotation (6 cases). QIN Sihe's surgical strategies included osteotomies, tendon releases, and tendon transfers for deformity correction, followed by external fixation for residual deformity adjustment and stabilization. Outcomes were assessed using QIN Sihe's Postoperative Evaluation Criteria for Lower Limb (Foot and Ankle) Deformity Correction and Functional Reconstruction. RESULTS: All patients were followed up 8-32 months (mean, 16.5 months). Complications included pin tract infection (1 case, 1 site), ankle pain (2 cases), delayed healing at the proximal tibial osteotomy site (1 case), and anterior talar dislocation (1 case). At last follow-up, insufficient correction of foot deformity was observed in 1 case; both knee and lower limb deformities were corrected, with only mild recurrence of knee flexion deformity in 1 case. The foot/ankle and knee joint function improved. Based on QIN Sihe's Postoperative Evaluation Criteria for Lower Limb (Foot and Ankle) Deformity Correction and Functional Reconstruction, outcomes were rated as excellent in 30 cases and good in 2 cases, with an excellent-good rate of 100%. CONCLUSION Foot and ankle deformities combined with knee and lower limb deformities are complex, QIN Sihe's surgical strategy can achieve satisfactory clinical outcomes for simultaneous correction.
Humans ; Male ; Female ; Adult ; Middle Aged ; Child ; Adolescent ; Aged ; Treatment Outcome ; Young Adult ; Plastic Surgery Procedures/methods* ; Lower Extremity Deformities, Congenital/surgery* ; Osteotomy/methods* ; Foot Deformities, Congenital/surgery* ; Ankle Joint/surgery* ; Knee Joint/surgery* ; Foot Deformities/surgery*

This study aims to establish an efficient protoplast-mediated genetic transformation sys-tem for Pochonia chlamydosporia(P.chlamydosporia)to facilitate gene transformation,genetic modification,and subsequent biological function research.Through orthogonal testing,the study systematically optimized key factors influencing electroporation,including voltage,osmotic stabi-lizer,pulse time,nucleic acid concentration,and protoplast concentration.The results showed that the optimal electroporation conditions were:voltage of 250 V,osmotic stabilizer as 0.6 mol/L su-crose solution,pulse time of 10 ms,plasmid concentration of 1％,and protoplast concentration of 1×107 protoplasts/mL,yielding a transformation efficiency of 0.4 × 103 CFU/pg.The interaction analysis revealed that the five factors affected transformation efficiency in the following order:plasmid concentration＞protoplast concentration＞pulse time＞osmotic stabilizer type＞voltage.Based on the positive transformants,the study further evaluated their colony morphology,growth rate,conidial yield,mycelial dry weight,and the ability to infect the eggs of three types of animal gastrointestinal nematodes.The results indicated that the electroporation process did not signifi-cantly affect the biological functions of P.chlamydosporia.The transformants successfully ex-pressed enhanced green fluorescent protein(EGFP),and PCR analysis confirmed the successful in-tegration of the thiostrepton resistance gene.In conclusion,this study successfully established a protoplast-based electroporation-mediated genetic transformation system for P.chlamydosporia,providing a valuable foundation for further research into the mechanism of egg parasitism and the underlying genes involved in its biocontrol activity.

Objective:To investigate the clinicopathological features, diagnosis, and prognosis of renal solitary fibrous tumor (SFT).Methods:Five cases of renal SFT with unequivocal diagnoses at the Affiliated Hospital of Qingdao University between January 2011 and July 2025 were subject to analyses of their clinical, morphological, immunophenotypic, and molecular characteristics, accompanied by a literature review.Results:Two males and three females aged between 45 and 62 years were included, all of whom presented with the discovery of a renal mass during routine physical examinations. Gross examination showed that the five tumors were all confined in the kidney. The tumors were nodular with maximum diameters ranging from 2.5 cm to 11.0 cm (mean, 5.8 cm). Upon cross-sectioning, they exhibited gray-white or gray-yellow cut surface. Histologically, the tumor cells exhibited oval or short spindle shapes in four cases, presenting with varying densities and arranged in short bundles, woven patterns, and irregular formation. Various amounts of coarse collagen and scattered staghorn blood-vessels were found in the stroma. In one case (case 5), the tumor cells were long spindle-shaped, densely organized in bundles, and interwoven, exhibiting inconspicuous boundaries, moderate nuclear atypia, and at least 4 mitotic figures per 10 high-power fields. Irregular patchy collagen deposition was particularly prominent at the edges of the tumor tissue. In two cases (cases 3 and 5), scattered and various amounts of renal tubules were observed in the tumor. Two cases (cases 4 and 5) demonstrated focal invasion of the renal parenchyma, although no necrosis was noted. Immunohistochemical staining showed that the tumor cells were diffusely and strongly positive for vimentin and STAT6 in all 5 cases, and positive for CD34. Bcl-2 positivity was present in 4 of the 5 cases. All cases were negative for CKpan, EMA, PAX8, HMB45, Melan A, SMA, and S-100 protein. The p53 status was wild type, and the Ki-67 index ranged from 1% to 8%. Next-generation sequencing was conducted on one case (case 4), revealing the NAB2 (exon 3)::STAT6 (exon 18) gene fusion. The 5 patients were followed up for 1 to 158 months (mean, 56 months), and all were alive with no recurrence or metastasis.Conclusions:SFT of the kidney are rare and morphologically similar to extrarenal SFT. Key morphological features include short spindle-shaped tumor cells arranged in bundles, interwoven patterns or irregularly, accompanied by staghorn blood-vessels and scattered coarse hyaline collagen fibers. SFT with epithelial inclusions may represent a relatively common histological subtype in the kidney. Immunohistochemical staining that demonstrates diffuse and strong positivity for STAT6 and CD34 is instrumental in diagnosing this tumor. The pathogenesis is linked to the centromeric inversion of chromosome 12q, resulting in the fusion of the NAB2 and STAT6 genes. Most of these tumors exhibit favorable prognosis.

Objective:To investigate the different expression levels of programmed cell death 1 ligand 1 (PD-L1) in non-small cell carcinoma (NSCLC) of distribution characteristics of TCM constitutions and prognosis.Methods:The clinical data of 355 NSCLC patients who had been treated with immune checkpoint inhibitors (ICIs) from January 2019 to June 2023 in the Cancer Medical Center of the First Affiliated Hospital of Hunan University of Chinese Medicine were retrospectively analyzed, and their TCM constitutions were determined. According to the expression level of PD-L1, they were divided into three groups: low expression group (TPS≤1%), medium expression group (1% < TPS < 49%) and high expression group (TPS≥50%). Overall survival (OS) of patients was followed up, and the median OS were compared. Kaplan-Meier method was used to draw survival curves, and Log-rank test was used to compare the difference of survival curves. The independent risk factors of OS were analyzed by COX regression.Results:The distribution of different TCM constitutions showed statistical significance across the three groups ( P<0.05). The median OS for the medium and high expression groups were 21.082 months and 25.714 months, respectively, both significantly higher than the 14.437 months for the low expression group ( P<0.05). The survival curve of TCM constitutions showed that the constitutions significantly correlated with the prognosis of ICIs treatment were qi deficiency, phlegm dampness, and blood stasis ( P<0.05 or P<0.01). The median OS from high to low was 44.971 months for phlegm-dampness constitution, 23.297 months for qi-deficiency constitution, and 11.763 months for blood-stasis constitution. COX regression analysis indicated that medium PD-L1 expression ( HR=0.622, 95% CI=0.459,0.844, P=0.002), high PD-L1 expression ( HR=0.509, 95% CI=0.361,0.718, P<0.001), phlegm-dampness constitution ( HR=0.556, 95% CI=0.335,0.924, P=0.024), and blood-stasis constitution ( HR=2.952, 95% CI=1.929,4.518, P<0.001) were independent prognostic factors. Conclusions:The higher the expression level of PD-L1 in NSCLC patients, the better the prognosis of ICIs treatment. The prognosis of ICIs treatment is better for people with phlegm-dampness constitution and poor for those with blood stasis constitution.

Objective To investigate the expression characteristics of poly(rC)-binding protein 1(PCBP1)in gastric cancer tissues and their clinical significances by bioinformatics analysis combined with experimental verification,and to identify its relationship with STIP1 homology and U-Box containing protein 1(STUB1).Specifically,this study aims to verify the expression patterns of PCBP1 and STUB1 in gastric cancer and determine their relationships with clinicopathological features by immunohistochemistry to provide a theoretical framework as well as potential intervention strategies for gastric cancer.Methods Data of PCBP1 expression in gastric cancer and adjacent tissues were obtained from TIMER 2.0 online analysis website.KEGG pathway enrichment analysis was performed using gastric cancer data(STAD)in the TCGA(the Cancer Genome Atlas)database,and its potential mechanism was determined.The main regulatory factor STUB1 was found in the fer-roptosis regulatory pathway.Subsequently,PCBP1 and STUB1 expressions in 33 cases of gastric cancer tissues and corresponding adjacent tissues were detected by immunohistochemistry.The collected cases were grouped according to different degrees of differentiation,age,gender,tumor size,depth of tumor invasion,TNM stage and pathological morphology.The positive expression rates of PCBP1 and STUB1 were observed.The correlation between the two proteins and the correlation between clinical and pathological features were analyzed by c2 test.Finally,the relationship between PCBP1 and STUB1 and malignancy of gastric cancer was further explored.Results Immunohistochemical results showed that the positive expression rate of PCBP1 in cancer tissues was 69.7%,which was significantly higher than that in adjacent tissues(48.5%).The positive expression rate of STUB1 in cancer tissues was 39.4%,which was lower than that in adjacent tissues(54.5%),statistically significant difference(P<0.05).The positive expression rate of PCBP1 was correlated with tumor differentiation,lymph node metastasis and Lauren classification(P<0.05),but not with patient's age,gender,depth of inva-sion,clinical stage,nerve infiltration,and intravascular tumor thrombus(P>0.05).The positive expression rate of STUB1 was correlated with tumor differentiation,depth of invasion,lymph node metastasis and Lauren classification(P<0.05).The Spearman correlation coefficient between PCBP1(cancer)and STUB1(cancer)was-0.413,with P=0.017(P<0.05),indicating that there was a significant negative correlation between them.Conclusion PCBP1 participates in the malignant progression of gastric cancer by regulating the main regulator STUB1 in the ferroptosis pathway.Theoretically,it provides a new insight into molecular mechanism as well as a potential therapeutic strategy for treating gastric cancer.

Objective To investigate the expression characteristics of poly(rC)-binding protein 1(PCBP1)in gastric cancer tissues and their clinical significances by bioinformatics analysis combined with experimental verification,and to identify its relationship with STIP1 homology and U-Box containing protein 1(STUB1).Specifically,this study aims to verify the expression patterns of PCBP1 and STUB1 in gastric cancer and determine their relationships with clinicopathological features by immunohistochemistry to provide a theoretical framework as well as potential intervention strategies for gastric cancer.Methods Data of PCBP1 expression in gastric cancer and adjacent tissues were obtained from TIMER 2.0 online analysis website.KEGG pathway enrichment analysis was performed using gastric cancer data(STAD)in the TCGA(the Cancer Genome Atlas)database,and its potential mechanism was determined.The main regulatory factor STUB1 was found in the fer-roptosis regulatory pathway.Subsequently,PCBP1 and STUB1 expressions in 33 cases of gastric cancer tissues and corresponding adjacent tissues were detected by immunohistochemistry.The collected cases were grouped according to different degrees of differentiation,age,gender,tumor size,depth of tumor invasion,TNM stage and pathological morphology.The positive expression rates of PCBP1 and STUB1 were observed.The correlation between the two proteins and the correlation between clinical and pathological features were analyzed by c2 test.Finally,the relationship between PCBP1 and STUB1 and malignancy of gastric cancer was further explored.Results Immunohistochemical results showed that the positive expression rate of PCBP1 in cancer tissues was 69.7%,which was significantly higher than that in adjacent tissues(48.5%).The positive expression rate of STUB1 in cancer tissues was 39.4%,which was lower than that in adjacent tissues(54.5%),statistically significant difference(P<0.05).The positive expression rate of PCBP1 was correlated with tumor differentiation,lymph node metastasis and Lauren classification(P<0.05),but not with patient's age,gender,depth of inva-sion,clinical stage,nerve infiltration,and intravascular tumor thrombus(P>0.05).The positive expression rate of STUB1 was correlated with tumor differentiation,depth of invasion,lymph node metastasis and Lauren classification(P<0.05).The Spearman correlation coefficient between PCBP1(cancer)and STUB1(cancer)was-0.413,with P=0.017(P<0.05),indicating that there was a significant negative correlation between them.Conclusion PCBP1 participates in the malignant progression of gastric cancer by regulating the main regulator STUB1 in the ferroptosis pathway.Theoretically,it provides a new insight into molecular mechanism as well as a potential therapeutic strategy for treating gastric cancer.

This study aims to establish an efficient protoplast-mediated genetic transformation sys-tem for Pochonia chlamydosporia(P.chlamydosporia)to facilitate gene transformation,genetic modification,and subsequent biological function research.Through orthogonal testing,the study systematically optimized key factors influencing electroporation,including voltage,osmotic stabi-lizer,pulse time,nucleic acid concentration,and protoplast concentration.The results showed that the optimal electroporation conditions were:voltage of 250 V,osmotic stabilizer as 0.6 mol/L su-crose solution,pulse time of 10 ms,plasmid concentration of 1％,and protoplast concentration of 1×107 protoplasts/mL,yielding a transformation efficiency of 0.4 × 103 CFU/pg.The interaction analysis revealed that the five factors affected transformation efficiency in the following order:plasmid concentration＞protoplast concentration＞pulse time＞osmotic stabilizer type＞voltage.Based on the positive transformants,the study further evaluated their colony morphology,growth rate,conidial yield,mycelial dry weight,and the ability to infect the eggs of three types of animal gastrointestinal nematodes.The results indicated that the electroporation process did not signifi-cantly affect the biological functions of P.chlamydosporia.The transformants successfully ex-pressed enhanced green fluorescent protein(EGFP),and PCR analysis confirmed the successful in-tegration of the thiostrepton resistance gene.In conclusion,this study successfully established a protoplast-based electroporation-mediated genetic transformation system for P.chlamydosporia,providing a valuable foundation for further research into the mechanism of egg parasitism and the underlying genes involved in its biocontrol activity.

Objective:To investigate the clinicopathological features, diagnosis, and prognosis of renal solitary fibrous tumor (SFT).Methods:Five cases of renal SFT with unequivocal diagnoses at the Affiliated Hospital of Qingdao University between January 2011 and July 2025 were subject to analyses of their clinical, morphological, immunophenotypic, and molecular characteristics, accompanied by a literature review.Results:Two males and three females aged between 45 and 62 years were included, all of whom presented with the discovery of a renal mass during routine physical examinations. Gross examination showed that the five tumors were all confined in the kidney. The tumors were nodular with maximum diameters ranging from 2.5 cm to 11.0 cm (mean, 5.8 cm). Upon cross-sectioning, they exhibited gray-white or gray-yellow cut surface. Histologically, the tumor cells exhibited oval or short spindle shapes in four cases, presenting with varying densities and arranged in short bundles, woven patterns, and irregular formation. Various amounts of coarse collagen and scattered staghorn blood-vessels were found in the stroma. In one case (case 5), the tumor cells were long spindle-shaped, densely organized in bundles, and interwoven, exhibiting inconspicuous boundaries, moderate nuclear atypia, and at least 4 mitotic figures per 10 high-power fields. Irregular patchy collagen deposition was particularly prominent at the edges of the tumor tissue. In two cases (cases 3 and 5), scattered and various amounts of renal tubules were observed in the tumor. Two cases (cases 4 and 5) demonstrated focal invasion of the renal parenchyma, although no necrosis was noted. Immunohistochemical staining showed that the tumor cells were diffusely and strongly positive for vimentin and STAT6 in all 5 cases, and positive for CD34. Bcl-2 positivity was present in 4 of the 5 cases. All cases were negative for CKpan, EMA, PAX8, HMB45, Melan A, SMA, and S-100 protein. The p53 status was wild type, and the Ki-67 index ranged from 1% to 8%. Next-generation sequencing was conducted on one case (case 4), revealing the NAB2 (exon 3)::STAT6 (exon 18) gene fusion. The 5 patients were followed up for 1 to 158 months (mean, 56 months), and all were alive with no recurrence or metastasis.Conclusions:SFT of the kidney are rare and morphologically similar to extrarenal SFT. Key morphological features include short spindle-shaped tumor cells arranged in bundles, interwoven patterns or irregularly, accompanied by staghorn blood-vessels and scattered coarse hyaline collagen fibers. SFT with epithelial inclusions may represent a relatively common histological subtype in the kidney. Immunohistochemical staining that demonstrates diffuse and strong positivity for STAT6 and CD34 is instrumental in diagnosing this tumor. The pathogenesis is linked to the centromeric inversion of chromosome 12q, resulting in the fusion of the NAB2 and STAT6 genes. Most of these tumors exhibit favorable prognosis.