E3 ubiquitin ligase UBR5 modulates circadian rhythm by facilitating the ubiquitination and degradation of the key clock transcription factor BMAL1.

The circadian clock is the inner rhythm of life activities and is controlled by a self-sustained and endogenous molecular clock, which maintains a ~ 24 h internal oscillation. As the core element of the circadian clock, BMAL1 is susceptible to degradation through the ubiquitin-proteasome system (UPS). Nevertheless, scant information is available regarding the UPS enzymes that intricately modulate both the stability and transcriptional activity of BMAL1, affecting the cellular circadian rhythm. In this work, we identify and validate UBR5 as a new E3 ubiquitin ligase that interacts with BMAL1 by using affinity purification, mass spectrometry, and biochemical experiments. UBR5 overexpression induced BMAL1 ubiquitination, leading to diminished stability and reduced protein level of BMAL1, thereby attenuating its transcriptional activity. Consistent with this, UBR5 knockdown increases the BMAL1 protein. Domain mapping discloses that the C-terminus of BMAL1 interacts with the N-terminal domains of UBR5. Similarly, cell-line-based experiments discover that HYD, the UBR5 homolog in Drosophila, could interact with and downregulate CYCLE, the BMAL1 homolog in Drosophila. PER2-luciferase bioluminescence real-time reporting assay in a mammalian cell line and behavioral experiments in Drosophila reveal that UBR5 or hyd knockdown significantly reduces the period of the circadian clock. Therefore, our work discovers a new ubiquitin ligase UBR5 that regulates BMAL1 stability and circadian rhythm and elucidates the underlying molecular mechanism. This work provides an additional layer of complexity to the regulatory network of the circadian clock at the post-translational modification level, offering potential insights into the modulation of the dysregulated circadian rhythm.

Linewidth Measurement of a Narrow-Linewidth Laser: Principles, Methods, and Systems.

Narrow-linewidth lasers mainly depend on the development of advanced laser linewidth measurement methods for related technological progress as key devices in satellite laser communications, precision measurements, ultra-high-speed optical communications, and other fields. This manuscript provides a theoretical analysis of linewidth characterization methods based on the beat frequency power spectrum and laser phase noise calculations, and elaborates on existing research of measurement technologies. In addition, to address the technical challenges of complex measurement systems that commonly rely on long optical fibers and significant phase noise jitter in the existing research, a short-delay self-heterodyne method based on coherent envelope spectrum demodulation was discussed in depth to reduce the phase jitter caused by 1/f noise. We assessed the performance parameters and testing conditions of different lasers, as well as the corresponding linewidth characterization methods, and analyzed the measurement accuracy and error sources of various methods.

The fungal quorum-sensing molecule, farnesol, regulates the immune response of vaginal epithelial cells against Candida albicans.

BACKGROUND: Farnesol is a Candida-secreted quorum-sensing molecule of great interest as a potential antifungal agent for serious and hardly curable infections-candidiasis, especially vulvovaginal candidiasis (VVC). METHODS: The effect of farnesol on cellular morphology and viability and evaluated the production of Th1 (IL-2), Th2 (IL-4), proinflammatory (IL-6), chemotactic (IL-8), and Th17 (IL-17) cytokines in the culture supernatants of vaginal epithelial cell line (VK2) were evaluated. Moreover, we tested the inhibitory effect of farnesol on C. albicans adhesion. Scanning electron microscopy was conducted to observe any VK2 cell ultrastructural changes. RESULTS: Only low concentrations (≤ 50 µmol/L) of farnesol did not affect the morphology and viability of the VK2 cells (P > 0.05). Farnesol reduced the adhesion of C. albicans to the VK2 cells. When treated with farnesol, statistical elevated levels of both IL-4 and IL-17 secreted by the infected VK2 cells were present in the culture supernatants (P < 0.05). CONCLUSIONS: Farnesol acts as a stimulator to up-regulate the Th17-type innate immune response, as well as Th2-type humoral immunity following C. albicans infection. Further research is required to select the optimal therapeutic dose to develop efficacious and safe mucosal immune adjuvant for treating VVCs.

miR-517b-3p promotes the progression of portal vein tumor thrombus via activating Wnt/ß-catenin signaling pathway in hepatocellular carcinoma.

AIMS: This study was aimed to investigate the expression patterns and prognostic value of microRNA-517b-3p (miR-517b-3p) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). METHODS: The expression of miR-517b-3p in PVTT tissues and cells was estimated using qRT-PCR. Through Kaplan-Meier survival analysis, Cox regression assay and ROC analysis, the significance of miR-517b-3p was explored. In addition, cell experiments were performed to examine the functional role of miR-517b-3p during progression of PVTT. Moreover, the biological process and biological pathway analysis analyses were conducted through GSEA and FunRich. Besides, the protein-protein interaction (PPI) network of the DEGs was established through cBioPortal website. RESULTS: Compared with the controls, the miR-517b-3p was upregulated in both PVTT tissues and cells. The upregulated miR-517b-3p, which served as a potential diagnostic biomarker to distinguish PVTT from PT and controls, was associated with poor overall survival and acted as an independent prognostic factor. The cell proliferation, migration and invasion were proved to be enhanced by overexpression of miR-517b-3p. Furthermore, Wnt/ß-catenin signaling was suppressed by miR-517b-3p knockdown and might be involved in the progression of PVTT. CONCLUSION: miR-517b-3p may promote PVTT cell proliferation, migration and invasion via activation of Wnt/ß-catenin signaling pathway. Meanwhile, miR-517b-3p has overexpression in PVTT samples, and serves as a candidate diagnostic and prognostic biomarker in HCC patients with PVTT.

miR-181b-5p Promotes the Progression of Cholangiocarcinoma by Targeting PARK2 via PTEN/PI3K/AKT Signaling Pathway.

This study combined with bioinformatics analysis and investigated the expression pattern of miR-181b-5p, as well as explored its role and mechanism in cholangiocarcinoma (CCA or CHOL). Several bioinformatics databases were used to analyze the expression of miR-181b and the enrichment of miR-181b in biological activities and biological pathways in CCA. The RT-qPCR analysis was used to examine the expression levels of miR-181b-5p. A receiver operation characteristics (ROC) curve analysis and the Kaplan-Meier survival assay were conducted to validate the diagnostic and prognostic implication of miR-181b-5p. Cell experiments were used to explore the possible functional role of miR-181b-5p in CCA progression. The bioinformatics assay was used to predict the target gene of miR-181b-5p and Western blot was used to confirm the related signaling pathway. The bioinformatics analysis results suggest that miR-181b-5p was highly expressed in cholangiocarcinoma and its expression was negatively related to PARK2 expression in CCA tissues. miR-181b-5p expression in the serum and tissues was upregulated and associated with lymph node metastasis and TNM stage. Increased expression of miR-181b-5p had relatively high diagnostic accuracy and showed poor prognosis in CCA patients. In addition, miR-181b-5p overexpression enhanced cell proliferation, migration, and invasion by targeting PARK2. Overexpression of miR-181b-5p activated the PI3K/AKT signaling pathway, while knockdown of miR-181b-5p suppressed the signaling pathway. Increased expression of miR-181b-5p in CCA may be a potential diagnostic or/and prognostic indicator for CCA patients. The present data indicated miR-181b-5p acted as an oncogene in CCA through promoting tumor cell proliferation, migration, and invasion of CCA via the PTEN/PI3K/AKT signaling pathway by targeting PARK2, which might be a promising therapeutic target or biomarker for CCA.

High failure rate after Beta-tricalcium phosphate grafting for the treatment of femoral head osteonecrosis: a retrospective analysis.

BACKGROUND: Non-vascularized bone grafting is a promising head-preserving technique for younger patients diagnosed as non-traumatic osteonecrosis of the femoral head (NONFH). Among the various types of bone grafting techniques, "light-bulb" procedure grafting with synthetic bone substitute is an attractive option. We aimed to assess the effectiveness of using beta-tricalcium phosphate (ß-TCP) for the treatment of pre-collapse and early post-collapse lesions NONFH. METHODS: From April 2010 to June 2014, 33 patients (47 hips) with NONFH were treated using the afore-mentioned technique. The clinical and radiological outcomes were recorded and compared statistically between pre- and post-operation. Harris hip score (HHS) was used to evaluate the clinical results, and Association Research Circulation Osseous (ARCO) stage was applied to assess the radiological outcomes. RESULTS: The 5-years survival rate of using ß-TCP grafting was accounting for 25.5%. HHS was decreased from 78.47 to 52.87 points, and a very significant worsening of radiological results were revealed (P <  0.05). Two hips collapsed more than 2 mm were awaiting for THA, and 33 of the 47 hips had converted to THAs in an average time to failure of 24.24 months postoperatively. Meanwhile, only 4 hips survived without collapse, and 8 hips collapsed less than 2 mm. After surgery, the time onset of head collapse was 3.65 months on average, and the first conversion to THA was performed at 5 months postoperative. CONCLUSIONS: Our results suggest that "light-bulb" procedure grafting with ß-TCP sticks presented with a high failure rate in the early postoperative period. It is not proposed for the treatment of pre-collapse and early post-collapse lesions NONFH.

[Radiologic Features of Nuclear Protein of the Testis Midline Carcinoma of the Nasal Cavity and Paranasal Sinuses:Report of One Case].

Nuclear protein of the testis midline carcinoma (NMC) is a rare malignant tumor that is mostly located in the upper trachea,mediastinal midline,and paravertebral midline,and few literature has described the imaging features of NMC in the nasal cavity and paranasal sinuses. In this article we summarize the clinical,radiologic,and pathologic data of one case of pathologically confirmed NMC in the nasal cavity and paranasal sinus by focusing on its CT and magnetic resonance imaging features.

Association of RUNX3 Methylation with Clinical Outcome and Cell Migration/Invasion in Laryngeal Squamous Cell Carcinoma.

This study identifies promoter methylation status of RUNX3 in 77 LSCC patient tissues and their paired adjacent healthy tissues. Hypermethylation percentage RUNX3 occurred in LSCC samples was significantly higher than that in normal tissues, as well as associated with suppression of RUNX3 expression, TNM classification of malignant tumors stage, lymph node metastasis and poor overall survival rate. Reduced methylation and increased expression of RUNX3 genes in vitro was observed and decreased cell migration was further confirmed following 5-azacytidine treatment. RUNX 3 promoter hypermethylation can lead to down-regulation of RUNX3 in LSCC cancerous tissue.

Prognostic utility of combination of NT-proBNP with high sensitive cTn I in patients with heart failure: Results from retrospective study in an emergency department.

BACKGROUND: N-terminal proBNP (NT-proBNP) and cardiac troponin I (cTn I) are widely used for the diagnosis of myocardial injury, but have not been used for routine evaluation in heart failure (HF) population. AIMS: To evaluate the prognostic utility of combination of NT-proBNP and cTn I in patients with HF, including serial NT-proBNP/cTn I measurements and discharge NT-proBNP/cTn I levels. PATIENTS AND METHODS: A total of 610 patients presenting in our emergency department for acute HF were studied. The mortality and HF-related readmission were endpoints in the study. NT-proBNP and cTn I were tested on admission including first 5 consecutive days, and on discharge. RESULTS: A discharge cTn I cut-off value at 24 ng/L and discharge NT-proBNP cut-off value at 350 ng/L were determined. The cTn I level more than 24 ng/L and NT-proBNP level more than 350 ng/L are associated with increased risk for mortality and readmission (p < 0.01). The mortality and HF-related readmission was significantly increased in patients with high cTn I + high NT-proBNP (p < 0.05), high cTn I + low NT-proBNP (p < 0.05), and low cTn I + high NT-proBNP (p < 0.0%). The increased cTn I or increased NT-proBNP measured in the first 5 consecutive days were significantly associated with 60-day HF-related events (p < 0.05), but the serial measurements did not have a predictive value of 1-year HF outcome. CONCLUSION: This study demonstrates that elevations of discharge cTn I and NT-proBNP are associated with increased 1-year mortality and HF-related readmission. Patients with increasing serial cTnI and NT-proBNP had increased risk for 60-day HF-related events. The two markers can act as independent predicators, and complete each other in prognostic utility of HF patients.

Lacking chloroplasts in guard cells of crumpled leaf attenuates stomatal opening: both guard cell chloroplasts and mesophyll contribute to guard cell ATP levels.

Controversies regarding the function of guard cell chloroplasts and the contribution of mesophyll in stomatal movements have persisted for several decades. Here, by comparing the stomatal opening of guard cells with (crl-ch) or without chloroplasts (crl-no ch) in one epidermis of crl (crumpled leaf) mutant in Arabidopsis, we showed that stomatal apertures of crl-no ch were approximately 65-70% those of crl-ch and approximately 50-60% those of wild type. The weakened stomatal opening in crl-no ch could be partially restored by imposing lower extracellular pH. Correspondingly, the external pH changes and K(+) accumulations following fusicoccin (FC) treatment were greatly reduced in the guard cells of crl-no ch compared with crl-ch and wild type. Determination of the relative ATP levels in individual cells showed that crl-no ch guard cells contained considerably lower levels of ATP than did crl-ch and wild type after 2 h of white light illumination. In addition, guard cell ATP levels were lower in the epidermis than in leaves, which is consistent with the observed weaker stomatal opening response to white light in the epidermis than in leaves. These results provide evidence that both guard cell chloroplasts and mesophyll contribute to the ATP source for H(+) extrusion by guard cells.

Magnetic resonance imaging of extraocular rectus muscles abnormalities in acute acquired concomitant esotropia.

AIM: To investigate the difference of medial rectus (MR) and lateral rectus (LR) between acute acquired concomitant esotropia (AACE) and the healthy controls (HCs) detected by magnetic resonance imaging (MRI). METHODS: A case-control study. Eighteen subjects with AACE and eighteen HCs were enrolled. MRI scanning data were conducted in target-controlled central gaze with a 3-Tesla magnetic resonance scanner. Extraocular muscles (EOMs) were scanned in contiguous image planes 2-mm thick spanning the EOM origins to the globe equator. To form posterior partial volumes (PPVs), the LR and MR cross-sections in the image planes 8, 10, 12, and 14 mm posterior to the globe were summed and multiplied by the 2-mm slice thickness. The data were classified according to the right eye, left eye, dominant eye, and non-dominant eye, and the differences in mean cross-sectional area, maximum cross-sectional area, and PPVs of the MR and LR muscle in the AACE group and HCs group were compared under the above classifications respectively. RESULTS: There were no significant differences between the two groups of demographic characteristics. The mean cross-sectional area of the LR muscle was significantly greater in the AACE group than that in the HCs group in the non-dominant eyes (P=0.028). The maximum cross-sectional area of the LR muscle both in the dominant and non-dominant eye of the AACE group was significantly greater than the HCs group (P=0.009, P=0.016). For the dominant eye, the PPVs of the LR muscle were significantly greater in the AACE than that in the HCs group (P=0.013), but not in the MR muscle (P=0.698). CONCLUSION: The size and volume of muscles dominant eyes of AACE subjects change significantly to overcome binocular diplopia. The LR muscle become larger to compensate for the enhanced convergence in the AACE.

Transanal endoscopic microsurgery versus laparoscopic lower anterior resection for the treatment of T1-2 rectal cancers.

BACKGROUND/AIMS: It remains unknown whether transanal endoscopic microsurgery (TEMS) is superior to laparoscopic lower anterior resection (LAR) for the treatment of rectal cancer. This study aimed to compare the surgical and oncological effectiveness as well as safety of TEMS and LAR in T1-2 rectal cancer patients. METHODOLOGY: T1-2N0 rectal cancer patients were prospectively and randomly assigned to local excision using TEMS (n=30) or radical resection using LAR (n=30). The primary outcome measures were postoperative recovery course. RESULTS: The operative duration of TEMS was significantly shorter than that of LAR (130.3±16.7 minutes vs. 198.7±16.8 minutes, p<0.01). The TEMS group restarted bowel movement significantly earlier than the LAR group (51.4±5.4h vs. 86.2±8.7h, p<0.01). The postoperative complications were mild and self-limited in the 2 groups. Local recurrences occurred in 2 T2 patients (2/28, 7.1%) at 8 months and 16 months following TEMS, respectively; no patient (0/30, 0.0%) developed local recurrence following LAR. CONCLUSIONS: TEMS was associated with more rapid postoperative recovery and minimal surgical morbidity in T1-2 rectal cancer patients as compared to LAR.

[Value of temporal bone dual phase contrast enhancement computed tomography in diagnosing causes of pulsatile tinnitus].

OBJECTIVE: To evaluate the value of temporal bone dual phase contrast enhancement computed tomography (DPCT) in diagnosing the causes of pulsatile tinnitus (PT). METHODS: We retrospectively analyzed the DPCT findings of 157 patients with unilateral PT. Temporal bone High-resolution CT (HRCT) was performed in 71 patients, magnetic resonance imaging (MRI) in 80 and digital subtraction angiography (DSA) in 89. RESULTS: In 71 patients with both DPCT and HRCT scan, a total of 68 causes were found. The accuracy of DPCT was 100% it was significant higher than that of HRCT (77.9%). In 80 patients with both DPCT and MRI, 83 causes were known. The accuracy of DPCT (94.0%) was significantly higher than that of MRI (8.4%). In 89 patients with both DPCT and DSA scan, 99 causes were identified. The accuracy of DPCT was 91.9% and it was significantly higher than that of DSA (15.2%). CONCLUSION: DPCT may be an ideal imaging modality for diagnosing the causes of PT.

[The proteasome inhibitor MG132 attenuates skeletal muscle atrophy in a rat model of chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the effect of the proteasome inhibitor MG-132 on skeletal muscle atrophy in a rat model of chronic obstructive pulmonary disease (COPD) and its potential mechanisms. METHODS: The COPD rat model was established by instillation of LPS and exposure to the cigarette smoke. Then the COPD rats were randomly divided into 3 groups (each group n = 12): COPD model control group, MG-132 high dose group (MG-132 0.1 mg·kg(-1)·d(-1)) and low dose group (MG-132 0.05 mg·kg(-1)·d(-1)), and normal control group. After 1 week and 4 week, 6 rats of each group were sacrificed, and then the following parameters were determined: the weight of the diaphragm muscle, the concentration of TNF-α in the serum and diaphragm via enzyme-linked immunosorbent assay (ELISA). Muscle atrophy F-box protein (MAFbx), NF-κBp65, and IκB-α mRNA levels were determined by RT-PCR. The protein levels of MAFbx, NF-κBp65 and IκB-α in diaphragm were measured by Western blot. The single factor analysis of variance was used for statistical analysis among the groups, while t test was used for comparison between 2 groups, and Pearson linear correlation analysis was also performed. RESULTS: The weight of diaphragm muscle from 1 week and 4 week normal control group [(0.99 ± 0.06) mg and (1.20 ± 0.04) mg] were reduced as compared to those of COPD model control group [(0.83 ± 0.09) mg and (1.01 ± 0.06) mg], high dose group [(0.85 ± 0.02) mg and (1.11 ± 0.06) mg], and low dose group [(0.83 ± 0.03) mg and (1.04 ± 0.02) mg]. The reduction of diaphragm muscle weight in the high dose group and the low dose group was significantly less than that in the COPD model control group, with a more marked difference as compared with the 4 week high dose group. The TNF-α levels in diaphragm from 4 week high dose group [(106 ± 8) ng/L] and low dose group [(122 ± 7) ng/L] were decreased as compared to that of the COPD model control group [(143 ± 24) ng/L]. The levels of NF-κBp65 and MAFbx mRNA from the 4 week high dose group (2.17 ± 0.42) and low dose group (1.74 ± 0.14) and the protein expression (1.13 ± 0.04 and 1.27 ± 0.05) were also decreased as compared to those of the COPD model control group (mRNA 2.81 ± 0.31 and 4.87 ± 0.34, protein expression 1.32 ± 0.04 and 1.44 ± 0.07). The levels of IκB-α mRNA and protein expression (0.96 ± 0.08 and 0.83 ± 0.06) were higher than those of the COPD model control group (0.25 ± 0.02 and 0.58 ± 0.06), (t = 1.57-24.9, P < 0.05). The levels of the TNF-α levels in serum and diaphragm were correlated positively with the levels of MAFbx and NF-κBp65 mRNA and protein expression (r = 0.672-0.875, P < 0.01), but negatively with the levels of IκB-α mRNA and protein expression (r = -0.656--0.927, P < 0.01). CONCLUSIONS: The proteasome inhibitor MG-132 significantly inhibited IκB-α degradation thus preventing NF-κB activation. This effect resulted in preventing skeletal muscle atrophy in the COPD rats.

[The correlation analysis between glucose level and its variability and prognosis in traumatic patients].

OBJECTIVE: To investigate the effect of glucose level, variability on the prognosis of traumatic patients. METHODS: A retrospective study involving 300 traumatic patients admitted to intensive care unit (ICU) was performed. The average glucose (GluAve), glucose standard deviation (GluSD) and glucose coefficient of variation (GluCV) during the first 72 hours were calculated. Patients were divided into survivor group (n=249) and non-survivor group (n=51) based on outcomes. The GluAve, GluSD and GluCV were compared between the two groups. Patients were allocated into five subgroups based on GluAve (3.9-5.5, 5.6-6.6, 6.7-7.7, 7.8-9.9, ≥10.0 mmol/L) as well as four subgroups on GluCV (<15%, 15%-30%, 30%-50%, >50%). The mortality in hospital was compared among the different subgroups and the different GluCV in the same level of GluAve subgroups, respectively. Multifactor logistic regression was used to determine the risk factor of hospital death. RESULTS: The levels of GluAve, GIuSD, GluCV of non-survivor group were higher than those of survivor group [11.31±4.38 mmol/L vs. 8.50±3.40 mmol/L, 2.85±1.94 mmol/L vs. 1.87±1.67 mmol/L, (28.30±23.08)% vs. (20.90±13.70)%, all P<0.05]. With the gradual increment of GluAve and GluCV level, the mortality was raised accordingly (χ (2)(1)=26.332, P=0.000; χ (2)(2)=65.522, P=0.000). In the subgroup of GluAve 7.8-9.9 mmol/L, the mortality was 9.09% (3/33) with GluCV <15% versus 46.15% (6/13) with GluCV >50% (P<0.01) respectively, and in the subgroup of GluAve ≥10.0 mmol/L, the mortality corresponding rates were 21.05% (4/19) with GluCV < 15% and 61.54% (8/13) with GluCV > 50% (P<0.05). The multivariable logistic regression analysis demonstrated that GluAve and GluCV were risk factors of mortality[GluAve odds ratio (OR)=1.150, 95% confidence interval (95%CI) was 1.042 to 1.270, P=0.006; GluCV OR=1.022, 95%CI was 0.999 to 1.040, P=0.040], GluSD had no effect on mortality. CONCLUSIONS: The increase in GluAve and GluCV in traumatic patients are significantly correlated with mortality. Control the level and the variability of blood glucose might be an important aspect of the multiple trauma death reduction.

miR-3178 as a prognostic indicator and tumor suppressor of gastric cancer.

BACKGROUND: Gastric cancer is a common malignant tumor with an increasing death rate. MicroRNA can serve as a promising biomarker for the progression and prognosis of various cancers. AIMS: The clinical significance and biological function of miR-3178 in gastric cancer was assessed in this study. METHODS: A total of 117 paired tissues were collected from gastric cancer patients. Quantitative real-time polymerase chain reaction was used to detect the expression of miR-3178 in gastric cancer tissues and cells. The association between miR-3178 expression and the clinicopathological features of patients were analyzed by χ2 test. Kaplan-Meier analysis and Cox regression were employed to investigate the prognostic value of miR-3178. Finally, the effect of miR-3178 on the cellular process of gastric cancer was investigated by CCK-8 and transwell assay. RESULTS: miR-3178 was downregulated in gastric cancer tissues and cells, which showed a significant association with the TNM stage and lymph node metastasis of patients and a poor prognosis. MiR-3178 and TNM stage were considered as two independent prognostic factors for gastric cancer. Furthermore, the downregulation of miR-3178 promoted cell proliferation, migration, and invasion of gastric cancer by regulating Notch1. CONCLUSION: miR-3178 may be involved in the progression of gastric cancer, which provides new insights into the treatment of gastric cancer.

[Effects of Long-term Straw Returning on Fungal Community, Enzyme Activity and Wheat Yield in Fluvo-aquic Soil].

To illustrate the effects of long-term straw returning on the fungal community, soil enzyme activity, and crop yield in a fluvo-aquic soil area typical of the Huang-Huai-Hai Plain, a 10-year field experiment (established in 2010) located in Dezhou City, Shandong province, was performed, including three fertilization regimes (NF, no fertilization control; NPK, fertilization with chemical N, P, and K fertilizers; NPKS, straw returning combined with chemical N, P, and K fertilizers). This study aimed to explore the regulation mechanisms of fungal communities on soil fertility, enzyme activities, and crop yield by employing co-occurrence network and structural equation model analyses. Our results showed that long-term straw returning significantly improved soil nutrients, enzyme activity, and wheat yield. Compared with the NPK and NF treatments, soil organic matter (SOM) increased by 9.20% and 34.75%, alkali-hydrolyzed nitrogen (AN) increased by 12.03% and 39.17%, dehydrogenase (DHA) increased by 37.21% and 50.91%, ß-glucosidase (ß-GC) increased by 17.29% and 73.48%, and wheat production increased by 16.22% and 125.53%, respectively. Different long-term fertilization regimes did not significantly change soil fungal α-diversity but resulted in significant differences in ß-diversity. Available phosphorus (AP), SOM, and AN were the main driving factors of fungal community differentiation based on redundancy analysis and hierarchical partitioning analysis. Different abundance analyses revealed significantly different fungal community compositions among fertilization regimes. The long-term NF treatment resulted in a significant enrichment of phosphate/potassium-solubilizing species (i.e., Mortierella, Aspergillus, Ceriporia, and Acremonium) and symbiotic species (i.e., Leohumicola and Hyalodendriella). The relative abundance of pathogenic fungi, namely Sarocladium, Fusarium, and Fusicolla, increased significantly in the NPK treatment. Long-term straw returning in the NPKS treatment significantly stimulated the growth of plant growth-promoting species (i.e., Pseudogymnoascus and Schizothecium) and straw-degrading species (i.e., Trichocladium and Lobulomyces). Co-occurrence network analysis showed that the fungal network was composed of four main modules; the cumulative relative abundance of module 2 was significantly increased under the NPKS treatment and showed a positive linear correlation with DHA and ß-GC. The structural equation model further indicated that the wheat yield was mainly regulated by SOM, whereas species of module 2 could indirectly affect SOM and wheat yield by positively regulating DHA and ß-GC. Taken together, long-term straw returning to the fluvo-aquic soil area of the Huang-Huai-Hai Plain could regulate fungal interspecific interactions, stimulate the growth of specific species groups, inhibit the activity of pathogens, increase the activity of soil enzymes, promote the accumulation of SOM, and achieve high crop yield.