The SPARC-related modular calcium binding 1 (Smoc1) regulated by androgen is required for mouse gubernaculum development and testicular descent.

ABSTRACT: Testicular descent occurs in two consecutive stages: the transabdominal stage and the inguinoscrotal stage. Androgens play a crucial role in the second stage by influencing the development of the gubernaculum, a structure that pulls the testis into the scrotum. However, the mechanisms of androgen actions underlying many of the processes associated with gubernaculum development have not been fully elucidated. To identify the androgen-regulated genes, we conducted large-scale gene expression analyses on the gubernaculum harvested from luteinizing hormone/choriogonadotropin receptor knockout (Lhcgr KO) mice, an animal model of inguinoscrotal testis maldescent resulting from androgen deficiency. We found that the expression of secreted protein acidic and rich in cysteine (SPARC)-related modular calcium binding 1 (Smoc1) was the most severely suppressed at both the transcript and protein levels, while its expression was the most dramatically induced by testosterone administration in the gubernacula of Lhcgr KO mice. The upregulation of Smoc1 expression by testosterone was curtailed by the addition of an androgen receptor antagonist, flutamide. In addition, in vitro studies demonstrated that SMOC1 modestly but significantly promoted the proliferation of gubernacular cells. In the cultures of myogenic differentiation medium, both testosterone and SMOC1 enhanced the expression of myogenic regulatory factors such as paired box 7 (Pax7) and myogenic factor 5 (Myf5). After short-interfering RNA-mediated knocking down of Smoc1, the expression of Pax7 and Myf5 diminished, and testosterone alone did not recover, but additional SMOC1 did. These observations indicate that SMOC1 is pivotal in mediating androgen action to regulate gubernaculum development during inguinoscrotal testicular descent.

Association study of brain structure-function coupling and glymphatic system function in patients with mild cognitive impairment due to Alzheimer's disease.

Background: Mild cognitive impairment (MCI) is a critical transitional phase from healthy cognitive aging to dementia, offering a unique opportunity for early intervention. However, few studies focus on the correlation of brain structure and functional activity in patients with MCI due to Alzheimer's disease (AD). Elucidating the complex interactions between structural-functional (SC-FC) brain connectivity and glymphatic system function is crucial for understanding this condition. Method: The aims of this study were to explore the relationship among SC-FC coupling values, glymphatic system function and cognitive function. 23 MCI patients and 18 healthy controls (HC) underwent diffusion tensor imaging (DTI) and resting-state functional MRI (fMRI). DTI analysis along the perivascular space (DTI-ALPS) index and SC-FC coupling values were calculated using DTI and fMRI. Correlation analysis was conducted to assess the relationship between Mini-Mental State Examination (MMSE) scores, DTI-ALPS index, and coupling values. Receiver operating characteristic (ROC) curves was conducted on the SC-FC coupling between the whole brain and subnetworks. The correlation of coupling values with MMSE scores was also analyzed. Result: MCI patients (67.74 ± 6.99 years of age) exhibited significantly lower coupling in the whole-brain network and subnetworks, such as the somatomotor network (SMN) and ventral attention network (VAN), than HCs (63.44 ± 6.92 years of age). Whole-brain network coupling was positively correlated with dorsal attention network (DAN), SMN, and visual network (VN) coupling. MMSE scores were significantly positively correlated with whole-brain coupling and SMN coupling. In MCI, whole-brain network demonstrated the highest performance, followed by the SMN and VAN, with the VN, DAN, limbic network (LN), frontoparietal network (FPN), and default mode network (DMN). Compared to HCs, lower DTI-ALPS index was observed in individuals with MCI. Additionally, the left DTI-ALPS index showed a significant positive correlation with MMSE scores and coupling values in the whole-brain network and SMN. Conclusion: These findings reveal the critical role of SC-FC coupling values and the ALPS index in cognitive function of MCI. The positive correlations observed in the left DTI-ALPS and whole-brain and SMN coupling values provide a new insight for investigating the asymmetrical nature of cognitive impairments.

Case report: Innovative treatment for one metastatic thyroid-like follicular carcinoma of the kidney with ATM and POLE mutations.

Thyroid-like follicular renal cell carcinoma (TLFRCC), also known as thyroid-like follicular carcinoma of the kidney or thyroid follicular carcinoma like renal tumor, is an exceedingly rare variant of renal cell carcinoma that has only recently been acknowledged. This neoplasm exhibits a distinct follicular morphology resembling that of the thyroid gland. Immunohistochemical analysis reveals positive expression of PAX8, Vimentin, and EMA, while thyroid-specific markers TG and TTF1 are consistently absent. Furthermore, there is a notable absence of any concurrent thyroid pathology on clinical evaluation. Previous reports have suggested that TLFRCC is an indolent, slow-growing malignancy with infrequent metastatic potential. In this report, we present a case of TLFRCC characterized by remarkable ossification and widespread metastasis, including multifocal pulmonary lesions, involvement of the abdominal wall, and infiltration into the psoas muscle. To our knowledge, this represents only the third documented instance of distant metastasis in thyroid follicular renal carcinoma. The current case demonstrates a therapeutic approach that combines radiotherapy with the utilization of toripalimab, a programmed cell death 1 (PD-1) receptor inhibitor, and pazopanib. This treatment regimen was tailored based on comprehensive genomic profiling, which identified mutations in the POLE (catalytic subunit of DNA polymerase epsilon) and ATM (ataxia-telangiectasia mutated) genes, both of which have been implicated in the pathogenesis of various malignant tumors. These findings represent a novel discovery, as such mutations have never been reported in association with TLFRCC. Thus far, this therapeutic approach has proven to be the most efficacious option for treating metastatic TLFRCC among previously reported, and it also marks the first mention of the potential benefits of radiotherapy in managing this particular subtype of renal cell carcinoma.

Deciphering the population structure and genetic basis of growth traits from whole-genome resequencing of the leopard coral grouper ( Plectropomus leopardus).

The leopard coral grouper ( Plectropomus leopardus) is a species of significant economic importance. Although artificial cultivation of P. leopardus has thrived in recent decades, the advancement of selective breeding has been hindered by the lack of comprehensive population genomic data. In this study, we identified over 8.73 million single nucleotide polymorphisms (SNPs) through whole-genome resequencing of 326 individuals spanning six distinct groups. Furthermore, we categorized 226 individuals with high-coverage sequencing depth (≥14×) into eight clusters based on their genetic profiles and phylogenetic relationships. Notably, four of these clusters exhibited pronounced genetic differentiation compared with the other populations. To identify potentially advantageous loci for P. leopardus, we examined genomic regions exhibiting selective sweeps by analyzing the nucleotide diversity ( θπ) and fixation index ( F ST) in these four clusters. Using these high-coverage resequencing data, we successfully constructed the first haplotype reference panel specific to P. leopardus. This achievement holds promise for enabling high-quality, cost-effective imputation methods. Additionally, we combined low-coverage sequencing data with imputation techniques for a genome-wide association study, aiming to identify candidate SNP loci and genes associated with growth traits. A significant concentration of these genes was observed on chromosome 17, which is primarily involved in skeletal muscle and embryonic development and cell proliferation. Notably, our detailed investigation of growth-related SNPs across the eight clusters revealed that cluster 5 harbored the most promising candidate SNPs, showing potential for genetic selective breeding efforts. These findings provide a robust toolkit and valuable insights into the management of germplasm resources and genome-driven breeding initiatives targeting P. leopardus.

Differential expression of miRNA-769-5p and Smad2 in patients with or without oral cGVHD.

BACKGROUND: Oral chronic graft-versus-host disease (cGVHD) impacts quality of life of patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, its precise pathogenesis remains unknown, with potential associations with differential microRNA (miRNA) expression and the TGF-â/Smad signaling pathway. OBJECTIVES: This study aims to explore miRNA expression profiles in the peripheral blood of oral cGVHD patients, focusing on miRNA-769-5p and its relationship with Smad2. MATERIAL AND METHODS: Peripheral venous blood samples were collected for RNA extraction from 8 patients with oral cGVHD, 8 patients without cGVHD and 8 participants from the healthy control group. The miRNA library was constructed using the Illumina Hiseq 2500 platform. We focused on identifying miRNAs associated with the TGF-â/Smad signaling pathway and subsequently conducted validation experiments. The oral cGVHD and without cGVHD groups were each expanded to include 15 individuals. Peripheral blood samples were subjected to polymerase chain reaction (PCR) analysis to assess miRNA levels and to evaluate Smad2 mRNA levels in peripheral blood mononuclear cells (PBMC). Additionally, enzyme-linked immunosorbent assay (ELISA) was conducted to determine the Smad2 protein levels in peripheral blood. RESULTS: The most significantly differentially expressed miRNAs among the 3 groups were miRNA-505-5p and miRNA-769-5p. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated an enrichment of the target genes of miRNA-769-5p in the TGF-â signaling pathway. It was observed that miRNA-769-5p expression was higher in patients without oral cGVHD in comparison to those with oral cGVHD. Receiver operating characteristic (ROC) analysis demonstrated that miRNA-769-5p holds diagnostic value for oral cGVHD. As a target of miRNA-769-5p, Smad2 mRNA exhibited a negative correlation with it. Moreover, both Smad2 mRNA and protein levels were higher in patients with oral cGVHD as opposed to those without cGVHD. CONCLUSIONS: Differential expression of miRNAs, particularly the downregulation of miRNA-769-5p, may influence the development of oral cGVHD by diminishing its inhibitory effect on the TGF-â/Smad signaling pathway through its interaction with Smad2.

Respiratory patterns and physical fitness in healthy adults: a cross-sectional study.

BACKGROUND: The altered respiratory patterns have a significant impact on our health. However, the links between respiration patterns during spontaneous breathing and physical fitness remain unknown. Therefore, we sought to examine how the respiratory pattern during spontaneous breathing interacts with physical fitness. METHODS: A total of 610 participants (aged 20-59 years) were enrolled; 163 men (age = 41 ± 11) and 401 women (age = 42 ± 9) were included for analysis. The parameters of the respiration pattern were respiration rate (RR) and inhalation/exhalation (I/E) ratio. The physical fitness components were body size, visuomotor reaction time, balance, flexibility, hand grip strength, back extension strength, vertical jump height, number of push-ups, number of sit-ups, and the maximum rate of oxygen consumption. The data were analyzed separately for two gender groups. Participants within each gender group were further divided into two age categories (young: 20-39 years, middle-aged: 40-59 years) for the analysis, and both correlational and comparative tests were used to solidify the results. RESULTS: Neither RRs nor the I/E ratios were substantially correlated with physical fitness in women. In addition, the I/E ratios showed no significant correlation with physical fitness in young men, while the results from correlational and comparative tests were inconsistent in middle-aged men. Consistently, men with lower RRs exhibited significantly shorter visuomotor reaction times in two age groups, and demonstrated significantly higher vertical jump heights in the middle-aged group. CONCLUSIONS: In women, respiratory patterns were not correlated with physical fitness. The relationship between middle-aged men's I/E ratios and their physical fitness warrants further investigation. Men with lower RRs may have better visual-motor coordination and/or sustained attention, while middle-aged men with lower RRs may also have greater leg explosive power and neuromuscular coordination, which should be considered for physical assessment and health improvement.

Corydalis saxicolaBunting total alkaloid eliminates Porphyromonas gingivalis strain 33277 internalized into macrophages by inhibition of TLR2.

OBJECTIVE: This study aimed to investigate the impact of Corydalis Saxicola Bunting Total Alkaloid (CSBTA) on Porphyromonas gingivalis internalization within macrophages and explore the potential role of Toll-Like Receptor 2 (TLR2) in this process. METHODS: We established a P. gingivalis internalization model in macrophages by treating P. gingivalis-infected macrophages (MOI=100:1) with 200 µg/mL metronidazole and 300 µg/mL gentamicin for 1 h. Subsequently, the model was exposed to CSBTA at concentrations of 0.02 g/L or 1 µg/mL Pam3CSK4. After a 6 h treatment, cell lysis was performed with sterile water to quantify bacterial colonies. The mRNA expressions of TLR2 and interleukin-8 (IL-8) in macrophages were analyzed using RT-qPCR, while their protein levels were assessed via Western blot and ELISA respectively. RESULTS: P. gingivalis could internalize into macrophages and enhance the expression of TLR2 and IL-8. Activation of TLR2 by Pam3CSK4 contributed to P. gingivalis survival within macrophages and increased TLR2 and IL-8 expression. Conversely, 0.02 g/L CSBTA effectively cleared intracellular P. gingivalis, achieving a 90 % clearance rate after 6 h. Moreover, it downregulated the expression of TLR2 and IL-8 induced by P. gingivalis. However, the inhibitory effect of CSBTA on the internalized P. gingivalis model was attenuated by Pam3CSK4. CONCLUSION: CSBTA exhibited the ability to reduce the presence of live intracellular P. gingivalis and lower IL-8 expression in macrophages, possibly by modulating TLR2 activity.

Repair of Asian nasal subunit defects using nasolabial perforator flaps: A retrospective study.

BACKGROUND: The application of nasolabial perforator flap for nasal reconstruction has been reported previously with satisfactory outcomes, but the outcomes and risk factors of postoperative adverse events have been unclear to plastic surgeons. AIMS: To statistically analyze the effectiveness of the nasolabial perforator flap in nasal reconstruction and the risk factor of postoperative complications and re-operation. PATIENTS/METHODS: This retrospective study evaluated 58 Chinese patients who underwent nasal reconstruction with the nasolabial perforator flap from 2009 to 2021. The esthetic and blood supply outcomes were measured by plastic surgeons on a 5-point Likert scale. Binary logistic regression was used to determine the risk factors associated with postoperative complications and re-operation. RESULTS: The mean age of the cohort was 66.4 ± 2.0 years. The defect size ranged from 6.5 × 5.5 mm2 to 40 × 70 mm2 , and 48.3% of defects covered more than one nasal subunit. Venous congestion occurred in 4.9% of flaps, and the immediate overall postoperative score was 7.72/10. More than one nasal subunit of involvement was the risk factor associated with re-operation (p = 0.004), but no risk factor was associated with complications. CONCLUSIONS: The nasolabial perforator flap is reliable for nasal reconstruction with good esthetic outcomes and fewer complications. However, a large number of involved subunits may lead to multiple surgeries for flap trimming in easterners.

A Safe Technique for Excising the Perpendicular Plate of the Ethmoid Bone in Patients with Crooked Nose: A Finite Element Analysis.

BACKGROUND: Correction of the crooked nose, especially the perpendicular plate of the ethmoid bone, has the potential to cause skull base injury. At present, the safe and effective method for perpendicular plate resection has not been clearly defined through biomechanics. METHOD: CT scan data of 48 patients with crooked nose and deviated nasal septum were divided into C-type, angular deformity-type, and S-type based on the morphology of the 3D model. Different types of finite element models of the nasal bony septum and skull base were established. The osteotomy depth, angle, and force mode of the PPE resection were simulated by assembling different working conditions for the models. The von Mises stress of the anterior cranial fossa was observed. RESULTS: When the osteotomy line length was 0.5 cm, the angle was at 30° to the Frankfurt plane, and 50 N·mm torque was applied, the von Mises stress of the skull base was minimal in the four models, showing 0.049 MPa (C-type), 0.082 MPa (S-type), 0.128 MPa (angular deformity-type), and 0.021 MPa (control model). The maximum von Mises stress values were found at the skull base when the osteotomy line was 1.5 cm, the angle was 50°, and the force was 10 N along the X-axis, showing 0.349 MPa (C-type), 0.698 MPa (S-type), 0.451 MPa (angular deformity-type), and 0.149 MPa (control model). CONCLUSION: The use of smaller resection angle with the Frankfurt plane, conservative resection depth, and torsion force can better reduce the stress value at the skull base and reduce the risk of basicranial fracture. It is a safe and effective technique for perpendicular plate resection of the ethmoid bone in the correction of crooked nose. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Morphological and Functional Effects of the Endoscope-Assisted One-Stage Approach for Crooked Nose.

BACKGROUND: A crooked nose is an external nose deformity predominantly caused by congenital aplasia or acquired secondary to trauma or surgery, often accompanied by a deviated nasal septum. Patients with crooked nose have dual needs to improve both esthetic and functional problems. METHODS: The clinical and photographic information of 48 patients diagnosed with a crooked nose and nasal septum deviation treated from January 2018 to January 2022 was acquired. The morphology and functional effects were investigated by evaluating the general condition of the operation, measuring the esthetic indexes of the nose, and subjectively scoring. RESULTS: For both morphology and function, endoscopy-assisted one-stage correction showed positive results in this study. The external nose deviation distance postoperatively measured 1.28 (0.85, 1.97) mm, which significantly decreased from the preoperative value of 3.96 (3.31, 5.29) mm. The scores of doctors and irrelevant medical students on nose morphology increased significantly from 4.75±1.88 and 3.84±0.76 to 6.48±1.21 and 7.21±0.67, respectively. The rhinoplasty outcome evaluation score and the "nasal obstruction symptom evaluation "score of patients were both significantly improved ( t = -7.508 and t =6.310, respectively, P < 0.001). CONCLUSION: Endoscope-assisted one-stage correction of the crooked nose can restore nasal morphology, improve the symptoms of nasal obstruction, and achieve patient satisfaction. It is a minimally invasive, safe, effective, and fast recovery approach for patients who need to solve both esthetic and functional problems.