Comprehensive analysis of the relationship between ubiquitin-specific protease 21 (USP21) and prognosis, tumor microenvironment infiltration, and therapy response in colorectal cancer.

BACKGROUND: Ubiquitin-specific proteases family is crucial to host immunity against pathogens. However, the correlations between USP21 and immunosurveillance and immunotherapy for colorectal cancer (CRC) have not been reported. METHODS: The differential expression of USP21 between CRC tissues and normal tissues was analyzed using multiple public databases. Validation was carried out in clinical samples through qRT-PCR and IHC. The correlation between USP21 and the prognosis, as well as clinical pathological characteristics of CRC patients, was investigated. Moreover, cell models were established to assess the influence of USP21 on CRC growth and progression, employing CCK-8 assays, colony formation assays, and wound-healing assays. Subsequently, gene set variation analysis (GSVA) was used to explore the potential biological functions of USP21 in CRC. The study also examined the impact of USP21 on cytokine levels and immune cell infiltration in the tumor microenvironment (TME). Finally, the effect of USP21 on the response to immunotherapy and chemotherapy in CRC was analyzed. RESULTS: The expression of USP21 was significantly upregulated in CRC. High USP21 is correlated with poor prognosis in CRC patients and facilitates the proliferation and migration capacities of CRC cells. GSVA indicated an association between low USP21 and immune activation. Moreover, low USP21 was linked to an immune-activated TME, characterized by high immune cell infiltration. Importantly, CRC with low USP21 exhibited higher tumor mutational burden, high PD-L1 expression, and better responsiveness to immunotherapy and chemotherapeutic drugs. CONCLUSION: This study revealed the role of USP21 in TME, response to therapy, and clinical prognosis in CRC, which provided novel insights for the therapeutic application in CRC.

Type 2 diabetic mellitus related osteoporosis: focusing on ferroptosis.

With the aging global population, type 2 diabetes mellitus (T2DM) and osteoporosis(OP) are becoming increasingly prevalent. Diabetic osteoporosis (DOP) is a metabolic bone disorder characterized by abnormal bone tissue structure and reduced bone strength in patients with diabetes. Studies have revealed a close association among diabetes, increased fracture risk, and disturbances in iron metabolism. This review explores the concept of ferroptosis, a non-apoptotic cell death process dependent on intracellular iron, focusing on its role in DOP. Iron-dependent lipid peroxidation, particularly impacting pancreatic ß-cells, osteoblasts (OBs) and osteoclasts (OCs), contributes to DOP. The intricate interplay between iron dysregulation, which comprises deficiency and overload, and DOP has been discussed, emphasizing how excessive iron accumulation triggers ferroptosis in DOP. This concise overview highlights the need to understand the complex relationship between T2DM and OP, particularly ferroptosis. This review aimed to elucidate the pathogenesis of ferroptosis in DOP and provide a prospective for future research targeting interventions in the field of ferroptosis.

Turning Ultra-Low Coercivity and Ultra-High Temperature Stability Within 897 K via Continuous Crystal Ordering Fluctuations.

High-performance soft magnetic materials are important for energy conservation and emission reduction. One challenge is achieving a combination of reliable temperature stability, high resistivity, high Curie temperature, and high saturation magnetization in a single material, which often comes at the expense of intrinsic coercivity-a typical trade-off in the family of soft magnetic materials with homogeneous microstructures. Herein, a nanostructured FeCoNiSiAl complex concentrated alloy is developed through a hierarchical structure strategy. This alloy exhibits superior soft magnetic properties up to 897 K, maintaining an ultra-low intrinsic coercivity (13.6 A m-1 at 297 K) over a wide temperature range, a high resistivity (138.08 µΩ cm-1 at 297 K) and the saturation magnetization with only a 16.7% attenuation at 897 K. These unusual property combinations are attributed to the dual-magnetic-state nature with exchange softening due to continuous crystal ordering fluctuations at the atomic scale. By deliberately controlling the microstructure, the comprehensive performance of the alloy can be tuned and controlled. The research provides valuable guidance for the development of soft magnetic materials for high-temperature applications and expands the potential applications of related functional materials in the field of sustainable energy.

A New Strategy for the High-Throughput Characterization of Materials' Mechanical Homogeneity Based on the Effect of Isostatic Pressing on Surface Microstrain.

A new strategy for the high-throughput characterization of the mechanical homogeneity of metallurgical materials is proposed. Based on the principle of hydrostatic transmission and the synergistic analysis of the composition, microstructure, defects, and surface profile of the chosen material, the microstrain characteristics and changes in surface roughness after isostatic pressing were analyzed. After isostatic pressing, two types of microstrains were produced: low microstrain (surface smoothening with decreasing roughness) and large microstrain (surface roughening with increasing roughness). Furthermore, the roughness of the roughened microregions could be further classified based on the strain degree. The phenomenon of weak-interface damage with a large microstrain (plastic deformation, cleavage fracture, and tearing near nonmetallic inclusions) indicated that the surface microstrain analysis could be a new method of high-throughput characterization for microregions with relatively poor micromechanical properties. In general, the effect of isostatic pressing on the surface microstrain of heat-resistant steel provides a promising strategy for achieving high-throughput screening and statistically characterizing microregions with poor micromechanical properties, such as microregions containing microcracks, nonmetallic inclusions, pores, and other surface defects.

Comprehensive analyses of solute carrier family members identify SLC12A2 as a novel therapy target for colorectal cancer.

As the largest transporter family impacting on tumor genesis and development, the prognostic value of solute carrier (SLC) members has not been elucidated in colorectal cancer (CRC). We aimed to identify a prognostic signature from the SLC members and comprehensively analyze their roles in CRC. Firstly, we downloaded transcriptome data and clinical information of CRC samples from GEO (GSE39582) and TCGA as training and testing dataset, respectively. We extracted the expression matrix of SLC genes and established a prognostic model by univariate and multivariate Cox regression. Afterwards, the low-risk and high-risk group were identified. Then, the differences of prognosis traits, transcriptome features, clinical characteristics, immune infiltration and drug sensitivity between the two groups were explored. Furthermore, molecular subtyping was also implemented by non-negative matrix factorization (NMF). Finally, we studied the expression of the screened SLC genes in CRC tumor tissues and normal tissues as well as investigated the role of SLC12A2 by loss of function and gain of function. As a result, we developed a prognostic risk model based on the screened 6-SLC genes (SLC39A8, SLC2A3, SLC39A13, SLC35B1, SLC4A3, SLC12A2). Both in the training and testing sets, CRC patients in the high-risk group had the poorer prognosis and were in the more advanced pathological stage. What's more, the high-risk group were enriched with CRC progression signatures and immune infiltration. Two groups showed different drug sensitivity. On the other hand, two distinct subclasses (C1 and C2) were identified based on the 6 SLC genes. CRC patients in the high-risk group and C1 subtype had a worse prognosis. Furthermore, we found and validated that SLC12A2 was steadily upregulated in CRC. A loss-of-function study showed that knockdown of SLC12A2 expression restrained proliferation and stemness of CRC cells while a gain-of-function study showed the contrary results. Hence, we provided a 6-SLC gene signature for prognosis prediction of CRC patients. At the same time, we identified that SLC12A2 could promote tumor progression in CRC, which may serve as a potential therapeutic target.

Chlamydospore dormancy and predatory activity of nematophagous fungus Duddingtonia flagrans.

The chlamydospores of Duddingtonia flagrans are an essential survival and reproductive structure and also an effective ingredient for the biocontrol of parasitic nematodes in livestock. In this study, entering and exiting dormancy conditions and predatory activity of the fungal chlamydospores were conducted. During this fungal growth process, the cultivation time is negatively correlated with spore germination rates. After the spores were processed by vacuum drying for 168 h, their germination rate dropped to 0.94%. In contrast, the percentage of living spores remained 54.82%, suggesting that the spores entered structural dormancy in the arid environment. Meanwhile, the efficacies of the spore against Haemonchus contortus larvae were 93.05% (0 h), 92.19% (16 h), 92.77% (96 h), and 86.45% (168 h), respectively. After dormant spores were stored at 4°C, -20°C, and 28°C (RH90 ~ 95%) for 7 days, their germination rate began to increase significantly (p < 0.05). For in vitro predation assay under the condition of 28°C (RH90 ~ 95%), the predation rate was significantly higher on the 7th day after incubation than that on the 3rd day (p < 0.05). During the period when spores were stored at room temperature for 8 months, their germination rate decreased in the first 5 months and then increased slowly to reach a peak in the 7th month. However, the reduction rate of H. contortus L3 in feces captured by spores remained above 71% for the first 7 months. These results will help us increase the end products yield and the quality of biological control of parasitic nematodes in livestock.

Micro X-ray fluorescence (µ-XRF) methodology for quantitative elemental imaging of Al-Zn-Mg-Cu alloys with varying chemical compositions.

The preparation and characterization of Al-Zn-Mg-Cu alloys with varying chemical compositions are helpful for rapid screening of the optimal compositions in the research and development of new materials. The traditional testing methods cannot accurately determine the composition gradient in samples because they have a low spatial resolution or are semi-quantitative and time-consuming. The micro X-ray fluorescence (µ-XRF) methodology has been used for the elemental imaging of Al-Zn-Mg-Cu alloys with varying chemical compositions. The experimental conditions, including testing voltages, testing currents and the dwell time for each pixel, were optimized systematically to improve the repeatability and accuracy of the µ-XRF methodology. The quantitative elemental imaging of an Al-Zn-Mg-Cu alloy rod sample using µ-XRF was performed, and the results were validated by conducting spark optical emission spectroscopy. The limits of detection of µ-XRF for Zn, Mg, and Cu were 0.007 wt%, 0.068 wt%, and 0.002 wt%, respectively. This versatile elemental imaging technique provided an effective means for the component analysis and process evaluation of alloy samples with a composition gradient and thus for research and development of new materials.

MuRF-1 is Involved in Laryngeal Muscle Denervation Atrophy by Regulating G-Actin Ubiquitination.

OBJECTIVE: Muscle RING-finger protein-1 (MuRF-1), an E3 ubiquitin ligase, has been reported to aggravate skeletal muscle denervated atrophy by mediating the ubiquitination degradation of multiple proteins, whereas the molecular mechanism underlying MuRF-1-mediated internal laryngeal muscle denervated atrophy remains unknown. METHODS: A rat unilateral recurrent laryngeal nerve (RLN) transection model was established to evaluate denervated muscle atrophy of the larynx. The expression of MuRF-1, G- and F-actin in thyroarytenoid muscle (TA) myocytes before and after RLN injury was analyzed by immunofluorescence and Western blotting. Coimmunoprecipitation experiments detected molecular interactions between MuRF-1 and G-actin. Immunoprecipitation tested MuRF-1-mediated ubiquitination of G-actin in denervated and innervated TA muscle tissues. The shRNA-MuRF-1 AAV was used to suppress MuRF-1 expression in denervated TA muscles in vivo. RESULTS: First, MuRF-1 expression was significantly elevated in denervated TA muscle compared to innervated TA muscle (p < 0.001). Second, there was a progressive increase in the G/F-actin ratio in TA myocytes from day 3 to 14 after RLNI (p < 0.01). Furthermore, colocalization of MuRF-1 and G-actin in denervated TA myocytes was observed. Moreover, the upregulation of MuRF-1 was closely associated with the ubiquitination of G-actin in denervated TA myocytes and muscle tissues. Knockdown of MuRF-1 decelerated the degree of TA muscle atrophy compared with that in the Blank and NC groups (p < 0.001) but seemed to promote the compensatory movement of the healthy side. CONCLUSION: Collectively, we illustrate a novel molecular mechanism underlying MuRF-1-mediated internal laryngeal muscle denervated atrophy in that MuRF-1 could promote disequilibrium of the G/F-actin ratio by regulating G-actin ubiquitination. LEVEL OF EVIDENCE: NA Laryngoscope, 134:855-864, 2024.

Quantitative Characterization of Elemental Segregation in Inconel 718 Superalloy by Micro-Beam X-ray Fluorescence Spectroscopy and Its Correlation Study.

Inconel 718 (IN718) nickel-based superalloy is widely used in aerospace and nuclear applications owing to its excellent comprehensive mechanical properties, oxidation resistance, and hot corrosion resistance. However, the elemental segregation caused by heterogeneous solidification during casting has great influence on the mechanical properties. Therefore, accurately characterizing the segregation behavior is necessary. Traditional quantitative characterization of elemental segregation uses various sampling methods, in which only macroscopic segregation results are obtained. In this study, micro-beam X-ray fluorescence (µ-XRF) is used for the quantitative characterization of element micro-segregation in IN718 superalloy. The concentration distributions of Cr, Fe, Mo, Nb, and Ti in IN718 alloy are determined with optimized testing parameters, and the degree of elemental segregation in different regions of the analytical area is calculated. It is found that the segregation degree of Nb and Ti in the testing area is larger than other alloying elements. The correlation between the microstructure distribution and the segregation degree of Nb and Ti has been studied using scanning electron microscopy (SEM) combined with energy-dispersive spectrometry (EDS). There is severe segregation of Nb and Ti in areas where Nb-containing precipitates are accumulated. The distribution of abnormal signals of Nb with a high fluorescence intensity has a close relationship with the area of precipitates-enriched Nb.

Chemical Composition of Litsea pungens Essential Oil and Its Potential Antioxidant and Antimicrobial Activities.

Litsea pungens is a plant with medicinal and edible properties, where the fruits are edible and the leaves have medicinal properties. However, there is limited research on the chemical and pharmacological activities of the plant. In this study, essential oils were extracted by steam distillation and their antioxidant and antibacterial activities were further evaluated. Gas chromatography-mass spectrometry (GC-MS) was used to identify the chemical components of L. pungens fresh fruit essential oil (FREO) and L. pungens fresh flower essential oil (FLEO), rapeseed oil (RO) and commercial Litsea oil (CEO). The results showed that 12 chemical components were identified in FREO. Twelve chemical components were identified from FLEO, four chemical components were identified from CEO, and thirteen chemical components were identified from RO. Except for RO, the other three oils were mainly composed of terpenes, among which limonene is the main chemical component. In terms of antioxidant activity, FREO, FLEO, CEO and RO have antioxidant capacity, mainly reflected in the scavenging DPPH free radicals and the iron ion chelating ability, and the antioxidant activity shows a certain dose effect, but the antioxidant activity of FLEO is the weakest among the four oils. Meanwhile, under the stress of hydrogen peroxide, CEO demonstrated a significant antioxidant protective effect on cells. It is worth mentioning that compared with the positive control, the FREO exhibited a better antibacterial rate. When the concentration of essential oil is 20 mg/mL, the bacteriostatic rate can reach 100%. Therefore, it could be a promising candidate among medicinal and edible plants.

Comprehensive analysis of the relationship between cuproptosis-related gene GCSH and prognosis, tumor microenvironment infiltration, and therapy response in endometrial cancer.

BACKGROUND: Cuproptosis, a novel form of cell death regulated by protein lipoylation and implicated in mitochondrial metabolism. However, the impact of the cuproptosis-related gene γ-glutamylcysteine synthetase (GCSH) on endometrial cancer (EC) prognosis, tumor immune microenvironment, and therapeutic response remains to be further researched. METHODS: The differential expression of GCSH between endometrial cancer and normal tissues was analyzed using multiple public databases. Additionally, cancer and adjacent tissues were prospectively collected from 17 EC patients, and immunohistochemical analysis was performed to further investigate GCSH expression differences. The relationship between GCSH and the prognosis and clinicopathological characteristics of EC patients was evaluated, and a nomogram was constructed to predict patient survival based on GCSH expression. Then, Gene set variation analysis (GSVA) was utilized to explore the potential biological functions of GCSH in EC. The impact of GCSH on the tumor microenvironment (TME) was estimated. Finally, the effect of GCSH on the response to immunotherapy and chemotherapeutic drugs in EC was investigated. RESULTS: The expression of GCSH was significantly upregulated in EC. High GCSH expression was associated with poor prognosis in EC patients. Enrichment analysis showed that high GCSH was associated with immune suppression. Furthermore, high GCSH was found to be associated with a non-inflamed TME, leading to decreased infiltration levels of immune cells. Finally, it was observed that patients with high GCSH were insensitive to both immunotherapy and chemotherapeutic drugs. CONCLUSION: This study revealed the role of GCSH in TME, response to therapy, and clinical prognosis in EC, which provided novel insights for the therapeutic application in EC.

Regression of a large prolapsed lumbar disc herniation achieved by conservative treatment: A case report and literature review.

A common spinal condition known as lumbar disc herniation (LDH) can result in radicular and low back discomfort. A 27-year-old man was admitted to our hospital with a 6-year history of persistent low back pain, and his low back pain had recurred with radiation to his lower extremities over the last two months. An extensive right-sided paracentral disc herniation in the L5/S1 intervertebral region, which compressed the nerve root, was discovered by magnetic resonance imaging (MRI) of his lumbar spine. After receiving conservative treatment, the patient reported that his lower back discomfort and neurogenic claudication had gradually subsided after 4 months. After one year, a follow-up MRI showed that the massive, prolapsed disc herniation at the L5/S1 level had totally disappeared. The sagittal protrusion length of the L5/S1 intervertebral disc shrank from 12.35 mm to 3.49 mm. However, there remained a chance of vertebral height loss. During the course of treatment, the height of the L5/S1 intervertebral space was still slightly reduced. The intervertebral space height declined from 7.705 mm to 7.201 mm after one year of treatment. The current case and a review of the literature demonstrate that LDH can decrease with conservative therapy over a short period of time. We stress the effectiveness of conservative treatment in very select LDH cases that lack a clear surgical justification.

A biomechanical investigation of a novel intramedullary nail used to salvage failed internal fixations in intertrochanteric fractures.

PURPOSE: The ideal approach for revision surgery following femoral head salvage treatments for an intertrochanteric fracture is still up for debate. A novel variety of proximal femoral bionic intramedullary nail (PFBN) has been created in clinical practice. We aimed to compare the biomechanical results of the novel implant to conventional intramedullary and extramedullary fixation in the treatment of intertrochanteric fracture following primary internal fixation failure. METHODS: Using finite element analysis, we created a three-dimensional model of the intertrochanteric fracture's helical blade cut-out for this investigation. The PFBN 1 group, the PFBN 2 group, the PFNA group, and the DHS group were our four test groups. For each fracture group, the von Mises stress and displacements of the femur and internal fixation components were measured under 2100 N axial loads. RESULTS: The values for the femoral displacement in the PFBN1 group, PFBN2 group, PFNA group, and DHS group were 6.802 mm, 6.716 mm, 8.080 mm, and 8.679 mm, respectively. The internal implant displacement values were 6.201 mm, 6.138 mm, 7.396 mm, and 8.075 mm in the PFBN1 group, PFBN2 group, PFNA group, and DHS group, respectively. The maximum von Mises Stress in the femoral was 187.2 MPa, 85.18 MPa, 106.6 MPa, and 386.2 MPa in the PFBN1 groups, PFBN2 groups, PFNA groups, and DHS groups, respectively. In the PFBN1 groups, PFBN2 groups, PFNA groups, and DHS groups, the maximum von Mises Stress in internal fixation was 586.7 MPa, 559.8 MPa, 370.7 MPa, and 928.4.8 MPa, respectively. CONCLUSION: Our biomechanical research demonstrates that intramedullary fixation is more stable than extramedullary fixation when salvaging failed internal fixations in intertrochanteric fracture. Compared with PFNA and DHS, PFBN showed better biomechanical stability in the treatment of patients with revised intertrochanteric fractures. In light of this, we advocate PFBN fixation as the method of choice for intertrochanteric fracture revision. This result still has to be confirmed in more clinical research.

A Promotion Role of MIR31 in the Process of Vocal Fold Wound Healing.

The role of MIR31 in the wound healing process, specifically in vocal fold wound healing (VFWH), remains uncertain despite its potential to facilitate the process. In this study, we first constructed a literature-based pathway to examine both the positive and negative effects of MIR31 on wound healing. We then conducted animal experiments on 20 rats to investigate MIR31 expression at different time points (1, 4, and 8 weeks) after vocal fold injury. Co-expression analysis and pathway analysis were performed to explore the potential function of MIR31 in VFWH. The literature-based pathway suggested that MIR31 could both impede and promote the wound healing process by regulating 14 and 47 wound healing upstream regulators, respectively. However, the rat experiment indicated that MIR31 expression significantly increased after vocal fold injury (p < 5.65 × 10-5) but decreased in the late stage of VFWH compared with the early and middle stages (p < 5.40 × 10-3. Strong co-expression was observed between MIR31 and 17 VFWH-significant genes (Pearson correlation coefficient ∈ (0.63, 0.83)), primarily involved in collagen production. Overall, our findings suggest that MIR31 plays a critical role in VFWH, particularly in collagen synthesis and other biological processes, which warrant further investigation.

Guanylate-binding proteins signature predicts favorable prognosis, immune-hot microenvironment, and immunotherapy response in hepatocellular carcinoma.

BACKGROUND: The role of guanylate-binding proteins (GBPs) in various cancers has been elucidated recently. However, our knowledge of the clinical relevance and biological characteristics of GBPs in hepatocellular carcinoma (HCC) remains limited. METHODS: A total of 955 HCC patients were enrolled from five independent public HCC cohorts. The role of GBP molecules in HCC was preliminarily investigated, and a GBP family signature, termed GBPs-score, was constructed by principal component analysis to combine the GBP molecule values. We revealed the effects of GBP genes and GBPs-score in HCC via well-established bioinformatics methods and validated GBP1-5 experimentally in a tissue microarray (TMA) cohort. RESULTS: GBPs molecules were closely associated with the prognosis of patients with HCC, and a high GBPs-score highly inferred a favorable survival outcome. We also revealed high GBPs-score was related to anti-tumor immunity, the immune-hot tumor microenvironment (TME), and immunotherapy response. Among the GBPs members, GBP1-5 rather than GBP6/7 may be dominant in these fields. The TMA analysis based on immunohistochemistry showed positive correlations between GBP1-5 and the immune-hot TME with abundant infiltration of CD8+ T cells in HCC. CONCLUSIONS: Our integrative study revealed the genetic and immunologic characterizations of GBPs in HCC and highlighted their potential values as promising biomarkers for prognosis and immunotherapy.

Novel oviduct endoscope combining optical coherence tomography with intratubal ultrasonography for fallopian tube exploration: An in vivo rabbit pilot study.

BACKGROUND AND STUDY AIM: Currently, several limitations exist in the examination of the oviduct. In this study, the usefulness and feasibility of a novel ultrafine dual-modality oviduct endoscopy device for in vivo assessment of the oviduct were evaluated. METHODS: Five Japanese white rabbits were selected to undergo oviduct probing using a combination of optical coherence tomography (OCT) and intratubal ultrasonography. The feasibility of the procedure was evaluated through 152 pairs of clear, clinically interpretable images obtained using spiral scanning via the pull-back method. OCT images were compared with the oviduct histopathology sections. RESULTS: Visualization of the oviduct using both OCT and ultrasound revealed a differentiated three-layer tissue; however, ultrasound showed a poorer clarity than OCT. By comparing OCT images with the histological morphology of the oviduct, the inner low-reflective layer of the oviduct corresponds to the mucosal layer, the middle high-reflective layer corresponds to the fibrous muscle layer, and the outer low-reflective layer corresponds to the connective tissue layer. Postoperatively, the general condition of the animals was good. CONCLUSION: This study demonstrated the feasibility and potential clinical value of the novel ultrafine dual-modality oviduct endoscope. Dual-modality imaging of OCT and intratubal ultrasonography can provide clearer microstructure of the oviduct wall.

Gastrointestinal pan-cancer landscape of tumor matrix heterogeneity identifies biologically distinct matrix stiffness subtypes predicting prognosis and chemotherapy efficacy.

Gastrointestinal (GI) cancers are a heterogeneous group of primary solid tumors, arising in GI tract from the esophagus to rectum. Matrix stiffness (MS) is a critical physical factor for cancer progression; however, its importance in tumor progression remains to be comprehensively recognized. Herein, we conducted a comprehensive pan-cancer analysis of MS subtypes across seven GI-cancer types. Using unsupervised clustering based on literature-derived MS-specific pathway signatures, the GI-tumor samples were divided into three MS subtypes, termed as the Soft, Mixed and Stiff. Then, distinct prognoses, biological features, tumor microenvironments and mutation landscapes among three MS subtypes were revealed. The Stiff tumor subtype was associated with the poorest prognosis, the most malignant biological behaviors, and the immunosuppressive tumor stromal microenvironment. Furthermore, multiple machine learning algorithms were used to develop an 11-gene MS-signature to identify the MS subtypes of GI-caner and predict chemotherapy sensitivity, which were further validated in two external GI-cancer cohorts. This novel MS-based classification on GI-cancers could enhance our understanding of the important role of MS in tumor progression, and may have implications for the optimization of individualized cancer management.

SOCS3 Silencing Promotes Activation of Vocal Fold Fibroblasts via JAK2/STAT3 Signaling Pathway.

Suppressor of cytokine signaling 3 (SOCS3) is a negative regulatory protein that has been identified as a key inhibitory regulator of JAK/STAT signaling pathway. However, the mutual regulatory relationship between SOCS3 and JAK2/STAT3 signaling pathway after vocal fold injury remains unclear. In this study, we used small interfering RNA (siRNA) to investigate the mechanism of SOCS3 regulating of fibroblasts through JAK2/STAT3 signaling pathway after vocal fold injury. Our data shows that SOCS3 silencing promotes the transformation of normal vocal fold fibroblasts (VFFs) into an fibrotic phenotype and activates the JAK2/STAT3 signaling pathway. JAK2 silencing significantly inhibits the increase in type I collagen and α-smooth muscle actin (α-SMA) secretion in VFFs induced by TGF-ß but has no significant effect on normal VFFs. The silencing of SOCS3 and JAK2 reverses the fibrotic phenotype of VFFs induced by SOCS3 silencing. Therefore, we suggest that SOCS3 can affect the activation of vocal fold fibroblasts by regulating the JAK2/STAT3 signaling pathway after vocal fold injury. It provides a new insight for promoting the repair of vocal fold injury and preventing the formation of fibrosis.

Polyps are detected more often in early colonoscopies.

OBJECTIVE: To examine the time variation in polyp detection for colonoscopies performed in a tertiary hospital and to explore independent factors that predict polyp detection rate (PDR). METHODS: Data on all patients who underwent colonoscopy for the diagnostic purpose at our endoscopy center in Zhongnan Hospital of Wuhan University from January 2021 to December 2021 were reviewed. The start time of included colonoscopies for eligible patients was recorded. PDR and polyps detected per colonoscopy (PPC) were calculated. The endoscopists' schedules were classified into full-day and half-day shifts according to their participation in the morning and afternoon colonoscopies. RESULTS: Data on a total of 12116 colonoscopies were analyzed, with a PDR of 38.03% for all the patients and 46.38% for patients ≥50 years. PDR and PPC significantly decreased as the day progressed (both p < .001). For patients ≥50 years, PDR declined below 40% at 13:00-13:59 and 16:00-16:59. The PDR in the morning was higher than that in the afternoon for both half-day (p = .019) and full-day procedures (p < .001). In multivariate analysis, start time, patient gender, age, conscious sedation, and bowel preparation quality significantly predicted PDR (p < .001). CONCLUSIONS: The polyp detection declined as the day progressed. A continuous work schedule resulted in a subpar PDR. Colonoscopies performed in the morning had a higher PDR than that in the afternoon. Patient gender, age, conscious sedation, and bowel preparation quality were identified as the independent predictors of PDR.

Multiphase migration and transformation of BTEX on groundwater table fluctuation in riparian petrochemical sites.

Light non-aqueous phase liquids (LNAPL) are considered to be a composition-based risk, containing multiple chemical ingredients that release dissolved- and vapor-phase plumes. In dissolved form, there is a saturation-based risk as the water source expands, affecting groundwater aquifers on a larger scale in the aquifer. As a typical pollutant found in petrochemical contaminated sites, the migration and transformation of benzene, toluene, ethylbenzene, and o-xylene (BTEX) between gas, aqueous, and NAPL phases are distinctly affected by groundwater table fluctuation (GTF). BTEX multiphase migration and transformation pattern in a petrochemical factory at the riverside was simulated based on the TMVOC model in differentiating pollution distribution and interphase transformation under stable or fluctuating groundwater tables conditions. TMVOC model performed an excellent simulation effect on the migration and transformation of BTEX in GTF circumstances. In comparison with the stable groundwater table condition, the BTEX pollution depth under GTF increased by 0.5 m, the pollution area increased by 25%, and the total mass increased by 0.12 × 102 kg. In both cases, the mass reduction of NAPL-phase pollutants was more significant than the total mass reduction of pollutants, and GTF further promoted the mass conversion of NAPL-phase pollutants to water pollutants. Prominently, as the groundwater table rises, the GTF can correct for evacuation, and the transport flux of gaseous pollutants at the atmospheric boundary decreases with increasing transport distance. Furthermore, descended groundwater table will intensify the transmission flux of gaseous pollutants at the atmospheric boundary with the transmission range expanding, which can be harmful to human health on the surface due to gaseous pollutants entering into the air.