Reactive Oxygen Species Amplifier for Apoptosis-Ferroptosis Mediated High-Efficiency Radiosensitization of Tumors.

Insufficient reactive oxygen species (ROS) production and radioresistance have consistently contributed to the failure of radiotherapy (RT). The development of a biomaterial capable of activating ROS-induced apoptosis and ferroptosis is a potential strategy to enhance RT sensitivity. To achieve precision and high-efficiency RT, the theranostic nanoplatform Au/Cu nanodots (Au/CuNDs) were designed for dual-mode imaging, amplifying ROS generation, and inducing apoptosis-ferroptosis to sensitize RT. A large amount of ROS is derived from three aspects: (1) When exposed to ionizing radiation, Au/CuNDs effectively absorb photons and emit various electrons, which can interact with water to produce ROS. (2) Au/CuNDs act as a catalase-like to produce abundant ROS through Fenton reaction with hydrogen peroxide overexpressed of tumor cells. (3) Au/CuNDs deplete overexpressed glutathione, which causes the accumulation of ROS. Large amounts of ROS and ionizing radiation further lead to apoptosis by increasing DNA damage, and ferroptosis by enhancing lipid peroxidation, significantly improving the therapeutic efficiency of RT. Furthermore, Au/CuNDs serve as an excellent nanoprobe for high-resolution near-infrared fluorescence imaging and computed tomography of tumors. The promising dual-mode imaging performance shows their potential application in clinical cancer detection and imaging-guided precision RT, minimizing damage to adjacent normal tissues during RT. In summary, our developed theranostic nanoplatform integrates dual-mode imaging and sensitizes RT via ROS-activated apoptosis-ferroptosis, offering a promising prospect for clinical cancer diagnosis and treatment.

VOx Matrix Confinement Approach to Generate Sub-3 nm L10-Pt-Based Intermetallic Catalysts for Fuel Cell Cathode.

Pt-based intermetallic compounds (IMCs) are considered as a class of promising fuel cell electrocatalysts, owing to their outstanding intrinsic activity and durability. However, the synthesis of uniformly dispersed IMCs with small sizes presents a formidable challenge during the essential high-temperature annealing process. Herein, a facile and generally applicable VOx matrix confinement strategy is demonstrated for the controllable synthesis of ordered L10-PtM (M = Fe, Co, and Mn) nanoparticles, which not only enhances the dispersion of intermetallic nanocrystals, even at high loading (40 wt%), but also simplifies the oxide removal and acid-washing procedures. Taking intermetallic PtCo as an example, the as-prepared catalyst displays a high-performance oxygen reduction activity (mass activity of 1.52 A mgPt -1) and excellent stability in the membrane electrode assemblies (MEAs) (the ECSA has just 7% decay after durability test). This strategy provides an economical and scalable route for the controlled synthesis of Pt-based intermetallic catalysts, which can pave a way for the commercialization of fuel cell technologies.

Long-term follow-up after the treatment of impacted canines in the maxilla causing severe root resorption of the lateral incisors: two case reports.

BACKGROUND: Root resorption of adjacent teeth due to impacted canines is common, and orthodontic treatment often leads to secondary resorption or even loss of adjacent roots. Clinical reports of long-term stability after treatment are rare. CASE PRESENTATION: This study reports two cases of maxillary impacted canines resulting in severe root resorption of the adjacent lateral incisors. Surgical exposure, orthodontic retraction, and alignment of the impacted canines were successful in both cases, and the resorbed lateral incisors were stable with no significant loosening and normal pulp vitality after treatment and at the 5- and 10-year follow-up appointments. CONCLUSIONS: Light orthodontic force may be used to move adjacent teeth with root resorption due to tooth obstruction. The path and direction in which the teeth are moved must be specifically designed so that the adjacent roots are not resorbed and so long-term stability can be achieved.

Prognostic values of tumor size and location in early stage endometrial cancer patients who received radiotherapy.

OBJECTIVE: To investigate the correlation between tumor size, tumor location, and prognosis in patients with early-stage endometrial cancer (EC) receiving adjuvant radiotherapy. METHODS: Data of patients who had been treated for stage I-II EC from March 1999 to September 2017 in 13 tertiary hospitals in China was screened. Cox regression analysis was performed to investigate associations between tumor size, tumor location, and other clinical or pathological factors with cancer-specific survival (CSS) and distant metastasis failure-free survival (DMFS). The relationship between tumor size as a continuous variable and prognosis was demonstrated by restricted cubic splines. Prognostic models were constructed as nomograms and evaluated by Harrell's C-index, calibration curves and receiver operating characteristic (ROC) curves. RESULTS: The study cohort comprised 805 patients with a median follow-up of 61 months and a median tumor size of 3.0 cm (range 0.2-15.0 cm). Lower uterine segment involvement (LUSI) was found in 243 patients (30.2%). Tumor size and LUSI were identified to be independent prognostic factors for CSS. Further, tumor size was an independent predictor of DMFS. A broadly positive relationship between poor survival and tumor size as a continuous variable was visualized in terms of hazard ratios. Nomograms constructed and evaluated for CSS and DMFS had satisfactory calibration curves and C-indexes of 0.847 and 0.716, respectively. The area under the ROC curves for 3- and 5-year ROC ranged from 0.718 to 0.890. CONCLUSION: Tumor size and LUSI are independent prognostic factors in early-stage EC patients who have received radiotherapy. Integrating these variables into prognostic models would improve predictive ability.

Clinical characteristics and radiation therapy modality of younger patients with early-stage endometrial cancer, a multicenter study in China's real world.

BACKGROUND: Endometrial cancer is a prevalent gynecologic malignancy found in postmenopausal women. However, in the last two decades, the incidence of early-stage has doubled in women under 40 years old. This study aimed to investigate the clinical and pathological characteristics and adjuvant therapeutic modalities of both young and not -young patients with early-stage endometrial cancer in China's real world. METHODS: This retrospective study analyzed patients with early-stage endometrial cancer at 13 medical institutions in China from 1999 to 2015. The patients were divided into two groups: young (≤ 45 years old) and non-young (> 45 years old). Statistical comparisons were conducted between the two groups for clinical characteristics, pathological features, and survival. The study also identified factors that affect local recurrence-free survival (LRFS) using Cox proportional risk regression analysis. Propensity score matching (1:1) was used to compare the effects of local control between vaginal brachytherapy (VBT) alone and pelvic external beam radiotherapy (EBRT) ± VBT. RESULTS: The study involved 1,280 patients, 150 of whom were 45 years old or younger. The young group exhibited a significantly higher proportion of stage II, low-risk, lower uterine segment infiltration (LUSI), and cervical invasion compared to the non-young group. Additionally, the young patients had significantly larger maximum tumor diameters. The young group also had a significantly higher five-year overall survival (OS) and a five-year LRFS. Age is an independent risk factor for LRFS. There was no significant difference in LRFS between young patients with intermediate- to high-risk early-stage endometrial cancer who received EBRT ± VBT and those who received VBT alone. CONCLUSIONS: In the present study, young patients had better characteristics than the non-young group, while they exhibited higher levels of aggressiveness in certain aspects. The LRFS and OS outcomes were better in young patients. Age is an independent risk factor for LRFS. Additionally, VBT alone may be a suitable option for patients under 45 years of age with intermediate- to high-risk early-stage endometrial cancer, as it reduces the risk of toxic reactions and future second cancers while maintaining similar local control as EBRT.

Stable, intense supercontinuum light generation at 1 kHz by electric field assisted femtosecond laser filamentation in air.

Supercontinuum (SC) light source has advanced ultrafast laser spectroscopy in condensed matter science, biology, physics, and chemistry. Compared to the frequently used photonic crystal fibers and bulk materials, femtosecond laser filamentation in gases is damage-immune for supercontinuum generation. A bottleneck problem is the strong jitters from filament induced self-heating at kHz repetition rate level. We demonstrated stable kHz supercontinuum generation directly in air with multiple mJ level pulse energy. This was achieved by applying an external DC electric field to the air plasma filament. Beam pointing jitters of the 1 kHz air filament induced SC light were reduced by more than 2 fold. The stabilized high repetition rate laser filament offers the opportunity for stable intense SC generation and its applications in air.

The role of SLC39A4 in the prognosis, immune microenvironment, and contribution to malignant behavior in vivo and in vitro of cervical cancer.

BACKGROUND: Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are becoming more common in younger women. Solute carrier family 39 member 4 (SLC39A4) produces a zinc ion transporter involved in metastasis and invasion of tumors. METHODS: The Cancer Genome Atlas RNA-seq data was used to investigate the expression of SLC39A4 and its prognostic potential. The assessment of the effect of SLC39A4 on cell growth and migration in CESC was conducted using MTT, colony formation, and Transwell assays. SLC39A4 was studied in vivo using a xenograft mouse model, and its functional involvement in oncogenesis was investigated by identifying the associated differentially expressed genes (DEGs). We evaluated the relationships among SLC39A4 levels, chemosensitivity, radiosensitivity and immune infiltration. RESULTS: SLC39A4 was upregulated in CESC samples, and individuals with greater SLC39A4 mRNA expression had shorter overall survival. SLC39A4 has been identified to be a regulator of tumor cell metastasis and proliferation in vivo and in vitro, with an area under the curve of 0.874 for diagnosing CESC. In total, 948 DEGs were discovered to be enriched in key CESC progression-related signaling pathways. Additionally, intratumoral immune checkpoint and infiltration activity were associated with SLC39A4 expression. High SLC39A4 expression exhibited poor chemosensitivity and radiosensitivity profiles. CONCLUSION: In conclusion, SLC39A4 is a key regulator of CESC development, prognosis, and the composition of the tumor immune microenvironment. SLC39A4 could be used as a prognostic or diagnostic screening tool and as a potential target for CESC treatment.

Enabling direct-growth route for highly efficient ethanol upgrading to long-chain alcohols in aqueous phase.

Upgrading ethanol to long-chain alcohols (LAS, C6+OH) offers an attractive and sustainable approach to carbon neutrality. Yet it remains a grand challenge to achieve efficient carbon chain propagation, particularly with noble metal-free catalysts in aqueous phase, toward LAS production. Here we report an unconventional but effective strategy for designing highly efficient catalysts for ethanol upgrading to LAS, in which Ni catalytic sites are controllably exposed on surface through sulfur modification. The optimal catalyst exhibits the performance well exceeding previous reports, achieving ultrahigh LAS selectivity (15.2% C6OH and 59.0% C8+OH) at nearly complete ethanol conversion (99.1%). Our in situ characterizations, together with theoretical simulation, reveal that the selectively exposed Ni sites which offer strong adsorption for aldehydes but are inert for side reactions can effectively stabilize and enrich aldehyde intermediates, dramatically improving direct-growth probability toward LAS production. This work opens a new paradigm for designing high-performance non-noble metal catalysts for upgrading aqueous EtOH to LAS.

A predictive model for residual lesions after LEEP surgery in CIN III patients.

Background and aims: The residual lesions after Loop Electrosurgical Excision Procedure (LEEP) contributes to poor prognosis in patients with Cervical Intraepithelial Neoplasia Grade 3 (CIN3). The aim of this study is to establish an effective clinical predictive model for residual lesions in CIN3 patients after LEEP. Methods: A retrospective analysis was performed on 436 CIN3 patients who underwent total hysterectomy within 3 months after LEEP. Based on the post-hysterectomy pathologic, the patients were divided into the no residual group and residual group. Clinical parameters were compared between the two groups, and univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for residual lesions in CIN3 patients after LEEP. Using R software, a nomogram model was established and its effectiveness was evaluated using calibration plots. Results: There were 178 cases in the residual group and 258 cases in the no residual group. The two groups had no significant difference in general characteristics (p > 0.05). It was found that Post-LEEP follow-up HPV, Post-LEEP follow-up TCT, and the Gland involvement were independent risk factors for residual lesions in CIN3 patients after LEEP (all p < 0.05). The consistency index (C-index) of the nomogram model for predicting residual lesions was 0.975 (0.962-0.988). Conclusion: The Post-LEEP follow-up HPV, Post-LEEP follow-up TCT, and Gland involvement are independent risk factors related to residual tissue after LEEP surgery in CIN3 patients. The constructed nomogram can effectively predict the presence of residual tissue after LEEP surgery in CIN3 patients and has good practical value.

Over 5 × 103-Fold Enhancement of Responsivity in Ga2O3-Based Solar Blind Photodetector via Acousto-Photoelectric Coupling.

The emergence of the wide-band-gap semiconductor Ga2O3 has propelled it to the forefront of solar blind detection activity owing to its key features. Although various architectures and designs of Ga2O3-based solar blind photodetectors have been proposed, their performance still falls short of commercial standards. In this study, we demonstrate a method to enhance the performance of a simple metal-semiconductor-metal-structured Ga2O3-based solar blind photodetector by exciting acoustic surface waves. Specifically, we demonstrate that under a bias voltage of 100 mV and a radio frequency signal of 20 dBm, the responsivity and detectivity can increase from 2.78 to 1.65 × 104 A/W and from 8.35 × 1014 to 2.66 × 1016 jones, respectively, rivaling a commercial photomultiplier tube. The over 5 × 103-fold enhancement in responsivity could be attributed to the acousto-photoelectric coupling mechanism. Furthermore, since surface acoustic waves can also serve as signal receivers, such photodetectors offer the prospect of dual-mode detection. Our findings reveal a promising pathway for achieving high-performance Ga2O3-based electronics and optoelectronics.

S100A10 Overexpression Correlates with Adverse Prognosis, Tumor Microenvironment, and Aggressive Behavior In Vitro and In Vivo of Cervical Cancer.

Background: The incidence of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is increasing in women. S100A10 overexpression is commonly reported in various malignancies and is closely associated with tumor cell characteristics and prognosis. Methods: The expression of S100A10 and its prognostic relevance were assessed utilizing RNA-seq data from The Cancer Genome Atlas. S100A10 regulation of CESC cell growth and migration was investigated using CCK-8, colony-forming, and Transwell-based approaches. Xenograft model mice were used to examine the in vivo effects of S100A10, and differentially expressed genes (DEGs) linked to S100A10 were identified to explore its functional role in oncogenesis. Associations between S100A10 levels, chemosensitivity, and the immune microenvironment were assessed, and the mutational and methylation status of S100A10 was evaluated using the cBioPortal and MethSurv databases, respectively. Results: S100A10 was upregulated in CESC samples, and higher S100A10 mRNA levels were associated in poor prognostic outcomes. The area under the curve for S100A10 when diagnosing CESC was 0.935, and S100A10 was found to regulate tumor cell proliferation and metastasis both in vitro and in vivo. Overall, 1125 DEGs enriched in crucial CESC progression-associated signaling pathways were identified. S100A10 expression was also associated with the intratumoral immune microenvironment and immune checkpoint activity. Patients expressing elevated S100A10 levels exhibited distinct chemotherapeutic susceptibility, and methylation of the S100A10 gene was correlated with patient survival outcomes. Conclusion: In summary, this research demonstrated that S100A10 plays a crucial role in regulating CESC development, prognosis, and the intratumoral immune microenvironment. Thus, S100A10 shows potential as a prognostic or diagnostic tool and as a potential target for CESC immunotherapy.

One Stone, Three Birds: Multifunctional Nanodots as "Pilot Light" for Guiding Surgery, Enhanced Radiotherapy, and Brachytherapy of Tumors.

Surgery, radiotherapy (RT), and brachytherapy are crucial treatments for localized deep tumors. However, imprecise tumor location often leads to issues such as positive surgical margins, extended radiotherapy target volumes, and radiation damage to healthy tissues. Reducing side effects in healthy tissue and enhancing RT efficacy are critical challenges. To address these issues, we developed a multifunctional theranostic platform using Au/Ag nanodots (Au/AgNDs) that act as a "pilot light" for real-time guided surgery, high-efficiency RT, and brachytherapy, achieving a strategy of killing three birds with one stone. First, dual-mode imaging of Au/AgNDs enabled precision RT, minimizing damage to adjacent normal tissue during X-ray irradiation. Au/AgNDs enhanced ionizing radiation energy deposition, increased intracellular reactive oxygen species (ROS) generation, regulated the cell cycle, promoted DNA damage formation, and inhibited DNA repair in tumor cells, significantly improving RT efficacy. Second, in brachytherapy, precise guidance provided by dual-mode imaging addressed challenges related to non-visualization of existing interstitial brachytherapy and multiple adjustments of insertion needle positions. Meanwhile, the effect of brachytherapy was improved. Third, the excellent fluorescence imaging of Au/AgNDs accurately distinguished tumors from normal tissue, facilitating their use as a powerful tool for assisting surgeons during tumor resection. Taken together, our multifunctional theranostic platform offers real-time guidance for surgery and high-efficiency RT, and improves brachytherapy precision, providing a novel strategy and vision for the clinical diagnosis and treatment of cancer.

Habitat visibility affects the behavioral response of a large herbivore to human disturbance in forest landscapes.

Wildlife can perceive humans as predators and human disturbance, whether lethal (e.g., hunting) or non-lethal (e.g., hiking, biking, and skiing), triggers antipredator behavior among prey. Visibility is the property that relates habitat structure to accessibility of visual information that allows animals to detect predators and evaluate predation risk. Thus, the visibility of a habitat (hereafter referred to as habitat visibility) for prey species alters the perceived risk of predation and therefore has a strong influence on their antipredator behavior. Yet, knowledge of how habitat visibility affects the response of animals to different types of human disturbance is limited, partly, because it is challenging to measure habitat visibility for animals at a fine spatial scale over a landscape, particularly in highly heterogeneous landscapes (e.g., forests). In this study, we employed a newly described approach that combines terrestrial and airborne LiDAR to contiguously measure fine-scale habitat visibility in a forested landscape. We applied the LiDAR-derived habitat visibility to examine how habitat visibility in forests affects the summer space use of 20 GPS-collared female red deer (Cervus elaphus) modeled with integrated step-selection functions in the Bavarian Forest National Park, Germany when exposed to various types of human disturbance including recreational activities, forest roads, hiking trails, and hunting. We found that red deer in our study area avoided areas with higher all types of human disturbance, especially during daylight hours. Furthermore, habitat visibility significantly modified the use of space by red deer in response to human recreational activities, forest roads, and hiking trails, but not to the hunting area. Red deer tended to tolerate a higher intensity of human recreational activities and to use areas closer to forest roads or hiking trails when they have lower habitat visibility (i.e., more cover). Our findings highlight the importance of considering visual perception when studying the response of wild animals to human disturbance. We emphasize the potential to mitigate negative consequences of human disturbance on wildlife, through measures such as maintaining vegetative buffers around recreational infrastructure (e.g., roads and skiing tracks) in order to reduce habitat visibility around areas frequented by humans.

Development and validation of prediction model for early warning of ovarian metastasis risk of endometrial carcinoma.

Ovarian metastasis of endometrial carcinoma (EC) patients not only affects the decision of the surgeon, but also has a fatal impact on the fertility and prognosis of patients. This study aimed build a prediction model of ovarian metastasis of EC based on machine learning algorithm for clinical diagnosis and treatment management guidance. We retrospectively collected 536 EC patients treated in Hubei Cancer Hospital from January 2017 to October 2022 and 487 EC patients from Tongji Hospital (January 2017 to December 2020) as an external validation queue. The random forest model, gradient elevator model, support vector machine model, artificial neural network model (ANNM), and decision tree model were used to build ovarian metastasis prediction model for EC patients. The predictive efficacy of 5 machine learning models was evaluated by receiver operating characteristic curve and decision curve analysis. For screening of candidate predictors of ovarian metastasis of EC, the degree of tumor differentiation, lymph node metastasis, CA125, HE4, Alb, LH can be used as a potential predictor of ovarian metastasis prediction model in EC patients. The effectiveness of the prediction model constructed by the 5 machine learning algorithms was between (area under curve [AUC]: 0.729, 95% confidence interval [CI]: 0.674-0.784) and (AUC: 0.899, 95% CI: 0.844-0.954) in the training set and internal verification set, respectively. Among them, the ANNM was equipped with the best prediction effectiveness (training set: AUC: 0.899, 95% CI: 0.844-0.954) and (internal verification set: AUC: 0.892, 95% CI: 0.837-0.947). The prediction model of ovarian metastasis of EC patients based on machine learning algorithm can achieve satisfactory prediction efficiency, among which ANNM is the best, which can be used to guide clinicians in diagnosis and treatment and improve the prognosis of EC patients.

Radiotherapy for extensive-stage small-cell lung cancer in the immunotherapy era.

Currently, chemoimmunotherapy is the first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC). However, only 0.8%-2.5% of the patients presented complete response after chemoimmunotherapy. Considering that ES-SCLC is highly sensitive to radiotherapy, the addition of radiotherapy after first-line treatment for ES-SCLC could further improve local control, which may be beneficial for patients' survival. Prior studies have shown that consolidative thoracic radiotherapy (cTRT) can decrease disease progression and improve overall survival in patients with ES-SCLC who respond well to chemotherapy. However, the efficacy and safety of cTRT in the immunotherapy era remain unclear owing to a lack of prospective studies. Prophylactic cranial irradiation (PCI) has been shown to decrease brain metastasis (BM) and prolong survival in patients with limited-stage SCLC in previous reports. However, according to current guidelines, PCI is not commonly recommended for ES-SCLC. Immunotherapy has the potential to reduce the incidence of BM. Whether PCI can be replaced with regular magnetic resonance imaging surveillance for ES-SCLC in the era of immunotherapy remains controversial. Whole brain radiation therapy (WBRT) is the standard treatment for BM in SCLC patients. Stereotactic radiosurgery (SRS) has shown promise in the treatment of limited BM. Considering the potential of immunotherapy to decrease BM, it is controversial whether SRS can replace WBRT for limited BM in the immunotherapy era. Additionally, with the addition of immunotherapy, the role of palliative radiotherapy may be weakened in patients with asymptomatic metastatic lesions. However, it is still indispensable and urgent for patients with obvious symptoms of metastatic disease, such as spinal cord compression, superior vena cava syndrome, lobar obstruction, and weight-bearing metastases, which may critically damage the quality of life and prognosis. To improve the outcome of ES-SCLC, we discuss the feasibility of radiotherapy, including cTRT, PCI, WBRT/SRS, and palliative radiotherapy with immunotherapy based on existing evidence, which may offer specific prospects for further randomized trials and clinical applications.

Recent Progress of Copper-Based Nanomaterials in Tumor-Targeted Photothermal Therapy/Photodynamic Therapy.

Nanotechnology, an emerging and promising therapeutic tool, may improve the effectiveness of phototherapy (PT) in antitumor therapy because of the development of nanomaterials (NMs) with light-absorbing properties. The tumor-targeted PTs, such as photothermal therapy (PTT) and photodynamic therapy (PDT), transform light energy into heat and produce reactive oxygen species (ROS) that accumulate at the tumor site. The increase in ROS levels induces oxidative stress (OS) during carcinogenesis and disease development. Because of the localized surface plasmon resonance (LSPR) feature of copper (Cu), a vital trace element in the human body, Cu-based NMs can exhibit good near-infrared (NIR) absorption and excellent photothermal properties. In the tumor microenvironment (TME), Cu2+ combines with H2O2 to produce O2 that is reduced to Cu1+ by glutathione (GSH), causing a Fenton-like reaction that reduces tumor hypoxia and simultaneously generates ROS to eliminate tumor cells in conjunction with PTT/PDT. Compared with other therapeutic modalities, PTT/PDT can precisely target tumor location to kill tumor cells. Moreover, multiple treatment modalities can be combined with PTT/PDT to treat a tumor using Cu-based NMs. Herein, we reviewed and briefly summarized the mechanisms of actions of tumor-targeted PTT/PDT and the role of Cu, generated from Cu-based NMs, in PTs. Furthermore, we described the Cu-based NMs used in PTT/PDT applications.

TPM3: a novel prognostic biomarker of cervical cancer that correlates with immune infiltration and promotes malignant behavior in vivo and in vitro.

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) has become increasingly prevalent in younger women. Tropomyosin 3 (TPM3), a thin filament actin-binding protein, has been implicated in various malignancies. In this study, TPM3 expression was evaluated using RNA-seq data from The Cancer Genome Atlas (TCGA), and its relationship with CESC prognosis was examined with receiver operating characteristic (ROC) curves. The effects of TPM3 on cellular proliferation and migration were examined in CESC cell lines using Cell Counting Kit-8 (CCK-8), colony formation, and Transwell assays, while in vivo effects were assessed in mouse xenograft models. Furthermore, differentially expressed genes (DEGs) associated with TPM3 were investigated to determine their tumorigenic functions. Associations between TPM3, chemosensitivity, and immune infiltration were analyzed, as were links between mutations, methylation, and prognosis using the cBioPortal and MethSurv databases. Upregulation of TMP3 mRNA and protein levels was observed in CESC samples, with elevated mRNA levels associated with reduced overall survival. TPM3 showed an area under the curve (AUC) of 0.946 for CESC diagnosis and was found to regulate tumor proliferation and metastasis in vitro and in vivo. Overall, 3099 DEGs were identified and found to be enriched in key CESC progression-related signaling pathways. TPM3 expression was also correlated with intratumoral immune cell infiltration and immune checkpoint activity. Patients with higher TPM3 expression showed distinctive chemosensitivity profiles, and TPM3 gene methylation was linked to poorer CESC patient prognostic outcomes. In conclusion, TPM3 is a key regulator of CESC progression, prognosis, and the tumor immune microenvironment, suggesting its potential as a diagnostic or prognostic biomarker and target for CESC immunotherapy.

Practice patterns of adjuvant radiotherapy in women with stage I to II endometrial carcinoma: a real-world multi-institutional analysis in China.

BACKGROUND: This study aimed to report clinical practice patterns of postoperative radiotherapy for stage I to II endometrial carcinoma (EC) patients treated in 13 Chinese medical centers. METHODS: We included early stage EC patients treated by hysterectomy and adjuvant RT between 2003 and 2017 from 13 institutions. Patients were classified into 4 risk groups based on ESMO-ESGO-ESTRO recommendations (2014). RESULTS: A total of 1,227 cases were analyzed. Along the 15 years of the study, an increasing tendency was found towards administration for vaginal brachytherapy (VBT) alone, while the proportion of external beam pelvic radiotherapy (EBRT) alone remained stable in the corresponding period. When radiation modalities were stratified by risk groups, proportion of VBT alone significantly increased in all risk groups. The higher the risk, the later VBT became the main adjuvant treatment modality. However, EBRT alone or with VBT remained the main adjuvant method for high-risk patients. There were 13 dose-fractionation schemes for VBT alone with the scheme of 30 Gy in 6 fractions prescribed at 0.5cm under the vaginal mucosa accounting for most. There were 17 schemes for VBT boost and the most common schedule was 10 Gy in 2 fractions. The upper 3-5cm part of vagina was the most frequent target. 89.6% of the practitioners performed two-dimensional VBT technique. The median dose for EBRT was 50 Gy. From 2003 to 2017, conventional radiotherapy was gradually replaced by three-dimensional conformal radiotherapy modality and intensity modulated radiotherapy. CONCLUSION: We report a significant shift from EBRT to VBT alone for high-intermediate-risk, intermediate-risk and low-risk EC patients from 2003 to 2017 while EBRT remained the main radiation modality for high-risk early stage patients. There has been remarkable heterogeneity among VBT dose fractionation schedules across China. TRIAL REGISTRATION: The clinical trial ID was ChiCTR-PRC-17010712. It was authorized by the Institutional Review Board of Peking Union Medical College Hospital (N0. S-K139).

Isolation and characterization of porcine epidemic diarrhea virus with a novel continuous mutation in the S10 domain.

Porcine epidemic diarrhea virus (PEDV), which re-emerged in China in 2010, has caused severe economic losses to the global pig industry. In this study, a PEDV strain, designated PEDV WMB, was isolated from piglets with severe diarrhea on a pig farm in Henan Province of China. Whole-genome sequencing and analysis revealed that the PEDV WMB strain belongs to subtype G2c and has a unique continuous mutation in the S10 antigenic epitope of the S protein. Moreover, the virus-neutralization (VN) test indicated that polyclonal antibodies against the S10 protein of other G1 and G2 strains showed reduced VN reactivity to PEDV WMB. The pathogenicity of PEDV WMB was further investigated in 3 day-old piglets. PEDV infection-related clinical symptoms and morphological lesions were observed and confirmed by histopathological and immunohistochemical examination (IHC). These results illustrated that continuous mutation of the S10 epitope might affect the immunogenicity or pathogenicity of PEDV, providing evidence of the need to monitor the genetic diversity of the virus and develop effective measures to prevent and control PEDV.

Combined orthodontic and prosthodontic treatment in an adolescent patient with traumatically ankylosed incisors: A case report.

Symmetric extraction of premolars is a frequently used orthodontic treatment for dental crowding and protrusion. However, when a patient has incisors with ankylosis, the establishment of a treatment protocol often plagues orthodontists. An adolescent patient with a history of incisor trauma sought treatment for dental protrusion and crowding. Upon percussion of his infrapositioned maxillary central incisors, characteristic dull metallic sounds were noted, and a lack of normal mobility of these teeth under the application of external forces was detected. Follow-up radiographs after the trauma showed replacement root resorption of the maxillary central incisors. Based on clinical and radiological findings, ankylosis of the maxillary central incisors was tentatively diagnosed. A combination of orthodontic and prosthodontic treatment options involving extraction of the maxillary central incisors and mandibular first premolars was chosen to resolve the functional and esthetic problems. After treatment, well-aligned dentition, improved smile esthetics, and a more harmonious facial profile were achieved, and these outcomes remained stable during the follow-up period. This case report illustrates a viable treatment strategy for tackling predicaments caused by ankylosed incisors, which is unusual in the literature.