Bithiophene-Functionalized Infrared Two-Photon Absorption Metal Complexes as Single-Molecule Platforms for Synergistic Photodynamic, Photothermal, and Chemotherapy.

A planar conjugated ligand functionalized with bithiophene and its Ru(II), Os(II), and Ir(III) complexes have been constructed as single-molecule platform for synergistic photodynamic, photothermal, and chemotherapy. The complexes have significant two-photon absorption at 808 nm and remarkable singlet oxygen and superoxide anion production in aqueous solution and cells when exposed to 808 nm infrared irradiation. The most potent Ru(II) complex Ru7 enters tumor cells via the rare macropinocytosis, locates in both nuclei and mitochondria, and regulates DNA-related chemotherapeutic mechanisms intranuclearly including DNA topoisomerase and RNA polymerase inhibition and their synergistic effects with photoactivated apoptosis, ferroptosis and DNA cleavage. Ru7 exhibits high efficacy in vivo for malignant melanoma and cisplatin-resistant non-small cell lung cancer tumors, with a 100 % survival rate of mice, low toxicity to normal cells and low residual rate. Such an infrared two-photon activatable metal complex may contribute to a new generation of single-molecule-based integrated diagnosis and treatment platform to address drug resistance in clinical practice and phototherapy for large, deeply located solid tumors.

Role of carboxysomes in cyanobacterial CO2 assimilation: CO2 concentrating mechanisms and metabolon implications.

Many carbon-fixing organisms have evolved CO2 concentrating mechanisms (CCMs) to enhance the delivery of CO2 to RuBisCO, while minimizing reactions with the competitive inhibitor, molecular O2 . These distinct types of CCMs have been extensively studied using genetics, biochemistry, cell imaging, mass spectrometry, and metabolic flux analysis. Highlighted in this paper, the cyanobacterial CCM features a bacterial microcompartment (BMC) called 'carboxysome' in which RuBisCO is co-encapsulated with the enzyme carbonic anhydrase (CA) within a semi-permeable protein shell. The cyanobacterial CCM is capable of increasing CO2 around RuBisCO, leading to one of the most efficient processes known for fixing ambient CO2 . The carboxysome life cycle is dynamic and creates a unique subcellular environment that promotes activity of the Calvin-Benson (CB) cycle. The carboxysome may function within a larger cellular metabolon, physical association of functionally coupled proteins, to enhance metabolite channelling and carbon flux. In light of CCMs, synthetic biology approaches have been used to improve enzyme complex for CO2 fixations. Research on CCM-associated metabolons has also inspired biologists to engineer multi-step pathways by providing anchoring points for enzyme cascades to channel intermediate metabolites towards valuable products.

The novel oncogenic factor TET3 combines with AHR to promote thyroid cancer lymphangiogenesis via the HIF-1α/VEGF signaling pathway.

BACKGROUND: Lymphangiogenesis has been reported to play crucial roles in the metastasis of thyroid cancer (THCA), but despite the significant research on lymphangiogenesis in THCA, the precise regulatory mechanism remains unclear. METHODS: Public databases including the Cancer Genome Atlas (TCGA), TIMER, and UALCAN were used to analyze and visualize the expression of TET3 and AHR in THCA, and the correlation between these molecules were used by TIMER. Additionally, RT-PCR and Western Blot were performed to determine the mRNA and protein expression of related proteins. Plate colony formation, wound healing, cell cycle, apoptosis, angiogenesis and transwell assay were used to examine the ability of proliferation, movement, lymphangiogenesis, migration and invasion of THCA cells. RESULTS: Analysis of the TCGA database revealed higher expression levels of TET3 and AHR in tumor tissue compared to normal tissue in THCA. Additionally, a strong correlation was observed between TET3 and AHR. UALCAN database demonstrated that high expression of TET3 and AHR was associated with advanced THCA TNM stages in THCA patients. Furthermore, TET3 activation accelerated THCA cell proliferation by inducing G2/M phase arrest and suppressing apoptosis, while AHR inactivation reduced THCA cell proliferation by decreasing G2/M phase arrest and promoting apoptosis in vitro. Notably, both TET3 and AHR significantly enhanced THCA cell lymphangiogenesis, migration and invasion. Moreover, TET3 activation and AHR inactivation regulated HIF-1α/VEGF signaling pathway, which ultimately, blocked the HIF-1α/VEGF in THCA cells and impaired their movement, migration and invasion abilities. CONCLUSIONS: The combined action of TET3 and AHR to promote lymphangiogenesis in THCA through the HIF-1α/VEGF signaling pathway, and targeting them might provide a potential treatment strategy for THCA.

CAFs-derived rho-associated kinase1 mediated EMT to promote laryngeal squamous cell carcinoma metastasis.

BACKGROUND: Cancer-associated fibroblasts (CAFs) play an essential role in tumorigenesis and development of cancers. Nevertheless, the specific molecular mechanism of tumorigenesis and development in Laryngeal squamous cell carcinoma (LSCC) still unknown. METHODS: CAFs, CPFs and NFs were isolated and identified from laryngeal cancer, para-laryngeal cancer and normal tissues. Immunofluorescent staining, Rt-PCR and Western Blot were used to detect the expression of related proteins. Wound healing, migration, invasion and animal experiments were used to examine the ability of movement, migration, invasion and metastasis of LSCC. RESULTS: ROCK1, was highly expressed in CAFs and CAFs enhanced LSCC metastasis in vivo and vitro, and downregulation of ROCK1 in CAFs inhibited the migration and invasion of LSCC cells. While increasing ROCK1 expression in NFs promoted the migration and invasion of LSCC cells. Further studies revealed that epithelial-mesenchymal transition (EMT) and JAK2/STAT3/ERK1/2 pathway might play an essential role in promoting metastasis of LSCC. In addition, inhibition activity of ROCK1 or JAK2/STAT3/ERK1/2 signal molecules significantly reduced EMT and metastasis. CONCLUSIONS: CAFs-derived ROCK1 via JAK2/STAT3/ERK1/2 axis mediated EMT to promote LSCC metastasis and targeting ROCK1 might provide a potential treatment strategy for LSCC.

Dissolved oxygen benefits N-decanoyl-homoserine lactone regulated biological nitrogen removal system to resist acute ZnO nanoparticle exposure.

The beneficial effects of N-decanoyl-homoserine lactone (C10-HSL), one of the typical N-acyl-homoserine lactones on biological nitrogen removal (BNR) system to resist the acute exposure of zinc oxide nanoparticles (ZnO NPs) has attracted extensive attentions. Nevertheless, the potential impact of dissolved oxygen (DO) concentration on the regulatory capacity of C10-HSL in the BNR system has yet to be investigated. This study conducted a systematic investigation of the impact of DO concentration on the C10-HSL-regulated BNR system against short-term ZnO NP exposure. Based on the findings, sufficient DO played a crucial role to improve the BNR system's resistance capacity to ZnO NPs. Under the micro-aerobic condition (0.5 mg/L DO), the BNR system was more sensitive to ZnO NPs. The ZnO NPs induced increased intracellular reactive oxygen species (ROS) accumulation, reduced antioxidant enzyme activities, and decreased specific ammonia oxidation rates in the BNR system. Furthermore, the exogenous C10-HSL had a positive effect on the BNR system's resistance to ZnO NP-induced stress, primarily by decreasing ZnO NPs-induced ROS generation and improving ammonia monooxygenase activities, especially under low DO concentrations. The findings contributed to the theoretical foundation for regulation strategy development of wastewater treatment plants under NP shock threat.

Human papillomavirus and Epstein-Barr virus infection in benign thyroid lesions.

INTRODUCTION: The objective was to investigate the correlation between Epstein-Barr virus (EBV) and human papillomavirus (HPV) infection in the development of benign thyroid lesions. MATERIAL AND METHODS: 29 cases of Hashimoto's thyroiditis (HT), 133 cases of thyroid adenoma, and 34 cases of HT with thyroid adenoma paraffin embedded tissue samples were used for EBV and HPV quantitative detection. RESULTS: None of the tissue samples carried HPV DNA. In HT tissue samples, the positive rate of EBV was 55.2% (16/29). In thyroid adenoma tissue samples, the positive rate was 37.6% (50/133). In HT combined with thyroid adenoma tissue samples, the positive rate of EBV was 67.6% (23/34). There was no correlation between EBV infection and clinical features such as age and gender. CONCLUSION: The occurrence and development of benign thyroid lesions are closely related to EBV infection. HT combined with thyroid adenoma may be more susceptible to EBV infection than simple HT and thyroid adenoma, which provides a new idea for the diagnosis and treatment of benign thyroid lesions.

Identification and validation of an anoikis-related genes signature for prognostic implication in papillary thyroid cancer.

Thyroid cancer, notably papillary thyroid cancer (PTC), is a global health concern with increasing incidence. Anoikis, a regulator of programmed cell death, is pivotal in normal physiology and, when dysregulated, can drive cancer progression and metastasis. This study explored the impact of anoikis on PTC prognosis. Analyzing data from GEO, TCGA, and GeneCards, we identified a prognostic signature consisting of six anoikis-related genes (ARGs): EZH2, PRKCQ, CD36, INHBB, TDGF1, and MMP9. This signature independently predicted patient outcomes, with high-risk scores associated with worse prognoses. A robust predictive ability was confirmed via ROC analysis, and a nomogram achieved a C-index of 0.712. Differences in immune infiltration levels were observed between high- and low-risk groups. Importantly, the high-risk group displayed reduced drug sensitivity and poor responses to immunotherapy. This research provides insights into anoikis in PTC, offering a novel ARG signature for predicting patient prognosis and guiding personalized treatment strategies.

Congenital Anterior Nostril Atresia in Old Age: A Case Report and Literature Review.

Atresia of the anterior nares is usually caused by acquired disorders such as iatrogenic damage, burns, and postoperative scar, but congenital cases are relatively rare. Here, we report a rare case of congenital anterior nostril atresia in an aged person with bilateral nasal congestion and snoring. The patient underwent surgery, and no recurrence was observed after a 2-year follow-up. To increase our understanding on this condition, we performed a literature review and discussed its associated clinical features, differential diagnoses, and treatment methods.

Giant Fibrovascular Polyp of Hypopharynx: A Case Report and Literature Review.

Fibrovascular polyps (FVPs) are rare benign submucosal tumor-like lesions originating in the cervical esophagus and sporadically in the hypopharynx. In this article, we report a rare case of FVPs of the hypopharynx (hFVPs) with a mass measuring 16.0 × 4.0 × 1.8 cm in size, discussed its surgical strategy, and additionally reviewed relevant literature on important factors, such as age, sex, symptoms, size, treatments, and recurrence, associated with hFVPs.

New insights into exogenous N-acyl-homoserine lactone manipulation in biological nitrogen removal system against ZnO nanoparticle shock.

The effects and mechanisms of three N-acyl-homoserine lactones (AHLs) (C4-HSL, C6-HSL, and C10-HSL) on responses of biological nitrogen removal (BNR) systems to zinc oxide nanoparticle (NP) shock were investigated. All three AHLs improved the NP-impaired ammonia oxidation rates by up to 50.0 % but inhibited the denitrification process via regulating nitrogen metabolism-related enzyme activities. C4-HSL accelerated the catalase activity by 13.2 %, while C6-HSL and C10-HSL promoted the superoxide dismutase activity by 26.6 % and 18.4 %, respectively, to reduce reactive oxygen species levels. Besides, the enhancements of tryptophan protein and humic acid levels in tightly-bound extracellular polymeric substance by AHLs were vital for NP toxicity attenuation. The metabonomic analysis demonstrated that all three AHLs up-regulated the levels of lipid- and antioxidation-related metabolites to advance the system's resistance to NP shock. The "dual character" of AHLs emphasized the concernment of legitimately employing AHLs to alleviate NP stress for BNR systems.

Spindle Epithelial Tumor With Thymus-Like Differentiation of Thyroid (SETTLE): A Case Report and Literature Review.

Spindle epithelial tumor with thymus-like differentiation of thyroid (SETTLE) is very rare neoplasm with 2 cellular forms, epithelial cell and spindle cell, and most reported cases have been in young people. An 11-year-old boy presented with painless swelling of the right neck lasting for more than 2 months. A tumor size measuring approximately 3 × 3 cm was resected, and intraoperative frozen pathology suggested a spindle cell tumor, which was confirmed as SETTLE by immunohistochemical staining and external hospital consultation. The immunohistochemical staining profile of the resected tumor tissue was as follows: cytokeratin (CK) (+), smooth muscle actin (weak+), vimentin (+), CK7 (focal+), B-cell lymphoma 2 (partial+), CD99 (-), calcitonin (+), galectin-3 (+), CK19 (+), and Ki-67 (10%+). Ultrasound at 1-year postoperative follow-up revealed no local recurrence of the lesion or lymph node metastasis in the thyroid gland. We summarized the disease characteristics of SETTLE among 6 cases reported to date and found that SETTLE is associated with a good prognosis and low postoperative recurrence rate. Thus, for this type of malignant thyroid tumor, diagnosis depends mainly on postoperative pathology and immunohistochemical staining and simple surgical resection is recommended.

Pluripotency of endogenous AHL-mediated quorum sensing in adaptation and recovery of biological nitrogen removal system under ZnO nanoparticle long-term exposure.

The impacts of quorum sensing (QS) on nanoparticle (NP)-stressed biological nitrogen removal (BNR) system have seldom been addressed yet. In this study, the contributions of endogenous N-acyl-homoserine lactone (AHL)-based QS regulation to the BNR system's adaptation to the zinc oxide (ZnO) NP stress and its recovery potential were systematically investigated. Although 1 mg/L ZnO NPs exerted little impact on the BNR system, chronic exposure to 10 mg/L ones depressed the system's BNR performance which irreversibly impaired the nitrification process even when the system entered the recovery period with no NP added anymore. Meanwhile, ZnO NPs exhibited hormesis effects on the production of AHLs and extracellular polymeric substance (EPS), and activities of superoxide dismutase and catalase. During the ZnO NP exposure period, C4-HSL, C6-HSL, and C10-HSL were discovered to be positively associated with nitrogen removal efficiency, tightly-bound EPS production, and antioxidase activities. Besides, the shifts of Nitrospira, Dechloromonas, Aeromonas, Acinetobacter, Delftia, and Bosea were expected to determine the AHL's dynamic distribution. During the system's recovery stage, Dechloromonas replaced Candidatus_Competibacter as the dominant denitrification-related genus. Dechloromonas abundance elevated with the increased contents of C4-HSL in the aqueous and EPS phases and C10-HSL in EPS and sludge phases, and were expected to promote the activities of BNR-related and antioxidant enzymes, and the EPS production to assist in the recovery of the impaired system's BNR performance. The QS-related BNR genera exhibited higher resilience to ZnO NPs than quorum quenching-related ones, indicating their critical role in nitrogen removal in the restored system. This work provided an insight into the potential pluripotency of AHL-based QS regulation on the ZnO NP-stressed BNR system's adaptation and recovery.

Correlation of mismatch repair deficiency with clinicopathological features and programmed death-ligand 1 expression in thyroid carcinoma.

BACKGROUND: Mutations in DNA mismatch repair (MMR) genes associated with thyroid carcinoma (TC) have rarely been reported, especially in East Asian populations. METHODS: We examined tumor tissue from a cohort of 241 patients diagnosed with TC between 2008 and 2020. MMR proteins were detected using tissue microarray-based immunohistochemistry in order to identify MMR-protein-deficient (MMR-D) and MMR-protein-intact (MMR-I) tumors. We retrospectively summarized the clinicopathologic characteristics of patients with MMR-D TC, measured the expression of PD-L1, and recorded overall survival (OS) and other clinical outcomes. RESULTS: In our cohort, there were 18 (7.5%) MMR-D (MLH1, MSH2, MSH6, and PMS2) patients, including 12 with papillary TC (PTC) (6.7%), 2 with poorly differentiated TC (PDTC) (4.7%), and 4 with anaplastic TC (ATC) (22.2%). Half of them (9/18) showed a specific deletion in MSH6, and 6 of them also carried variants in the MSH6 and PMS2 gene. Survival was significantly better in patients with MMR-D ATC than in those with MMR-I tumors (p = 0.033). Four of the 18 MMR-D patients (22%) were found to be PD-L1 positive. Their OS was much shorter than that of PD-L1-negative patients. CONCLUSIONS: MMR-D and PD-L1 positivity appear to be associated with clinicopathological characteristics and prognosis in TC. The results indicate that MMR status may have important prognostic significance in TC. Therefore, immune checkpoint inhibitors that target the PD-1/PD-L1 pathway may be a treatment option for TCs.

Photobiological production of high-value pigments via compartmentalized co-cultures using Ca-alginate hydrogels.

Engineered cyanobacterium Synechococcus elongatus can use light and CO2 to produce sucrose, making it a promising candidate for use in co-cultures with heterotrophic workhorses. However, this process is challenged by the mutual stresses generated from the multispecies microbial culture. Here we demonstrate an ecosystem where S. elongatus is freely grown in a photo-bioreactor (PBR) containing an engineered heterotrophic workhorse (either ß-carotene-producing Yarrowia lipolytica or indigoidine-producing Pseudomonas putida) encapsulated in calcium-alginate hydrogel beads. The encapsulation prevents growth interference, allowing the cyanobacterial culture to produce high sucrose concentrations enabling the production of indigoidine and ß-carotene in the heterotroph. Our experimental PBRs yielded an indigoidine titer of 7.5 g/L hydrogel and a ß-carotene titer of 1.3 g/L hydrogel, amounts 15-22-fold higher than in a comparable co-culture without encapsulation. Moreover, 13C-metabolite analysis and protein overexpression tests indicated that the hydrogel beads provided a favorable microenvironment where the cell metabolism inside the hydrogel was comparable to that in a free culture. Finally, the heterotroph-containing hydrogels were easily harvested and dissolved by EDTA for product recovery, while the cyanobacterial culture itself could be reused for the next batch of immobilized heterotrophs. This co-cultivation and hydrogel encapsulation system is a successful demonstration of bioprocess optimization under photobioreactor conditions.

Dinuclear osmium complexes as mitochondrion-targeting antitumor photothermal agents in vivo.

Four dinuclear osmium complexes have been constructed for antitumor phototherapy. The most potent Os4 has extremely high photothermal conversion capability under irradiation of an 808 nm low-power laser, targets mitochondria in human melanoma cells without nucleus affinity, and acts as an antitumor photothermal therapy agent in vitro and in vivo.