Dynamic Regulation of Cell Mechanotransduction through Sequentially Controlled Mobile Surfaces.

The physical properties of nanoscale cell-extracellular matrix (ECM) ligands profoundly impact biological processes, such as adhesion, motility, and differentiation. While the mechanoresponse of cells to static ligands is well-studied, the effect of dynamic ligand presentation with "adaptive" properties on cell mechanotransduction remains less understood. Utilizing a controllable diffusible ligand interface, we demonstrated that cells on surfaces with rapid ligand mobility could recruit ligands through activating integrin α5ß1, leading to faster focal adhesion growth and spreading at the early adhesion stage. By leveraging UV-light-sensitive anchor molecules to trigger a "dynamic to static" transformation of ligands, we sequentially activated α5ß1 and αvß3 integrins, significantly promoting osteogenic differentiation of mesenchymal stem cells. This study illustrates how manipulating molecular dynamics can directly influence stem cell fate, suggesting the potential of "sequentially" controlled mobile surfaces as adaptable platforms for engineering smart biomaterial coatings.

An analysis of health-related quality of life in children and adolescents after parotidectomy based on patient-reported outcomes.

PURPOSE: To assess health-related quality of life (HRQoL) and its influencing factors in these pediatric patients undergoing parotidectomy. METHODS: This was a cross-sectional study that included 37 children and adolescents (≤ 19 years) with parotid gland tumors who were treated in Sichuan Cancer Hospital between January 2006 and November 2021. HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30). The Wilcoxon rank sum test was used to analyze the factors influencing patients' HRQoL. RESULTS: 37 children and adolescents were included in the study, including 22 cases of benign tumors and 15 cases of malignant tumors. All patients underwent surgery, and some patients with malignant tumors received radiotherapy or chemotherapy. Malignancy, permanent facial palsy, and Frey syndrome were associated with worse HRQoL in children and adolescents with parotid gland tumors. Radiotherapy and no cervical lymph node dissection were associated with worse HRQoL in pediatric patients with malignancy. The surgical approach of parotid is not a factor influencing HRQoL. CONCLUSION: Factors associated with HRQoL in children and adolescents with parotid gland tumors include pathological types, permanent facial palsy, and Frey syndrome. In addition, factors affecting patients with malignancy include lateral lymph node dissection and radiotherapy.

The updated surgical steps of gasless transaxillary endoscopic thyroidectomy with neck level and region orientation for thyroid cancer.

Introduction: We previously made a detailed expansion to the gasless transaxillary endoscopic thyroidectomy(GTET) procedure described in the previous literatures. In this study, we optimized the procedure focused on the limitation of the approach in terms of trauma and lymph node dissection and made a comparison with the early procedure. Materials and methods: This paper gave a detailed description of the updated procedure and prospectively collected data about patients with papillary thyroid carcinoma(PTC) performed by the two procedures from December 2020 to April 2023. The differences in surgical outcome, surgical trauma and parathyroid gland(PG) function protection were analyzed. Results: Of the 302 patients, 184 underwent with early procedure(EP), and 118 underwent with updated procedure(UP). The surgical outcomes of operative time, time of thyroidectomy and central neck dissection, blood loss, drainage and postoperative hospital stay were shorter in UP than that of the EP. The mean number of lymph nodes retrieved and weight of dissection lymphatic tissue in the UP were significantly more than that in EP without increasing the mean number of metastatic lymph nodes. Postoperative complications did not differ between the two procedures. The UP had more advantages in the identification and preservation of the superior parathyroid gland, however, it did not improve the preservation in situ of the inferior parathyroid gland. The visual analog scale score for pain and the changes among inflammation factors was lower in the UP. Conclusion: The UP of GTET could perform safely and efficiently while reducing surgical trauma in selected patients.

Characteristics and risk factors of cervical lymph node metastasis in cN0 papillary thyroid microcarcinoma of the isthmus.

The surgical resection range of papillary thyroid microcarcinoma of the isthmus (PTMCI) is controversial, and the guidelines do not fully guide the central lymph node dissection (CLND).We retrospectively studied the comparison of PTMCI (Group A, n = 65 cases) and non-PTMCI (Group B, n = 80 cases). Based on whether central lymph node metastasis (CLNM) was further detected, they were further divided into the PTMCI with CLNM (group C, n = 42 cases), the PTMCI without CLNM (group D, n = 23 cases), the non-PTMCI with CLNM (group E, n = 45 cases), the non-PTMCI without CLNM (group F, n = 35 cases). All patients underwent total thyroidectomy and CLND. The CLNM pathological examination was divided into right recurrent laryngeal nerve superficial lymph nodes (Right VI a), right recurrent laryngeal nerve deep lymph nodes (Right VI b), left VI area lymph nodes (Left VI), prelaryngeal lymph node, and pretracheal lymph node. The extent of lymph node metastasis and risk factors of PTMCI were analyzed by univariate and multivariate analysis. The ROC curve was used to calculate the maximum diameter of the tumor and the Youden index was calculated to analyze the impact of diameter on the risk factors for CLNM in PTMCI. To construct a prediction model of transfer risk of high risk factors by Nomogram, there were significant differences in prelaryngeal lymph nodes (p = 0.034) and pretracheal lymph nodes ( n = 0.035) between group A and group B, and the risk factors of lymph node metastasis were tumor invasion (p = 0.003), multifocality (p = 0.001), and the maximum tumor diameter≧6.5 mm. PTMCI is more prone to metastasis of pretracheal lymph nodes and prelaryngeal lymph nodes, and the presence of tumor invasion, multifocality, and tumor diameter≧6.5 mm are high risk factors for metastasis in PTMCI. According to the prediction model, with all risk factors the risk of cervical lymph node metastasis is up to 90%.

Quantum-enhanced diamond molecular tension microscopy for quantifying cellular forces.

The constant interplay and information exchange between cells and the microenvironment are essential to their survival and ability to execute biological functions. To date, a few leading technologies such as traction force microscopy, optical/magnetic tweezers, and molecular tension-based fluorescence microscopy are broadly used in measuring cellular forces. However, the considerable limitations, regarding the sensitivity and ambiguities in data interpretation, are hindering our thorough understanding of mechanobiology. Here, we propose an innovative approach, namely, quantum-enhanced diamond molecular tension microscopy (QDMTM), to precisely quantify the integrin-based cell adhesive forces. Specifically, we construct a force-sensing platform by conjugating the magnetic nanotags labeled, force-responsive polymer to the surface of a diamond membrane containing nitrogen-vacancy centers. Notably, the cellular forces will be converted into detectable magnetic variations in QDMTM. After careful validation, we achieved the quantitative cellular force mapping by correlating measurement with the established theoretical model. We anticipate our method can be routinely used in studies like cell-cell or cell-material interactions and mechanotransduction.

A Cell Surface-Binding Antibody Atlas Nominates a MUC18-Directed Antibody-Drug Conjugate for Targeting Melanoma.

Recent advances in targeted therapy and immunotherapy have substantially improved the treatment of melanoma. However, therapeutic strategies are still needed for unresponsive or treatment-relapsed patients with melanoma. To discover antibody-drug conjugate (ADC)-tractable cell surface targets for melanoma, we developed an atlas of melanoma cell surface-binding antibodies (pAb) using a proteome-scale antibody array platform. Target identification of pAbs led to development of melanoma cell killing ADCs against LGR6, TRPM1, ASAP1, and MUC18, among others. MUC18 was overexpressed in both tumor cells and tumor-infiltrating blood vessels across major melanoma subtypes, making it a potential dual-compartment and universal melanoma therapeutic target. AMT-253, an MUC18-directed ADC based on topoisomerase I inhibitor exatecan and a self-immolative T moiety, had a higher therapeutic index compared with its microtubule inhibitor-based counterpart and favorable pharmacokinetics and tolerability in monkeys. AMT-253 exhibited MUC18-specific cytotoxicity through DNA damage and apoptosis and a strong bystander killing effect, leading to potent antitumor activities against melanoma cell line and patient-derived xenograft models. Tumor vasculature targeting by a mouse MUC18-specific antibody-T1000-exatecan conjugate inhibited tumor growth in human melanoma xenografts. Combination therapy of AMT-253 with an antiangiogenic agent generated higher efficacy than single agent in a mucosal melanoma model. Beyond melanoma, AMT-253 was also efficacious in a wide range of MUC18-expressing solid tumors. Efficient target/antibody discovery in combination with the T moiety-exatecan linker-payload exemplified here may facilitate discovery of new ADC to improve cancer treatment. SIGNIFICANCE: Discovery of melanoma-targeting antibodies using a proteome-scale array and use of a cutting-edge linker-payload system led to development of a MUC18-targeting antibody-exatecan conjugate with clinical potential for treating major melanoma subtypes.

Patterns of lymph node metastasis in level IIB and contralateral level VI for papillary thyroid carcinoma with pN1b and safety of low collar extended incision for neck dissection in level II.

OBJECTIVE: To explore relevant clinical factors of level IIB and contralateral level VI lymph node metastasis and evaluate the safety of low-collar extended incision (LCEI) for lymph node dissection in level II for papillary thyroid carcinoma (PTC) with pN1b. METHOD: A retrospective analysis was performed on 218 patients with PTC with pN1b who were treated surgically in the Head and Neck Surgery Center of Sichuan Cancer Hospital from September 2021 to May 2022. Data on age, sex, body mass index (BMI), tumor location, maximum tumor diameter, multifocality, Braf gene, T staging, surgical incision style, and lymph node metastasis in each cervical subregion were collected. The chi-square test was used for comparative analysis of relevant factors. All statistical analyses were completed by SPSS 24 software. RESULT: Each subgroup on sex, age, BMI, multifocality, tumor location, extrathyroidal extension, Braf gene, and lymphatic metastasis in level III, level IV, and level V had no significant difference in the positive rate of lymph node metastasis in level IIB (P > 0.05). In contrast, patients with bilateral lateral cervical lymphatic metastasis were more likely to have level IIB lymphatic metastasis than those with unilateral lateral cervical lymphatic metastasis, with a statistically significant difference (P = 0.000). In addition, lymph node metastasis in level IIA was significantly associated with lymph node metastasis in level IIB (P = 0.001). After multivariate analysis, lymph node metastasis in level IIA was independently associated with lymph node metastasis in level IIB (P = 0.010). The LCEI group had a similar lymphatic metastasis number and lymphatic metastasis rate in both level IIA and level IIB as the L-shaped incision group (P > 0.05). There were 86 patients with ipsilateral central lymphatic metastasis (78.2%). Patients with contralateral central lymphatic metastasis accounted for 56.4%. The contralateral central lymphatic metastasis rate was not correlated with age, BMI, multifocality, tumor invasion, or ipsilateral central lymphatic metastasis, and there was no significant difference (P > 0.05). The contralateral central lymphatic metastasis in males was slightly higher than that in females, and the difference was statistically significant (68.2% vs. 48.5%, P = 0.041). CONCLUSION: Lymphatic metastasis in level IIA was an independent predictor of lymphatic metastasis in level IIB. When bilateral lateral cervical lymphatic metastasis or lymph node metastasis of level IIA is found, lymph node dissection in level IIB is strongly recommended. When unilateral lateral cervical lymphatic metastasis and lymphatic metastasis in level IIA are negative, lymph node dissection in level IIB may be performed as appropriate on the premise of no damage to the accessory nerve. LCEI is safe and effective for lymph node dissection in level II. When the tumor is located in the unilateral lobe, attention should be given to contralateral central lymph node dissection because of the high lymphatic metastasis rate.

AMT-562, a Novel HER3-targeting Antibody-Drug Conjugate, Demonstrates a Potential to Broaden Therapeutic Opportunities for HER3-expressing Tumors.

HER3 is a unique member of the EGFR family of tyrosine kinases, which is broadly expressed in several cancers, including breast, lung, pancreatic, colorectal, gastric, prostate, and bladder cancers and is often associated with poor patient outcomes and therapeutic resistance. U3-1402/Patritumab-GGFG-DXd is the first successful HER3-targeting antibody-drug conjugate (ADC) with clinical efficacy in non-small cell lung cancer. However, over 60% of patients are nonresponsive to U3-1402 due to low target expression levels and responses tend to be in patients with higher target expression levels. U3-1402 is also ineffective in more challenging tumor types such as colorectal cancer. AMT-562 was generated by a novel anti-HER3 antibody Ab562 and a modified self-immolative PABC spacer (T800) to conjugate exatecan. Exatecan showed higher cytotoxic potency than its derivative DXd. Ab562 was selected because of its moderate affinity for minimizing potential toxicity and improving tumor penetration purposes. Both alone or in combination therapies, AMT-562 showed potent and durable antitumor response in low HER3 expression xenograft and heterogeneous patient-derived xenograft/organoid models, including digestive system and lung tumors representing of unmet needs. Combination therapies pairing AMT-562 with therapeutic antibodies, inhibitors of CHEK1, KRAS, and tyrosine kinase inhibitor showed higher synergistic efficacy than Patritumab-GGFG-DXd. Pharmacokinetic and safety profiles of AMT-562 were favorable and the highest dose lacking severe toxicity was 30 mg/kg in cynomolgus monkeys. AMT-562 has potential to be a superior HER3-targeting ADC with a higher therapeutic window that can overcome resistance to generate higher percentage and more durable responses in U3-1402-insensitive tumors.

MTX-13, a Novel PTK7-Directed Antibody-Drug Conjugate with Widened Therapeutic Index Shows Sustained Tumor Regressions for a Broader Spectrum of PTK7-Positive Tumors.

Protein tyrosine kinase 7 (PTK7) is a Wnt signaling pathway protein implicated in cancer development and metastasis. When using a potent microtubule inhibitor (Aur0101), PTK7-targeting antibody-drug conjugate (ADC), h6M24-vc0101 (PF-06647020/cofetuzumab pelidotin) is efficacious only in limited tumor types with low response rates in a phase I trial. To improve patient response and to expand responding tumor types, we designed MTX-13, a PTK7-targeting ADC consisting of a novel antibody (Ab13) conjugated to eight molecules of topoisomerase I inhibitor exatecan through T1000, a novel self-immolative moiety. MTX-13 exhibited PTK7-specific cell binding, efficient internalization, and exatecan release to cause cytotoxic activity through DNA damage and apoptosis induction, and a strong bystander killing. MTX-13 displayed potent antitumor activities on cell line-derived xenograft and patient-derived xenograft models from a wide range of solid tumors, significantly outperforming h6M24-vc0101. PTK7 was shown to be an actionable target in small cell lung cancer for which MTX-13 showed complete and durable responses. With a consistent overexpression of PTK7 in squamous cell carcinomas derived from diverse anatomic sites, strong potency of MTX-13 in this group of heterogenous tumors suggested a common treatment strategy. Finally, MTX-13 inhibited tumor growth and metastasis in an orthotopic colon cancer xenograft model. MTX-13 displayed a favorable pharmacokinetic and safety profile in monkeys with the highest non-severely toxic dose (HNSTD) of ≥30 mg/kg, significantly higher than 3-5 mg/kg of HNSTD for h6M24-vc0101. The higher therapeutic index of MTX-13 bodes well for its clinical translation with the potential to expand the responding patient population beyond that of current PTK7-targeting ADCs.

Antibody-Exatecan Conjugates with a Novel Self-immolative Moiety Overcome Resistance in Colon and Lung Cancer.

Antibody-drug conjugates (ADC) using DNA topoisomerase I inhibitor DXd/SN-38 have transformed cancer treatment, yet more effective ADCs are needed for overcoming resistance. We have designed an ADC class using a novel self-immolative T moiety for traceless conjugation and release of exatecan, a more potent topoisomerase I inhibitor with less sensitivity to multidrug resistance (MDR). Characterized by enhanced therapeutic indices, higher stability, and improved intratumoral pharmacodynamic response, antibody-T moiety-exatecan conjugates targeting HER2, HER3, and TROP2 overcome the intrinsic or treatment resistance of equivalent DXd/SN-38 ADCs in low-target-expression, large, and MDR+ tumors. T moiety-exatecan ADCs display durable antitumor activity in patient-derived xenograft and organoid models representative of unmet clinical needs, including EGFR ex19del/T790M/C797S triple-mutation lung cancer and BRAF/KRAS-TP53 double-mutant colon cancer, and show synergy with PARP/ATR inhibitor and anti-PD-1 treatment. High tolerability of the T moiety-exatecan ADC class in nonhuman primates supports its potential to expand the responding patient population and tumor types beyond current ADCs. SIGNIFICANCE: ADCs combining a novel self-immolative moiety and topoisomerase I inhibitor exatecan as payload show deep and durable response in low-target-expressing and MDR+ tumors resistant to DXd/SN-38 ADCs without increasing toxicity. This new class of ADCs has the potential to benefit an additional patient population beyond current options. See related commentary by Gupta et al., p. 817. This article is highlighted in the In This Issue feature, p. 799.

Papillary Thyroid Carcinoma with Extensive Cervical Lymph Node Metastasis and Initial Retropharyngeal Lymph Node Metastasis: A Case Report and Literature Review.

Papillary thyroid carcinoma (PTC) is prone to regional lymph node metastasis, which is more common in central lymph nodes and lateral cervical lymph nodes, and retropharyngeal lymph node metastasis (RLNM) is extremely rare. A male with PTC presented with extensive cervical lymph node metastasis and the initial RLNM. After full evaluation by preoperative imaging examination, the patient underwent total thyroidectomy + left central lymph node dissection + left neck lymph node dissection (II III IV V) + left retropharyngeal tumor resection, and the postoperative recovery was good without recurrence long-term complications, and no local recurrence and metastasis were found during one-year follow-up.

The prognostic role of surgery and a nomogram to predict the survival of stage IV breast cancer patients.

Background: Since numerous retrospective studies and prospective trials have shown divergent results, whether the surgical excision of the primary tumor results in survival benefits for de novo stage IV breast cancer patients is inconclusive. Consequently, we need a prediction model of prognosis, judge the efficiency of breast surgery, and identify the advanced breast cancer patients who would benefit from surgery. Methods: We analyzed the data of 2,747 metastatic breast cancer patients (the surgery group) and 4,508 patients (the non-surgery group) from the Surveillance, Epidemiology, and End Results (SEER) database during 2010-2015. Propensity score matching (PSM) was used to attain a balance between the covariates of both groups. We then assessed the potential risk factors for the breast cancer-specific survival (BCSS) of patients in the non-surgery group by Cox regression and constructed a nomogram to predict BCSS. All the patients were classified into different risk groups based on the median risk score obtained from the nomogram. The hazard ratios of BCSS and overall survival (OS) of patients in the two groups were calculated. Results: After PSM, 2,288 patients severally in the two groups (the surgery group and the non-surgery group) were enrolled in the study. A nomogram incorporating 13 potential risk factors (i.e., age, race, cohabitation status, income, tumor grade, histotype, tumor size, lymph node status, molecular subtype, metastasis to brain, liver, lung, and chemotherapy) was constructed using the data of patients in the non-surgery group. The C statistics for the internal (patients in the non-surgery group) and external (patients in the surgery group) validation of the nomogram were 0.70 [95% confidence interval (CI), 0.69-0.71] and 0.73 (95% CI, 0.72-0.74), respectively. In the low-risk group, patients in the surgery group had lower risks of breast cancer-specific mortality (BCSM) (hazard ratio =0.53; 95% CI, 0.47-0.59; P for interaction =0.014) and overall mortality (OM) (hazard ratio =0.52; 95% CI, 0.46-0.58; P for interaction =0.002) than those in the non-surgery group. Conclusions: Breast surgery might improve the survival of metastatic breast cancer patients in the low-risk group. The established nomogram could provide a reference for clinicians in enabling personalized treatment among advanced breast cancer patients.

Stretchable and self-healable hydrogel artificial skin.

Hydrogels have emerged as promising materials for the construction of skin-like mechanical sensors. The common design of hydrogel-based artificial skin requires a dielectric sandwiched between two hydrogel layers for capacitive sensing. However, such a planar configuration limits the sensitivity, stretchability and self-healing properties. Here, we report the design of single-layer composite hydrogels with bulk capacitive junctions as mechanical sensors. We engineer dielectric peptide-coated graphene (PCG) to serve as homogenously dispersed electric double layers in hydrogels. Any mechanical motions that alter the microscopic distributions of PCG in the hydrogels can significantly change the overall capacitance. We use peptide self-assembly to render strong yet dynamic interfacial interactions between the hydrogel network and graphene. The resulting hydrogels can be stretched up to 77 times their original length and self-heal in a few minutes. The devices can effectively sense strain and pressure in both air and aqueous environments, providing tremendous opportunities for next-generation iontronics.

Elevated Hexose-6-Phosphate Dehydrogenase Regulated by OSMR-AS1/hsa-miR-516b-5p Axis Correlates with Poor Prognosis and Dendritic Cells Infiltration of Glioblastoma.

Objective Glioblastoma (GBM), a type of malignant glioma, is the most aggressive type of brain tumor and is associated with high mortality. Hexose-6-phosphate dehydrogenase (H6PD) has been detected in multiple tumors and is involved in tumor initiation and progression. However, the specific role and mechanism of H6PD in GBM remain unclear. Methods We performed pan-cancer analysis of expression and prognosis of H6PD in GBM using the Genotype-Tissue Expression Project (GTEx) and The Cancer Genome Atlas (TCGA). Subsequently, noncoding RNAs regulating H6PD expression were obtained by comprehensive analysis, including gene expression, prognosis, correlation, and immune infiltration. Finally, tumor immune infiltrates related to H6PD and survival were performed. Results Higher expression of H6PD was statistically significantly associated with an unfavorable outcome in GBM. Downregulation of hsa-miR-124-3p and hsa-miR-516b-5p in GBM was detected from GSE90603. Subsequently, OSMR-AS1 was observed in the regulation of H6PD via hsa-miR-516b-5p. Moreover, higher H6PD expression significantly correlated with immune infiltration of dendritic cells, immune checkpoint expression, and biomarkers of dendritic cells. Conclusions The OSMR-AS1/ miR-516b-5p axis was identified as the highest-potential upstream ncRNA-related pathway of H6PD in GBM. Furthermore, the present findings demonstrated that H6PD blockading might possess antitumor roles via regulating dendritic cell infiltration and immune checkpoint expression.

TJP1, a Membrane-Expressed Protein, is a Potential Therapeutic and Prognostic Target for Lung Cancer.

Objective: Lung cancer is a malignant tumor with the highest mortality rate in the world. It is necessary to develop effective biomarkers for diagnosis or prognostic treatment to improve the survival rate of patients. In this prospective study, we identified a membrane-expressed protein Tight Junction Protein 1 (TJP1), which is an ideal therapeutic target for lung cancer, and demonstrated its role in invasion, migration, and proliferation of lung cancer. Methods: High-throughput monoclonal antibody microarrays were used to screen for differential expression of monoclonal antibodies (mAbs) in lung cancer and normal lung tissue. Differentially expressed antibodies were used to immunoprecipitate their cellular targets to be identified by mass spectrometry. The identified target TJP1 was knocked down to observe the effect of reduced gene expression on lung cancer cell function. Immunohistochemistry on human tumor tissues and The Cancer Genome Atlas (TCGA) database was used to explore the relationship between TJP1 expression in multiple cancer types and patient prognosis. Results: The antibody CL007473 was overexpressed in tumor tissue and its target protein was identified by mass spectrometry and immunofluorescence as TJP1, a membrane-expressed protein. Knockdown of TJP1 in lung cancer cell lines showed that reduced expression of TJP1 could inhibit the invasion and migration of lung cancer cells and inhibit the proliferation of cancer cells, suggesting that membrane-expressed protein TJP1 may be used as a therapeutic target for lung cancer. TCGA database analysis showed that TJP1 was highly expressed in pancreatic cancer (PAAD) tissues compared with normal tissues, and low expression was more beneficial to the prognosis and survival of PAAD patients. Conclusion: Membrane-expressed protein TJP1 may be a good therapeutic and prognostic target for lung cancer and has the potential to be a prognostic biomarker in pancreatic cancer.

An AIEgen/graphene oxide nanocomposite (AIEgen@GO)-based two-stage "turn-on" nucleic acid biosensor for rapid detection of SARS-CoV-2 viral sequence.

The ongoing outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has posed significant challenges in early viral diagnosis. Hence, it is urgently desirable to develop a rapid, inexpensive, and sensitive method to aid point-of-care SARS-CoV-2 detection. In this work, we report a highly sequence-specific biosensor based on nanocomposites with aggregation-induced emission luminogens (AIEgen)-labeled oligonucleotide probes on graphene oxide nanosheets (AIEgen@GO) for one step-detection of SARS-CoV-2-specific nucleic acid sequences (Orf1ab or N genes). A dual "turn-on" mechanism based on AIEgen@GO was established for viral nucleic acids detection. Here, the first-stage fluorescence recovery was due to dissociation of the AIEgen from GO surface in the presence of target viral nucleic acid, and the second-stage enhancement of AIE-based fluorescent signal was due to the formation of a nucleic acid duplex to restrict the intramolecular rotation of the AIEgen. Furthermore, the feasibility of our platform for diagnostic application was demonstrated by detecting SARS-CoV-2 virus plasmids containing both Orf1ab and N genes with rapid detection around 1 h and good sensitivity at pM level without amplification. Our platform shows great promise in assisting the initial rapid detection of the SARS-CoV-2 nucleic acid sequence before utilizing quantitative reverse transcription-polymerase chain reaction for second confirmation.

A Versatile, Incubator-Compatible, Monolithic GaN Photonic Chipscope for Label-Free Monitoring of Live Cell Activities.

The ability to quantitatively monitor various cellular activities is critical for understanding their biological functions and the therapeutic response of cells to drugs. Unfortunately, existing approaches such as fluorescent staining and impedance-based methods are often hindered by their multiple time-consuming preparation steps, sophisticated labeling procedures, and complicated apparatus. The cost-effective, monolithic gallium nitride (GaN) photonic chip has been demonstrated as an ultrasensitive and ultracompact optical refractometer in a previous work, but it has never been applied to cell studies. Here, for the first time, the so-called GaN chipscope is proposed to quantitatively monitor the progression of different intracellular processes in a label-free manner. Specifically, the GaN-based monolithic chip enables not only a photoelectric readout of cellular/subcellular refractive index changes but also the direct imaging of cellular/subcellular ultrastructural features using a customized differential interference contrast (DIC) microscope. The miniaturized chipscope adopts an ultracompact design, which can be readily mounted with conventional cell culture dishes and placed inside standard cell incubators for real-time observation of cell activities. As a proof-of-concept demonstration, its applications are explored in 1) cell adhesion dynamics monitoring, 2) drug screening, and 3) cell differentiation studies, highlighting its potential in broad fundamental cell biology studies as well as in clinical applications.

Chip-Scale In Situ Salinity Sensing Based on a Monolithic Optoelectronic Chip.

Salinity is an indispensable parameter for various applications such as biomedical diagnostics, environmental chemical analysis, marine monitoring, etc. Miniaturized salinity sensors have significant potential in portable applications in various scenarios and designs with highly desirable features of convenience, reliability, economy, and high sensitivity and also the capability of real-time measurements. Herein, we demonstrate a highly refractive index-sensitive sensor based on a microscale III-nitride chip that consists of a light emitter and a photodetector. This highly monolithically integrated chip shows an excellent sensitivity of salinity of 2606 nA/(mol/L) (or 446 nA/%) and a response time of 0.243 s. In addition, wireless communication technologies can be easily integrated with the sensing device, which enables automatic remote control for data collection and postprocessing. Remarkably, a polymer-based antifouling coating on the surface of the sensing chip has been established to significantly improve its long-term stability in mimicked marine water. The demonstrated ultrasensitive, ultracompact, cost-effective, fast response, wireless-compatible, and easy-to-use features endow the current device with a huge potential for in situ salinity sensing under varying environmental conditions.

A Metal-Ion-Incorporated Mussel-Inspired Poly(Vinyl Alcohol)-Based Polymer Coating Offers Improved Antibacterial Activity and Cellular Mechanoresponse Manipulation.

Cobalt (CoII ) ions have been an attractive candidate for the biomedical modification of orthopedic implants for decades. However, limited research has been performed into how immobilized CoII ions affect the physical properties of implant devices and how these changes regulate cellular behavior. In this study we modified biocompatible poly(vinyl alcohol) with terpyridine and catechol groups (PVA-TP-CA) to create a stable surface coating in which bioactive metal ions could be anchored, endowing the coating with improved broad-spectrum antibacterial activity against Escherichia coli and Staphylococcus aureus, as well as enhanced surface stiffness and cellular mechanoresponse manipulation. Strengthened by the addition of these metal ions, the coating elicited enhanced mechanosensing from adjacent cells, facilitating cell adhesion, spreading, proliferation, and osteogenic differentiation on the surface coating. This dual-functional PVA-TP-CA/Co surface coating offers a promising approach for improving clinical implantation outcomes.

FOXN3 is downregulated in osteosarcoma and transcriptionally regulates SIRT6, and suppresses migration and invasion in osteosarcoma.

Forkhead box N3 (FOXN3) has been reported to be downregulated in numerous cancers, including laryngeal, oral squamous cell and hepatocellular carcinomas, and diffuse large B­cell lymphoma. FOXN3 was proposed to serve as a tumor suppressor; however, the function of FOXN3 in osteosarcoma (OS) remains unknown. The present study suggested that FOXN3 was notably downregulated in OS tissues compared with in adjacent normal tissues, and the expression of FOXN3 was negatively correlated with tumor size, metastasis and tumor, node and metastasis stage. Additionally, low expression levels of FOXN3 predicted a poor prognosis of patients with OS. Additionally, the present study revealed that FOXN3 was also downregulated in OS cells. Numerous functional experiments, including colony formation, Cell Counting Kit­8, wound healing and Transwell invasion assays, were performed. The results of the present study revealed that FOXN3 suppressed the proliferation, migration and invasion of OS cells. SIRT6 has been reported to serve a key role in OS; chromatin­immunoprecipitation (ChIP) and quantitative ChIP, as well as a luciferase reporter assay, demonstrated that SIRT6 was transcriptionally regulated by FOXN3. Furthermore, FOXN3 also regulated matrix metalloproteinase­9 secretion via the regulation of SIRT6 expression. The findings of the present study indicated that FOXN3 serves as a tumor suppressor in OS and proposed FOXN3 as a prognostic predictor and a therapeutic target for patients with OS.