Porphyromonas gingivalis lipopolysaccharide regulates cell proliferation, apoptosis, autophagy in esophageal squamous cell carcinoma via TLR4/MYD88/JNK pathway.

The study aimed to explore the impact and potential mechanism of Porphyromonas gingivalis lipopolysaccharide (LPS-PG) on esophageal squamous cell carcinoma (ESCC) cell behavior. ESCC cells from the Shanghai Cell Bank were used, and TLR4, MYD88, and JNK interference vectors were constructed using adenovirus. The cells were divided into six groups: Control, Model, Model + radiotherapy + LPS-PG, Model + radiotherapy + 3-MA, Model + radiotherapy + LPS-PG + 3-MA, and Model + radiotherapy. Various radiation doses were applied to determine the optimal dose, and a radioresistant ESCC cell model was established and verified. CCK8 assay measured cell proliferation, flow cytometry and Hoechst 33258 assay assessed apoptosis, and acridine orange fluorescence staining tested autophagy. Western blot analyzed the expression of LC3II, ATG7, P62, and p-ULK1. Initially, CCK8 and acridine orange fluorescence staining identified optimal LPS-PG intervention conditions. Results revealed that 10 ng/ml LPS-PG for 12 h was optimal. LPS-PG increased autophagy activity, while 3-MA decreased it. LPS-PG + 3-MA group exhibited reduced autophagy. LPS-PG promoted proliferation and autophagy, inhibiting apoptosis in radioresistant ESCCs. LPS-PG regulated TLR4/MYD88/JNK pathway, enhancing ESCC autophagy, proliferation, and radioresistance. In conclusion, LPS-PG, through the TLR4/MYD88/JNK pathway, promotes ESCC proliferation, inhibits apoptosis, and enhances radioresistance by inducing autophagy.

LINC00963 Promotes Cisplatin Resistance in Esophageal Squamous Cell Carcinoma by Interacting with miR-10a to Upregulate SKA1 Expression.

Long non-coding RNA (lncRNA) is associated with a large number of tumor cellular functions together with chemotherapy resistance in a variety of tumors. LINC00963 was identified to regulate the malignant progression of various cancers. However, whether LINC00963 affects drug resistence in esophageal squamous cell carcinoma (ESCC) and the relevant molecular mechanisms have never been reported. This study aims to investigate the effect of LINC00963 on cisplatin resistance in ESCC. After detecting the level of LINC00963 in human esophageal squamous epithelial cells (HET-1 A), ESCC cells (TE-1) and cisplatin resistant cells of ESCC (TE-1/DDP), TE-1/DDP cell line and nude mouse model that interfered with LINC00963 expression were established. Then, the interaction among LINC00963, miR-10a, and SKA1 was clarified by double luciferase and RNA immunoprecipitation (RIP) assays. Meanwhile, the biological behavior changes of TE-1/DDP cells with miR-10a overexpression or SKA1 silencing were observed by CCK-8, flow cytometry, scratch, Transwell, and colony formation tests. Finally, the biological function of the LINC00963/SKA1 axis was elucidated by rescue experiments. LINC00963 was upregulated in TE-1 and TE-1/DDP cell lines. LINC00963 knockdown inhibited SKA1 expression of both cells and impaired tumorigenicity. Moreover, LINC00963 has a target relationship with miR-10a, and SKA1 is a target gene of miR-10a. MiR-10a overexpression or SKA1 silencing decreased the biological activity of TE-1/DDP cells and the expression of SKA1. Furthermore, SKA1 overexpression reverses the promoting effect of LINC00963 on cisplatin resistance of ESCC. LINC00963 regulates TE-1/DDP cells bioactivity and mediates cisplatin resistance through interacting with miR-10a and upregulating SKA1 expression.

3D-printed liquid metal polymer composites as NIR-responsive 4D printing soft robot.

4D printing combines 3D printing with nanomaterials to create shape-morphing materials that exhibit stimuli-responsive functionalities. In this study, reversible addition-fragmentation chain transfer polymerization agents grafted onto liquid metal nanoparticles are successfully employed in ultraviolet light-mediated stereolithographic 3D printing and near-infrared light-responsive 4D printing. Spherical liquid metal nanoparticles are directly prepared in 3D-printed resins via a one-pot approach, providing a simple and efficient strategy for fabricating liquid metal-polymer composites. Unlike rigid nanoparticles, the soft and liquid nature of nanoparticles reduces glass transition temperature, tensile stress, and modulus of 3D-printed materials. This approach enables the photothermal-induced 4D printing of composites, as demonstrated by the programmed shape memory of 3D-printed composites rapidly recovering to their original shape in 60 s under light irradiation. This work provides a perspective on the use of liquid metal-polymer composites in 4D printing, showcasing their potential for application in the field of soft robots.

A Non-Newtonian liquid metal enabled enhanced electrography.

Biopotential signals, like electrocardiography (ECG), electromyography (EMG), and electroencephalography (EEG), can help diagnose cardiological, musculoskeletal and neurological disorders. Dry silver/silver chloride (Ag/AgCl) electrodes are commonly used to obtain these signals. While a conductive hydrogel can be added to Ag/AgCl electrodes to improve the contact and adhesion between the electrode and the skin, dry electrodes are prone to movement. Considering that the conductive hydrogel dries over time, the use of these electrodes often creates an imbalanced skin-electrode impedance and a number of sensing issues in the front-end analogue circuit. This issue can be extended to several other electrode types that are commonly in use, in particular, for applications with a need for long-term wearable monitoring such as ambulatory epilepsy monitoring. Liquid metal alloys, such as eutectic gallium indium (EGaIn), can address key critical requirements around consistency and reliability but present challenges on low viscosity and the risk of leakage. To solve these problems, here, we demonstrate the use of a non-eutectic Ga-In alloy as a shear-thinning non-Newtonian fluid to offer superior performance to commercial hydrogel electrodes, dry electrodes, and conventional liquid metals for electrography measurements. This material has high viscosity when still and can flow like a liquid metal when sheared, preventing leakage while allowing the effective fabrication of electrodes. Moreover, the Ga-In alloy not only has good biocompatibility but also offers an outstanding skin-electrode interface, allowing for the long-term acquisition of high-quality biosignals. The presented Ga-In alloy is a superior alternative to conventional electrode materials for real-world electrography or bioimpedance measurement.

RNF106 aggravates esophageal squamous cell carcinoma progression through LATS2/YAP axis.

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal solid tumors in China, with the 5-year overall survival rate less than 20%. Although the carcinogenic process of ESCC is still not clear, recent studies using whole genomic profiling revealed that dysregulation of Hippo signaling pathway might play important roles in ESCC progression. The ubiquitin-like with PHD and RING finger domain 1 (RNF106) was a modifier of DNA methylation and histone ubiquitination. In this study, we evaluate the oncogenic function of RNF106 in ESCC both in vitro and in vivo. Wound healing and transwell data showed that RNF106 was required for ESCC cell migration and invasion. RNF106 depletion dramatically restrained Hippo signaling targeted gene expression. The bioinformatics analysis displayed that RNF106 was increased in ESCC tumor tissues and related with poor survival in ESCC patients. Mechanistic studies demonstrated that RNF106 was associated with LATS2 and facilitate LATS2 K48-linked ubiquitination and degradation, which subsequently inhibited YAP phosphorylation and promoted YAP oncogenic function in ESCC. Taken together, our study revealed a novel link between RNF106 and Hippo signaling in ESCC, suggesting that RNF106 could be a promising target for ESCC therapy.

LncRNA BCAR4 promotes migration, invasion, and chemo-resistance by inhibiting miR-644a in breast cancer.

BACKGROUND: Metastasis and drug resistance of breast cancer have become a barrier to treating patients successfully. Long noncoding RNAs (lncRNAs) are known as vital players in cancer development and progression.  METHODS: The RT-qPCR were used to detect the gene expression. Colony formation assay, would healing assay, and transwell assay were performed to investigate oncogenic functions of cells. CCK8 assay was used to detect the cell viability. Western blot was applied to detect the protein level. Dual-luciferase reporter assay was used to determine the relationship between molecules. Mouse orthotopic xenograft tumor models were established to evaluate the effects of BCAR4 on tumor growth and metastasis in vivo.  RESULTS: LncRNA BCAR4 was significantly increased in breast cancer patients' tissues and plasma and upregulated in breast cancer cell lines. BCAR4 upregulation was correlated with the TNM stages and decreased after surgical removal of breast tumors. Silencing of BCAR4 suppressed breast cancer cell colony formation, migration, invasion, and xenograft tumor growth and promoted chemo-sensitivity. Mechanistically, BCAR4 facilitates breast cancer migration and invasion via the miR-644a-CCR7 axis of the MAPK pathway. BCAR4 promotes ABCB1 expression indirectly by binding to and down-regulating miR-644a to induce chemo-resistance in breast cancer. CONCLUSIONS: Our findings provide insights into the oncogenic role of BCAR4 and implicate BCAR4 as a potential diagnostic biomarker and a promising therapeutic agent to suppress metastasis and inhibit chemo-resistance of breast cancer.

Electro-mechano responsive elastomers with self-tunable conductivity and stiffness.

Materials with programmable conductivity and stiffness offer new design opportunities for next-generation engineered systems in soft robotics and electronic devices. However, existing approaches fail to harness variable electrical and mechanical properties synergistically and lack the ability to self-respond to environmental changes. We report an electro-mechano responsive Field's metal hybrid elastomer exhibiting variable and tunable conductivity, strain sensitivity, and stiffness. By synergistically harnessing these properties, we demonstrate two applications with over an order of magnitude performance improvement compared to state-of-the-art, including a self-triggered multiaxis compliance compensator for robotic manipulators, and a resettable, highly compact, and fast current-limiting fuse with an adjustable fusing current. We envisage that the extraordinary electromechanical properties of our hybrid elastomer will bring substantial advancements in resilient robotic systems, intelligent instruments, and flexible electronics.

Silver Nanoflakes-Enhanced Anisotropic Hybrid Composites for Integratable Pressure Sensors.

Flexible pressure sensors based on polymer elastomers filled with conductive fillers show great advantages in their applications in flexible electronic devices. However, integratable high-sensitivity pressure sensors remain understudied. This work improves the conductivity and sensitivity of PDMS-Fe/Ni piezoresistive composites by introducing silver flakes and magnetic-assisted alignment techniques. As secondary fillers, silver flakes with high aspect ratios enhance the conductive percolation network in composites. Meanwhile, a magnetic field aligns ferromagnetic particles to further improve the conductivity and sensitivity of composites. The resistivity of the composite decreases sharply by 1000 times within a tiny compression strain of 1%, indicating excellent sensing performance. On the basis of this, we demonstrate an integratable miniature pressure sensor with a small size (2 × 2 × 1 mm), high sensitivity (0.966 kPa-1), and wide sensing range (200 kPa). Finally, we develop a flexible E-skin system with 5 × 5 integratable sensor units to detect pressure distribution, which shows rapid real-time response, high resolution, and high sensitivity.

Short-Term Surgical Outcomes for Lobectomy Between Robot-Assisted Thoracic Surgery and Uniportal Video-Assisted Thoracoscopic Surgery.

Objectives: To evaluate the short-term outcomes of uniportal video-assisted thoracoscopic surgery (UVATS) and Da Vinci robot-assisted thoracoscopic surgery (RATS) in lobectomy and lymph node (LN) dissection. Methods: The two groups of patients with primary non-small cell lung cancer (NSCLC; RATS group, UVATS group) were matched by the propensity score to compare LN dissection and recent clinical outcomes. The results were analyzed by univariate analysis. From November 2020 to November 2021, 412 NSCLC patients (54 RATS and 358 UVATS) from a single institution of the Provincial Hospital affiliated with Shandong First Medical University were included in the analysis. Age, sex, lung lobe, surgical resection scope, solid nodules, and core tumor ratios were matched according to different surgical methods. Results: From November 2020 to November 2021, 412 patients with NSCLC (54 RATS, 358 UVATS) from the Provincial Hospital affiliated with Shandong First Medical University were included in the analysis. According to our matching results, LN dissection was more thorough in the RATS group. Conclusion: RATS has potential advantages over UVATS in radical lung cancer surgery.

Efficacy and Safety of Limertinib (ASK120067) in Patients With Locally Advanced or Metastatic EGFR Thr790Met-Mutated NSCLC: A Multicenter, Single-Arm, Phase 2b Study.

INTRODUCTION: Limertinib (ASK120067) is a newly developed third-generation EGFR tyrosine kinase inhibitor targeting both sensitizing EGFR and EGFR Thr790Met (T790M) mutations. This study aimed to evaluate the efficacy and safety of limertinib in patients with locally advanced or metastatic EGFR T790M-mutated NSCLC. METHODS: This is a single-arm, open-label, phase 2b study conducted at 62 hospitals across the People's Republic of China. Patients with locally advanced or metastatic NSCLC with centrally confirmed EGFR T790M mutations in tumor tissue or blood plasma who progressed after first- or second-generation EGFR tyrosine kinase inhibitors or with primary EGFR T790M mutations were enrolled. Patients received limertinib 160 mg orally twice daily until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) assessed by independent review committee per the Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included disease control rate, progression-free survival (PFS), duration of response (DoR), overall survival, and safety. Safety was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. RESULTS: From July 16, 2019, to March 10, 2021, a total of 301 patients were enrolled and started the treatment of limertinib. All patients entered the full analysis set and safety set. By the data cutoff date on September 9, 2021, 76 (25.2%) remained on treatment. The median follow-up time was 10.4 months (range: 0.3-26.3). On the basis of full analysis set, the independent review committee-assessed ORR was 68.8% (95% confidence interval [CI]: 63.2%-74.0%) and disease control rate was 92.4% (95% CI: 88.8%-95.1%). The median PFS was 11.0 months (95% CI: 9.7-12.4), median DoR was 11.1 months (95% CI: 9.6-13.8), and median OS was not reached (95% CI 19.7 months-not evaluable). Objective responses were achieved across all prespecified subgroups. For 99 patients (32.9%) with central nervous system (CNS) metastases, the ORR was 64.6% (95% CI: 54.4%-74.0%), median PFS was 9.7 months (95% CI: 5.9-11.6), and median DoR was 9.6 months (95% CI: 8.1-15.2). For 41 patients who had assessable CNS lesion, the confirmed CNS-ORR was 56.1% (95% CI: 39.7%-71.5%) and median CNS-PFS was 10.6 months (95% CI: 5.6-not evaluable). In safety set, 289 patients (96.0%) experienced at least one treatment-related adverse event (TRAE), with the most common being diarrhea (81.7%), anemia (32.6%), rash (29.9%), and anorexia (28.2%). Grade ≥3 TRAEs occurred in 104 patients (34.6%), with the most common including diarrhea (13.0%), hypokalemia (4.3%), anemia (4.0%), and rash (3.3%). TRAEs leading to dose interruption and dose discontinuation occurred in 24.6% and 2% of patients, respectively. No TRAE leading to death occurred. CONCLUSIONS: Limertinib (ASK120067) was found to have promising efficacy and an acceptable safety profile for the treatment of patients with locally advanced or metastatic EGFR T790M-mutated NSCLC. CLINICAL TRIAL INFORMATION: NCT03502850.

[Clinical analysis and literature review of six cases of neurogenic pulmonary edema].

OBJECTIVE: To explore the early diagnosis and correct treatment of neurogenic pulmonary edema (NPE) and review the literature. METHODS: Retrospective analysis was performed in six patients diagnosed as NPE who were admitted to the emergency department of Tianjin Third Central Hospital from March 2017 to March 2021. RESULTS: Six patients had acute onset, presenting severe dyspnea and hypoxemia, and obvious wet rales could be heard in both lungs. The white blood cell count (WBC) increased to varying degrees (11-22)×109/L, procalcitonin (PCT) was normal, or slightly increased, sputum bacteriological examination was negative, and oxygenation index was < 200 mmHg (1 mmHg ≈ 0.133 kPa). Chest CT mainly showed patchy or patchy exudation. The lesions were of different sizes and were not distributed according to lobes. By reducing intracranial pressure, ventilator assisted breathing, liquid therapy, anti-infection therapy with antibiotics, nutritional support, all six patients were well and discharged, and no one died of NPE. CONCLUSIONS: NPE has complex condition, acute onset and rapid development. Early diagnosis and correct treatment can improve the success rate of treatment and prognosis of patients with NPE.

Knockdown of DEAD-box 51 inhibits tumor growth of esophageal squamous cell carcinoma via the PI3K/AKT pathway.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent malignancies that seriously threaten people's health worldwide. DEAD-box helicase 51 (DDX51) is a member of the DEAD-box (DDX) RNA helicase family, and drives or inhibits tumor progression in multiple cancer types. AIM: To determine whether DDX51 affects the biological behavior of ESCC. METHODS: The expression of DDX51 in ESCC tumor tissues and adjacent normal tissues was detected by Immunohistochemistry (IHC) analyses and quantitative PCR (qPCR). We knocked down DDX51 in ESCC cell lines by using a small interfering RNA (siRNA) transfection. The proliferation, apoptosis, and mobility of DDX51 siRNA-transfected cells were detected. The effect of DDX51 on the phosphoinositide 3-kinase (PI3K)/AKT pathway was investigated by western blot analysis. A mouse xenograft model was established to investigate the effects of DDX51 knockdown on ESCC tumor growth. RESULTS: DDX51 exhibited high expression in ESCC tissues compared with normal tissues and represented a poor prognosis in patients with ESCC. Knockdown of DDX51 induced inhibition of ESCC cell proliferation and promoted apoptosis. Moreover, DDX51 siRNA-expressing cells also exhibited lower migration and invasion rates. Investigations into the underlying mechanisms suggested that DDX51 knockdown induced inactivation of the PI3K/AKT pathway, including decreased phosphorylation levels of phosphate and tensin homolog, PI3K, AKT, and mammalian target of rapamycin. Rescue experiments demonstrated that the AKT activator insulin-like growth factor 1 could reverse the inhibitory effects of DDX51 on ESCC malignant development. Finally, we injected DDX51 siRNA-transfected TE-1 cells into an animal model, which resulted in slower tumor growth. CONCLUSION: Our study suggests for the first time that DDX51 promotes cancer cell proliferation by regulating the PI3K/AKT pathway; thus, DDX51 might be a therapeutic target for ESCC.

Long noncoding RNA PVT1 promotes breast cancer proliferation and metastasis by binding miR-128-3p and UPF1.

BACKGROUND: Mounting evidence supports that long noncoding RNAs (lncRNAs) have critical roles during cancer initiation and progression. In this study, we report that the plasmacytoma variant translocation 1 (PVT1) lncRNA is involved in breast cancer progression. METHODS: qRT-PCR and western blot were performed to detect the gene and protein expression. Colony formation would healing and transwell assays were used to detect cell function. Dual-luciferase reporter assay and RNA pull-down experiments were used to examine the mechanisms interaction between molecules. Orthotopic mouse models were established to evaluate the influence of PVT1 on tumor growth and metastasis in vivo. RESULTS: PVT1 is significant upregulated in breast cancer patients' plasma and cell lines. PVT1 promotes breast cancer cell proliferation and metastasis both in vitro and in vivo. Mechanistically, PVT1 upregulates FOXQ1 via miR-128-3p and promotes epithelial-mesenchymal transition. In addition, PVT1 binds to the UPF1 protein, thereby inducing epithelial-mesenchymal transition, proliferation and metastasis in breast cancer cells. CONCLUSION: PVT1 may act as an oncogene in breast cancer through binding miR-128-3p and UPF1 and represents a potential target for BC therapeutic development.

Partial Maxwell fish-eye lens inspired by the Gutman lens and Eaton lens for wide-angle beam scanning.

This paper presents a novel two-dimensional (2-D) partial Maxwell fish-eye (PMFE) lens with the capability of wide-angle beam scanning inspired by the Gutman lens and Eaton lens, which is obtained by cutting a part from the 2-D Maxwell fish-eye (MFE) lens along a straight line. In terms of the refractive index profile, the MFE lens is similar to the Gutman lens near the center and the Eaton lens near the edge, respectively. We demonstrate the potential of the PMFE lens in wide-angle beam scanning based on its Gutman-like focusing and Eaton-like rotating characteristics corresponding to different feed points. As an example, a fully metallic PMFE lens antenna in the Ka-band composed of a bed of nails and a series of linearly arranged waveguide feeders is designed and experimentally verified. The measured results reveal wide-angle scanning ranges, especially about ±90° at 36 GHz, low reflections and low mutual couplings. The frequency scanning due to the dispersion of the lens is also discussed.

Effect of miR-132-3p on sepsis-induced acute kidney injury in mice via regulating HAVCR1/KIM-1.

OBJECTIVE: To investigate the effect of miR-132-3p and HAVCR1/kidney injury molecule (KIM)-1 on sepsis-induced acute kidney injury (AKI) in mice. METHODS: One hundred C57BL/6 mice were divided into five groups with 20 mice in each group: the normal group (normal mice), the model group (mice with sepsis), the miR-132-3p mimic group (miR-132-3p overexpression), the oe-HAVCR1/KIM-1 group (HAVCR1/KIM-1 overexpression), and the miR-132-3p mimic + oe-HAVCR1/KIM-1 group. Dual-luciferase reporter assay was performed to verify the targeting relationship between miR-132-3p and HAVCR1/KIM-1. The expressions of miR-132-3p and HAVCR1/KIM-1 in mice' kidneys, the levels of renal function markers, the expressions of apoptosis-associated proteins, the renal cell apoptosis rate, and the inflammatory factors in serum were all examined. RESULTS: We found that miR-132-3p can target HAVCR1/KIM-1 and regulate its expression. Compared with the normal mice, the septic mice exhibited lower miR-132-3p level and higher HAVCR1/KIM-1 level (both P<0.05). Moreover, the septic mice had higher levels of cleaved caspase-3, Bax, blood urea nitrogen, creatinine, tumor necrosis factor-α, interleukin-1ß, and interleukin-6, higher renal cell apoptosis rate, and lower Bcl-2 level than the normal mice (all P<0.05). MiR-132-3p overexpression could improve the renal function of the mice with sepsis and inhibit renal cell apoptosis and inflammatory progression, whereas HAVCR1/KIM1 overexpression exhibited an opposite effect and could block the renal protective effects of miR-132-3p overexpression on the septic mice. CONCLUSION: MiR-132-3p overexpression can inhibit renal cell apoptosis and inflammatory progression via suppressing HAVCR1/KIM-1 expression, thereby exert renal protective effects on mice with sepsis.

HBV Reactivation During the Treatment of Non-Hodgkin Lymphoma and Management Strategies.

Hepatitis B virus reactivation (HBV-R), which can lead to HBV-related morbidity and mortality, is a common and well-known complication that occurs during the treatment of non-Hodgkin lymphoma (NHL) patients with current or past exposure to HBV infection. HBV-R is thought to be closely associated with chemotherapeutic or immunosuppressive therapies. However, immunosuppressive agents such as anti-CD20 antibodies (e.g., rituximab and ofatumumab), glucocorticoids, and hematopoietic stem cell transplantation (HSCT) administered to NHL patients during treatment can cause deep immunodepression and place them at high risk of HBV-R. In this review, we explore the current evidence, the guidelines of several national and international organizations, and the recommendations of expert panels relating to the definition, risk factors, screening and monitoring strategies, whether to use prophylaxis or pre-emptive therapy, and the optimal antiviral agent and duration of antiviral therapy for HBV-R.

Reversible Underwater Adhesion for Soft Robotic Feet by Leveraging Electrochemically Tunable Liquid Metal Interfaces.

Soft crawling robots have potential applications for surveillance, rescue, and detection in complex environments. Despite this, most existing soft crawling robots either use nonadjustable feet to passively induce asymmetry in friction to actuate or are only capable of moving on surfaces with specific designs. Thus, robots often lack the ability to move along arbitrary directions in a two-dimensional (2D) plane or in unpredictable environments such as wet surfaces. Here, leveraging the electrochemically tunable interfaces of liquid metal, we report the development of liquid metal smart feet (LMSF) that enable electrical control of friction for achieving versatile actuation of prismatic crawling robots on wet slippery surfaces. The functionality of the LMSF is examined on crawling robots with soft or rigid actuators. Parameters that affect the performance of the LMSF are investigated. The robots with the LMSF prove capable of actuating across different surfaces in various solutions. Demonstration of 2D locomotion of crawling robots along arbitrary directions validates the versatility and reliability of the LMSF, suggesting broad utility in the development of advanced soft robotic systems.