Silencing of the long non-coding RNA LINC00265 triggers autophagy and apoptosis in lung cancer by reducing protein stability of SIN3A oncogene.

Background: Long non-coding RNAs are important regulators in cancer biology and function either as tumor suppressors or as oncogenes. Their dysregulation has been closely associated with tumorigenesis. LINC00265 is upregulated in lung adenocarcinoma and is a prognostic biomarker of this cancer. However, the mechanism underlying its function in cancer progression remains poorly understood. Methods: Here, the regulatory role of LINC00265 in lung adenocarcinoma was examined using lung cancer cell lines, clinical samples, and xenografts. Results: We found that high levels of LINC00265 expression were associated with shorter overall survival rate of patients, whereas knockdown of LINC00265 inhibited proliferation of cancer cell lines and tumor growth in xenografts. Western blot and flow cytometry analyses indicated that silencing of LINC00265 induced autophagy and apoptosis. Moreover, we showed that LINC00265 interacted with and stabilized the transcriptional co-repressor Switch-independent 3a (SIN3A), which is a scaffold protein functioning either as a tumor repressor or as an oncogene in a context-dependent manner. Silencing of SIN3A also reduced proliferation of lung cancer cells, which was correlated with the induction of autophagy. These observations raise the possibility that LINC00265 functions to promote the oncogenic activity of SIN3A in lung adenocarcinoma. Conclusions: Our findings thus identify SIN3A as a LINC00265-associated protein and should help to understand the mechanism underlying LINC00265-mediated oncogenesis.

Taraxasterol exhibits dual biological effects on anti-aging and anti-cancer in lung cells.

As numerous countries around the world have entered an aging society currently, understanding the impact of aging on human health becomes critically important. Notably, aging is associated with increased prevalence of age-related diseases, with the lungs being particularly susceptible. Aging contributes to a decline in lung function, including respiratory disorders, inflammation, and oxidative stress. Therefore, it is a very important to identify and develop active substances that can mitigate lung cell aging. In current study, we evaluated the impact of Taraxasterol on lung cell senescence, showing that Taraxasterol can alleviate lung cell senescence, as evidenced by reductions in senescence-related marker molecules, including p16 and p21. Additionally, Taraxasterol was found to ameliorate inflammation and oxidative stress in lung cells. Further mechanistic studies indicated that Taraxasterol exerts anti-aging effects through the PGC1α/NRF1 signaling pathway in lung cell models. Since aging is also closely related to lung cancer, we also explored the potential anti-tumor effect of taraxasterol. Utilizing non-small cell lung cancer cells (NSCLC) as a model, we systematically study the anti-tumor effect of Taraxasterol both in vivo and in vitro. Our findings suggest that Taraxasterol exhibited anti-cancer effect through EGFR-mediated signaling. Taken together, Taraxasterol shows dual biological activities, offering promising anti-aging and anti-lung cancer benefits.

Radiomics-Based Prediction of Microvascular Invasion Grade in Nodular Hepatocellular Carcinoma Using Contrast-Enhanced Magnetic Resonance Imaging.

Objective: The aim of this study is to develop and verify a magnetic resonance imaging (MRI)-based radiomics model for predicting the microvascular invasion grade (MVI) before surgery in individuals diagnosed with nodular hepatocellular carcinoma (HCC). Methods: A total of 198 patients were included in the study and were randomly stratified into two groups: a training group consisting of 139 patients and a test group comprising 59 patients. The tumor lesion was manually segmented on the largest cross-sectional slice using ITK SNAP, with agreement reached between two radiologists. The selection of radiomics features was carried out using the LASSO (Least Absolute Shrinkage and Selection Operator) algorithm. Radiomics models were then developed through maximum correlation, minimum redundancy, and logistic regression analyses. The performance of the models in predicting MVI grade was assessed using the area under the receiver operating characteristic curve (AUC) and metrics derived from the confusion matrix. Results: There were no notable statistical differences in sex, age, BMI (body mass index), tumor size, and location between the training and test groups. The AP and PP radiomic model constructed for predicting MVI grade demonstrated an AUC of 0.83 (0.75-0.88) and 0.73 (0.64-0.80) in the training group and an AUC of 0.74 (0.61-0.85) and 0.62 (0.48-0.74) in test group, respectively. The combined model consists of imaging data and clinical data (age and AFP), achieved an AUC of 0.85 (0.78-0.91) and 0.77 (0.64-0.87) in the training and test groups, respectively. Conclusion: A radiomics model utilizing-contrast-enhanced MRI demonstrates strong predictive capability for differentiating MVI grades in individuals with nodular HCC. This model could potentially function as a dependable and resilient tool to support hepatologists and radiologists in their preoperative decision-making processes.

Impact of an AI-Based laparoscopic cholecystectomy coaching program on the surgical performance: a randomized controlled trial.

BACKGROUND: Laparoscopic cholecystectomy (LC) is the gold standard for treating symptomatic gallstones but carries inherent risks like bile duct injury (BDI). While critical view of safety (CVS) is advocated to mitigate BDI, its real-world adoption is limited. Additionally, significant variations in surgeon performance impede procedural standardization, highlighting the need for a feasible, innovative, and effective training approach. The aim of this study is to develop an Artificial Intelligence (AI)-assisted coaching program for LC to enhance surgical education and improve surgeon's performance. MATERIALS AND METHODS: We conducted a multi-center, randomized controlled trial from May 2022 to August 2023 to assess the impact of an AI-based coaching program, SmartCoach, on novice performing LC. Surgeons and patients meeting specific inclusion criteria were randomly assigned to either a coaching group with AI-enhanced feedback or a self-learning group. The primary outcome was assessed using the Laparoscopic Cholecystectomy Rating Form (LCRF), with secondary outcomes including surgical safety, efficiency, and adverse events. Statistical analyses were performed using SPSS, with significance set at P-value less than 0.05. RESULTS: Between May 2022 and August 2023, 22 surgeons were initially enrolled from 10 hospitals, with 18 completing the study. No demographic differences were noted between coaching and self-learning groups. In terms of surgical performance (LCRF scores), the coaching group showed significant improvement over time (31 to 40, P=0.008), outperforming the self-learning group by study end (40 vs 38, P=0.032). Significant improvements in CVS achievement were also noted in the coaching group (11% to 78%, P=0.021). Overall, the coaching program was well-received, outpacing traditional educational methods in both understanding and execution of CVS and participants in the intervention group expressed strongly satisfaction with the program. CONCLUSIONS: The AI-assisted surgical coaching program effectively improved surgical performance and safety for novice surgeons in LC procedures. The model holds significant promise for advancing surgical education.

Phytostabilization of Heavy Metals and Fungal Community Response in Manganese Slag under the Mediation of Soil Amendments and Plants.

The addition of soil amendments and plants in heavy metal-contaminated soil can result in a significant impact on physicochemical properties, microbial communities and heavy metal distribution, but the specific mechanisms remain to be explored. In this study, Koelreuteria paniculata was used as a test plant, spent mushroom compost (SMC) and attapulgite (ATP) were used as amendments, and manganese slag was used as a substrate. CK (100% slag), M0 (90% slag + 5% SMC + 5% ATP) and M1 (90% slag + 5% SMC + 5% ATP, planting K. paniculata) groups were assessed in a pilot-scale experiment to explore their different impacts on phytoremediation. The results indicated that adding the amendments significantly improved the pH of the manganese slag, enhancing and maintaining its fertility and water retention. Adding the amendments and planting K. paniculata (M1) significantly reduced the bioavailability and migration of heavy metals (HMs). The loss of Mn, Pb and Zn via runoff decreased by 15.7%, 8.4% and 10.2%, respectively, compared to CK. K. paniculata recruited and enriched beneficial fungi, inhibited pathogenic fungi, and a more stable fungal community was built. This significantly improved the soil quality, promoted plant growth and mitigated heavy metal toxicity. In conclusion, this study demonstrated that the addition of SMC-ATP and planting K. paniculata showed a good phytostabilization effect in the manganese slag and further revealed the response process of the fungal community in phytoremediation.

Vertically Oriented Perovskites with Minimized Intrinsic Boundaries for Efficient Photovoltaics.

Intrinsic boundaries formed by grain stacks of randomly oriented perovskite crystallites seriously restrict charge transport in the resultant photovoltaic devices, whereas direct passivation of these defects remains unexplored, and it is desirable to modulate perovskite growth with uniform orientation. Herein, we report a simple but effective method to regulate perovskite crystallization by employing a volatile and polymerizable monomer of hydroxyethyl methacrylate (HEMA), which can simultaneously interact with both FA+ and Pb2+ via hydrogen and coordination bonding, respectively, to seed perovskite crystallization with accelerated nucleation and retarded crystal growth. Upon thermal annealing, the gradual volatilization and partial self-condensation of the HEMA drive the perovskite growth perpendicularly to the substrate, leading to largely suppressed defect states, improved crystallinity, and a reduced Young's modulus of the perovskite film. As a result, champion efficiencies exceeding 24 and 22% with improved operational and mechanical stability of the optimized perovskite solar cells based on rigid and flexible substrates were finally achieved.

Endothelin-1-mediated Brainstem Glial Activation Produces Asthmatic Airway Vagal Hypertonia Via Enhanced ATP-P2X4 Receptor Signaling in Sprague-Dawley Rats.

The occurrence of major asthma symptoms is largely attributed to airway vagal hypertonia, of which the central mechanisms remain unclear. This study tests the hypotheses that endothelin-1-mediated brainstem glial activation produces asthmatic airway vagal hypertonia via enhanced action of adenosine 5'-triphosphate on neuronal purinergic P2X4 receptors. A rat model of asthma was prepared using ovalbumin. Airway vagal tone was evaluated by the recurrent laryngeal discharge and plethysmographic measurement of pulmonary function. The changes in the brainstem were examined using ELISA, Western blot, luciferin-luciferase, quantitative reverse transcription-polymerase chain reaction, enzyme activity assay and immunofluorescent staining, respectively. The results showed that in the medulla of rats, endothelin receptor type B and P2X4 receptors were primarily expressed in astrocytes and neurons, respectively, and both of which, along with endothelin-1 content, were significantly increased after ovalbumin sensitization. Ovalbumin sensitization significantly increased recurrent laryngeal discharge, which was blocked by acute intracisternal injection of P2X4 receptor antagonist 5-BDBD, knockdown of brainstem P2X4 receptors, and chronic intraperitoneal injection of endothelin receptor type B antagonist BQ788, respectively. Ovalbumin sensitization activated microglia and astrocytes and significantly decreased ecto-5'-nucleotidase activity in the medulla, and all of which, together with the increase of medullary P2X4 receptor expression and decrease of pulmonary function, were reversed by chronic BQ788 treatment. These results demonstrated that in rats, allergic airway challenge activates both microglia and astrocytes in the medulla via enhanced endothelin-1/endothelin receptor type B signaling, which subsequently causes airway vagal hypertonia via augmented adenosine 5'-triphosphate/P2X4 receptor signaling in central neurons of airway vagal reflex.

Effects of high tibial osteotomy compared with unicondylar knee arthroplasty on the surgical site wound infection and pain in patients with medial knee osteoarthritis.

This study aims to comprehensively compare the effects of unicondylar knee arthroplasty (UKA) and high tibial osteotomy (HTO) on wound infection and pain in patients with medial knee osteoarthritis. A computerized search was conducted in Embase, PubMed, Google Scholar, China National Knowledge Infrastructure, Cochrane Library and Wanfang databases, from database inception to October 2023, for studies comparing UKA and HTO for medial knee osteoarthritis. Studies selection, data extraction and study quality evaluation were independently conducted by two researchers. Stata 17.0 software was employed for data analysis. Overall, 10 studies involving 870 patients with medial knee osteoarthritis were included. It was found that the UKA group had significantly lower wound visual analogue scale scores compared to the HTO group (SMD = -0.53, 95%CI: -0.87 to -0.20, p < 0.001). The incidence of wound infection in the UKA group was higher than in the HTO group (OR = 1.92, 95%CI: 0.65-5.69, p = 0.240), and the incidence of complications was lower (OR = 0.89, 95%CI: 0.52-1.54, p = 0.684), though these differences were not statistically significant. This study indicates that UKA is effective in alleviating postoperative wound pain in medial knee osteoarthritis. However, the rates of postoperative wound infection and complications are comparable to those of HTO. Clinicians should consider factors such as patient age and disease severity in making individualized treatment decisions.

Prognostic significance of systemic immune-inflammation index in patients with nonfunction pancreatic neuroendocrine tumor undergoing surgical resection.

PURPOSE: The purpose of our study was to investigate the clinical significance and prognostic role of the systemic immune-inflammation index (SII) in patients who underwent surgical resection for nonfunctioning pancreatic neuroendocrine tumors (pNETs). METHODS: We conducted a retrospective analysis of 364 patients with nonfunctioning pNETs. The association between the SII level and clinical parameters was investigated. The receiver operating characteristic (ROC) curve was used to calculate the optimal SII value. Cox proportional hazard analysis was performed to evaluate the prognostic factors. RESULTS: Our study included 364 patients with nonfunctioning pNETs who underwent surgery. The median age was 51.0 (43.0, 59.3), and 164 (45.1%) were male. The optimal threshold of SII determined by ROC analysis was 523.95. Higher SII levels were significantly associated with older age (p = 0.001), sex (p = 0.011), tumor size (p = 0.032), and tumor grade (p = 0.002). Recurrence was observed in 70 (19.2%) patients following a median follow-up of 98 months. Univariate analysis showed that higher SII (p < 0.0001), tumor size >4 cm (p = 0.015), and G2/G3 grade (p = 0.002) were significantly associated with disease-free survival (DFS). Multivariate analysis revealed that higher SII (HR: 7.35; 95% CI: 3.44, 15.70; p < 0.0001) and G2/G3 grade (HR: 3.11; 95% CI: 1.42, 6.82; p = 0.005) remained significantly associated with tumor recurrence. Furthermore, 46 (12.6%) patients died during the follow-up. Higher SII (HR: 8.43; 95% CI: 3.19, 22.72; p < 0.0001) and G2/G3 grade (HR: 3.16; 95% CI: 1.01, 9.86; p = 0.048) were independent predictors of overall survival (OS) by multivariate analysis. CONCLUSION: In conclusion, our study revealed that a higher SII level was associated with tumor-related features (larger tumor size and advanced grade) and subsequent shorter DFS and OS in patients with nonfunctioning pNETs. These results indicated that the SII could serve as an efficient prognostic biomarker for nonfunctioning pNETs.

Communication in Social Networking Sites on Offline and Online Social Support and Life Satisfaction Among University Students: Tie Strength Matters.

PURPOSE: Use of social networking sites (SNS) is highly prevalent among college and university students. Conflicting findings were found on the effects of SNS use on well-being, and very few studies examined the effects of social interaction with strong ties and weak ties on SNS on online and offline social support. The present study examined the association between social interaction with weak ties and strong ties on SNS and life satisfaction among Chinese college and university students. The mediating role of online social support and offline social support was also examined. METHODS: A cross-sectional survey was conducted among 26,547 students from 30 colleges/universities in Shanxi province, China. RESULTS: Social interaction with strong ties on SNS was associated with increased offline social support but had no significant association with online support. Social interaction with weak ties on SNS was associated with higher level of online support, but lower level of offline social support. Both offline and online social support were associated with life satisfaction. The direct effects of social interaction with strong ties and weak ties on life satisfaction were not significant. Mediation analyses supported the full mediating effect of offline social support in the relationship between social interaction with strong ties and life satisfaction, while online and offline support mediated the relationship between social interaction with weak ties and life satisfaction. DISCUSSION: Social interaction with strong ties and weak ties on the SNS was associated with life satisfaction through different pathways. Interventions to maximize the benefits of SNS use are warranted.

A nomogram to preoperatively predict the aggressiveness of non-functional pancreatic neuroendocrine tumors based on CT features.

OBJECTIVES: To develop a nomogram to predict the aggressiveness of non-functional pancreatic neuroendocrine tumors (NF-pNETs) based on preoperative computed tomography (CT) features. METHODS: This study included 176 patients undergoing radical resection for NF-pNETs. These patients were randomly divided into the training (n = 123) and validation sets (n = 53). A nomogram was developed based on preoperative predictors of aggressiveness of the NF-pNETs which were identified by univariable and multivariable logistic regression analysis. The aggressiveness of NF-pNETs was defined as a composite measure including G3 grading, N+, distant metastases, and/ or disease recurrence. RESULTS: Altogether, the number of patients with highly aggressive NF-pNETs was 37 (30.08 %) and 15 (28.30 %) in the training and validation sets, respectively. Multivariable logistic regression analysis identified that tumor size, biliopancreatic duct dilatation, lymphadenopathy, and enhancement pattern were preoperative predictors of aggressiveness. Those variables were used to develop a nomogram with good concordance statistics of 0.89 and 0.86 for predicting aggressiveness in the training and validation sets, respectively. With a nomogram score of 59, patients with NF-pNETs were divided into low-aggressive and high-aggressive groups. The high-aggressive group had decreased overall survival (OS) and disease-free survival (DFS). Moreover, the nomogram showed good performance in predicting OS and DFS at 3, 5, and 10 years. CONCLUSION: The nomogram integrating CT features helped preoperatively predict the aggressiveness of NF-pNETs and could potentially facilitate clinical decision-making.

From Skin Movement to Wearable Robotics: The Case of Robotic Gloves.

Previous research on wearable robotics focused on developing actuation mechanisms while overlooking influences of skin movement. During finger flexion, skins on the opisthenar and finger back are stretched. Impeding such skin movement will obstruct normal finger motions. In this research, a statistical study on skin movement is proposed and conducted to quantify skin movement on human hands. Results of 30 subjects (15 men and 15 women) reveal that skin at the finger back extends by an average of 29.3 ± 7.2% in fist clenching. Based on this study, design guidelines for robotic gloves are proposed, and nominal strain values at different hand regions are tabulated for references in robotic glove design. To explore the influence of skin movement on wearable robotics, an elastomer-constrained flat tube actuator is proposed based on which two prototype robotic gloves are developed: one with an ergonomic strap interface that has small constraint to skin motion, and the other based on the commonly used fabric glove that is supposed to have large constraint to skin motion. With the same power input to the robotic gloves, the strap-based design achieves a finger motion range of 2.5 times and a gripping force of 4.3 times that of the conventional fabric glove.

Immunogenicity and risk factors for poor humoral immune response to SARS-CoV-2 vaccine in patients with autoimmune hepatitis: a systematic review and meta-analysis.

BACKGROUND: Research on the immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in patients with autoimmune hepatitis (AIH) has produced varied results, and the determinants of the immunological response remain largely elusive. METHODS: A comprehensive search of three primary databases (PubMed, Embase, and Web of Science) yielded pertinent studies on the topic. The data extraction was a collaborative effort among three independent researchers, who subsequently reconvened to validate the key data that were collated. The primary outcomes were the magnitudes of humoral and cellular immune responses to the vaccines. The secondary outcomes were related to factors affecting the humoral immune response post-vaccination. RESULT: Our systematic review incorporated eight studies, and the meta-analysis involved three. The average antibody response rates after one, two, and three doses of the SARS-CoV-2 vaccine were 86%, 82%, and 91%, respectively. Unexpectedly, the antibody concentrations of seropositive patients were markedly lower than those of their healthy counterparts. The cellular immune response rates after two and three vaccine doses were 74% and 56%, respectively. Treatment with mycophenolate mofetil and corticosteroids was associated with a notable decrease in seropositivity [pooled odds ratio (95% confidence interval): 2.62 (2.12-3.25) and 2.4 (1.51-3.82), respectively]. In contrast, azathioprine had no discernable impact on the humoral response. CONCLUSION: In patients with AIH, the immune response to COVID-19 vaccination is attenuated. Specific immunosuppressive agents, such as steroids and MMF, have been found to reduce antibody responses. Recognizing these determinants is foundational to formulating individualized vaccination strategies for patients with AIH. Further research with an emphasis on post-vaccination cellular immunity will be essential to refine the vaccination approaches for this demographic.

Decoding surgical skill: an objective and efficient algorithm for surgical skill classification based on surgical gesture features -experimental studies.

BACKGROUND: Various surgical skills lead to differences in patient outcomes and identifying poorly skilled surgeons with constructive feedback contributes to surgical quality improvement. The aim of the study was to develop an algorithm for evaluating surgical skills in laparoscopic cholecystectomy based on the features of elementary functional surgical gestures (Surgestures). MATERIALS AND METHODS: Seventy-five laparoscopic cholecystectomy videos were collected from 33 surgeons in five hospitals. The phase of mobilization hepatocystic triangle and gallbladder dissection from the liver bed of each video were annotated with 14 Surgestures. The videos were grouped into competent and incompetent based on the quantiles of modified global operative assessment of laparoscopic skills (mGOALS). Surgeon-related information, clinical data, and intraoperative events were analyzed. Sixty-three Surgesture features were extracted to develop the surgical skill classification algorithm. The area under the receiver operating characteristic curve of the classification and the top features were evaluated. RESULTS: Correlation analysis revealed that most perioperative factors had no significant correlation with mGOALS scores. The incompetent group has a higher probability of cholecystic vascular injury compared to the competent group (30.8 vs 6.1%, P =0.004). The competent group demonstrated fewer inefficient Surgestures, lower shift frequency, and a larger dissection-exposure ratio of Surgestures during the procedure. The area under the receiver operating characteristic curve of the classification algorithm achieved 0.866. Different Surgesture features contributed variably to overall performance and specific skill items. CONCLUSION: The computer algorithm accurately classified surgeons with different skill levels using objective Surgesture features, adding insight into designing automatic laparoscopic surgical skill assessment tools with technical feedback.

Clusterin is upregulated by erastin, a ferroptosis inducer and exerts cytoprotective effects in pancreatic adenocarcinoma cells.

Ferroptosis is a novel form of cell death, which is distinguished from apoptosis and necrosis, and characterized by accumulation of lipid-based reactive oxygen species (ROS) in an iron-dependent manner. Erastin, a small molecule, was widely reported to trigger ferroptosis in various kinds of cancer cells, including pancreatic cancer cells by inducing ROS accumulation. However, how erastin treatment exerts cytotoxicity is not still fully understood. In this study, the effects of erastin in causing pancreatic cancer cell death via inducing ferroptosis and apoptosis are investigated. As expected, erastin treatment caused ROS accumulation, increase in iron concentration and non-apoptotic cell death, which is different from that of induced by apoptosis inducer, staurosporine. Interestingly, erastin treatment caused the upregulation of clusterin, which contributes to the regulation of malignant behaviors of pancreatic cancer, including preventing apoptosis and inducing chemoresistance. Without erastin treatment, overexpressed clusterin significantly promoted cell proliferation, which is consistent with its cytoprotective roles. After erastin treatment, overexpressed clusterin decreased erastin-induced ROS accumulation and cell death. By measuring iron concentration, reduced glutathione (GSH) and glutathione peroxidase 4 (GPX4), it is revealed that clusterin caused resistance to erastin-induced ferroptosis potentially via maintaining the enzymatic activity of GPX4, without disturbing GSH amount. Thus, ferroptosis inducer, erastin, may crosstalk with apoptotic cell death via regulating clusterin, indicating a more complex regulatory network between ferroptosis and apoptosis.

Dinaciclib exerts a tumor-suppressing effect via ß-catenin/YAP axis in pancreatic ductal adenocarcinoma.

Dinaciclib, a cyclin-dependent kinase-5 (CDK5) inhibitor, has significant anti-tumor properties. However, the precise mechanism of dinaciclib requires further investigation. Herein, we investigated the anti-tumor functions and molecular basis of dinaciclib in pancreatic ductal adenocarcinoma (PDAC). PDAC and matched para-carcinoma specimens were collected from the patients who underwent radical resection. Immunohistochemistry was performed to assess CDK5 expression. Cell proliferation ability, migration, and invasion were measured using Cell Counting Kit-8, wound healing, and transwell assay, respectively. The cell cycle and apoptosis were assessed using flow cytometry. Gene expression was examined using RNA-seq and quantitative real-time PCR. Protein expression of proteins was measured by western blot analysis and immunofluorescence microscopy. Tumor-bearing mice were intraperitoneally injected with dinaciclib. CDK5 is highly expressed in PDAC. The expression level of CDK5 was significantly related to tumor size, T stage, and the American Joint Committee on Cancer stage. High CDK5 expression can predict poor survival in PDAC patients. In addition, the expression level of CDK5 might be an independent prognostic factor for PDAC patients. Dinaciclib inhibits the growth and motility of PDAC cells and induces apoptosis and cell cycle arrest in the G2/M phase. Mechanistically, dinaciclib down-regulated yes-associated protein (YAP) mRNA and protein expression by reducing ß-catenin expression. Moreover, dinaciclib significantly inhibited PDAC cell growth in vivo . Our findings reveal a novel anti-tumor mechanism of dinaciclib in which it decreases YAP expression by down-regulating ß-catenin at the transcriptional level rather than by activating Hippo pathway-mediated phosphorylation-dependent degradation.

Phase-Pure α-FAPbI3 Perovskite Solar Cells via Activating Lead-Iodine Frameworks.

Narrow bandgap cubic formamidine perovskite (α-FAPbI3) is widely studied for its potential to achieve record­breaking efficiency. However, its high preparation difficulty caused by lattice instability is criticized. A popular strategy for stabilizing the α-FAPbI3 lattice is to replace intrinsic FA+ or I- with smaller ions of MA+, Cs+, Rb+, and Br-, whereas this generally leads to broadened optical bandgap and phase separation. Studies show that ions substitution-free phase-pure α-FAPbI3 can achieve intrinsic phase stability. However, the challenging preparation of high-quality films has hindered its further development. Here, a facile synthesis of high-quality MA+, Cs+, Rb+, and Br--free phase-pure α-FAPbI3 perovskite film by a new solution modification strategy is reported. This enables the activation of lead-iodine (Pb─I) frameworks by forming the coated Pb⋯O network, thus simultaneously promoting spontaneous homogeneous nucleation and rapid phase transition from δ to α phase. As a result, the efficient and stable phase-pure α-FAPbI3 PSC is obtained through a one-step method without antisolvent treatment, with a record efficiency of 23.15% and excellent long-term operating stability for 500 h under continuous light stress.

TSPO is a novel biomarker for prognosis that regulates cell proliferation through influencing mitochondrial functions in HCC.

The disorder of mitochondrial functions plays a key role in oncogenesis. It is known that TSPO (18-kDa translocator protein) lies in a peculiar location at the interface between the mitochondria and the cytosol. TSPO is found in many types of tissues and is associated with multiple cellular processes, including apoptosis, cell proliferation and the regulation of mitochondria. However, the involvement of TSPO in hepatocellular carcinoma (HCC) remains unclear. In this study, we found that TSPO is upregulated in HCC tissue and is associated with poor differentiation and poor survival. Multivariate analyses showed that TSPO was an independent predictive factor for poor prognosis in HCC patients. For the first time, we provided evidence that TSPO knockdown suppressed HCC cell proliferation in vitro. Hence, TSPO knockdown-induced apoptosis by disturbing mitochondrial function by enhancing the formation of reactive oxygen species (ROS) and decreasing the mitochondrial membrane potential (ΔΨm). An assay exploring the underlying mechanism revealed that TSPO knockdown modulated apoptotic regulatory proteins by regulating the ERK signaling pathway. Through a functional assay and an in vivo mouse model, the anti-cancer effect of PK11195, a specific ligand of TSPO, on HCC was revealed. In summary, TSPO may potentially serve as a prognostic biomarker, and TSPO might be a potential therapeutic target for HCC.

An Untethered Soft Robotic Dog Standing and Fast Trotting with Jointless and Resilient Soft Legs.

Soft robots are compliant, impact resistant, and relatively safe in comparison to hard robots. However, the development of untethered soft robots is still a major challenge because soft legs cannot effectively support the power and control systems. Most untethered soft robots apply a crawling or walking gait, which limits their locomotion speed and mobility. This paper presents an untethered soft robot that can move with a bioinspired dynamic trotting gait. The robot is driven by inflatable soft legs designed on the basis of the pre-charged pneumatic (PCP) actuation principle. Experimental results demonstrate that the developed robot can trot stably with the fastest speed of 23 cm/s (0.97 body length per second) and can trot over different terrains (slope, step, rough terrain, and natural terrains). The robotic dog can hold up to a 5.5 kg load in the static state and can carry up to 1.5 kg in the trotting state. Without any rigid components inside the legs, the developed robotic dog exhibits resistance to large impacts, i.e., after withstanding a 73 kg adult (46 times its body mass), the robotic dog can stand up and continue its trotting gait. This innovative robotic system has great potential in equipment inspection, field exploration, and disaster rescue.