PSMD9 promotes the malignant progression of hepatocellular carcinoma by interacting with c-Cbl to activate EGFR signaling and recycling.

BACKGROUND: Mounting evidences shows that the ubiquitin‒proteasome pathway plays a pivotal role in tumor progression. The expression of 26S proteasome non-ATPase regulatory subunit 9 (PSMD9) is correlated with recurrence and radiotherapy resistance in several tumor types. However, the role and mechanism of PSMD9 in hepatocellular carcinoma (HCC) progression remain largely unclear. METHODS: PSMD9 was identified as a prognosis-related biomarker for HCC based on analysis of clinical characteristics and RNA-seq data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and the JP Project of the International Cancer Genome Consortium (ICGC-LIRI-JP). PSMD9 expression was analyzed in cancer tissues and adjacent noncancerous tissues via immunohistochemistry and Western blotting. Multiple in vivo and in vitro experimental techniques (such as CCK-8, colony formation, EdU, and Transwell assays; flow cytometry; Western blotting; quantitative RT-PCR; Coimmunoprecipitation assay and immunofluorescence confocal imaging) were used to assess the functions of PSMD9 in the pathogenesis of HCC. RESULTS: We found that the expression of PSMD9 was upregulated and associated with a poor prognosis in HCC patients. PSMD9 promoted HCC cell proliferation, migration, invasion and metastasis. Knockdown of PSMD9 significantly inhibited HCC cell proliferation by inducing G1/S cell cycle arrest and apoptosis. Mechanistically, we demonstrated that PSMD9 promoted HCC cell proliferation and metastasis via direct interaction with the E3 ubiquitin ligase c-Cbl, suppresses EGFR ubiquitination, influenced EGFR endosomal trafficking and degradation and subsequently activated ERK1/2 and Akt signaling. In addition, we showed that PSMD9 knockdown sensitized HCC cells to the tyrosine kinase inhibitor erlotinib in vitro and in vivo. CONCLUSIONS: Collectively, our results indicate that PSMD9 drives HCC progression and erlotinib resistance by suppressing c-Cbl mediated EGFR ubiquitination and therefore can be a potential therapeutic target for HCC.

Tumor-repopulating cells evade ferroptosis via PCK2-dependent phospholipid remodeling.

Whether stem-cell-like cancer cells avert ferroptosis to mediate therapy resistance remains unclear. In this study, using a soft fibrin gel culture system, we found that tumor-repopulating cells (TRCs) with stem-cell-like cancer cell characteristics resist chemotherapy and radiotherapy by decreasing ferroptosis sensitivity. Mechanistically, through quantitative mass spectrometry and lipidomic analysis, we determined that mitochondria metabolic kinase PCK2 phosphorylates and activates ACSL4 to drive ferroptosis-associated phospholipid remodeling. TRCs downregulate the PCK2 expression to confer themselves on a structural ferroptosis-resistant state. Notably, in addition to confirming the role of PCK2-pACSL4(T679) in multiple preclinical models, we discovered that higher PCK2 and pACSL4(T679) levels are correlated with better response to chemotherapy and radiotherapy as well as lower distant metastasis in nasopharyngeal carcinoma cohorts.

Site-Recognition-Induced Structural and Photoluminescent Evolution of the Gold-Pincer Nanocluster.

The induced structural transformation provides an efficient way to precisely modulate the fine structures and the corresponding performance of gold nanoclusters, thus constituting one of the important research topics in cluster chemistry. However, the driving forces and mechanisms of these processes are still ambiguous in many cases, limiting further applications. In this work, based on the unique coordination mode of the pincer ligand-stabilized gold nanocluster Au8(PNP)4, we revealed the site-recognition mechanism for induced transformations of gold nanoclusters. The "open nitrogen sites" on the surface of the nanocluster interact with different inducers including organic compounds and metals and trigger the conversion of Au8(PNP)4 to Au13 and Au9Ag4 nanoclusters, respectively. Control experiments verified the site-recognition mechanism, and the femtosecond and nanosecond transient absorption spectroscopy revealed the electronic and photoluminescent evolution accompanied by the structural transformation.

Avulsion fracture of the anterior superior iliac crest following autograft for anterior lumbar fusion: case report and literature review.

Avulsion fracture of the anterior superior iliac crest (ASIC) following autogenous bone grafting for anterior lumbar fusion (ALF) is an extremely rare complication. We describe a very rare case of avulsion fracture of the ASIC following autograft for ALF in a revision surgery for treating lumbar tuberculosis. A 68-year-old woman with lumbar tuberculosis underwent posterior debridement and posterior iliac crest bone graft fusion; however, her lumbar tuberculosis recurred 9 months after surgery. She then underwent a lumbar revision surgery, including removal of the posterior instrumentation and debridement, followed by anterior L2 corpectomy, debridement, anterior left iliac crest bone graft fusion, and internal fixation. When walking for the first time on postoperative day 3, she experienced a sharp, sudden-onset pain in the anterior iliac crest harvest area. X-ray revealed an avulsion fracture of the ASIC. Considering her failure to respond to conservative treatment for one week and large displacement of the fracture ends, an open reduction and internal fixation surgery was scheduled. Her pain symptoms were significantly relieved after the operation. Although rare, fracture of the ASIC following autograft for ALF should not be ignored. Fracture of the ASIC is usually treated conservatively. Additional surgical treatment is required only when intractable pain fails to respond to conservative treatment or when there is a large displacement of fracture ends that are not expected to heal spontaneously.

Silver dendrite metasurface SERS substrates prepared by photoreduction method for perfluorooctanoic acid detection.

Perfluorooctanoic acid (PFOA), a novel organic pollutant, has been shown to be toxic, persistent, bioaccumulative, long-range transportable, and globally prevalent. This article is based on surface enhanced Raman scattering (SERS) spectroscopy analysis technology. The monolayer of SiO2 was prepared by chemical reduction etching self-assembly method and silver dendrites were grown on it, thus forming the SERS substrate with silver dendrite Metasurface structure with Raman detection enhancement factor up to 2.32 × 105. The prepared silver dendrite Metasurface SERS substrate was applied to the qualitative and quantitative detection of PFOA, with a quantitative detection limit of 15.89 ppb. The results of this paper provide a new, simple, and quick method for the detection of PFOA in the environment.

Anisotropic carrier dynamics and laser-fabricated luminescent patterns on oriented single-crystal perovskite wafers.

Perovskite materials and their applications in optoelectronics have attracted intensive attentions in recent years. However, in-depth understanding about their anisotropic behavior in ultrafast carrier dynamics is still lacking. Here we explore the ultrafast dynamical evolution of photo-excited carriers and photoluminescence based on differently-oriented MAPbBr3 wafers. The distinct in-plane polarization of carrier relaxation dynamics of the (100), (110) and (111) wafers and their out-of-plane anisotropy in a picosecond time scale were found by femtosecond time- and polarization-resolved transient transmission measurements, indicating the relaxation process dominated by optical/acoustic phonon interaction is related to photoinduced transient structure rearrangements. Femtosecond laser two-photon fabricated patterns exhibit three orders of magnitude enhancement of emission due to the formation of tentacle-like microstructures. Such a ultrafast dynamic study carried on differently-oriented crystal wafers is believed to provide a deep insight about the photophysical process of perovskites and to be helpful for developing polarization-sensitive and ultrafast-response optoelectronic devices.

The stage-dependent prognostic role of ARID1A in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death. Although novel treatment currently achieves a better response, the majority of HCC patients develop resistance and cannot benefit. Hence, novel biomarkers for guiding therapy and predicting the prognosis are needed. Methods: Tissue microarrays of 206 HCC patients were used, and ARID1A expression was determined by immunohistochemistry. Databases were used for the verification and expansion of our results. The "rms" package of R software was used for the construction of the nomogram. Results: ARID family alterations were associated with disease-free survival (P=0.0325) and overall survival (OS) (P=0.0076). Subgroup analysis confirmed the prognostic effect of ARID1A, ARID1B, and ARID2 alterations. In addition, ARID family genomic alterations, especially ARID1A, were closely related to poor progression-free survival (ARID: P=0.0011; ARID1A: P=0.0082) and OS (ARID: P=0.0161; ARID1A: P=0.0220) after sorafenib treatment. ARID1A expression was found to display a stage-dependent effect on the prognosis, serving as a risk factor in stage I-II patients (P<0.0001) and a protective factor in stage III-IV patients (P=0.0180). Conclusions: ARID1A has dual roles in HCC in a tumor stage-dependent manner, and further study is required to uncover the complex function of ARID1A in HCC development, disease progression, and therapy.

Robustness of hypofractionated breast radiotherapy after breast-conserving surgery with free breathing.

Purpose: This study aimed to evaluate the robustness with respect to the positional variations of five planning strategies in free-breathing breast hypofractionated radiotherapy (HFRT) for patients after breast-conserving surgery. Methods: Twenty patients who received breast HFRT with 42.72 Gy in 16 fractions were retrospectively analyzed. Five treatment planning strategies were utilized for each patient, including 1) intensity-modulated radiation therapy (IMRT) planning (IMRTpure); 2) IMRT planning with skin flash tool extending and filling the fluence outside the skin by 2 cm (IMRTflash); 3) IMRT planning with planning target volume (PTV) extended outside the skin by 2 cm in the computed tomography dataset (IMRTePTV); 4) hybrid planning, i.e., 2 Gy/fraction three-dimensional conformal radiation therapy combined with 0.67 Gy/fraction IMRT (IMRThybrid); and 5) hybrid planning with skin flash (IMRThybrid-flash). All plans were normalized to 95% PTV receiving 100% of the prescription dose. Six additional plans were created with different isocenter shifts for each plan, which were 1 mm, 2 mm, 3 mm, 5 mm, 7 mm, and 10 mm distally in the X (left-right) and Y (anterior-posterior) directions, namely, (X,Y), to assess their robustness, and the corresponding doses were recalculated. Variation of dosimetric parameters with increasing isocenter shift was evaluated. Results: All plans were clinically acceptable. In terms of robustness to isocenter shifts, the five planning strategies followed the pattern IMRTePTV, IMRThybrid-flash, IMRTflash, IMRThybrid, and IMRTpure in descending order. V 95% of IMRTePTV maintained at 99.6% ± 0.3% with a (5,5) shift, which further reduced to 98.2% ± 2.0% with a (10,10) shift. IMRThybrid-flash yielded the robustness second to IMRTePTV with less risk from dose hotspots, and the corresponding V 95% maintained >95% up until (5,5). Conclusion: Considering the dosimetric distribution and robustness in breast radiotherapy, IMRTePTV performed best at maintaining high target coverage with increasing isocenter shift, while IMRThybrid-flash would be adequate with positional uncertainty<5 mm.

Novel 1,8-Naphthalimide Derivatives As Antitumor Agents and Potent Demethylase Inhibitors.

Functional 1,8-naphthalimide derivatives are rapidly developing in the field of anticancer research. Herein, we designed and synthesized a series of naphthalimide derivatives with different substituents. Interestingly, 1,8-naphthalimide derivatives 1 and 7 inhibited a human demethylase FTO (the fat mass and obesity-associated protein). Computer simulation studies further indicated that 1 and 7 entered the FTO's structural domain II binding pocket through hydrophobic and hydrogen bonding interactions. Anticancer mechanism studies showed that 1 and 7 induced DNA damage and autophagic cell death in A549 cells. The high antiproliferative activity of 1 and 7 was further confirmed by 3D multicellular A549 tumor spheroid assays. This study focuses on the cytotoxicity and mode of action of naphthalimide derivatives, which not only have potential anticancer activity but also are potent demethylase inhibitors.

RIT1 regulates mitosis and promotes proliferation by interacting with SMC3 and PDS5 in hepatocellular carcinoma.

BACKGROUND: As a small G protein of Ras family, Ras-like-without-CAAX-1 (RIT1) plays a critical role in various tumors. Our previous study has demonstrated the involvement of RIT1 in promoting malignant progression of hepatocellular carcinoma (HCC). However, its underlying mechanism remains unclear. METHODS: Gene set enrichment analysis (GSEA) was conducted in the TCGA LIHC cohort to investigate the underlying biological mechanism of RIT1. Live cell imaging, immunofluorescence (IF) and flow cytometry assays were used to verify biological function of RIT1 in HCC mitosis. Subcutaneous xenografting of human HCC cells in BALB/c nude mice was utilized to assess tumor proliferation in vivo. RNA-seq, co-immunoprecipitation (Co-IP), mass spectrometry analyses, western blot and IF assays were employed to elucidate the mechanisms by which RIT1 regulates mitosis and promotes proliferation in HCC. RESULTS: Our findings demonstrate that RIT1 plays a crucial role in regulating mitosis in HCC. Knockdown of RIT1 disrupts cell division, leading to G2/M phase arrest, mitotic catastrophe, and apoptosis in HCC cells. SMC3 is found to interact with RIT1 and knockdown of SMC3 attenuates the proliferative effects mediated by RIT1 both in vitro and in vivo. Mechanistically, RIT1 protects and maintains SMC3 acetylation by binding to SMC3 and PDS5 during mitosis, thereby promoting rapid cell division and proliferation in HCC. Notably, we have observed an upregulation of SMC3 expression in HCC tissues, which is associated with poor patient survival and promotion of HCC cell proliferation. Furthermore, there is a significant positive correlation between the expression levels of RIT1, SMC3, and PDS5. Importantly, HCC patients with high expression of both RIT1 and SMC3 exhibit worse prognosis compared to those with high RIT1 but low SMC3 expression. CONCLUSIONS: Our findings underscore the crucial role of RIT1 in regulating mitosis in HCC and further demonstrate its potential as a promising therapeutic target for HCC treatment.

Syntaxin-6 promotes the progression of hepatocellular carcinoma and alters its sensitivity to chemotherapies by activating the USF2/LC3B axis.

Syntaxin-6 (STX6), a protein of the syntaxin family, is located in the trans-Golgi network and is involved in a variety of intracellular membrane transport events. STX6 is overexpressed in different human malignant tumors. However, little is known about its exact function and molecular mechanism in hepatocellular carcinoma (HCC). In this study, we found that the expression of STX6 was significantly increased in HCC tissues and was associated with poor survival. Gain- and loss-of-function experiments showed that STX6 promotes cell proliferation and metastasis of HCC cells both in vitro and in vivo. Mechanistically, STX6 was negatively regulated by the upstream stimulatory factor 2 (USF2). In addition, STX6 facilitates the association of autophagosomes with lysosomes. Importantly, we demonstrated that STX6 overexpression, despite enhanced resistance to lenvatinib, sensitizes HCC cells to the autophagy activator rapamycin. This study revealed that, under the control of USF2, STX6 accelerates the degradation of microtubule-associated protein 1 light chain 3 beta (LC3) by promoting autophagic flux, ultimately promoting HCC progression. Collectively, we suggest that the USF2-STX6-LC3B axis is a potential therapeutic target in liver cancer.

Simultaneous and Sequential Use of Molecular Targeted Agents Plus Immune Checkpoint Inhibitors for Advanced Hepatocellular Carcinoma: A Real-World Practice in China.

Purpose: Molecular targeted agents (MTAs) plus immune checkpoint inhibitors (ICIs) treatment for advanced hepatocellular carcinoma (HCC) has shown an exciting prospect. This study aimed to report the efficacy of the Simultaneous and Sequential use of them in a real-world practice. Patients and Methods: From April 2019 to December 2020, patients with advanced HCC in three Chinese medical centers receiving MTAs and ICIs as their initial systemic therapy were enrolled. Participants were classified into the Simultaneous group (treated with them simultaneously) and the Sequential group (treated with MTAs initially and added ICIs after tumor progression). Toxicity, tumor response, survival outcomes and prognostic factors were investigated. Results: One hundred and ten consecutive patients participated in the study (64 in the Simultaneous group and 46 in the Sequential group). A total of 93 (84.5%) patients experienced treatment-related adverse events (AEs), of which 55 (85.9%) in the Simultaneous group and 38 (82.6%) in the Sequential group (P=0.19). Grade 3/4 AEs were observed in 9 (8.2%) patients. Patients in the Simultaneous group achieved a higher objective response rate than those in the Sequential group (25.0% vs 4.3%, p=0.04). The median overall survival (OS) of the entire cohort was 14.8 [95% confidence interval (CI): 4.6-25.5] months and the OS rates at 6 and 12 months were 80.6% and 60.9%, respectively. Patients in the Simultaneous group achieved better survival outcomes than those in the Sequential group, but without statistically significant differences. Child-Pugh 6 scores (HR: 2.97, 95% CI: 1.33-6.61, P=0.008), tumor number ≤3 (HR: 0.18, 95% CI: 0.04-0.78, P=0.022), extrahepatic metastasis (HR: 3.05, 95% CI: 1.35-6.87, P=0.007) were independent prognostic factors for survival. Conclusion: The combined treatment of MTAs and ICIs shows good tumor response and survival outcomes with acceptable toxicity for advanced HCC in the real-world practice, in particular when they are applied simultaneously.

Drug Repurposing Flubendazole to Suppress Tumorigenicity via PCSK9-dependent Inhibition and Potentiate Lenvatinib Therapy for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most lethal malignant cancers across the world. It has a poor prognosis and lacks effective therapies, especially for patients with advanced-stage cancer, indicating an urgent need for new therapies and novel therapeutic targets. Here, by screening the U.S. Food and Drug Administration drug library against HCC cell lines, we identified that flubendazole, a traditional anthelmintic drug, could prominently suppress HCC cells in vivo and in vitro. RNA sequence analysis and cellular thermal shift assays showed that flubendazole reduced the expression of PCSK9 protein by direct targeting. The increased expression of PCSK9 in HCC tissues was demonstrated to be correlated with poor prognosis, and the inhibitory ability of flubendazole was selectively dependent on PCSK9 expression. PCSK9 knockdown abolished the antitumor effects of flubendazole in HCC. Mechanistically, flubendazole inhibited the Hedgehog signaling pathway induced by PCSK9, resulting in the downregulation of smoothened (SMO) and GLI Family Zinc Finger 1 (Gli1). Moreover, combining flubendazole with lenvatinib was found more effective than administering lenvatinib only for HCC treatment in vivo and in vitro. These findings reveal the therapeutic potential of flubendazole against HCC and provide clues on new repurposed drugs and targets for cancer treatment.

Microstructure and Mechanical Properties of Gradient Nanostructured Q345 Steel Prepared by Ultrasonic Severe Surface Rolling.

In this work, ultrasonic severe surface rolling (USSR), a new surface nanocrystallization technique, is used to prepare gradient nanostructure (GNS) on the commercial Q345 structural steel. The microstructure of the GNS surface layer is characterized by employing EBSD and TEM, and the result indicates that a nanoscale substructure is formed at the topmost surface layer. The substructures are composed of subgrains and dislocation cells and have an average size of 309.4 nm. The GNS surface layer after USSR processing for one pass has a thickness of approximately 300 µm. The uniaxial tensile measurement indicates that the yield strength of the USSR sample improves by 25.1% compared to the as-received sample with slightly decreased ductility. The nanoscale substructure, refined grains, high density of dislocations, and hetero-deformation-induced strengthening are identified as responsible for the enhanced strength. This study provides a feasible approach to improving the mechanical properties of structural steel for wide applications.

Nitrous oxide emissions from tea plantations: A review.

Tea plantations are an important N2O source. Fertilizer-induced N2O emission factors of tea plantations are much higher than other upland agricultural ecosystems. According to the basic information on characteristics and knowledge of N2O emissions from tea plantations around the world, we comprehensively reviewed N2O emission characteristics, production process, influencing factors, and reduction measures from tea plantations. The global means of ambient N2O emission and N2O emission stimulated by nitrogen fertilizer application from tea plantations were (2.68±2.92) kg N·hm-2 and (11.29±9.45) kg N·hm-2, respectively. The fertilizer-induced N2O emission factor in tea plantations (2.2%±2.1%) was much higher than the IPCC-estimated N2O emission factor for agricultural land (1%). N2O emission from tea plantation soil (a typical acid soil) were mainly produced during nitrification and denitrification, with denitrification being dominant. N2O emission from tea plantations were significantly related to the amount of fertilizer application. Other factors, such as fertilizer type, could also affect soil N2O emissions in tea plantations. The main reduction methods of N2O emission from tea plantations included optimizing the amount and type of fertilizer, amending biochar, and rationally using nitrification inhibitors. In future, we should strengthen in-situ observations of soil N2O emission from tea plantations at both temporal and spatial scales, combine lab incubation and field studies to elucidate the mechanisms underling tea plantation soil N2O emissions, and use a data-model fusion approach to reduce uncertainties in the estimation of global N2O emission. These would provide theoretical support and practical guidance for reasonable N2O emission reduction in tea plantations.

AKR1C3 suppresses ferroptosis in hepatocellular carcinoma through regulation of YAP/SLC7A11 signaling pathway.

AKR1C3 is frequently overexpressed and it is a validated therapeutic target in various tumors including hepatocellular carcinoma (HCC). Our previous study showed that AKR1C3 facilitated HCC proliferation and metastasis by forming a positive feedback loop of AKR1C3-NF-κB-STAT3. Ferroptosis is a form of iron-dependent cell death driven by iron-dependent accumulation of lipid reactive oxygen species and plays an important role in tumor suppression. However, little is known about the role of AKR1C3 in ferroptosis susceptibility. In this study, we found that knockdown of AKR1C3 potently enhanced the sensitivity of HCC cells to ferroptosis inducers both in vitro and in vivo. Overexpression of AKR1C3 protected against ferroptosis in HCC cells. Mechanistically, AKR1C3 regulated ferroptosis through YAP/SLC7A11 signaling in HCC. AKR1C3 knockdown led to a decrease in YAP nuclear translocation, resulted in the inhibition of cystine transporter SLC7A11, and a subsequent increase in the intracellular levels of ferrous iron and ultimately ferroptosis. Moreover, we found that the combination of AKR1C3 and SLC7A11 was a strong predictor of poor prognosis in HCC. Collectively, these findings identify a novel role of AKR1C3 in ferroptosis, and highlighting a candidate therapeutic target to potentially improve the effect of ferroptosis-based antitumor therapy.

Efficacy and safety of immune checkpoint inhibitors with or without radiotherapy in metastatic non-small cell lung cancer: A systematic review and meta-analysis.

Background and purpose: Although immune checkpoint inhibitors (ICIs) have become the first-line treatment for metastatic non-small cell lung cancer (mNSCLC), their efficacy is limited. Meanwhile, recent reports suggest that radiotherapy (RT) can activate the systemic antitumor immune response by increasing the release of antigens from tumor tissues. Therefore, in patients with mNSCLC treated with ICIs, investigations were performed to determine whether the addition of RT improved the outcomes. Furthermore, the adverse events rate was evaluated. Methods and materials: Pubmed, Embase, and Cochrane Library were searched using the keywords "radiotherapy," "immune checkpoint inhibitors," and "non-small cell lung cancer" from the date of inception to 2 May 2022. Randomized controlled trials (RCTs) and nonRCTs (NRCTs) comparing the efficacy and safety of RT combined with ICIs versus ICIs alone in metastatic NSCLC were assessed. The primary outcomes were progression-free survival (PFS) and overall survival (OS), and the secondary outcomes were abscopal response rate (ARR), abscopal control rate (ACR), adverse events rate, and pneumonia rate. The analyses were conducted using the Mantel-Haenszel fixed-effects or random-effects model. The I2 statistic was used to determine heterogeneity, whereas funnel plots and Egger's test were used to assess publication bias. Results: In 15 clinical studies, 713 patients received RT combined with ICIs and 1,275 patients received only ICIs. With regard to PFS and OS, the hazard ratios of RT combined with ICIs were 0.79 (0.70, 0.89) and 0.72 (0.63, 0.82), respectively. In terms of ARR and ACR, the odds ratios (ORs) of RT combined with ICIs were 1.94 (1.19, 3.17) and 1.79 (1.08, 2.97), respectively. Subgroup analyses based on study type (RCT/NRCT), RT target (intracranial/extracranial), number of RT sites (single site), previous ICI resistance (yes/no), and sequencing of RT and ICIs (concurrent/post-RT ICIs) revealed that the addition of RT significantly prolonged PFS and OS. However, subgroup analyses based on radiation dose/fractionation indicated that the addition of hypofractionated RT significantly prolonged OS but not PFS. When grouped according to the level of PD-L1 expression, the addition of RT prolonged PFS only in patients who were PD-L1-negative. Furthermore, subgroup analyses of ARR and ACR signified that the combination therapy resulted in better local control of lesions outside the irradiation field in the hypofractionated RT, extracranial RT, and ICI-naïve subgroups. In terms of adverse events, the addition of RT did not significantly increase the adverse events rate but was associated with a higher pneumonia rate [OR values were 1.24 (0.92, 1.67) and 1.76 (1.12, 2.77), respectively]. Conclusion: Meta-analysis of existing data suggests that the addition of RT can significantly prolong PFS and OS in patients with metastatic NSCLC receiving ICIs. In addition to lesions in the irradiation field, RT can improve the local control rate of lesions outside the irradiation field via immune activation. Combination therapy does not increase the overall risk of adverse reactions, except for pneumonia.

Polymer-Assisted Compressed Flux Growth: A Universal and High-Yield Method for Dimension-Controlled Single Crystals.

Single crystals possess the most perfect and stable morphology and represent the intrinsic and upper limits of performance when integrated into various application scenarios. However, for a large portion of the newly emerging low-dimensional and molecular materials, the mass production of crystals with a desirable shape is still challenging. Here, a universal and high-yield method to grow functional single crystals with controlled dimensions is provided that can be directly integrated into a device. By utilizing a polymeric flux in combination with a compressed growth space, numerous materials can be grown into size-controllable single crystalline flakes, with millions produced in one batch. This scalable growth method shows promise for the large-scale integration of micro-single-crystals as functional components, as exemplified by the construction of a 5 in. field-effect transistor array.

Silencing of OGDHL promotes liver cancer metastasis by enhancing hypoxia inducible factor 1 α protein stability.

Hepatocellular carcinoma (HCC) is one of the most common malignant diseases associated with a high rate of mortality. Frequent intrahepatic spread, extrahepatic metastasis, and tumor invasiveness are the main factors responsible for the poor prognosis of patients with HCC. Hypoxia-inducible factor 1 (HIF-1) has been verified to play a critical role in the metastasis of HCC. HIFs are also known to be modulated by small molecular metabolites, thus highlighting the need to understand the complexity of their cellular regulation in tumor metastasis. In this study, lower expression levels of oxoglutarate dehydrogenase-like (OGDHL) were strongly correlated with aggressive clinicopathologic characteristics, such as metastasis and invasion in three independent cohorts featuring a total of 281 postoperative HCC patients. The aberrant expression of OGDHL reduced cell invasiveness and migration in vitro and HCC metastasis in vivo, whereas the silencing of OGDHL promoted these processes in HCC cells. The pro-metastatic role of OGDHL downregulation is most likely attributed to its upregulation of HIF-1α transactivation activity and the protein stabilization by promoting the accumulation of L-2-HG to prevent the activity of HIF-1α prolyl hydroxylases, which subsequently causes an epithelial-mesenchymal transition process in HCC cells. These results demonstrate that OGDHL is a dominant factor that modulates the metastasis of HCC.

Formation Behaviors of Coated Reactive Explosively Formed Projectile.

The formation behavior of coated reactive explosively formed projectiles (EFP) is studied by the combination of experiments and simulations. The results show that the coated EFP can be obtained by explosively crushing the double-layer liners, and the simulation agrees with the experiment well. Then, the interaction process between the two liners is discussed in detail, and the formation and coating mechanism are revealed. It can be found that there are three phases in the formation process, including the impact, closing and stretching phases. During the impact phase, the velocities of two liners rise in turns with the kinetic energy exchange. In the closing phase, the copper liner is collapsed forward to the axis and completely coats the reactive liner. It is mentioned that the edge of the copper liner begins to form a metal precursor penetrator in this stage. During the stretching phase, the coated reactive EFP is further stretched and fractured, resulting in the separation of the metal precursor penetrator and the following coated reactive projectile. Further studies show both the edge thickness and the curvature radius of the copper liner have significant influences on formation behaviors. By decreasing the edge thickness or the curvature radius, the difficulty of closing decreases, but the tip velocity and the length of precursor penetrator increases. As the thickness and diameter of the reactive liner decrease, the coating velocity increases slightly, but the total length of coated reactive EFP tends to decrease.