Loss of NEIL3 activates radiotherapy resistance in the progression of prostate cancer

Objective:To explore the genetic changes in the progression of castration-resistant prostate cancer(CRPC)and neuroendocrine prostate cancer(NEPC)and the reason why these cancers resist existing therapies.Methods:We employed our CRPC cell line microarray and other CRPC or NEPC datasets to screen the target gene NEIL3.Lentiviral transfection and RNA interference were used to construct overexpression and knockdown cell lines.Cell and animal models of radiotherapy were established by using a medical electron linear accelerator.Flow cytometry was used to detect apoptosis or cell cycle progression.Western blot and qPCR were used to detect changes in the protein and RNA levels.Results:TCGA and clinical patient datasets indicated that NEIL3 was downregulated in CRPC and NEPC cell lines,and NEIL3 was correlated with a high Gleason score but a good prognosis.Further functional studies demonstrated that NEIL3 had no effect on the proliferation and migration of PCa cells.However,cell and animal radiotherapy models revealed that NEIL3 could facilitate the radiotherapy sensitivity of PCa cells,while loss of NEIL3 activated radiotherapy resistance.Mechanistically,we found that NEIL3 negatively regulated the expression of ATR,and higher NEIL3 expression repressed the ATR/CHK1 pathway,thus regulating the cell cycle.Conclusions:We demonstrated that NEIL3 may serve as a diagnostic or therapeutic target for therapy-resistant patients.

Bilirubin inhibits the anticancer activity of sorafenib by blocking MCL-1 degradation in hepatocellular carcinoma cells

Objective:Sorafenib is a first-line drug for advanced hepatocellular carcinoma(HCC).Unfortunately,most patients with HCC do not respond to sorafenib,mainly because of the frequent development of drug resistance.Bilirubin is an end metabolite of heme catabolism and an indicator of liver function,but its direct role in regulating the anticancer activity of sorafenib in HCC cells is unclear.In the current study,we aimed to investigate the mechanism of action of bilirubin in sorafenib-mediated tumor suppression in HCC.Methods:A retrospective observational cohort of 100 patients receiving sorafenib was conducted to evaluate the potential role of bilirubin in predicting the prognosis of patients with HCC.Human HCC cell lines were treated with sorafenib in the absence or presence of bilirubin,and cell proliferation,apoptosis,and signaling pathways were assayed.The antagonistic effect of bilirubin toward sorafenib was assessed in nude mice bearing HCC xenografts.Results:Serum levels of bilirubin(including total,direct,and indirect bilirubin)negatively correlated with the overall survival of patients with HCC treated with sorafenib(P<0.05).Both in vitro and in vivo analyses demonstrated that bilirubin significantly abrogated sorafenib-mediated proliferation inhibition and apoptosis induction in HCC cells(P<0.05).Mechanically,bilirubin inhibited sorafenib-induced activation of GSK-3βand subsequent downstream MCL-1 degradation.Conclusions:Our study provides experimental evidence of the antagonistic effect of bilirubin toward sorafenib-mediated anticancer activity in HCC,and it suggests that bilirubin could be used to predict the efficacy of sorafenib treatment.

Cytoprotective effect of amniotic membrane extracts on human corneal epithelial cells exposed to benzalkonium chloride in vitro

Background:The goal was to explore the protective effect and potential mechanism of amniotic membrane extracts(AME)on the ocular surface exposed to benzalkonium chloride(BAC).Methods:The human corneal epithelial cell(HCEC)line SD-HCEC1s was cultured in 5 groups:normal control(NC),NC+AME,BAC,BAC+NC,and BAC+AME.Cell viability analysis,flow cytometry analysis,real-time polymerase chain reaction(PCR),and western blot were employed to measure changes in cell function.Matrix metalloproteinases(MMPs)and inflammatory cytokines were assayed by enzyme-linked immunosorbent assay(ELISA)and activity assays.Results:Real-time PCR and western blot analysis demonstrated that the expressional level of caspase-8 was increased while the levels of Muc1,Muc4,and Muc16 were decreased after treatment with 0.02%BAC for 1 h.When the SD-HCEC1s were withdrawn from the BAC and switched to media containing 10%AME for 2 days,the expression level of capsase-8 was decreased while the levels of Muc1,Muc4,and Muc16 were increased.Real-time PCR and ELISA demonstrated that the mRNA and protein levels of MMP-1,MMP-3,MMP-13,CXCL1,interleukin(IL)-1β,IL-6,and tumor necrosis factor-alpha(TNF-α)were significantly increased after treatment with 0.02%BAC,whereas those of MMP-8 were decreased.When the 0.02%BAC was withdrawn and the SD-HCEC1s were cultured in 10%AME,the mRNA and protein levels of MMP-1,MMP-3,MMP-13,CXCL1,IL-1β,IL-6,and TNF-αwere decreased,while those of MMP-8 were increased.MMP-8 activity assays confirmed that IL-1βand TNF-αdownregulated the protein levels of MMP-8.Conclusions:AME protects SD-HCEC1s when stressed in BAC via upregulation of MMP-8 and downregulation of IL-1βand TNF-α.AME may have the potential functions to be employed as a topical adjunctive therapy in eyes chronically exposed to BAC.

Biomedical applications of magnetosomes: State of the art and perspectives

Magnetosomes, synthesized by magnetotactic bacteria (MTB), have been used in nano- and biotechnological applications, owing to their unique properties such as superparamagnetism, uniform size distribution, excellent bioavailability, and easily modifiable functional groups. In this review, we first discuss the mechanisms of magnetosome formation and describe various modification methods. Subsequently, we focus on presenting the biomedical advancements of bacterial magnetosomes in biomedical imaging, drug delivery, anticancer therapy, biosensor. Finally, we discuss future applications and challenges. This review summarizes the application of magnetosomes in the biomedical field, highlighting the latest advancements and exploring the future development of magnetosomes.

Effects of bilateral subthalamic nucleus deep brain stimulation on motor symptoms in Parkinson’s disease: a retrospective cohort study

Deep brain stimulation of the bilateral subthalamic nucleus(STN)is a therapeutic option for patients with Parkinson’s disease(PD)in whom medical therapies have been ineffective.This retrospective cohort study analyzed the motor function of 27 patients with advanced PD,from the First Affiliated Hospital of Guangzhou Medical University,China,who received deep brain stimulation of the bilateral subthalamic nucleus and evaluated its therapeutic effects.The 10-year follow-up data of patients was analyzed in Qingyuan People’s Hospital,Sixth Affiliated Hospital of Guangzhou Medical University,China.The follow-up data were divided into two categories based on patients during levodopa treatment(on-medication)and without levodopa treatment(off-medication).Compared with baseline,the motor function of onmedication PD patients improved after deep brain stimulation of the bilateral subthalamic nucleus.Even 2 years later,the motor function of off-medication PD patients had improved.On-medication PD patients exhibited better therapeutic effects over the 5 years than offmedication PD patients.On-medication patients’akinesia,speech,postural stability,gait,and cognitive function worsened only after 5 years.These results suggest that the motor function of patients with advanced PD benefitted from treatment with deep brain stimulation of the bilateral subthalamic nucleus over a period up to 5 years.The overall therapeutic effects were more pronounced when levodopa treatment was combined with deep brain stimulation of the bilateral subthalamic nucleus.This study was approved by Institutional Review Board of Qingyuan People’s Hospital,The Sixth Affiliated Hospital of Guangzhou Medical University,China(approval No.QPH-IRB-A0140)on January 11,2018.

Predilection site and risk factor of second primary cancer:A pancancer analysis based on the SEER database

To the Editor:Over the past few years,the number of cancer survivors has continued to increase,primarily driven by the growing and aging population and the improvements in cancer detection and treatment.More than 16.9 million Americans with prior cancers were alive on January 1,2019,and the number of cancer survivors was estimated to reach>22.1 million by January 1,2030.[1]The lifetime risk of individual second primary cancer(SPC)has been confirmed when confronted with such a large amount of cancer survivors.[2]Definition of specific site is shown in supplementary material,http://links.lww.com/CM9/B616.

Ring finger protein 157 is a prognostic biomarker and is associated with immune infiltrates in human breast cancer

Background: The protein encoded by ring finger protein 157 (RNF157) is known to function as an E3 ubiquitinligase. However, whether the level of RNF157 expression in breast cancer correlates with prognosis and immune cellinfiltration among breast cancer patients remains to be further explored. Methods: In this study, publicly availabledatasets were used for evaluating RNF157 expression in different tumors compared with normal samples. Severalindependent datasets were screened for investigating the relationship between RNF157 and breast cancer survival,different mutation profiles, and tumor immune cell infiltration. We conducted a pathway enrichment analysis toidentify signaling pathways associated with RNF157. Results: Analysis of public and online databases revealed thatRNF157 expression markedly decreased in breast cancer tissue samples compared to non-carcinoma counterparts.Consistently, immunohistochemistry assays also demonstrated this RNF157 down-regulation in breast cancer samples.RNF157 up-regulation could predict the improved survival of breast cancer cases. Further, different RNF157expression level groups exhibited different mutational profiles. Pathway enrichment profiling of RNF157-related genessuggested its possible involvement in regulating breast cancer via the mitogen-activated protein kinase (MAPK)pathway. RNA sequencing (RNA-seq) data and genomic enrichment analysis showed that RNF157 downregulatedseveral genes positively associated with the MAPK signaling pathway. We also explored RNF157 expression andimmune cell infiltration in breast cancer and found that RNF157 mRNA levels were negatively related to non-Timmune cell infiltration. Conclusion: According to our work, RNF157 may be a promising diagnostic biomarker andtherapeutic target for breast cancer.

Overlooked risk for needle tract seeding following endoscopic ultrasound-guided minimally invasive tissue acquisition

Endoscopic ultrasound-guided minimally invasive tissue acquisition can be performed by two approaches as follows: Endoscopic ultrasound-guided fineneedle aspiration(EUS-FNA) and endoscopic ultrasound-guided fine-needle biopsy(EUS-FNB). These have been evolved into leading approaches and widely used for the histological diagnosis of tumors in the gastrointestinal tract and adjacent organs. However, the role of EUS-FNA and EUS-FNB in disease diagnosis and evaluation remains controversial. Although the incidence of surgery-associated complications remains low, the consequences of needle tract seeding can be serious or even life-threatening. Recently, increasing case reports of needle tract seeding are emerging, especially caused by EUS-FNA. This complication needs serious consideration. In the present work, we integrated these case reports and the related literature, and summarized the relevant cases and technical characteristics of needle tract seeding caused by EUS-FNA and EUSFNB. Collectively, our findings provided valuable insights into the prevention and reduction of such serious complication.

Gli1 promotes epithelial-mesenchymal transition and metastasis of non-small cell lung carcinoma by regulating snail transcriptional activity and stability

Metastasis is crucial for the mortality of non-small cell lung carcinoma(NSCLC) patients.The epithelial-mesenchymal transition(EMT) plays a critical role in regulating tumor metastasis.Glioma-associated oncogene 1(Gli1) is aberrantly active in a series of tumor tissues. However, the molecular regulatory relationships between Gli1 and NSCLC metastasis have not yet been identified. Herein,we reported Gli1 promoted NSCLC metastasis. High Gli1 expression was associated with poor survival of NSCLC patients. Ectopic expression of Gli1 in low metastatic A549 and NCI-H460 cells enhanced their migration, invasion abilities and facilitated EMT process, whereas knock-down of Gli1 in high metastatic NCI-H1299 and NCI-H1703 cells showed an opposite effect. Notably, Gli1 overexpression accelerated the lung and liver metastasis of NSCLC in the intravenously injected metastasis model. Further research showed that Gli1 positively regulated Snail expression by binding to its promoter and enhancing its protein stability, thereby facilitating the migration, invasion and EMT of NSCLC. In addition, administration of GANT-61, a Gli1 inhibitor, obviously suppressed the metastasis of NSCLC. Collectively, our study reveals that Gli1 is a critical regulator for NSCLC metastasis and suggests that targeting Gli1 is a prospective therapy strategy for metastatic NSCLC.

Targeting the Rac1 pathway for improved prostate cancer therapy using polymeric nanoparticles to deliver of NSC23766

Prostate cancer(PCa)is the second most commonly diagnosed cancer in men.The Rac1-GTP inhibitor NSC23766 has been shown to suppress PCa growth.However,these therapies have low tumor-targeting efficacy in vivo.Therefore,it is essential to produce a drug delivery system that specifically targets the tumor site.Herein,novel l-phenylalanine-based poly(ester amide)(Phe-PEA)polymers were synthesized and loaded with NSC23766(NSC23766@8P6 NPs),which had a small particle size(162.3±6.7nm)and high NSC23766 loading(8.0%±1.1%)with a more rapid release of NSC23766 at pH 5.0.In vitro cellu-lar uptake and cytotoxicity assays demonstrated that NSC23766@8P6 NPs were rapidly taken up by PC3 cells and showed significant effects of PCa cell proliferation inhibition and G2/M phase arrest.Further-more,in vivo studies using PC3-bearing mice demonstrated that NSC23766@8P6 NPs delivered by in-travenous injection not only increased the drug concentration with prolonged retention(96h)at the tumor site,but also inhibited tumor growth and induced apoptosis.In conclusion,we have discovered that NSC23766@8P6 NPs can serve as a delivery system that targets the tumor site and is therefore a promising therapeutic approach for PCa treatment.

The mitophagy pathway and its implications in human diseases

Mitochondria are dynamic organelles with multiple functions.They participate in necrotic cell death and programmed apoptotic,and are crucial for cell metabolism and survival.Mitophagy serves as a cytoprotective mechanism to remove superfluous or dysfunctional mitochondria and maintain mitochondrial fine-tuning numbers to balance intracellular homeostasis.Growing evidences show that mitophagy,as an acute tissue stress response,plays an important role in maintaining the health of the mitochondrial network.Since the timely removal of abnormal mitochondria is essential for cell survival,cells have evolved a variety of mitophagy pathways to ensure that mitophagy can be activated in time under various environments.A better understanding of the mechanism of mitophagy in various diseases is crucial for the treatment of diseases and therapeutic target design.In this review,we summarize the molecular mechanisms of mitophagy-mediated mitochondrial elimination,how mitophagy maintains mitochondrial homeostasis at the system levels and organ,and what alterations in mitophagy are related to the development of diseases,including neurological,cardiovascular,pulmonary,hepatic,renal disease,etc.,in recent advances.Finally,we summarize the potential clinical applications and outline the conditions for mitophagy regulators to enter clinical trials.Research advances in signaling transduction of mitophagy will have an important role in developing new therapeutic strategies for precision medicine.

Self-enhanced photothermal-chemodynamic antibacterial agents for synergistic anti-infective therapy

Cu_(2-x)S nanostructures have been intensively studied as outstanding chemodynamic therapy(CDT)and good photothermal therapy(PTT)antibacterial agents due to their highly efficient Cu(Ⅰ)-initiated Fenton-like catalytic activity and good photothermal conversion property.However,they still suffer from shortage of Cu(Ⅰ)supply in the long-term and comparatively low inherent photothermal conversion efficiency.Herein,we constructed a self-enhanced synergistic PTT/CDT nanoplatform(Cu_(1.94)S@MPN)by coating Cu_(1.94)S nanoparticles with Fe(Ⅲ)/tannic acid based metal-polyphenol networks(MPN).Activated by the acidic bacterial infection microenvironment,Cu_(1.94)S@MPN could be decomposed to continuously release Cu(Ⅱ),Fe(Ⅲ)ions and tannic acid.As the result of tannic acid-involved Cu and Fe redox cycling,Cu(Ⅰ)/Fe(Ⅱ)-rich CDT could be achieved through the highly accelerated catalytic Fenton/Fenton-like reactions.More importantly,experimental results demonstrated that Cu_(1.94)S@MPN exhibited both excellent photothermal antibacterial and photothermal-enhanced CDT properties to eradicate bacteria in vitro and in vivo.Overall,this novel nanotherapeutics has great potential to become a clinic candidate for anti-infective therapy in future.

Single-cell analyses identify anaphase-promoting complex subunit 11 as a switch controlling neuronal differentiation of glioblastoma cells

Glioblastoma(GBM)is the most common and lethal malignancy in the central nervous system.1 One of the major difficulties in treatment is that the initial clinical diagnosis of GBM is already WHO grade IV,without recognizable lower-grade precursor lesions.Copy number variations(CNVs)were found to appear in malignant cells several years before the initial diagnosis of GBM.2 Less differentiation and more aggressive phenotypes were observed in GBM cells with a higher degree of CNVs.3 Additionally,CNVs provide more accurate stratification of clinical outcomes than does the WHO grade system.4 Therefore,we reasoned that differentially expressed genes(DEGs)among GBM cells with different CNV statuses would be significant for the aggressiveness of GBM.Here we leveraged the single-cell RNA-sequencing(scRNA-seq)to construct the CNV profile of GBM at single-cell resolution,divided GBM cells into different clusters according to their CNV statuses,and investigated the molecular functions of DEGs among GBM clusters.Through a series of experiments,we identified anaphase-promoting complex subunit 11(ANAPC11)as a switch controlling the neuronal differentiation of GBM cells,providing a novel alternative for the development of differentiation-inducing therapy to overcome GBM.

Inaugurating a novel adjuvant therapy in urological cancers:Ferroptosis

Ferroptosis,a distinctive form of programmed cell death,is involved in numerous diseases with specific characteristics,including certain cell morphology,functions,biochemistry,and genetics,that differ from other forms of programmed cell death,such as apoptosis.Many studies have explored ferroptosis and its associated mechanisms,drugs,and clinical applications in diseases such as kidney injury,stroke,ischemia-reperfusion injury,and prostate cancer.In this review,we summarize the regulatory mechanisms of some ferroptosis inducers,such as enzalutamide and erastin.These are current research focuses and have already been studied extensively.In summary,this review focuses on the use of ferroptosis induction as a therapeutic strategy for treating tumors of the urinary system.

Study of blood exposure-related mental health illness among clinical nurses

Nurses are subjected to high amount of stress in the medical setting, and work-related stress often leads to mental problems. This study aims to investigate the mental health status of nurses exposed to blood through needlestick injuries. A total of 302 nurses working in the hospital of Guangdong, China, participated in this study. Out of the 302 nurses, 140 did not experience any needlestick injuries during the previous week, whereas 162 nurses experienced needlestick injuries. The General Health Questionnaire （GHQ）-28 Standardized Questionnaire, which uses physical, anxiety, social function, and depression subscales, was used in this study. No significant difference between nurses exposed to blood and nurses not exposed to blood was found in terms of gender, age, length of employment, and civil status （P 〉 0.05）. Results from the GHQ-28 Standardized Questionnaire showed that 75.9% （123/162） of nurses exposed to blood were suspected to suffer from mental disorders, whereas 40% （56/140） of nurses not exposed to blood were suspected to suffer from mental disorders. The mean mental health scores of nurses exposed to blood and those not exposed were 8.73 ± 7.32 and 5.69 ± 5.70, respectively. From these results, we can conclude that blood exposure from needlestick injuries leads to higher prevalence of depression, anxiety, and stress symptoms in nurses. This finding highlights the importance of providing efficient, adequate, and appropriate support services after nurses are exposed to blood from needlestick injuries.

Risk Factors and Pregnancy Outcome in Women with a History of Cesarean Section Complicated by Placenta Accreta

Objective:To explore the risk factors and pregnancy outcomes in women with a history of cesarean section complicated by placenta accreta(PA).Methods:This case-control study included clinical data from singleton mothers with a history of cesarean section in 11 public tertiary hospitals in seven provinces of China between January 2017 and December 2017.According to the intraoperative findings after delivery,the study population was divided into PA and non-PA groups.We compared the pregnancy outcomes between the two groups,used multivariate logistic regression to analyze the risk factors for placental accreta.Results:For this study we included 11,074 pregnant women with a history of cesarean section;and of these,869 cases were in the PA group and 10,205 cases were in the non-PA group.Compared with the non-PA group,the probability of postpartum hemorrhage(236/10,205,2.31%vs.283/869,32.57%),severe postpartum hemorrhage(89/10,205,0.87%vs.186/869,21.75%),diffuse intravascular coagulation(3/10,205,0.03%vs.4/869,0.46%),puerperal infection(33/10,205,0.32%vs.12/869,1.38%),intraoperative bladder injury(1/10,205,0.01%vs.16/869,1.84%),hysterectomy(130/10,205,1.27%vs.59/869,6.79%),and blood transfusion(328/10,205,3.21%vs.231/869,26.58%)was significantly increased in the PA group(P<0.05).At the same time,the neonatal birth weight 3250.00(2950.00–3520.00)g vs.2920.00(2530.00–3250.00)g),the probability of neonatal comorbidities(245/10,205,2.40%vs.61/869,7.02%),and the rate of neonatal intensive care unit admission(817/10,205,8.01%vs.210/869,24.17%)also increased significantly(P<0.05).Weight(odds ratio)(OR)=1.03,95%confidence interval(CI):1.01–1.05)),parity(OR=1.18,95%CI:1.03–1.34),number of miscarriages(OR=1.31,95%CI:1.17–1.47),number of previous cesarean sections(OR=2.57,95%CI:2.02–3.26),history of premature rupture of membrane(OR=1.61,95%CI:1.32–1.96),previous cesarean-section transverse incisions(OR=1.38,95%CI:1.12–1.69),history of placenta previa(OR=2.44,95%CI:1.50–3.96),and the combination of prenatal hemorrhage(OR=9.95,95%CI:8.42–11.75)and placenta previa(OR=91.74,95%CI:74.11–113.56)were all independent risk factors for PA.Conclusion:There was an increased risk of adverse outcomes in pregnancies complicated by PA in women with a history of cesarean section,and this required close clinical attention.Weight before pregnancy,parity,number of miscarriages,number of previous cesarean sections,history of premature rupture of membranes,past transverse incisions in cesarean sections,a history of placenta previa,prenatal hemorrhage,and placenta previa were independent risk factors for pregnancies complicated with PA in women with a history of cesarean section.These independent risk factors showed a high value in predicting the risk for placentab accreta in pregnancies of women with a history of cesarean section.

MPZL1 as an HGF/MET signaling amplifier promotes cell migration and invasion in glioblastoma

The extremely poor prognosis of patients is largely due to hepatocyte growth factor(HGF)/MET signaling,which promotes migration and invasion of glioblastoma(IDH wildtype;GBM;WHO grade 4).1,2 Clinical trials targeting MET,the only receptor of HGF,have yielded unimpressive results in GBM.3,4 Here we found that HGF induced strong chemotaxis on GBM cells,but MET expression was extremely low.We,therefore,used single-cell RNA sequencing(scRNA-seq)coupled with label-free proteome profiling to identify membrane proteins associated with HGF/MET signaling amplification in GBM and to provide a novel modulator,MPZL1,for HGF/MET-targeted therapy.

Effects of Luteinizing Hormone Supplementation on Ovarian Response and Assisted Reproductive Technology Outcomes in Antagonist In vitro Fertilization/Intracytoplasmic Sperm Injection Cycles: A Meta-analysis

Objective:The study objective was to investigate the effects of luteinizing hormone(LH)supplementation on ovarian response and assisted reproductive technology(ART)outcomes in in vitro fertilization/intracytoplasmic sperm injection cycles with a gonadotropin(Gn)-releasing hormone antagonist protocol.Methods:This is a meta-analysis,and nine published randomized controlled trials(1,685 patients)were included.Continuous data were extracted in the form of mean±standard deviation and population size,whereas dichotomous data were extracted in the form of odds ratio.Results:The total amount of follicle-stimulating hormone(FSH)used,the duration of stimulation(DOS),the number of eggs in MII stage,the total number of formed embryos,the clinical pregnancy rate,and live birth rates were similar between groups,but the estrogen level on the day of human chorionic Gn(hCG)administration was slightly higher in the LH supplementation group.On subgroup analysis,it was reported that the addition of LH could significantly increase estrogen levels on the day of hCG administration in patients older than 35 years,and LH supplementation starting on the day of FSH administration may slightly extend the DOS.Moreover,regardless of the timing of LH supplementation,an increase in estrogen levels was found on the day of hCG administration.Conclusions:LH supplementation of an antagonist protocol increases estrogen levels on the day of hCG administration,but does not increase the number of mature oocytes retrieved,and also fails to improve ART outcomes.

Light-induced tumor theranostics based on chemical-exfoliated borophene

Among 2D materials(Xenes)which are at the forefront of research activities,borophene,is an exciting new entry due to its uniquely varied optical,electronic,and chemical properties in many polymorphic forms with widely varying band gaps including the lightest 2D metallic phase.In this paper,we used a simple selective chemical etching to prepare borophene with a strong near IR light-induced photothermal effect.The photothermal efficiency is similar to plasmonic Au nanoparticles,with the added benefit of borophene being degradable due to electron deficiency of boron.We introduce this selective chemical etching process to obtain ultrathin and large borophene nanosheets(thickness of ~4 nm and lateral size up to ~600 nm)from the precursor of AlB_(2).We also report first-time observation of a selective Acid etching behavior showing HCl etching of Al to form a residual B lattice,while HF selectively etches B to yield an Al lattice.We demonstrate that through surface modification with polydopamine(PDA),a biocompatible smart delivery nanoplatform of B@PDA can respond to a tumor environment,exhibiting an enhanced cellular uptake efficiency.We demonstrate that borophene can be more suitable for safe photothermal theranostic of thick tumor using deep penetrating near IR light compared to gold nanoparticles which are not degradable,thus posing longterm toxicity concerns.With about 40 kinds of borides,we hope that our work will open door to more discoveries of this top-down selective etching approach for generating borophene structures with rich unexplored thermal,electronic,and optical properties for many other technological applications.

Bilirubin inhibits lung carcinogenesis by up-regulating cystatin A expression in tumor-infiltrating macrophages

As one of the leading causes of cancer deaths worldwide,the pathogenesis of lung cancer is still not completely understood.Bilirubin,a product of heme metabolism,has long been considered a waste product of the body.Increasing evidence suggests that bilirubin has additional antioxidant,anti-inflammatory,and proteasome inhibitory activities.However,the specific role of bilirubin in the formation and development of lung cancer has not been elucidated.