Antitumor activity of Z15-0-2, a bispecific nanobody targeting PD-1 and CTLA-4.

The combination of programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies has potential for enhancing clinical efficacy. We described the development and antitumor activity of Z15-0, a bispecific nanobody targeting both the PD-1 and CTLA-4 pathways simultaneously. We designed and optimized the mRNA sequence encoding Z15-0, referred to as Z15-0-2 and through a series of in vitro and in vivo experiments, we established that the optimized Z15-0-2 mRNA sequence significantly increased the expression of the bispecific nanobody. Administration of Z15-0-2 mRNA to tumor-bearing mice led to greater inhibition of tumor growth compared to controls. In aggregate, we introduced a novel bispecific nanobody and have re-engineered it to boost expression of mRNA, representing a new drug development paradigm.

Iron(II)-Catalyzed Radical [3 + 2] Cyclization of N-Aryl Cyclopropylamines for the Synthesis of Polyfunctionalized Cyclopentylamines.

A facile iron(II)-catalyzed radical [3 + 2] cyclization of N-aryl cyclopropylamines with various alkenes to access the structurally polyfunctionalized cyclopentylamine scaffolds has been developed. Using low-cost FeCl2·4H2O as catalyst, N-aryl cyclopropylamines could be utilized to react with a wide range of alkenes including exocyclic/acyclic terminal alkenes, cycloalkenes, alkenes from the natural-occurring compounds (Alantolactone, Costunolide), and known drugs (Ibuprofen, l-phenylalanine, Flurbiprofen) to obtain a variety of cyclopentylamines fused with different useful motifs in generally good yields and diastereoselectivities. The highlight of this protocol is also featured by no extra oxidant, no base, EtOH as the solvent, gram-scale synthesis, and further diverse transformations of the synthetic products. More importantly, an iron(II)-mediated hydrogen radical dissociation pathway was proposed based on the mechanism research experiments.

A multi-omics study reveals the therapeutic effect of Linderae Radix water extract on irritable bowel syndrome (IBS-D).

ETHNOPHARMACOLOGICAL RELEVANCE: Linderae Radix (Lindera aggregata (Sims) Kosterm) is a traditional Chinese medicine known for its capability to regulate qi and relieve pain, particularly in the context of gastrointestinal disorders. AIM OF THE STUDY: While our previous research has demonstrated the efficacy of the Linderae Radix water extract (LRWE) in the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D), the precise mechanisms remain elusive. This study aims to provide a comprehensive understanding of the therapeutic effects of LRWE on IBS-D through multi-omics techniques. MATERIALS AND METHODS: 16 S rRNA gene sequencing combined with LC-MS metabolomics was employed to investigate the effect of LRWE on the gut microbiota and metabolites of IBS-D rats. Spearman correlation analysis was performed on the gut microbiota and metabolites. RESULTS: LRWE administration significantly ameliorated IBS-D rats' symptoms, including diarrhea, visceral hypersensitivity, and low-grade intestinal inflammation. Gut microbiota analysis revealed that LRWE influenced the diversity of the gut microbiota in IBS-D rats by significantly reducing the relative abundance of Patescibacteria and Candidatus Saccharimonas, while increasing the relative abundance of Jeotgalicoccus. Serum metabolomic analysis identified 16 differential metabolites, associated with LRWE's positive effects on IBS-D symptoms, focusing on glyoxylate and dicarboxylic acid metabolism, and cysteine and methionine metabolism. Spearman analysis demonstrated a strong correlation between cecal microbiota composition and serum metabolite levels. CONCLUSIONS: This study elucidates that LRWE plays a crucial role in the comprehensive therapeutic approach to IBS-D by restoring the relative abundance of gut microbiota and addressing the disturbed metabolism of endogenous biomarkers. The identified bacteria and metabolites present potential therapeutic targets for IBS-D.

An endoplasmic reticulum stress-related signature featuring ASNS for predicting prognosis and immune landscape in prostate cancer.

Prostate cancer (PRAD) is one of the common malignant tumors of the urinary system. In order to predict the treatment results for PRAD patients, this study proposes to develop a risk profile based on endoplasmic reticulum stress (ERS). Based on the Memorial Sloan-Kettering Cancer Center (MSKCC) cohort and the Gene Expression Omnibus database (GSE70769), we verified the predictive signature. Using a random survival forest analysis, prognostically significant ERS-related genes were found. An ERS-related risk score (ERscore) was created using multivariable Cox analysis. In addition, the biological functions, genetic mutations and immune landscape related to ERscore are also studied to reveal the underlying mechanisms related to ERS in PRAD. We further explored the ERscore-related mechanisms by profiling a single-cell RNA sequencing (scRNA-seq) dataset (GSE137829) and explored the oncogenic role of ASNS in PRAD through in vitro experiments. The risk signature composed of eight ERS-related genes constructed in this study is an independent prognostic factor and validated in the MSKCC and GSE70769 data sets. The scRNA-seq data additionally revealed that several carcinogenic pathways were noticeably overactivated in the group with high ERS scores. As one of the prognostic genes, ASNS will significantly inhibit the proliferation, migration and invasion abilities of PRAD cells after its expression is interfered with. In conclusion, this study developed a novel risk-specific ERS-based clinical treatment strategy for patients with PRAD.

Epithelioid Subtype Gastrointestinal Stromal Tumors of Stomach in an Endoscopic Biopsy: A Potential Diagnostic Pitfall.

Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract with a broad morphological spectrum. Although epithelioid GISTs account for 20% of GISTs, their morphological features may pose a diagnostic pitfall for pathologists due to their morphological similarities to poorly differentiated adenocarcinoma and lymphoma. Case Presentation: Herein, we report a 65-year-old male patient with gastric epithelioid GIST misdiagnosed as adenocarcinoma for four years. During this period, he was treated with chemotherapy combined with PD-L1 immunotherapy. The clinicians thought the treatments were effective. However, there was no significant change in tumor size. The patient's clinical symptoms did not improve significantly as well. Finally, an endoscopic biopsy was performed again and gastric epithelioid GIST was confirmed in our hospital through morphology, immunohistochemistry, and whole-genome sequencing. Conclusion: A broad morphological spectrum and diverse immunophenotypic changes of GISTs could represent a pitfall for pathologists. However, predisposed anatomical sites, morphology, and corresponding immunohistochemical markers are of great significance for the diagnosis of GISTs and the differential diagnosis from other diseases. On the other hand, clinicians should diagnose and comprehensively evaluate treatment effects based on the patient's clinical symptoms and relevant laboratory examinations, instead of over-reliance on pathological diagnosis.

Thymic hyperplasia with lymphoepithelial sialadenitis (LESA)-like features: a case report and literature review.

BACKGROUND: Thymic hyperplasia with lymphoepithelial sialadenitis-like features (LESA-like TH) is a rare form of thymic hyperplasia, characterized by a prominent expansion of the thymic medulla containing hyperplastic lymphoid follicles with germinal centers, while an almost total absence of thymic cortex. Since the first report in 2012, only a few cases of LESA-like TH have been reported in the literature to date. Due to the rarity of LESA-like TH and the tumor-like morphology, it is easy to be misdiagnosed as other common diseases of the thymus in routine practice, such as thymoma and lymphoma. CASE PRESENTATION: Herein, we present a case report of a 52-year-old Chinese female patient with LESA-like TH, without any discomforting symptoms. Computer-tomography imaging revealed a cystic solid mass in the anterior mediastinum, with well-defined boundaries and multiple internal septa. Histologically, prominent features were florid lymphoid follicles containing germinal centers, as well as hyperplasia of thymic epithelial cells and proliferation of Hassall bodies. However, the thymic cortex rich in immature T cells was almost completely absent. Furthermore, mature plasma cells, lymphoepithelial lesions, and cholesterol clefts were frequently seen. CONCLUSION: We made a diagnosis of LESA-like TH and performed a literature review to better understand the clinicopathological features of LESA-like TH and reduce misdiagnosis.

Matrix stiffness, endothelial dysfunction and atherosclerosis.

Atherosclerosis (AS) is the leading cause of the human cardiovascular diseases (CVDs). Endothelial dysfunction promotes the monocytes infiltration and inflammation that participate fundamentally in atherogenesis. Endothelial cells (EC) have been recognized as mechanosensitive cells and have different responses to distinct mechanical stimuli. Emerging evidence shows matrix stiffness-mediated EC dysfunction plays a vital role in vascular disease, but the underlying mechanisms are not yet completely understood. This article aims to summarize the effect of matrix stiffness on the pro-atherosclerotic characteristics of EC including morphology, rigidity, biological behavior and function as well as the related mechanical signal. The review also discusses and compares the contribution of matrix stiffness-mediated phagocytosis of macrophages and EC to AS progression. These advances in our understanding of the relationship between matrix stiffness and EC dysfunction open the avenues to improve the prevention and treatment of now-ubiquitous atherosclerotic diseases.

Identification and validation of the pyroptosis-related long noncoding rna signature to predict the prognosis of patients with bladder cancer.

Bladder cancer ranked the second most frequent tumor among urological malignancies. This work investigated bladder cancer prognosis, including the relevance of pyroptosis-related long noncoding RNA (lncRNA) in it and its potential roles. The Cancer Genome Atlas database offered statistics on lncRNAs and clinical data from 411 bladder cancer patients. Pearson correlation analysis was used to evaluate pyroptosis-related lncRNAs. To explore prognosis-associated lncRNAs, we performed univariate Cox regression, least absolute shrinkage and selection operator regression analyses, as well as the Kaplan-Meier method. Multivariate Cox analysis was leveraged to establish the risk score model. Afterward, a nomogram was constructed according to the risk score and clinical variables. Finally, to investigate the potential functions of pyroptosis-related lncRNAs, gene set enrichment analysis was employed. Eleven pyroptosis-related lncRNAs were screened to be closely associated with patients prognosis. On this foundation, a risk score model was created to classify patients into high and low risk groups. The signature was shown to be an independent prognostic factor (P < .001) with an area under the curve of 0.730. Then a nomogram was established including risk scores and clinical characteristics. The nomogram prediction effect is excellent, with a concordance index of 0.86. The 11-lncRNAs signature was associated with the supervision of oxidative stress, epithelial-mesenchymal transition, cell adhesion, TGF-ß, and Wingless and INT-1 signaling pathway, according to the gene set enrichment analysis. Our findings indicate that pyroptosis-related lncRNAs, which may affect tumor pathogenesis in many ways, might be exploited to assess the prognosis of bladder cancer patients.

Secondary Sinonasal Collision Tumor of Papillary Squamous Cell Carcinoma and Small Cell Neuroendocrine Carcinoma After Nasopharyngeal Carcinoma Radiotherapy: A Case Report and Literature Review of Sinonasal Collision Carcinomas.

In the head and neck region, small cell neuroendocrine carcinoma (SmNEC) is extraordinary infrequent. Collision malignancy is also a rare entity in the nasal cavity, with merely sporadic 6 case reports on primary collision tumor associated with neuroendocrine carcinoma. The development of a secondary SmNEC within the previous radiation field had uncommonly been described, and there was no report on secondary sinonasal collision carcinoma with SmNEC component as a side reaction of nasopharyngeal carcinoma (NPC) radiotherapy. In light of the rarity of these neoplasms, we presented a case of a sinonasal collision carcinoma of papillary squamous cell carcinoma (PSCC) and SmNEC after NPC radiotherapy. To our knowledge, it may be the first case of a secondary coexistence of two malignancies synchronously in the nasal cavity after NPC treatment. Recognizing this peculiar kind of collision tumor associated SmNEC could promote our understanding of this entity and hence propose optimal treatment strategies.

Melatonin Suppresses Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes Signaling and Delays the Development of Hearing Loss in the C57BL/6J Presbycusis Mouse Model.

Melatonin supplementation has been shown to delay age-related hearing loss (ARHL) progression. Previously, melatonin was found to inhibit neuronal mitochondrial DNA (mtDNA) release, as well as inhibit cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling, thereby delaying the onset of central nervous system diseases. Therefore, we hypothesized that melatonin may delay the progression of hearing loss in the C57BL/6J presbycusis mouse model by inhibiting cGAS-STING signaling in the auditory pathway. Oral melatonin at 10 mg/kg/d was administered to 3-month-old C57BL/6J mice until 12 months of age. The auditory brainstem response (ABR) threshold was used to assess their hearing ability. By real-time polymerase chain reaction and Western blot analysis, the levels of cytosolic mtDNA, cGAS/STING, and cytokines were examined in the mouse cochlea, inferior colliculus, and auditory cortex. We found that the 12-month-old control mice exhibited significant hearing loss, increased cytosolic mtDNA, increased expression of inflammatory factors TNF-α, IL-6, IFN-ß, Cxcl10, and Ifit3, up-regulated cGAS and STING expression, and enhanced interferon regulatory factor 3 (IRF3) phosphorylation in the C57BL/6J mouse cochlea, inferior colliculus, and auditory cortex. Melatonin treatment significantly improved hearing, decreased cytosolic mtDNA, suppressed the expression of inflammatory cytokines TNF-α, IL-6, IFN-ß, Ifit3, and Cxcl10, down-regulated cGAS and STING expression, and attenuated IRF3 phosphorylation in the C57BL/6J mouse cochlea, inferior colliculus, and auditory cortex. This study suggested that melatonin had a protective effect on auditory function in the C57BL/6J presbycusis mouse model, which may be mediated through reducing mtDNA release, inhibiting the cGAS-STING signaling pathway in the auditory pathway.

Microplastic pollution threats coastal resilience and sustainability in Xiamen City, China.

Microplastics have raised growing awareness due to their ubiquity and menaces to coastal resilience and sustainability. The abundance, distribution, and characteristics of microplastics in water and organisms in Xiamen were evaluated. Results showed that the average abundance of microplastics in the surface water of Xiamen Bay was 1.55 ± 1.94 items/m3. The dominant color, size, shape, and polymer type were white, 1.0-2.5 mm, and fragments and lines, and polyethylene and polypropylene, respectively. The average abundance of microplastics in the fish in Xiamen was 2.44 ± 1.56 items/g wet weight. They were dominated by fibers of blue polyethersulfone and polyethylene terephthalate, and sizes <2.5 mm. There was a negative correlation between the polymer type in fish and that in water, while a positive correlation between shapes of microplastics of both fish species. Results will aid in formulating management measures for preventing microplastic pollution in Xiamen, ultimately promoting coastal resilience and sustainability of coastal communities.

Transport of nanoscale zero-valent iron in saturated porous media: Effects of grain size, surface metal oxides, and sulfidation.

Knowledge of the fate and transport of nanoscale zero-valent iron (nZVI) in saturated porous media is crucial to the development of in situ remediation technologies. This work systematically compared the retention and transport of carboxymethyl cellulose (CMC) modified nZVI (CMC-nZVI) and sulfidated nZVI (CMC-S-nZVI) particles in saturated columns packed with quartz sand of various grain sizes and different surface metal oxide coatings. Grain size reduction had an inhibitory effect on the transport of CMC-S-nZVI and CMC-nZVI due to increasing immobile zone deposition and straining in the columns. Metal oxide coatings had minor effect on the transport of CMC-S-nZVI and CMC-nZVI because the sand surface was coated by the free CMC in the suspensions, reducing the electrostatic attraction between the nZVI and surface metal oxides. CMC-S-nZVI displayed greater breakthrough (C/C0 = 0.82-0.90) and higher mass recovery (84.9%-89.3%) than CMC-nZVI (C/C0 = 0.70-0.80 and mass recovery = 70.9%-79.6%, respectively) under the same experimental conditions. A mathematical model based on the advection-dispersion equation simulated the experimental data of nZVI breakthrough curves very well. Findings of this study suggest sulfidation could enhance the transport of CMC-nZVI in saturated porous media with grain and surface heterogeneities, promoting its application in situ remediation.

Novel targets for immunotherapy associated with exhausted CD8 + T cells in cancer.

In response to prolonged stimulation by tumour antigens, T cells gradually become exhausted. There is growing evidence that exhausted T cells not only lose their potent effector functions but also express multiple inhibitory receptors. Checkpoint blockade (CPB) therapy can improve cancer by reactivating exhausted effector cell function, leading to durable clinical responses, but further improvements are needed given the limited number of patients who benefit from treatment, even with autoimmune complications. Here, we suggest, based on recent advances that tumour antigens are the primary culprits of exhaustion, followed by some immune cells and cytokines that also play an accomplice role in the exhaustion process, and we also propose that chronic stress-induced hypoxia and hormones also play an important role in promoting T-cell exhaustion. Understanding the classification of exhausted CD8+ T-cell subpopulations and their functions is important for the effectiveness of immune checkpoint blockade therapies. We mapped the differentiation of T-cell exhausted subpopulations by changes in transcription factors, indicating that T-cell exhaustion is a dynamic developmental process. Finally, we summarized the novel immune checkpoints associated with depletion in recent years and combined them with bioinformatics to construct a web of exhaustion-related immune checkpoints with the aim of finding novel therapeutic targets associated with T-cell exhaustion in malignant tumours, aiming to revive the killing ability of exhausted T cells and restore anti-tumour immunity through combined targeted immunotherapy.

Sinonasal mucosal melanoma with smooth muscle differentiation: a potential pathological diagnostic pitfall.

BACKGROUND: Sinonasal mucosal melanoma (SNMM) is a rare malignant melanoma originating from melanocytes derived from multipotent neural crest cells. Its incidence accounts for less than 1 % of all malignant melanomas, with five-year survival rate about 25 %. Occasionally, it is incredibly formidable to make a compelling diagnosis when malignant melanoma with other diverse differentiation. CASE PRESENTATION: Herein, we presented a 54-year-old male case of SNMM with smooth muscle differentiation, defined by histopathology and positive immunostaining for the smooth muscle specific markers of a-SMA, H-caldesmon, calponin and Desmin, as well as specific melanocyte markers of HMB-45, Melan-A, SOX10, and PNL2. CONCLUSIONS: Mucosal melanoma with smooth muscle differentiation is remarkably infrequent, and reported only 4 cases to date. It would be a potential pathological diagnostic pitfall. It is important to understand this variation of malignant melanoma for avoiding misdiagnosis.

EphA2 recognizes Dermatophagoidespteronyssinus to mediate airway inflammation in asthma.

Most of the asthma with low Th2 is severe steroid-resistant asthma, the exact pathogenesis of which has not yet been fully elucidated. We found that IL-6 and IL-8 were highly expressed in the sputum supernatant of severe asthma and ephrin type-A receptor 2 (EphA2) was highly expressed on bronchial epithelial cells. So, is there a connection between these two phenomena? To clarify this issue, we stimulated bronchial epithelial cells 16HBE with Dermatophagoides pteronyssinus and its compontents LPS, respectively, and detected the activation of EphA2, activation of downstream pathways and secretion of inflammatory cytokines. A mouse asthma model was established, and the therapeutic effects of inhibiting or blocking EphA2 on mouse asthma were investigated. The results showed that D. pteronyssinus and its component LPS phosphorylated EphA2 on 16HBE, activated downstream signaling pathways STAT3 and p38 MAPK, and promoted the secretion of IL-6 and IL-8. After knockout of EphA2 on 16HBE, the activation of inflammatory pathways was attenuated and the secretion of IL-6 and IL-8 was significantly reduced. Inhibition or blockade of EphA2 on mouse airways resulted in a significant reduction in airway hyperresponsiveness and airway inflammation, and a significant decrease in the expression levels of IL-6, IL-17F, IL-1α, IL-1ß and TNF in bronchoalveolar lavage fluid and lung tissue. Our study uncovers a novel role for EphA2 expressed on airway epithelial cells in the pathogenesis of asthma; EphA2 recognizes D. pteronyssinus or its component LPS and promotes the secretion of IL-6 and IL-8 by airway epithelial cell, thereby mediating airway inflammation. Thus, it is possible to provide a new molecular therapy for severe asthma.

Comprehensive analysis of the endoplasmic reticulum stress-related long non-coding RNA in bladder cancer.

Background: Bladder cancer is ranked the second most frequent tumor among urological malignancies. The research strived to establish a prognostic model based on endoplasmic reticulum stress (ERS)-related long non-coding RNA (lncRNA) in bladder cancer. Methods: We extracted the ERS-related genes from the published research and bladder cancer data from the Cancer Genome Atlas database. ERS-related lncRNAs with prognostic significance were screened by univariate Cox regression, least absolute shrinkage and selection operator regression analysis and Kaplan-Meier method. Multivariate Cox analysis was leveraged to establish the risk score model. Moreover, an independent dataset, GSE31684, was used to validate the model's efficacy. The nomogram was constructed based on the risk score and clinical variables. Furthermore, the biological functions, gene mutations, and immune landscape were investigated to uncover the underlying mechanisms of the ERS-related signature. Finally, we employed external datasets (GSE55433 and GSE89006) and qRT-PCR to investigate the expression profile of these lncRNAs in bladder cancer tissues and cells. Results: Six ERS-related lncRNAs were identified to be closely coupled with patients' prognosis. On this foundation, a risk score model was created to generate the risk score for each patient. The ERS-related risk score was shown to be an independent prognostic factor. And the results of GSE31684 dataset also supported this conclusion. Then, a nomogram was constructed based on risk scores and clinical characteristics, and proven to have excellent predictive value. Moreover, the gene function analysis demonstrated that ERS-related lncRNAs were closely linked to fatty extracellular matrix, cytokines, cell adhesion, and tumor pathways. Further analysis revealed the association of the 6-lncRNAs signature with gene mutations and immunity in bladder cancer. Finally, the external datasets and qRT-PCR verified high expressions of the ERS-related lncRNAs in bladder cancer tissues and cells. Conclusions: Overall, our findings indicated that ERS-related lncRNAs, which may affect tumor pathogenesis in a number of ways, might be exploited to assess the prognosis of bladder cancer patients.

Compatibility of Niuhuang Jiedu Tablets Results in Attenuated Arsenic Bioaccumulation and Consequent Protection against Realgar-Induced Toxicity in Mice.

Niuhuang Jiedu Tablets (NJT) is a popular over-the-counter traditional Chinese medicine (TCM) preparation. It is composed of realgar (As2S2) and seven other TCMs. The safety of NJT is of growing concern because arsenic (As) is carcinogenic to humans. The toxicity of realgar in vivo can mainly be attributed to the absorbed and accumulated As. This study investigated the correlation between the detoxification effects of the other TCMs in NJT on realgar and their influences on arsenic accumulation of realgar in mice. Histopathological examination, clinical biochemical test, and metabolic profiling analysis were used to evaluate the toxicity of realgar. The concentration of arsenic in mice whole blood as the hazard indicator was determined by inductively coupled plasma mass spectrometry (ICP-MS). The compatibility of NJT could decrease arsenic bioaccumulation of realgar in mice whole blood and consequently reduce the toxicity of realgar, which could be considered as one detoxification mechanism to realgar in NJT. The combination of Rhei Radix et Rhizoma, Scutellariae Radix, Platycodonis Radix, and Glycyrrhizae Radix et Rhizoma exhibited almost the same effects as NJT in regulating the serum biochemical parameters and metabolic profiles disturbed by realgar and in reducing arsenic accumulation of realgar in mice whole blood.

[Bioinformatics analysis of IκB gene family expression in human lung adenocarcinoma].

Objective To explore the clinical significance of inhibitor of NF-κB (IκB) family in lung adenocarcinoma (LUAD) through bioinformatics analysis. Methods The differentially expressed genes of IκB family in LUAD were screened by R language for survival analysis. The correlation between the expression of IκB family genes and clinicopathological characteristics was analyzed by R language, and the genes related to survival rate were selected for further study. GO and KEGG enrichment analyses were performed with LinkedOmics. The infiltration of immune cells was analyzed with TIMER. The correlation between the candidate genes and the prognosis of LUAD was analyzed through COX model. Results The expression levels of NF-κB inhibitor δ (NFKBID) and NF-κB inhibitor Zeta (NFKBIZ) were significantly downregulated in tumor tissues, and the patients with low expression levels of NFKBID and NFKBIZ had shorter overall survival. NFKBID and NFKBIZ were significantly correlated with T stage of LUAD. Enrichment analysis showed that low expression levels of NFKBID and NFKBIZ were correlated with energy metabolism and protein expression and transport. The expression levels of NFKBID and NFKBIZ were positively correlated with the infiltration of B cells, CD4+ T cells, neutrophils, and dendritic cells. COX analysis indicated that NFKBIZ could be an independent prognostic factor for LUAD. Conclusion The expression levels of NFKBID and NFKBIZ were significantly downregulated in tumor tissues, and were correlated with overall survival. NFKBID and NFKBIZ could be involved in the occurrence and development of LUAD by regulating glycometabolism and multiple immune cells infiltration. NFKBIZ could be considered as an independent prognostic factor for LUAD.

Hydroa vacciniforme-like lymphoproliferative disorder: A retrospective study on clinicopathological characteristics of 32 cases.

The clinicopathological features of 32 patients (17 females and 15 males) with a median age of 8 years (range, 1.5-21 years) from Southwestern China diagnosed with hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) were reviewed. At presentation, 6 patients showed only skin lesions, while 26 patients showed both skin lesions and systemic symptoms, including fever, lymphadenopathy and hepatosplenomegaly. As the disease progressed, systemic symptoms occurred in all patients. Follow-up data of 29 patients showed that 14 patients were still alive with disease with a median follow-up time of 22 months (range 3.6-71 months), and 15 patients died within a median follow-up of 6 months (range 0-60 months).

Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy.

Reactive oxygen species (ROS) play a dual role in the initiation, development, suppression, and treatment of cancer. Excess ROS can induce nuclear DNA, leading to cancer initiation. Not only that, but ROS also inhibit T cells and natural killer cells and promote the recruitment and M2 polarization of macrophages; consequently, cancer cells escape immune surveillance and immune defense. Furthermore, ROS promote tumor invasion and metastasis by triggering epithelial-mesenchymal transition in tumor cells. Interestingly, massive accumulation of ROS inhibits tumor growth in two ways: (1) by blocking cancer cell proliferation by suppressing the proliferation signaling pathway, cell cycle, and the biosynthesis of nucleotides and ATP and (2) by inducing cancer cell death via activating endoplasmic reticulum stress-, mitochondrial-, and P53- apoptotic pathways and the ferroptosis pathway. Unfortunately, cancer cells can adapt to ROS via a self-adaption system. This review highlighted the bidirectional regulation of ROS in cancer. The study further discussed the application of massively accumulated ROS in cancer treatment. Of note, the dual role of ROS in cancer and the self-adaptive ability of cancer cells should be taken into consideration for cancer prevention.