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Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of non‐small cell lung cancer (NSCLC). While rapid progression (RP) has been proposed as a non‐negligible pattern of response to ICIs, its definition and related factors remain unclear. This study aimed to develop a clinical definition of RP and to identify related factors. Methods: We retrospectively evaluated Chinese patients who had received an ICI as second‐line or later treatment for locally advanced or metastatic NSCLC at a single center. We defined RP as radiological progression at the first response assessment (<2 months after starting the ICI), as well as confirmation of progressive disease or cancer‐related death occurring at <3 months. The clinical outcomes were compared for patients with RP or non‐RP to identify prognostic factors. Results: The study evaluated 74 eligible patients with detailed records regarding their ICI therapy, including 25 patients (33.8%) who had experienced RP. Relative to patients with non‐RP, patients with RP had significantly shorter median progression‐free survival (1.7 months [95% CI: 1.4–2.0 months] vs. 6.3 months [95% CI 5.2–7.3 months], P < 0.001; hazard ratio: 0.14, 95% CI: 0.08–0.25) and significantly shorter median overall survival (8.2 months [95% CI 3.0–13.4 months] vs. 22.6 months [95% CI 17.0–28.1 months], P < 0.001; hazard ratio: 0.27, 95% CI: 0.15–0.49). Multivariate analysis revealed that RP was independently predicted by the presence of ≥3 metastatic sites (P = 0.039) and a neutrophil‐to‐lymphocyte ratio of ≥3 (P = 0.044). Conclusions: Among NSCLC patients, RP was a common response to ICI monotherapy and was associated with dramatically reduced progression‐free and overall survival. Care is needed when selecting ICI monotherapy for these patients, especially if they have ≥3 metastatic sites or a neutrophil‐to‐lymphocyte ratio of ≥3. Key points: Significant findings of the study: Patients with rapid progression after immune checkpoint inhibitor monotherapy had poor survival outcomes. The number of metastatic sites and the neutrophil‐to‐lymphocyte ratio may independently predict treatment response in this setting.What this study adds: This is the first study to evaluate rapid progression after second‐line or later single‐agent immunotherapy in a Chinese population. Our findings may help establish effective immunotherapy strategies for NSCLC. [ABSTRACT FROM AUTHOR]

The authors were unable to provide a satisfactory explanation for the alleged image duplication and requested to retract the article. Following publication of an Expression of concern for their article, the authors became aware of subsequent image duplication concerns which had been raised regarding their article. The image duplication concerns relate to the duplication of invasion and migration images with the same images from other unrelated articles. [Extracted from the article]

Increased expression of CD169 on monocytes has been reported in HIV-1-infected humans. Using rhesus macaque models of HIV infection, we sought to investigate whether simian immunodeficiency virus (SIV) infection upregulates CD169 expression on monocytes/macrophages. We also sought to determine whether CD8 T cells and plasma viral load directly impact the expression of CD169 on monocytes during SIV infection. We longitudinally assessed monocyte expression of CD169 during the course of SIV infection by flow cytometry, and examined the expression of CD169 on macrophages by immunohistochemistry in the spleen and lymph nodes of uninfected and infected macaques. CD169 expression on monocytes was substantially upregulated as early as 4 days during the hyperacute phase and peaked by 5-15 days after infection. After a transient decrease following the peak, its expression continued to increase during progression to AIDS. Monocyte CD169 expression was directly associated with plasma viral loads. To determine the contribution of CD8+ T lymphocytes and virus to the control of monocyte CD169 expression, we used experimental CD8+ lymphocyte depletion and antiretroviral therapy (ART) in SIV-infected macaques. Rapid depletion of CD8 T cells during acute infection of rhesus macaques induced an abrupt increase in CD169 expression. Importantly, levels of CD169 expression plummeted following initiation of ART and rebounded upon cessation of therapy. Taken together, our data reveal independent roles for virus and CD8+ T lymphocytes in controlling monocyte CD169 expression, which may be an important link in further investigating the host response to viral infection. [ABSTRACT FROM AUTHOR]

A polyether-substituted cellulase (Cell-Mal) has been synthesized by the site-specific modification of free cysteine residues (–SH) in commercial natural cellulase. Cell-Mal allows the homogeneous enzymolysis of cellulose and self-thermoregulated separation in NaOH/urea solution, in which different kinds of cellulose are highly soluble but natural cellulase is swiftly deactivated. The modification process is simple and Cell-Mal shows high activity and thermosensitivity in the NaOH/urea solution. Significantly, Cell-Mal could hydrolyze all kinds of cellulose into glucose with a high yield within 24 h at 30 °C in a homogeneous alkaline system. Furthermore, Cell-Mal was automatically separated from the reaction system on cooling to below −10 °C. This system provides a potential method for environmentally benign and effective utilization of cellulose. [ABSTRACT FROM AUTHOR]

Abstract: The modification by MnO x significantly enhanced the activity and stability of Co3O4 for the preferential oxidation of CO in H2-rich stream. The MnO x -promoted Co3O4 catalyst with a Mn/Co molar ratio of 1/8 exhibited the best performance; CO conversion was 56% at 40°C and increased to >90% as the temperature was raised to >75°C. This catalyst could provide 100% CO conversion at 125–175°C. CO conversions of 97% and 100% remained unchanged for 100h at 100 and 125°C, respectively, whereas the deactivation was observed over Co3O4 alone. Our characterizations using XRD, XPS and TEM indicated that the modification of Co3O4 with MnO x caused the formation of smaller Mn x Co3−x O4 solid-solution particles. The O2-TPD, CO-TPD, and pulse reaction studies suggest that the incorporation of MnO x into Co3O4 increased the amounts of reactive oxygen species and adsorbed CO species over catalyst surfaces and enhanced the regeneration ability of the reduced catalyst by O2. All these enhancements are proposed to be responsible for the improved catalytic performance of the MnO x -promoted Co3O4. [ABSTRACT FROM AUTHOR]

A series of Co–Cu composite oxides with different Co/Cu atomic ratios were prepared by a co-precipitation method. XRD, N2 sorption, TEM, XPS, H2-TPR, CO-TPR, CO-TPD and O2-TPD were used to characterize the structure and redox properties of the composite oxides. Only spinel structure of Co3O4 phase was confirmed for the Co–Cu composite oxides with Co/Cu ratios of 4/1 and 2/1, but the particle sizes of these composite oxides decreased evidently compared with Co3O4. These composite oxides could be reduced at lower temperatures than Co3O4 by either H2 or CO. CO and O2 adsorption amounts over the composite oxides were significantly higher than those over Co3O4. These results indicated a strong interaction between cobalt and copper species in the composite samples, possibly suggesting the formation of Cu x Co3− x O4 solid solution. For the preferential oxidation of CO in a H2-rich stream, the Co–Cu composite oxides (Co/Cu = 4/1–1/1) showed distinctly higher catalytic activities than both Co3O4 and CuO, and the formation of Cu x Co3− x O4 solid solution was proposed to contribute to the high catalytic activity of the composite catalysts. The Co–Cu composite oxide was found to exhibit higher catalytic activity than several other Co3O4-based binary oxides including Co–Ce, Co–Ni, Co–Fe and Co–Zn oxides. [ABSTRACT FROM AUTHOR]

A cDNA, designated PTX1, has been isolated by subtractive hybridization on the basis that it is expressed in normal prostate but not in prostate carcinoma. The full-length cDNA was subsequently established by 5′ and 3′ RACE. Nucleotide sequence analysis of the 5′- and 3′-RACE clones yielded a composite cDNA of 1327 bp, which predicted a protein of 377 amino acid residues with a putative nuclear import signal (RRLNRKK) at its N terminus. The PTX1 gene was localized to human chromosome 12 and was found to be ubiquitously expressed. A segment of the cDNA was expressed in E. coli to produce a fragment of the PTX1 protein for the generation of specific antibodies. The resulting antibodies detected a 73-kDa protein in both nuclear and cytoplasmic extracts of prostate, although the level in the cytoplasmic extract was much lower. Using immunohistochemical analysis, the PTX1 protein was localized mainly in the nuclei of glandular epithelia of normal prostate. The nuclear staining was greatly reduced in prostate carcinoma. The gene organization of PTX1 was established by comparing the cDNA sequence with the published human genomic sequence. [ABSTRACT FROM AUTHOR]

Correction for ‘Design of a thermoregulated phase-separable system for homogeneous enzymolysis of cellulose’ by Lu Li et al., Green Chem., 2015, 17, 3067–3074. [ABSTRACT FROM AUTHOR]

• Alterations in TP53 , ERBB2 or FGF19 correlated with poorer prognosis in TKI1st treated NSCLCs. • EGFR- mutant and TP53 -WT NSCLCs benefited more from the combined A + T therapy. • NSCLC patients with CNV correlated with a shorter PFS in response to TKI3rd. Although the majority of epidermal growth factor receptor (E GFR)-mutant non-small cell lung cancer (NSCLC) patients respond to EGFR tyrosine kinase inhibitors (TKIs), significant heterogeneity in clinical response is observed which might be attributed to the distinct sub-molecular characteristics. The present study aims to identify genetic alterations correlated with clinical outcomes and treatment response to different EGFR -TKI inhibitors. We integrated the genomic data and clinical outcomes including progression-free survival (PFS) and overall survival (OS) in 179 patients with advanced EGFR-mutant NSCLC who were treated with EGFR-TKI as 1st line of treatment. We found that EGFR -mutant patients harboring concomitant TP53 mutation (OS: 21 vs. 40 months, P = 0.05), ERBB2 amplification (PFS: 6.1 vs. 12.5 months, P = 0.01) or FGF19 amplification (OS: 11.2 vs. 27.1 months, P = 0.01) were significantly associated with a poorer clinical prognosis after treated with 1st generation EGFR-TKI. In contrast, the presence of TP53 mutation did not affect the PFS nor OS of patients treated with 2nd generation EGFR-TKI. Furthermore, EGFR -mutant and TP53 -wild type (WT) patients benefited more from a combinatorial treatment consisting of EGFR-TKI and bevacizumab comparing to EGFR-TKI as a single agent (PFS: 21.7 vs. 9.3 months, P < 0.01). Copy number variation (CNV) (PFS: 4.6 vs.9.4 months, p = 0.018) was identified as an unfavorable predictive factor to 3rd-generation TKI. We also revealed distinct resistance mechanisms associated with different EGFR-TKIs. Our study highlights the heterogeneity both in the primary molecular landscape and acquired alterations in EGFR -mutated NSCLCs, which might play a role in determining the clinical efficacy of EGFR-TKIs. We also revealed the differential prognostic role of TP53 mutation in patients treated with the 1st or 2nd generation of EGFR-TKI. Our study also suggests that EGFR -mutant and TP53 -WT patients may benefit more from combinatorial treatment consisting of EGFR-TKI and bevacizumab, highlighting the importance of further stratifying EGFR -mutant patients. [ABSTRACT FROM AUTHOR]

Background: Chronic Kidney Disease (CKD) stands as a formidable health challenge, recognized not only for its growing prevalence but also for its association with elevated mortality rates. Emerging evidence suggests that CKD is inherently linked to inflammatory processes, marking it as an inflammatory disorder. In this landscape, the systemic inflammatory response index (SIRI) emerges as a novel inflammation marker, yet to be applied for assessing the risk of mortality in CKD patients., Objective: This study aims to investigate the prognostic significance of the SIRI in all-cause and cardiovascular disease (CVD) mortality among patients with CKD., Method: This study conducted a retrospective observational study using the National Health and Nutrition Examination Survey (NHANES) database, encompassing data from 1999 to 2018. This analysis included 9,115 CKD patients, categorized based on SIRI quartiles. Key outcomes were all-cause and CVD mortality, analyzed using Kaplan-Meier survival curves, restricted cube splines (RCS) and cox proportional hazards models., Result: In this study of 9,115 CKD patients, the Kaplan-Meier survival analysis revealed a greater incidence of all-cause death among groups with higher SIRI (P-log rank <0.001). In the fully adjusted model (Model 3), each unit increase in SIRI led to a 20% increase in the risk of all-cause mortality. Additionally, higher SIRI quartiles (Q3 and Q4) were associated with increased risk compared to the lowest quartile (Q1) (Q3: HR: 1.16, 95% CI: 1.01-1.34; Q4: HR: 1.63, 95% CI: 1.40-1.90; P for trend <0.001). Similarly, for CVD mortality, each unit increase in SIRI in Model 3 increased the risk by 33%, with Q3 and Q4 showing higher risk than Q1 (Q3: HR: 1.39, 95% CI: 1.11-1.70; Q4: HR: 2.26, 95% CI: 1.72-2.98; P for trend <0.001)., Conclusion: SIRI was positively associated with all-cause and CVD mortality in patients with CKD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Wei, Mao, Liu and Zhu.)

Objective: KRAS mutation is one of important driver genes in non-small-cell lung cancer (NSCLC) and the patients with KRAS G12C mutations benefit from the inhibitor AMG510. However, the frequency, concurrent pathogenic mutations, and clinical characteristic of KRAS G12C is unknown in the NSCLC population of Northeast China., Methods: The retrospective analysis was derived from 431 NSCLC patients in Jilin Cancer Hospital between January 2018 and June 2019. The mutation frequency and concurrent mutations of KRAS G12C in tumor or peripheral blood was detected by next-generation sequencing (NGS)., Results: The RAS mutant rate was observed in 10.7% (46/431) of this cohort. All RAS -driver cancers are caused by mutations in the KRAS isoform, while the NRAS and HRAS isoforms were not detected. Among KRAS- mutant patients, 42 (91.3%) showed exon 2 mutation in 12 codon and 13 codon. KRAS G12C showed a 4.6% (20/431) mutation rate in this cohort and the highest frequency (43.5%, 20/46) in KRAS -mutant-positive patients. There was no difference between tumor tissue and plasma in terms of either KRAS or KRAS G12C mutation. The most frequent co-occurrence mutations with KRAS G12C were TP53 , followed by PTEN . Furthermore, KRAS G12C was exclusive with STK11 mutation. KRAS G12C mutation was associated with age, disease stage, and smoking status ( P =0.024; P =0.02; P =0.006), smoking remained an independent factor for KRAS G12C mutation ( P =0.037), and higher mutation frequency in patients older than 60, stage I-III, or smoking in NSCLC ( P =0.0151, P =0.0343, P =0.0046, respectively)., Conclusion: KRAS mutation was the only isoforms of RAS family, of these 43.5% harbored the KRAS G12C subtype in northeastern Chinese NSCLC patients. KRAS G12C is associated with age, pathological stage and smoking status, more commonly harbored TP53 / PTEN mutations, and providing more genome profile for targeted therapy in local clinical practice., Competing Interests: Qiang Zhang is an employee of Burning Rock Biotech. The authors report no other potential conflicts of interests in this work., (© 2021 Liu et al.)

Histone acetyltransferases (HATs) regulate many critical cancer events, including transcriptional regulation of oncogene and tumor suppressors, chromatin structure and DNA damage response. Abnormal expression of HATs has been reported in a number of cancers. However, cellular functions of HATs in cancer and molecular mechanisms remain largely unclear. Here, we performed a lentiviral vector-mediated RNAi screen to systematically address the function of HATs in lung cancer cell growth and viability. We identified 8 HATs genes involved in A549 cell viability. Further experiments showed that KAT8 regulates G2/M cell cycle arrest through AKT/ERK-cyclin D1 signaling. Moreover, KAT8 inhibition led to p53 induction and subsequently reduced bcl-2 expression. Our results demonstrate an important role of KAT8 in cancer and suggest that KAT8 could be a novel cancer therapeutic target.

PTX1 is a gene identified by subtractive hybridization on the basis that it is expressed in normal prostate and not in prostate carcinoma. It is unrelated to the pituitary homeobox protein (Ptx1 or Pitx1), which regulates pituitary hormone gene expression, and its function is currently unknown. Recently, it was found to be a homolog of the yeast Erv41p, an endoplasmic reticulum (ER) resident protein involved in protein trafficking between ER and Golgi, and was renamed as ERGIC2. Ectopic expression of a partial sequence of PTX1 (Met84 - Leu225) as a VP22-fusion protein in prostate cancer cell line, PC-3, induced cellular senescence. Gene expression microarray analyses showed that interferon-beta (IFN-beta) and a number of IFN-inducible genes, among other genes, were upregulated by the PTX1-VP22 fusion protein. Upregulation of IFN-beta was confirmed by RTPCR and promoter-reporter assay. However, the upregulation of IFN-beta by the PTX1-VP22 fusion protein was not due to nuclear translocation of the PTX1 luminal domain.

PTX1 is a gene identified by subtractive hybridization on the basis that it is expressed in normal prostate and not in prostate carcinoma. It encodes a nuclear protein that is downregulated in prostate carcinoma. Expression constructs containing PTX1 cDNA in both sense and antisense orientations were transfected into prostate tumor cell line, PC-3 cells. The effects of the expression of PTX1 and antisense PTX1 on PC-3 cells were examined using cell growth, proliferation, soft agar, invasion chamber, senescence-associated beta-galactosidase, and nude mice assays. Cells transfected with PTX1 construct in the sense orientation were growth-arrested. These cells displayed multiple morphological changes consistent with cellular senescence, including the expression of a senescence-associated beta-galactosidase. On the other hand, expression of antisense PTX1 RNA in PC-3 cells resulted in uncontrolled cell growth and increase of invasive potential. In nude mice, cells expressing antisense PTX1 grew sixfold faster than the control. These results suggest that PTX1 may play an important role in the growth and tumorigenicity of PC-3 cells.