Reconnoitering correlation between human papillomavirus infection-induced vaginal microecological abnormality and squamous intraepithelial lesion (SIL) progression.

OBJECTIVE: This study aims to investigate the relationship between abnormal vaginal microecology and human papillomavirus (HPV) infection, as well as the squamous intraepithelial lesions (SIL) progression. METHODS: A total of 383 patients diagnosed with HPV infection in our hospital between March 2017 and February 2022 were selected as the experimental group. In addition, several volunteers (n = 898) who underwent physical examination during the same period were randomly selected as the control group. Subsequently, we conducted several investigations, such as HPV detection and gene typing, examined vaginal microecological imbalances, and performed cytological examinations to analyze the correlation between microecological changes, different types of HPV infection, and SIL progression. RESULTS: HPV detection primarily included single and high-risk types of HPV infections. Moreover, significant disparities in the vaginal microecological environment between patients with persistent HPV infection and the control group, as well as patients with low-grade and high-grade SIL (LSIL and HSIL), were observed. The regression analysis revealed a correlation between LSIL and microflora density, diversity, bacteriological vaginosis (BV), vulvovaginal candidiasis (VVC), trichomonas vaginalis (TV), sialidase, as well as Lactobacillus. In addition, we identified an association between HSIL and pH, flora density, diversity, BV, VVC, candida vaginitis (CV), leukocyte esterase, catalase, and Lactobacillus levels. CONCLUSION: These findings revealed a significant association between abnormal vaginal microecology and both HPV infection and the SIL progression.

Reconstruction algorithm of haze image based on blind separation model of polarized orthogonal airlight.

Polarization-based dehazing methods can enhance the quality of haze images. However, existing methods tend to a manual selection of sky area and bias coefficient to estimate the degree of polarization (DoP) of the airlight, which leads to inaccurate estimation of the airlight. Aiming at the problem, a reconstruction algorithm based on the blind separation model of polarized orthogonal airlight is proposed. Importantly, the depth-dependent DoP of the airlight is automatically estimated without manual selection of sky area and bias coefficient. To reduce the interference of white objects on the estimation of airlight at infinity, an adaptive estimation method using the deviation between the DoP of the airlight and incident light is proposed. In order to accurate estimate the airlight from the airlight at infinity, a blind separation model of the airlight with multi-regularization constraints is established based on the decomposition of the airlight at infinity into a pair of polarized components with orthogonal angles. The experimental results show that the method effectively improves the visibility of scenes under different haze concentrations, especially in dense or heavy haze weather.

Local linear model and restoration method of underwater images.

When light transports in water, it will be scattered and absorbed by the water body and water particles, resulting in blurred images and color distortion. In order to improve the quality of underwater imaging, the local linear model and restoration method of underwater images are proposed in this paper. Based on the distance-invariant feature in the local region, the local linear model is established, and the slope and intercept of the model represent the transmission rate and the backscattered light of the local region of the image, respectively. Utilizing this model, the problem of underwater image restoration has been transformed into the problem of solving the slope and intercept of linear equations. To solve the linear imaging model, the concept of local special-value is defined in this paper, and several fitting points can be obtained through the special-value. Then the linear model is solved by the fitting method, and the restoration of underwater images is completed. The restoration results of different underwater scene images verify that the linear model has a good effect in improving the image clarity and removing the color distortion.

LncRNA KCNQ1OT1-mediated cervical cancer progression by sponging miR-1270 as a ceRNA of LOXL2 through PI3k/Akt pathway.

BACKGROUND: Dysregulated noncoding RNAs participated in progressions of cervical cancer. PURPOSE: To verify impacts of KCNQ1OT1 on modulating progressions of cervical cancer cells. METHOD: Expressions of KCNQ1OT1, miR-1270, and LOXL2 were analyzed through RT-qPCR and protein expressions of LOXL2, p-AKT, and AKT were validated using western blot. Bindings of miR-1270 with KCNQ1OT1 or LOXL2 were verified using luciferase reporter assay. CCK-8 and flow cytometry evaluated cell viability and apoptosis, respectively. The PI3K/AKT signaling pathway suppressor, LY294002, was applied to treat the cells and the changes of KCNQ1OT1 expression and LOXL2, p-AKT, and AKT protein expressions were examined. RESULTS: KCNQ1OT1 expression was the highest in HeLa cells but lowest in SiHa cells whose upregulation improved the viability but inhibited the apoptosis in SiHa cells while knockdown of KCNQ1OT1 caused opposite results in HeLa cells. MiR-1270 was sponged and negatively modulated by KCNQ1OT1. MiR-1270 mimics caused low viability and high apoptosis of SiHa cells but miR-1270 inhibitor reverse its roles in HeLa cells. LOXL2, the target of miR-1270, positively interplayed with KCNQ1OT1 but had negative interaction with miR-1270. LOXL2 overexpression promoted viability and decreased apoptosis of SiHa cells but knockdown of LOXL2 restored its effects in HeLa cells. Moreover, LOXL2 and phosphorylated AKT (p-AKT) protein expressions were downregulated by suppressed KCNQ1OT1 and LOXL2 and miR-1270 mimics but promoted by overexpressed KCNQ1OT1 and LOXL2 and miR-1270 inhibitor. Additionally, LY294002 treatment caused low KCNQ1OT1 RNA expression and decreased LOXL2 and p-AKT protein expressions. CONCLUSION: KCNQ1OT1/miR-1270/LOXL2 axis modulated viability and apoptosis of cervical cancer cells.

Neutral point detection using the AOP of polarized skylight patterns.

The neutral points are one of the most significant characteristics of the polarized skylight pattern in the whole sky. At present, detection of the neutral points mostly utilizes ellipse fitting of the degree of polarization. However, because the degree of polarization distribution characteristics of a polarized skylight pattern is easily affected by the environment, the robustness of the detection is unstable. Aiming at the problem, we analyzed the angle of polarization distribution characteristics of polarized skylight patterns in the region around the neutral point by measurement experiments. Based on this, we proposed an automatic detection method of neutral points using the angle of polarization of the polarized skylight pattern. The experimental results of different times in a continuous period of time show that compared with ellipse fitting of the degree of polarization, the detection accuracy of the proposed method is almost the same, but the robustness is better. It provides a novel method for the position detecting of the neutral point, which is in favor of the measurement applications of polarization technology.

Clinical observation on 120 cases of lumbar disc herniation treated with Yaotongning capsule.

This clinical observation aims to observe and analyze the effect of Yaotongning capsule in the treatment of lumbar disc herniation, and provide valuable guidance for clinical practice. A total of 120 patients who confirmed with lumbar disc herniation in our hospital from January 2016 to December 2018 were enrolled as research objects in this study. On the other hand, another 120 patients who were treated for lumbar disc herniation in our hospital during the same period were classified in the control group. General routine treatment mode was adopted for the control group, while Yaotongning capsule was given to the study group on the basis of general routine treatment. The therapeutic effect was observed and compared between the two groups. The overall treatment efficiency, VAS score, serum cytokine levels and quality of life were compared between the two groups. The results showed the study group exhibited significant improvement compared with control group, p<0.05. The application of Yaotongning capsule can achieve markedly good results in treatment of lumbar disc herniation, which is worthy of popularization and application.

DANCR-mediated microRNA-665 regulates proliferation and metastasis of cervical cancer through the ERK/SMAD pathway.

Emerging evidence has indicated that microRNAs (miRNAs) play an important role in cervical cancer (CC). However, the role of miRNA (miR)-665 in cervical cancer remains unclear. The aim of the present study was to investigate the potential functions of miR-665 in CC and to identify the underlying mechanisms of action. Herein, we show that miR-665 was downregulated in CC tissues and cell lines, which is negatively correlated with tumor size, distant metastasis, advanced TNM stage and poor prognosis. Functionally, miR-665 inhibited cell proliferation, migration and invasion and resistance of cisplatin for CC cells, as well as tumor growth. We validated that transforming growth factor beta receptor 1 (TGFBR1) was a direct target of miR-665 and mediated the ERK/SMAD pathway. In addition, we identified miR-665 as the competing endogenous RNA for long noncoding (lnc)-DANCR. These observations suggested that lnc-DANCR-mediated miR-665 downregulation regulates the malignant phenotype of CC cells by targeting TGFBR1 through the ERK/SMAD pathway, which may present a pathway for novel therapeutic stratagems for CC therapy.

MiR-212/132 is epigenetically downregulated by SOX4/EZH2-H3K27me3 feedback loop in ovarian cancer cells.

Both miR-212 and miR-132 are usually downregulated in ovarian cancer and act as tumor suppressors. However, the mechanism of their downregulation in ovarian cancer is not clear. In this study, we investigated the regulative effects of miR-212 and miR-132 on SOX4 expression in ovarian cancer cells and also studied whether there is a feedback regulation between miR-212/miR-132 and SOX4 via an epigenetic mechanism. The results showed that both EZH2 and SOX4 overexpressions significantly repressed miR-212 and miR-132 expressions in SKOV3 and OV2008 cells. Immunoprecipitation assay showed that there are interactions among SOX4, EZH2, and H3K27me3, and ChIP assay confirmed significant enrichment of EZH2 and H3K27me3 in the promoter region of miR-212/132. Both pri-miR-212 and pri-miR-132 expressions decreased after enforced EZH2 or SOX4 expression. Western blot and dual-luciferase assay confirmed that miR-212 and miR-132 can target the same sites in the 3'UTR of SOX4 mRNA and suppress its expression in ovarian cancer cells. MiR-132 or miR-212 overexpression or knockdown of endogenous SOX4 reduced epithelial-mesenchymal transition (EMT)-like properties. Therefore, we infer that the SOX4/EZH2 complex can silence miR-212 and miR-132 expressions via binding to the promoter region and promoting H3K27me3, while miR-212 and miR-132 can directly bind to the 3'UTR of SOX4 and suppress its expression. This forms a MiR-132/212-SOX4/EZH2-H3K27me3 feedback loop in ovarian cancer cells. Functionally, SOX4 is a downstream effector of miR-212/132 modulating EMT of ovarian cancer cells.

Engineering the substrate specificity of ADP-ribosyltransferases for identifying direct protein targets.

Adenosine diphosphate ribosyltransferases (ARTDs; ARTD1-17 in humans) are emerging as critical regulators of cell function in both normal physiology and disease. These enzymes transfer the ADP-ribose moiety from its substrate, nicotinamide adenine dinucleotide (NAD(+)), to amino acids of target proteins. The functional redundancy and overlapping target specificities among the 17 ARTDs in humans make the identification of direct targets of individual ARTD family members in a cellular context a formidable challenge. Here we describe the rational design of orthogonal NAD(+) analogue-engineered ARTD pairs for the identification of direct protein targets of individual ARTDs. Guided by initial inhibitor studies with nicotinamide analogues containing substituents at the C-5 position, we synthesized an orthogonal NAD(+) variant and found that it is used as a substrate for several engineered ARTDs (ARTD1, -2, and -6) but not their wild-type counterparts. Comparing the target profiles of ARTD1 (PARP1) and ARTD2 (PARP2) in nuclear extracts highlighted the semi-complementary, yet distinct, protein targeting. Using affinity purification followed by tandem mass spectrometry, we identified 42 direct ARTD1 targets and 301 direct ARTD2 targets. This represents a powerful new technique for identifying direct protein targets of individual ARTD family members, which will facilitate studies delineating the pathway from ARTD activation to a given cellular response.

Relationship Between Occupational Noise Exposure and Gestational Hypertension in Pregnant Women in Taizhou City: Cross-Sectional Study.

OBJECTIVE: In view of the hazards of occupational noise exposure, this study investigated the relationship between occupational noise exposure and gestational hypertension in Taizhou City, Zhejiang Province, China to provide inspiration and reference for reducing the occurrence of gestational hypertension. METHODS: This cross-sectional study analyzed the clinical data of 316 pregnant women in Taizhou City admitted to Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University from May 2020 to May 2023. In accordance with Acoustic Environment Quality Standards (GB3096-2008), 60 dB was used as the cut-off point. These pregnant women were divided into the low noise group (LNG, n = 161) and high noise group (HNG, n = 155) according to the noise exposure level in the working environment. This also study compared the noise exposure, blood pressure (BP), fasting blood glucose (FBG), blood lipid (BL), fetal size, and heart rate (HR), and analyzed the relationship of noise exposure with BP, FBG, BL, fetal size, HR, and occurrence of gestational hypertension. RESULTS: The HNG had higher noise exposure level (P < 0.001), BP, FBG, BL and HR (P < 0.001), larger fetal size (P < 0.001) and higher occurrence of gestational hypertension (P < 0.05) compared with the LNG. Correlation analysis showed that noise exposure level was positively correlated with BP, FBG, BL, HR, and fetal size (P < 0.001) and had the strongest association with gestational hypertension. CONCLUSION: Occupational noise exposure has adverse effects on pregnant women and fetuses. Pregnant women should pay attention to their exposure to occupational noise to prevent gestational hypertension. The results of this study must be further verified and generalized.

Investigation of the relationship between the changes in vaginal microecological enzymes and human papillomavirus (HPV) infection.

This study aims to investigate the relationship between the human papillomavirus (HPV) infection and the altered vaginal microecological environment of patients. Initially, HPV genotyping and microecological detection were performed in 1281 subjects in the Department of Obstetrics and Gynecology of The First Hospital of Qinhuangdao (Qinhuangdao, China). The relationship between the enzymes of vaginal microecology, that is, proline aminopeptidase and acetylglucosaminidase, and vaginal inflammatory diseases, as well as the prognosis of HPV infection, was analyzed. The experimental findings indicated a close relationship between the expression of positive prolyl aminopeptidase and trichomonas vaginitis, as well as bacterial vaginitis. In addition, the expression of acetylglucosaminidase is closely associated with trichomonas vaginitis and vulvovaginal candidiasis. Furthermore, the observations indicated that positive prolyl aminopeptidase and acetylglucosaminidase could increase the risk of various subtypes of HPV infection in patients. The receiver operating characteristic curve analysis presented that the expression of prolyl aminopeptidase and acetylglucosaminidase could offer exceptional diagnostic efficacy, indicating their association with persistent HPV infection. In summary, our results highlighted that the expression of positive prolyl aminopeptidase and acetylglucosaminidase in the vaginal microecology could be substantially correlated to the occurrence and the development of vaginal inflammatory diseases, as well as the outcome and the risk of persistent HPV infection.

Expression and clinical significance of RHCG in endometrial cancer.

Endometrial cancer (EC) is the most common gynecological cancer. Rhesus family, C glycoprotein (RHCG) has been evidenced to be involved in the occurrence and development of various tumors. This study aimed to investigate the expression and clinical significance of RHCG in EC. Bioinformatics analysis was based on the RNAseq counts data from TCGA database, and the prognosis analysis was performed using the Kaplan-Meier method; 4 cases of endometrioid adenocarcinomas samples and 4 cases of normal proliferative endometrium were collected for qPCR and western blot; immunohistochemistry analysis was employed to assess the expression of RHCG in a tissue microarray; the correlation between RHCG and clinicopathological factors was analyzed through Mann-Whitney U test. The lentiviral interference vector was further constructed. The results demonstrated that RHCG was highly expressed in EC tissues, and RHCG was an independent factor affecting the overall survival of patients. Additionally, the expression of RHCG was related to FIGO stage and tumor infiltrate. After interfering with shRHCG, the proliferation activity of EC cells decreased, the migration ability of cells decreased, the apoptosis of cells increased, and the tumor outgrowth was arrested. In summary, RHCG promotes the malignant proliferation and migration of EC, and makes the cells have anti-apoptotic activity. Our study provides a theoretical basis for RHCG to become a potential therapeutic target for EC in the future.

Lead-induced nitric oxide generation plays a critical role in lead uptake by Pogonatherum crinitum root cells.

The effects of lead (Pb) on endogenous nitric oxide (NO) generation, the role of NO in Pb uptake and the origin of Pb-induced NO production in Pogonatherum crinitum root cells were evaluated. Pb treatment induced rapid NO generation, showing that Pb exposure triggered endogenous NO signaling of the cells. Pre-treatment of the cells with the NO-specific scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline -1-oxyl-3-oxide (cPTIO) not only abolished the Pb-triggered NO burst but also reduced Pb contents of the cells. Moreover, Pb exposure enhanced nitrate reductase (NR) activity of the cells. The NR inhibitors tungstate and glutamine not only suppressed the Pb-enhanced NR activities but also reduced the Pb-triggered NO generation. Pre-treatment of the cells with tungstate and glutamine suppressed Pb accumulation and the suppression could be restored by application of exogenous NO via its donors sodium nitroprusside (SNP) and S-nitrosoglutathione (GSNO). Together, our results indicated that Pb exposure enhanced NR activity and triggered the NO burst of P. crinitum root cells. Furthermore, the data demonstrated that NR was responsible for the Pb-triggered NO burst and that NR-mediated NO generation played a critical role in Pb uptake by P. crinitum root cells. Thus, our results suggest a potential strategy for controlling Pb uptake by plants by targeting NR as a source of Pb-triggered NO production.

CDCA3 exhibits a role in promoting the progression of ovarian cancer.

OBJECTIVE: Ovarian cancer (OC) is one of the common gynecological malignant tumors. Cell division cycle-associated protein-3 (CDCA3) is involved in the regulation of cell cycle progression. The role of CDCA3 in OC was explored in this study. METHODS: The expression of CDCA3 in OC was evaluated in the Gene Expression Omnibus (GEO) database and further verified by qRT-PCR and Western blot (WB). Subsequently, we established lentivirus-mediated CDCA3 knockdown in OC cell lines HO-8910 and A2780. The biological roles of CDCA3 on proliferation, sensitivity to cisplatin, apoptosis, migration and tumor formation of OC were investigated using loss-of-function assays. RESULTS: CDCA3 was frequently up-regulated in OC. Knockdown of CDAC3 inhibited proliferation and migration, and enhanced apoptosis as well as sensitivity of OC cells to cisplatin. In vivo results further confirmed the inhibitory effect of CDCA3 knockdown on tumor growth. CONCLUSIONS: Our findings indicated that CDCA3 may play an important role in OC progression, and may serve as a potential therapeutic target for the OC treatment.

Modifying SnS2 With Carbon Quantum Dots to Improve Photocatalytic Performance for Cr(VI) Reduction.

The photoreduction for hazardous Cr(VI) in industrial wastewater has been considered a "green" approach with low-cost and easy-to-go operation. SnS2 is a promising narrow bandgap photocatalyst, but its low charge carrier separation efficiency should be solved first. In this work, N-doped carbon quantum dots (CQDs) were prepared and loaded onto SnS2 nanoparticles via an in situ method. The resulting composite samples (NC@SnS2) were characterized, and their photocatalytic performance was discussed. SnS2 nanoparticles were obtained as hexagonal ones with a bandgap of 2.19 eV. The optimal doping level for NC@SnS2 was citric acid: urea:SnS2 = 1.2 mmol:1.8 mmol:3.0 mmol. It showed an average diameter of 40 nm and improved photocatalytic performance, compared to pure SnS2, following a pseudo-first-order reaction with a kinetic rate constant of 0.1144 min-1. Over 97% of Cr(VI) was photo-reduced after 30 min. It was confirmed that modification of SnS2 with CQDs can not only improve the light-harvesting ability but also stimulate the charge separation, which therefore can enhance the photoreactivity of SnS2 toward Cr(VI) reduction. The excellent stability of NC@SnS2 indicates that it is promising to be practically used in industrial wastewater purification.

Evolution of sulfate reduction behavior in leachate saturated zones in landfills.

The sulfate reduction behavior of the landfill leachate saturated zone under different temperatures was investigated. The results showed that temperature had significant effects on sulfate reduction behavior. The sulfate reduction efficiency was the highest at high temperatures (55 °C and 45 °C), followed by mesophilic temperature (35 °C). Normal temperature 25 °C was far less effective than 55 °C, 45 °C and 35 °C. High abundances of aprA and dsrA genes were distributed under high temperatures. Through indicator species analysis and functional comparison, some key taxa were identified as putative key genera for sulfate reduction. Under high temperature, Paenibacillus could effectively degrade dimethyl sulfide. DsrAB is present in the genome of Tissierella. Gordonia, Syntrophomonas, and Lysinibacillus under mesophilic temperature indicates the potential of these organisms to degrade heterogenous biomass, environmental pollutants or other natural polymers with slow biodegradation. This microbial function is similar to that of the putative key genera under normal (25 °C) temperature. Most of the putative key genera belong to Firmicutes, Proteobacteria and Myxococcota. This study provides theoretical support for the control of hydrogen sulfide release from landfills.

Artificial Intelligence Based Study Association between p53 Gene Polymorphism and Endometriosis: A Systematic Review and Meta-analysis.

Background: The P53 gene is critical to the onset and progression of cancers. Currently, relevant study findings indicate that the p53 gene may have a strong association with the risk of endometriosis, but these findings have not been united. To gather more statistically meaningful clinical data, we used meta-analysis to examine the relationship between the rs1042522 single nucleotide polymorphism of the tumor suppressor gene p53 and the incidence of endometriosis. Methods: Through a comprehensive literature survey of PubMed, MEDLINE, EMBASE, Springer, and Web of Science literature databases, we obtained a clinical control case study on the relationship between p53 gene polymorphism and the prevalence of female endometriosis and finally traced the relevant references included. The quality of the literature included in this study was evaluated, and Revman5.3 was used to complete the meta-analysis. Results: This research includes eight publications. The total number of cases in the study group was 1551, whereas the total number of cases in the control group was 1440. The findings of the sensitivity analyses of each omitted piece of the literature revealed no significant difference. The results of the meta-analysis showed that there were significant differences in the GG gene frequency (OR = 0.56, 95%CI (0.38, 0.92), P = 0.003), allele G (OR = 2.46, 95%CI (1.41,4.29), P = 0.002), and allele C (OR = 0.62, 95%CI (0.46, 0.84), P = 0.002) between the study group and the control group (P < 0.01), but there was no significant difference in the GC gene frequency (OR = 1.17, 95%CI (1.01,1.36), P = 0.03), and the CC gene frequency (OR = 1.25, 95%CI (0.85,1.82), P = 0.26) (P > 0.01). Conclusion: Our study results show that there is a significant correlation between the single nucleotide of the p53 gene and the incidence rate of female endometriosis, in which the decrease of the GG gene frequency and the increase of allele C are likely to increase the risk of such diseases.

Corrigendum: Modifying SnS2 with carbon quantum dots to improve photocatalytic performance for Cr(VI) reduction.

[This corrects the article DOI: 10.3389/fchem.2022.911291.].

Identification and Characterization of Small-Molecule IRF3-Dependent Immune Activators for Pharmaceutical Development.

We sought to develop a small-molecule activator of interferon regulatory factor 3 (IRF3), an essential innate immune transcription factor, which could potentially be used therapeutically in multiple disease settings. Using a high-throughput screen, we identified small-molecule entities that activate a type I interferon response, with minimal off-target NFκB activation. We identified 399 compounds at a hit rate of 0.24% from singlicate primary screening. Secondary screening included the primary hits and additional compounds with similar chemical structures obtained from other library sources and resulted in 142 candidate compounds. The hit compounds were sorted and ranked to identify compound groups with activity in both human and mouse backgrounds to facilitate animal model engagement for translational development. Chemical modifications within two groups of small molecules produced leads with improved activity over original hits. Furthermore, these leads demonstrated activity in ex vivo cytokine release assays from human blood- and mouse bone marrow-derived macrophages. Dependence on IRF3 was demonstrated using bone marrow-derived macrophages from IRF3-deficient mice, which were not responsive to the molecules. To identify the upstream pathway leading to IRF3 activation, we used a library of CRISPR knockout cell lines to test the key innate immune adaptor and receptor molecules. These studies indicated a surprising toll-interleukin-1 receptor-domain-containing-adapter-inducing interferon-ß-dependent but TLR3/4-independent mechanism of IRF3 activation.

Structure-guided design and characterization of a clickable, covalent PARP16 inhibitor.

PARP16-the sole ER-resident PARP family member-is gaining attention as a potential therapeutic target for cancer treatment. Nevertheless, the precise function of the catalytic activity of PARP16 is poorly understood. This is primarily due to the lack of inhibitors that are selective for PARP16 over other PARP family members. Herein, we describe a structure-guided strategy for generating a selective PARP16 inhibitor by incorporating two selectivity determinants into a phthalazinone pan-PARP inhibitor scaffold: (i) an acrylamide-based inhibitor (DB008) designed to covalently react with a non-conserved cysteine (Cys169, human numbering) in the NAD+ binding pocket of PARP16 and (ii) a dual-purpose ethynyl group designed to bind in a unique hydrophobic cavity adjacent to the NAD+ binding pocket as well as serve as a click handle. DB008 exhibits good selectivity for PARP16 versus other PARP family members. Copper-catalyzed azide-alkyne cycloaddition (CuAAC) confirmed that covalent labeling of PARP16 by DB008 in cells is dependent on Cys169. DB008 exhibits excellent proteome-wide selectivity at concentrations required to achieve saturable labeling of endogenous PARP16. In-cell competition labeling experiments using DB008 provided a facile strategy for evaluating putative PARP16 inhibitors. Lastly, we found that PARP16 is sequestered into a detergent-insoluble fraction under prolonged amino acid starvation, and surprisingly, treatment with PARP16 inhibitors prevented this effect. These results suggest that the catalytic activity of PARP16 regulates its solubility in response to nutrient stress.