Silver peroxide-incorporated carbon dots with high photothermal performance for combating bacteria.

The widespread use of antibiotics often increases bacterial resistance. Herein, we reported a silver peroxide-incorporated carbon dots (defined as Ag2O2-CDs) with high photothermal conversion efficiency viain situoxidation process. The prepared Ag2O2-CDs exhibited ultra-small size of 2.0 nm and hybrid phase structure. Meanwhile, the Ag2O2-CDs were of a similar optical performance comparing with traditional carbon dots (CDs). Importantly, the incorporation of Ag2O2into CDs significantly enhanced photothermal conversion efficiency from 3.8% to 28.5%. By combining silver ion toxicity and photothermal ablation, the Ag2O2-CDs were capable of destroying gram-positive and gram-negative bacterium effectively. These findings demonstrated that the Ag2O2-CDs could be served as a potential antibacterial agent for clinical applications.

Applications of Circulating Tumor DNA in Myelodysplastic Syndromes and Acute Myeloid Leukemia: Promises and Challenges.

The term 'liquid biopsy' has become widely used by clinicians with the development of non-invasive diagnostic and monitoring techniques for malignancies. Liquid biopsy can provide genetic information for early diagnosis, risk stratification, treatment selection and postoperative follow-up. In the era of personalized medicine, liquid biopsy is an important research direction. In recent years, research on circulating tumour DNA (ctDNA) in hematological malignancies has also made great progress. This review provides an overview of the current understanding of circulating tumour DNA in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Additionally, recent advancements in the monitoring of minimal/measurable residual disease (MRD) through ctDNA are discussed.

PEGylated porcine-human recombinant uricase: A novel fusion protein with improved efficacy and safety for the treatment of hyperuricemia and renal complications.

The growing prevalence of hyperuricemia necessitates the urgent development of more potent treatments. This study aimed to develop, optimize, and evaluate the safety and efficacy of porcine-human recombinant uricase (PHRU) both in vitro and in vivo. The study employed gene editing of PHRU through site-directed mutagenesis, with recombinant proteins expressed in vitro utilizing Escherichia coli. The polyethylene glycol (PEG) approach was employed to augment uricase stability and diminish immunogenicity. The pharmacokinetics and pharmacodynamics of PHRU were tested in vitro and in Sprague Dawley rats. Successful expression of the fusion protein in E. coli and the development of the PEGylated drug were achieved. In vitro experiments confirmed the efficacy of PEG-PHRU in degrading uric acid, with PEGylation not markedly affecting the biological activity of PHRU. Animal studies revealed that PEG-PHRU significantly lowered plasma uric acid levels and mitigated hyperuricemia-induced renal damage in rats. Both drug metabolism and pharmacokinetics exhibited favorable characteristics without observable adverse effects in experimental animals. This novel fusion protein shows the potential for ameliorating hyperuricemia and related renal complications, highlighting it as a promising drug candidate with substantial market applications.

Systemic subchronic toxicity and comparison of four selenium nutritional supplements by 90-day oral exposure in Sprague-Dawley rats.

To evaluate and compare the safety of four selenium supplements, namely Se-enriched peptides (SeP), yeast selenium (SeY), L-Se-methylselenocysteine (L-SeMc) and sodium selenite (Na2SeO3), the subchronic toxicity study was designed by 90-day gavage administration in Sprague-Dawley rats. The doses of SeP, SeY, L-SeMc and Na2SeO3 were 0.15, 0.30 and 0.60 mg/kg bw/day, with additional dose of 0.45 mg/kg L-SeMc (All dose calculated as Se). Symptoms like growling, hair loss and significant weight loss were found at 0.60 mg/kg of L-SeMc, but not in other groups. At the dose of 0.60 mg/kg, females in Na2SeO3, SeY and L-SeMc groups showed significant elevations in ALT and/or ALP. Pathologic manifestations such as bile duct hyperplasia and cholestasis were predominantly found in females at 0.6 mg/kg of L-SeMc and SeY groups, and in males at same dose of L-SeMc group showed marked testicular atrophy. 0.60 mg/kg of SeY and Na2SeO3, and 0.30, 0.45, 0.60 mg/kg of L-SeMc induced significant reductions in sperm motility rates, rapid movement and amount. In conclusion, the NOAEL of SeP, SeY, L-SeMc, Na2SeO3 was all 0.30 mg/kg for female, and 0.60, 0.30, 0.15 and 0.30 mg/kg for male respectively. Liver and reproductive organs are possible toxic target organs of hyper selenium.

Extended one generation reproductive toxicity study and effect on gut flora of genetically modified rice rich in ß-carotene in wistar rats.

To evaluate the reproductive toxicity of gene modified rice generated by introducing phytoene synthase (Psy) and bacterial phytoene desaturase (CrtI) from maize and Erwinia uredovora, Wistar rats were allocated into 3 groups and fed with Psy and CrtI gene modified rice mixture diet (GM group), non-gene modified rice mixture diet (non-GM group), and AIN-93 diet (Blank control group) from parental generation (F0) to the offsprings (F1). GM rice, Heijinmi (HJM) and Non-GM rice, Heishuai (HS), were both formulated into diets at ratios of 73.5% and 75.5% according to the AIN93 diet for rodent animals, respectively. Relative to the non-GM group, no biologically relevant differences were observed in GM group rats concerning reproductive performance such as fertility rate, gestation rate, mean duration, hormone level, and reproductive organ pathology. The developmental parameters results were not significantly different from the non-GM group such as body weight, food consumption, developmental neurotoxicity, behavior, hematology, and serum chemistry. In terms of immunotoxicity, the IgG indicators of offspring from the GM group improved in contrast with the non-GM group. Additional gut flora analysis of F0 generation rats resulted as that the treatment elicited an increased gut microflora diversity of F0 rats. And no horizontal gene transfer of Psy and CrtI genes in rats fed a GM rice HJM diet. In conclusion, we found no adverse effects related to GM rice in the extended one-generation reproductive toxicity study, indicating that GM rice is a safe alternative for its counterpart rice regarding reproductive toxicity.

Distribution and survival outcomes of primary head and neck hematolymphoid neoplasms in older people: a population-based study.

Primary head and neck hematolymphoid neoplasms (PHNHLN) are defined as a series of hematolymphoid system-derived neoplasms which primarily emanate in head and neck region. Due to the rarity and absence of symptomatic specificity, PHNHLN is easily neglected. The objective of this study is to investigate demographics, pathological subtype distribution, anatomical location, survival outcomes and prognostic factors of PHNHLN among older patients aged ≥ 60. The individual patient information in our study was derived from Surveillance, Epidemiology and End Results database. Descriptive epidemiological methods were used to analyze the distribution of histologic subtypes and primary anatomical sites. Kaplan-Meier survival curves and log-rank test were conducted to evaluate the effect of variables on the prognosis. Cox hazard regression was conducted to identify the independent prognostic factors. The male-to-female ratio in most pathological subtypes was close to 1:1. The most common pathological subtype was diffuse large B-cell lymphoma. The most commonly involved sites outside the lymph nodes were salivary glands, especially parotid gland, followed by tonsil, thyroid gland and tongue. The prognosis of mature T- and NK-cell non-Hodgkin lymphoma (NHL) was bleaker than Hodgkin lymphoma, mature B-cell NHL and plasma cell neoplasm. Age at diagnosis, presence of second primary malignancy (SPM), pathological subtype, Ann-Arbor stage, chemotherapy and radiation were independent prognostic factors of overall survival. Our study comprehensively reported the subtype distribution, anatomical sites and survival outcomes of PHNHLN among older patients, improving understanding of this rare group of cancer entities.

Comparison of missed adenomas in deep-sedated and unsedated colonoscopy: A multicenter retrospective study.

BACKGROUND: Deep-sedated colonoscopy with propofol is widely used in China. However, its impact on quality metrics remains controversial. We aimed to investigate the effects of deep-sedated colonoscopy on missed adenomas, specifically in each colorectal segment. METHODS: Data of 3710 individuals from seven hospitals in China who underwent an initial colonoscopy with or without propofol sedation and a second colonoscopy without sedation within six months for surveillance or polypectomy by endoscopist of the same level between October 2020 and September 2021 were retrospectively analyzed. RESULTS: A total of 1113 missed adenomas in 3710 patients were evaluated. The adenoma miss rate (AMR) was significantly higher in deep-sedated colonoscopy than in unsedated colonoscop [19.14% (578/3020) vs. 16.15% (535/3313), P < 0.05]. The risk of missing adenomas in deep-sedated colonoscopy was 1.229 times higher than in unsedated colonoscopy (OR, 1.229; 95% CI: 1.080-1.399). AMRs of the splenic flexure (26.02% [96/369] vs. 16.04% [47/293], P < 0.05) and descending colon (20.86% [102/489] vs. 13.37% [54/404], P < 0.05) were significantly higher in deep-sedated colonoscopy than in unsedated colonoscopy when performed by middle-level endoscopists rather than high-level endoscopists (P < 0.05). CONCLUSIONS: AMR was higher in deep-sedated colonoscopy than in unsedated colonoscopy. Furthermore, adenomas in the splenic flexure and descending colon were more frequently missed in deep-sedated colonoscopy than in unsedated colonoscopy, particularly when performed by less experienced endoscopists.

Forensic efficiency evaluation of a novel multiplex panel of InDels and STRs in the Guizhou Han population and its phylogenetic relationships with other reference populations.

BACKGROUND: Insertion/deletion polymorphism (InDel), as the third genetic marker, has been given a lot of attention by forensic geneticists since it has the advantages of extensive distributions in the human genome, small amplicon, and low mutation rate. However, the extant InDel panels were only viewed as supplemental tools for kinship analyses. In addition, these panels were not conductive to mixture deconvolution because InDels in these panels mainly displayed two alleles. AIMS: The purpose of this study is to investigate genetic distributions of a novel panel of InDels and STRs in the Guizhou Han population; assess the forensic application value of the panel; and conduct population genetic analyses of the Guizhou Han and other reference populations based on the overlapping loci. SUBJECTS AND METHODS: The bloodstain samples of 209 Guizhou Han were gathered and genotyped by the novel panel. Allelic frequencies and forensic parameters of two miniSTRs and 59 InDels in the panel were estimated. In addition, we assessed phylogenetic relationships among the Guizhou Han and other reference populations by principal component analysis, DA genetic distance, and neighbor-joining tree. RESULTS: A total of 139 alleles of 61 loci could be observed in the Guizhou Han population. Polymorphic information content values of 59 InDels were greater than 0.3 in the Guizhou Han population. The cumulative power of discrimination and probability of exclusion of two miniSTRs and 59 InDels in the Guizhou Han population were 0.999999999999999999999999997984 and 0.9999986, respectively. Principal component analysis of 14 populations showed that the Guizhou Han population located closer to Hunan Han and Southern Han Chinese (CHS) populations. Similar results were also discerned from DA genetic distances and the neighbor-joining tree. CONCLUSION: To sum up, the novel panel could be employed for forensic personal identification and paternity testing in the Guizhou Han population as a promising independent tool. Besides, the principal component analysis and phylogenetic tree of the Guizhou Han and other compared populations revealed that the Guizhou Han population possesses close genetic affinities with Hunan Han, CHS, and Han Chinese in Beijing (CHB) populations.

Modeling the biogenic isoprene emission and its impact on ozone pollution in Zhejiang province, China.

Isoprene is the most abundantly emitted biogenic volatile organic compound (BVOC), which plays an essential role in producing tropospheric ozone (O3). However, the simulations of isoprene emissions have not been sufficiently verified over Yangtze River Delta (YRD), and few studies have specifically addressed its impact on O3 formation. In this study, we simulated the isoprene emissions in Zhejiang Province (ZJ), a region with the largest BVOC emission in YRD, in August 2020 using the Model of Emissions of Gases and Aerosols from Nature (MEGAN) and the latest Moderate Resolution Imaging Spectroradiometer (MODIS) products, and investigated its contributions to O3 using the Weather Research and Forecasting (WRF)-Community Multiscale Air Quality (CMAQ) model. The model has a good performance on isoprene simulations over urban and suburban areas, with mean biases of -0.16-0.12 ppb, but underestimated the concentrations at forest sites (mainly due to bamboo). Regionally, the simulated formaldehyde concentrations over forests agree well with the satellite observations. In August 2020, the total isoprene emission in ZJ was 125.1 GgC, with higher emissions in western ZJ and relatively lower emissions in eastern coastal regions. The spatial pattern of isoprene concentrations is similar to its emissions, and the maximum daytime average concentrations are above 3.5 ppb. The spatial pattern of its contribution to daily maximum 8 h average O3 concentrations is significantly different from the emissions and concentrations, which shows a higher impact in northern ZJ (>6 ppb) and relatively lower impact in southern ZJ (1-3 ppb). The mean contribution over ZJ is 8.9 %, with daily variation in the range of 3.1 % to 13.4 %. For different cities, the monthly mean contribution is in the range of 4.6 % to 14.3 %, and the maximum daily contribution reaches about 25 %. These findings help understand the summertime O3 pollution in ZJ and the YRD region of China.

Increased diurnal difference of NO2 concentrations and its impact on recent ozone pollution in eastern China in summer.

Nitrogen dioxide (NO2) is a key tropospheric O3 precursor. Since 2013, efforts to decrease air pollution in China have driven substantial declines in annual NO2 concentrations, whereas ozone (O3) concentrations have increased. Based on nationwide NO2 observations and a regional air quality model (WRF-CMAQ), we analyzed trends in the diurnal difference (DD, the difference between nighttime and daytime concentrations) of NO2 concentrations across eastern China and in five national urban agglomerations (UAs) from 2014 to 2021, and explored the factors underlying such changes and the potential impacts on O3 pollution. We found that the observed DD of NO2 has increased in most cities and UAs, and that this trend can be primarily attributed to changes in anthropogenic emissions, based on comparison with DDs simulated with fixed anthropogenic emissions, which generally showed much weaker trends and little interannual variation. A sensitivity analysis using the WRF-CMAQ model was conducted to investigate the impact of a modified diurnal cycle of nitrogen oxides (NOx) emissions on O3 concentrations. The result revealed that enhancing the DD of NO2 would increase O3 concentrations in the morning and the daily maximum 8-h O3 concentrations in the cities with high NOx concentrations, as well as downwind areas of cities, indicating that greater DDs in NO2 is one of the reasons that have led to the enhanced China's O3 pollution in recent years.

MSC Senescence-Related Genes Are Associated with Myeloma Prognosis and Lipid Metabolism-Mediated Resistance to Proteasome Inhibitors.

Background: Complex carcinogenic mechanisms and the existence of tumour heterogeneity in multiple myeloma (MM) prevent the most commonly used staging system from effectively interpreting the prognosis of patients. Since the microenvironment plays an important role in driving tumour development and MM occurs most often in middle-aged and elderly patients, we hypothesize that ageing of bone marrow mesenchymal stem cells (BM-MSCs) may be associated with the progression of MM. Methods: In this study, we collected the transcriptome data on MM from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Differentially expressed genes in both senescent MSCs and MM tumour cells were considered relevant damaged genes. GO and KEGG analyses were applied for functional evaluation. A PPI network was constructed to identify hub genes. Subsequently, we studied the damaged genes that affected the prognosis of MM. Least absolute shrinkage and selection operator (lasso) regression was used to identify the most important features, and a risk model was created. The reliability of the risk model was evaluated with the other 3 GEO validation cohorts. In addition, ROC analysis was used to evaluate the novel risk model. An analysis of immune checkpoint-related genes, tumour immune dysfunction and exclusion (TIDE), and immunophenotypic scoring (IPS) were performed to assess the immune status of risk groups. pRRophetic was utilized to predict the sensitivity to administration of chemotherapeutic agents. Results: We identified that MAPK, PI3K, and p53 signalling pathways were activated in both senescent MSCs and tumour cells, and we also located hub genes. In addition, we constructed a 14-gene prognostic risk model, which was analysed with the ROC and validated in different datasets. Further analysis revealed significant differences in predicted risk values across the International Staging System (ISS) stage, sex, and 1q21 copy number. A high-risk group with higher immunogenicity was predicted to have low proteasome inhibitor sensitivity and respond poorly to immunotherapy. Lipid metabolism pathways were found to be significantly different between high-risk and low-risk groups. A nomogram was created by combining clinical data, and the optimization model was further improved. Finally, real-time qPCR was used to validate two bortezomib-resistant myeloma cell lines, and the test confirmed that 10 genes were detected to be expressed in resistant cell lines with the same trend as in the high-risk cohort compared to nonresistant cells. Conclusion: Fourteen genes related to ageing in BM-MSCs were associated with the prognosis of MM, and by combining this genotypic information with clinical factors, a promising clinical prognostic model was established.

Chromosome 1q21 gain is an adverse prognostic factor for newly diagnosed multiple myeloma patients treated with bortezomib-based regimens.

Chromosome 1q21 aberration is one of the most common cytogenetic abnormalities in multiple myeloma, and is considered an important prognostic factor. The present study analyzed the clinical relevance and prognostic impact of 1q21 gain in 194 patients with newly diagnosed multiple myeloma treated with bortezomib-based regimens. 1q21 gain was detected in 45.9% (89/194) of patients, and those with 1q21 gain had a worse prognosis. Strikingly, our results showed that excluding the effects of other coinciding genetic anomalies, patients carrying at least four copies of 1q21 had worse survival outcome. Moreover, del(13q) strongly correlates with 1q21 gain, and the coexistence of del(13q) and 1q21 gain plays an important role in reducing PFS and OS times. Therefore, 1q21 gain should be considered a high-risk feature in multiple myeloma patients treated with a bortezomib-based regimen.

Study on chronic toxicity of rhubarb extract in Sprague-Dawley rats.

Objective: The purpose of this study was to evaluate the safety of rhubarb extract. Methods: SD rats were treated with rhubarb extract at 0, 101, 405 and 1620 mg/kg/day for 52 weeks. food consumption and body weights were recorded. Blood and urine samples were collected for serum biochemical evaluation and urinalysis, and organ tissues were collected for histopathological examination. Results: The rats of 1620 mg/kg group developed diarrhea symptoms with dark brown loose stool after exposure; decreased body weight and increased food consumption were observed in the 1620 mg/kg and 405 mg/kg groups; urine WBC and NIT was significantly increased in the male and female rats of 1620 mg/kg group, and the urine pH was decreased in male rats of 1620 mg/kg group; renal tubular pigmentation was observed in the 1620 mg/kg group. Conclusion: The NOAEL of rhubarb extract on chronic toxicity (52 weeks) of Sprague-Dawley rats was 101 mg/kg in female and 94 mg/kg in male, and the LOAEL was 408 mg/kg in female and 381 mg/kg in male. The target organ of toxicity was the kidney, and the target cells was tubular epithelial cells.

Does Ozone Pollution Share the Same Formation Mechanisms in the Bay Areas of China?

As important regions of transition between land and sea, the three bay areas of Bohai Bay (BHB), Hangzhou Bay (HZB), and Pearl River Estuary (PRE) in China often suffer from severe photochemical pollution despite scarce anthropogenic emissions. To understand the causes of high ozone (O3) concentrations, the high O3 episode days associated with special synoptic systems in the three bays were identified via observations and simulated by the weather research and forecasting coupled with community multiscale air quality (WRF-CMAQ) model. It was revealed that the interaction between synoptic winds and mesoscale breezes resulted in slow wind speeds over the HZB and PRE, where air pollutants transported from upwind cities gained a long residence time and subsequently participated in intensive photochemical reactions. The net O3 production rates within the bay areas were even comparable to those in surrounding cities. This finding was also applicable to BHB but with lower net O3 production rates, while high levels of background O3 and the regional transport from farther upwind BHB partially elevated the O3 concentrations. Hence, these three bay areas served as O3 "pools" which caused the accumulation of air pollutants via atmospheric dynamics and subsequent intense photochemical reactions under certain meteorological conditions. The results may be applicable to other similar ecotones around the world.

[Clinical Characteristics and Prognosis of Systemic Anaplastic Large Cell Lymphoma].

OBJECTIVE: To evaluate the clinical characteristics, treatment and prognosis of systemic anaplastic large cell lymphoma(sALCL). METHODS: The clinical data of 90 cases with sALCL treated in the Department of Hematology of the Affiliated Xijing Hospital of Air Force Medical University from November 2018 to October 2021 were retrospectively analyzed. The clinical features, treatment and prognosis were summarized and the prognostic factors were investigated. RESULTS: There were 58 males and 32 females, with a median age of 32 (12-73) years old. 69 (76.7%) patients had Ann Arbor stage Ⅲ-Ⅳ disease and half of the patients had extranodal infiltration. The median age was 27(12-72) years of the 60 ALK+ patients while 53(15-73) years of the 30 ALK- patients, and it was significantly different in the age of onset between the two group(P<0.01). 88 patients received first line chemotherapy, and 50(568%) cases achieved complete remission(CR). IPI score≥3 was an independent risk factor for CR. The median progressive free survival(PFS) and overall survival(OS) of the patients were not reached. Multivariate analysis showed that no achievement of CR after first-line therapy was a significant prognostic factor influencing PFS and OS. CONCLUSION: sALCL mainly occurs in males and most patients were in advanced stage. Half of the patients had extranodal involvement. The CR rate after first-line chemotherapy was 568%, and IPI score≥3 was a significant prognostic factor for CR. No achievement of CR after first-line therapy is poorly prognostic for PFS and OS.

Tibetan Medicine Shi-Wei-Gan-Ning-San Alleviates Carbon Tetrachloride-Induced Chronic Liver Injury by Inhibiting TGF-ß1 in Wistar Rats.

Background: Shi-Wei-Gan-Ning-San (SWGNS) is a classic Tibetan prescription, which has obvious clinical effects in the treatment of viral hepatitis, fatty liver, liver fibrosis, liver cirrhosis, liver cancer, and other liver injuries. However, animal studies and mechanism studies are still lacking. This study aimed to investigate its hepatoprotective efficacy and pharmacological mechanism in animal experiments. Methods: Chronic liver injury was induced by oral administration of carbon tetrachloride (CCl4) in Wistar rats for 13 weeks. SWGNS was administered orally to rats at doses of 235, 705, and 1410 mg/kg for 13 weeks. Blood samples were collected for biochemical, ELISA, and radioimmunoassay. Livers were harvested for H&E and immunohistochemical staining. The major constituents of SWGNS were analyzed by HPLC. In vitro experiments were used to explore the protective effect of Crocin on BRL-3A in the environment of H2O2. Results: SWGNS reversed weight loss is induced by CCl4. Serum assays showed that SWGNS reduced CCl4-induced alanine aminotransferase, aspartate aminotransferase, total bilirubin, and γ-glutamyltransferase levels and increased the total protein and albumin levels. Histopathological evaluation showed that SWGNS alleviated hepatic steatosis, fibrosis, and inflammation. Furthermore, SWNGS reduced CCl4-induced elevations of TGF-ß1, hyaluronic acid, laminin, and collagen IV in serum and reduced the high expression of α-SMA in tissues. Moreover, Crocin I and II are the main components of SWGNS. Crocin attenuated the damaging effects of H2O2 on BRL-3A. Conclusions: In conclusion, SWGNS alleviated CCl4-induced chronic liver injury by inhibiting the TGF-ß1 pathway. This plays an important role in promoting traditional Tibetan medicine in clinical practice.

Manipulation of Elastic Instability of Viscoelastic Fluid in a Rhombus Cross Microchannel.

This paper reports the manipulation of elastic instability of the viscoelastic fluid in a rhombus cross microchannel (RCM) structure. The bistable instability and unsteady instability of the flow is firstly demonstrated in a standard cross microchannel (SCM) for reference. We then keep the bi-stable instability over a much wider injection rate range in the RCM, which is attributed to the stabilizing effect of the rhombus structure. A semi-bistable instability was also established in the RCM at a high enough injection rate. In addition, the unsteady elastic instability is realized in the RCM through an asymmetric injection rate condition.

Role of Adipose Tissue Derived Exosomes in Metabolic Disease.

Adipose tissues perform physiological functions such as energy storage and endocrine, whose dysfunction will lead to severe metabolic disorders. Accumulating evidences show that exosomes can meditate communications between different tissues by transporting nucleic acids, proteins and other biological factors. More importantly, exosomes secreted by adipose tissue function as critical contributing factors that elucidate specific mechanisms in metabolic disturbance such as obesity, adipose inflammation and diabetes etc. Adipose tissue is the major source of circulating exosomal miRNAs. miRNA secreted from adipose tissues not only altered in patients with metabolic disease, but also result in an increase in metabolic organ talk. Here we have reviewed the latest progress on the role of adipose tissue derived exosomes roles in metabolic disorders. Moreover, the current obstacles hindering exosome-based therapeutic strategies have also been discussed.

The PARP1 Inhibitor Niraparib Represses DNA Damage Repair and Synergizes with Temozolomide for Antimyeloma Effects.

Purpose: Poly(ADP-ribose) polymerase 1 (PARP1) is necessary for single-strand break (SSB) repair by sensing DNA breaks and facilitating DNA repair through poly ADP-ribosylation of several DNA-binding and repair proteins. Inhibition of PARP1 results in collapsed DNA replication fork and double-strand breaks (DSBs). Accumulation of DSBs goes beyond the capacity of DNA repair response, ultimately resulting in cell death. This work is aimed at assessing the synergistic effects of the DNA-damaging agent temozolomide (TMZ) and the PARP inhibitor niraparib (Nira) in human multiple myeloma (MM) cells. Materials and Methods: MM RPMI8226 and NCI-H929 cells were administered TMZ and/or Nira for 48 hours. CCK-8 was utilized for cell viability assessment. Cell proliferation and apoptosis were detected flow-cytometrically. Immunofluorescence was performed for detecting γH2A.X expression. Soft-agar colony formation assay was applied to evaluate the antiproliferative effect. The amounts of related proteins were obtained by immunoblot. The combination index was calculated with the CompuSyn software. A human plasmacytoma xenograft model was established to assess the anti-MM effects in vivo. The anti-MM activities of TMZ and/or Nira were evaluated by H&E staining, IHC, and the TUNEL assay. Results: The results demonstrated that cotreatment with TMZ and Nira promoted DNA damage, cell cycle arrest, and apoptotic death in cultured cells but also reduced MM xenograft growth in nude mice, yielding highly synergistic effects. Immunoblot revealed that TMZ and Nira cotreatment markedly increased the expression of p-ATM, p-CHK2, RAD51, and γH2A.X, indicating the suppression of DNA damage response (DDR) and elevated DSB accumulation. Conclusion: Inhibition of PARP1 sensitizes genotoxic agents and represents an important therapeutic approach for MM. These findings provide preliminary evidence for combining PARP1 inhibitors with TMZ for MM treatment.

Precise laser linewidth measurement by feature extraction with short-delay self-homodyne.

We propose a precision measurement method of laser linewidth based on short-delay self-homodyne, using the second peak-valley difference (SPVD) feature of the coherent power spectrum to fit laser linewidth. The SPVD model of the self-homodyne coherent envelope spectrum was established. One-to-one correspondence among the values of SPVD, the delay length, and the laser linewidth was determined theoretically and through simulations, while the reliability and stability of the method was verified experimentally. By comparing the detected results, it is found that the fitted laser linewidth obtained by the self-homodyne system is closer to its true value than that obtained by the self-heterodyne system. Hence, the simpler structure of the short-delay self-homodyne coherent envelope laser linewidth measurement method proposed is expected to substitute the previous laser linewidth measurement method, including complex short-delay self-heterodyne coherent envelope laser linewidth measurement method and traditional self-homodyne/heterodyne laser linewidth measurement method, to achieve more precise laser linewidth value.