The prognostic value of tumor-associated macrophages detected by immunostaining in diffuse large B cell lymphoma: A meta-analysis

BackgroundThe prognostic implication of tumor-associated macrophages (TAMs) in the microenvironment of diffuse large B cell lymphoma (DLBCL) remains controversial.MethodsA systematic and comprehensive search of relevant studies was performed in PubMed, Embase and Web of Science databases. The quality of the included studies was estimated using Newcastle-Ottawa Scale (NOS).ResultsTwenty-three studies containing a total of 2992 DLBCL patients were involved in this study. They were all high-quality studies scoring ≥ 6 points. High density of M2 TAMs in tumor microenvironment significantly associated with both advanced disease stage (OR= 1.937, 95% CI: 1.256-2.988, P = 0.003) and unfavorable overall survival (OS) (HR = 1.750, 95% CI: 1.188-2.579, P = 0.005) but not associated with poor progression free survival (PFS) (HR = 1.672, 95% CI: 0.864-3.237, P = 0.127) and international prognostic index (IPI) (OR= 1.705, 95% CI: 0.843-3.449, P = 0.138) in DLBCL patients. No significant correlation was observed between the density of CD68+ TAMs and disease stage (OR= 1.433, 95% CI: 0.656-3.130, P = 0.366), IPI (OR= 1.391, 95% CI: 0.573-3.379, P = 0.466), OS (HR=0.929, 95% CI: 0.607-1.422, P = 0.734) or PFS (HR= 0.756, 95% CI: 0.415-1.379, P = 0.362) in DLBCL patients.ConclusionThis meta-analysis demonstrated that high density of M2 TAMs in the tumor microenvironment was a robust predictor of adverse outcome for DLBCL patients.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42022343045

Design, synthesis, and biological evaluation of NAD(P)H: quinone oxidoreductase (NQO1)-targeted oridonin prodrugs possessing indolequinone moiety for hypoxia-selective activation

The enzyme NQO1 is a potential target for selective cancer therapy due to its overexpression in certain hypoxic tumors. A series of prodrugs possessing a variety of cytotoxic diterpenoids (oridonin and its analogues) as the leaving groups activated by NQO1 were synthesized by functionalization of 3-(hydroxymethyl)indolequinone, which is a good substrate of NQO1. The target compounds (29a-m) exhibited relatively higher antiproliferative activities against NQO1-rich human colon carcinoma cells (HT-29) and human lung carcinoma (A549) cells (IC50 ¼ 0.263e2.904 mM), while NQO1-defficient lung adenosquamous carcinoma cells (H596) were less sensitive to these compounds, among which, compound 29h exhibited the most potent antiproliferative activity against both A549 and HT-29 cells, with IC50 values of 0.386 and 0.263 mM, respectively. Further HPLC and docking studies demonstrated that 29h is a good substrate of NQO1. Moreover, the investigation of anticancer mechanism showed that the representative compound 29h affected cell cycle and induced NQO1 dependent apoptosis through an oxidative stress triggered mitochondria-related pathway in A549 cells. Besides, the antitumor activity of 29h was also verified in a liver cancer xenograft mouse model. Biological evaluation of these compounds concludes that there is a strong correlation between NQO1 enzyme and induction of cancer cell death. Thus, this suggests that some of the target compounds activated by NQO1 are novel prodrug candidates potential for selective anticancer therapy

Prevalence and factors associated with post-traumatic stress disorder in healthcare workers exposed to COVID-19 in Wuhan, China: a cross-sectional survey

BackgroundThe COVID-19 pandemic has posed significant threats to both the physical and psychological health of healthcare workers working in the front-line combating COVID-19. However, studies regarding the medium to long term impact of COVID-19 on mental health among healthcare workers are limited. Therefore, we conducted this cross-sectional survey to investigate the prevalence, factors and impact of post-traumatic stress disorder (PTSD) in healthcare workers exposed to COVID-19 8 months after the end of the outbreak in Wuhan, China.MethodsA web-based questionnaire was delivered as a link via the communication application WeChat to those healthcare workers who worked at several COVID-19 units during the outbreak (from December 2019 to April 2020) in Wuhan, China. The questionnaire included questions on social-demographic data, the post-traumatic stress disorder checklist-5 (PCL-5), the family care index questionnaire (Adaptation, Partnership, Growth, Affection and Resolve, APGAR), and the quality-of-life scale (QOL). The prevalence, risk and protective factors, and impact of PTSD on healthcare workers were subsequently analyzed.ResultsAmong the 659 participants, 90 healthcare workers were still suffering from PTSD 8 months after the end of the outbreak of COVID-19 in Wuhan, in which avoidance and negative impact were the most affected dimensions. Suffering from chronic disease, experiencing social isolation, and job dissatisfaction came up as independent risk factors for PTSD, while obtaining COVID-19 related information at an appropriate frequency, good family function, and working in well-prepared mobile cabin hospitals served as protective factors. The impact of PTSD on COVID-19 exposed healthcare workers was apparent by shortened sleeping time, feeling of loneliness, poorer quality of life and intention to resign.ConclusionsEight months after the end of the COVID-19 outbreak in Wuhan, the level of PTSD in healthcare workers exposed to COVID-19 was still high. Apart from the commonly recognized risk factors, comorbid chronic disease was identified as a new independent risk factor for developing PTSD. For countries where the pandemic is still ongoing or in case of future outbreaks of new communicable diseases, this study may contribute to preventing cases of PTSD in healthcare workers exposed to infectious diseases under such circumstances

AluScan: a method for genome-wide scanning of sequence and structure variations in the human genome

<p>Abstract</p> <p>Background</p> <p>To complement next-generation sequencing technologies, there is a pressing need for efficient pre-sequencing capture methods with reduced costs and DNA requirement. The Alu family of short interspersed nucleotide elements is the most abundant type of transposable elements in the human genome and a recognized source of genome instability. With over one million Alu elements distributed throughout the genome, they are well positioned to facilitate genome-wide sequence amplification and capture of regions likely to harbor genetic variation hotspots of biological relevance.</p> <p>Results</p> <p>Here we report on the use of inter-Alu PCR with an enhanced range of amplicons in conjunction with next-generation sequencing to generate an Alu-anchored scan, or 'AluScan', of DNA sequences between Alu transposons, where Alu consensus sequence-based 'H-type' PCR primers that elongate outward from the head of an Alu element are combined with 'T-type' primers elongating from the poly-A containing tail to achieve huge amplicon range. To illustrate the method, glioma DNA was compared with white blood cell control DNA of the same patient by means of AluScan. The over 10 Mb sequences obtained, derived from more than 8,000 genes spread over all the chromosomes, revealed a highly reproducible capture of genomic sequences enriched in genic sequences and cancer candidate gene regions. Requiring only sub-micrograms of sample DNA, the power of AluScan as a discovery tool for genetic variations was demonstrated by the identification of 357 instances of loss of heterozygosity, 341 somatic indels, 274 somatic SNVs, and seven potential somatic SNV hotspots between control and glioma DNA.</p> <p>Conclusions</p> <p>AluScan, implemented with just a small number of H-type and T-type inter-Alu PCR primers, provides an effective capture of a diversity of genome-wide sequences for analysis. The method, by enabling an examination of gene-enriched regions containing exons, introns, and intergenic sequences with modest capture and sequencing costs, computation workload and DNA sample requirement is particularly well suited for accelerating the discovery of somatic mutations, as well as analysis of disease-predisposing germline polymorphisms, by making possible the comparative genome-wide scanning of DNA sequences from large human cohorts.</p

High-temperature humidity sensors based on WO3-SnO2 composite hollow nanospheres

National Natural Science Foundation of China [61376073]Three kinds of humidity sensors were fabricated from WO3-SnO2 composite hollow nanospheres (WO3-SnO2 HNS), WO3 nanoparticles (WO3 NPs) and SnO2 nanoparticles (SnO2 NPs). WO3-SnO2 HNS were prepared by a facile hydrothermal process with a diameter and thickness of about 550 nm and 30 nm, respectively. Temperature-dependent properties of as-prepared humidity sensors were investigated at various values of relative humidity and temperature. It was found that the WO3-SnO2 HNS humidity sensor showed good performance at 80 degrees C. The response time, recovery time and sensitivity were evaluated while switching the humidity between 35% RH and 98% RH. The response time decreased from 289 to 29 s, the recovery time reduced from 22 to 8 s, and the sensitivity changed from 16.2 to 11.4 as the work temperature was raised from 24 to 80 degrees C. An opposite humidity sensing phenomenon was observed between WO3 NPs and SnO2 NPs at a high temperature, which might explain the temperature-dependent properties of the WO3-SnO2 HNS humidity sensor. This work could stimulate a right approach to design practical humidity sensors with high sensitivity, long stability and fast response

Expression of SET Protein in the Ovaries of Patients with Polycystic Ovary Syndrome

Background. We previously found that expression of SET gene was up-regulated in polycystic ovaries by using microarray. It suggested that SET may be an attractive candidate regulator involved in the pathophysiology of polycystic ovary syndrome (PCOS). In this study, expression and cellular localization of SET protein were investigated in human polycystic and normal ovaries. Method. Ovarian tissues, six normal ovaries and six polycystic ovaries, were collected during transsexual operation and surgical treatment with the signed consent form. The cellular localization of SET protein was observed by immunohistochemistry. The expression levels of SET protein were analyzed by Western Blot. Result. SET protein was expressed predominantly in the theca cells and oocytes of human ovarian follicles in both PCOS ovarian tissues and normal ovarian tissues. The level of SET protein expression in polycystic ovaries was triple higher than that in normal ovaries (P<0.05). Conclusion. SET was overexpressed in polycystic ovaries more than that in normal ovaries. Combined with its localization in theca cells, SET may participate in regulating ovarian androgen biosynthesis and the pathophysiology of hyperandrogenism in PCOS

Social Cognitive Role of Schizophrenia Candidate Gene GABRB2

10.1371/journal.pone.0062322PLoS ONE84

Evaluation of spatial-temporal variations and trends in surface water quality across a rural-suburban-urban interface

Water quality degradation is often a severe consequence of rapid economic expansion in developing countries. Methods to assess spatial-temporal patterns and trends in water quality are essential for guiding adaptive management efforts aimed at water quality remediation. Temporal and spatial patterns of surface water quality were investigated for 54 monitoring sites in the Wen-Rui Tang River watershed of eastern China to identify such patterns in water quality occurring across a rural-suburban-urban interface. Twenty physical and chemical water quality parameters were analyzed in surface waters collected once every 4-8 weeks from 2000 to 2010. Temporal and spatial variations among water quality parameters were assessed between seasons (wet/dry) and among major land use zones (urban/suburban/rural). Factor analysis was used to identify parameters that were important in assessing seasonal and spatial variations in water quality. Results revealed that parameters related to organic pollutants (dissolved oxygen (DO), chemical oxygen demand (manganese) (COD(Mn)), and 5-day biochemical oxygen demand (BOD₅)), nutrients (ammonia nitrogen (NH₄ ⁺-N), total nitrogen (TN), total phosphorus (TP)), and salt concentration (electrical conductivity (EC)) were the most important parameters contributing to water quality variation. Collectively, they explained 70.9 % of the total variance. A trend study using the seasonal Kendall test revealed reductions in COD(Mn), BOD₅, NH₄ ⁺-N, petrol, V-phen, and EC concentrations over the 11-year study period. Cluster analysis was employed to evaluate variation among 14 sampling sites representative of dominant land use categories and indicated three, three, and four clusters based on organic, nutrient, and salt water quality characteristics, respectively. Factors that are typically responsible for water quality degradation (including population, topography, and land use) showed no strong correlation with water quality trends implying considerable point source inputs in the watershed. The results of this study help inform ongoing water quality remediation efforts by documenting trends in water quality across various land use zones