Non-uniformity correction algorithm for DoFP adapted to integration time variations.

Division of the focal plane (DoFP) polarization detector is a pivotal technology in real-time polarization detection. This technology integrates a micropolarization array (MPA) onto the conventional focal plane, introducing a more intricate non-uniformity than traditional focal plane detectors. Current non-uniformity correction algorithms for DoFP are difficult to adapt to changes in integration time and perform poorly in low-polarization scenarios. Analyzing the characteristics of DoFP, formulating a pixel response model, and introducing an adaptive non-uniformity correction algorithm tailored for varying integration time. The DoFP analysis vectors are decomposed into average polarization response and unit analysis vectors for correction separately to improve the performance of the correction algorithm in different polarization scenarios. The performance of modern correction algorithms was tested and evaluated using standard uniform images, and the proposed method outperformed existing algorithms in terms of polarization measurement accuracy under the root mean square error (RMSE) metric. Moreover, in natural scene images, our proposed algorithm shows favorable visual effects and distinguishes itself from its superior stability amid changes in the integration time.

Disinfection Byproducts of Haloacetaldehydes Disrupt Hepatic Lipid Metabolism and Induce Lipotoxicity in High-Fat Culture Conditions.

Unhealthy lifestyles, obesity, and environmental pollutants are strongly correlated with the development of nonalcoholic fatty liver disease (NAFLD). Haloacetaldehyde-associated disinfection byproducts (HAL-DBPs) at various multiples of concentrations found in finished drinking water together with high-fat (HF) were examined to gauge their mixed effects on hepatic lipid metabolism. Using new alternative methods (NAMs), studying effects in human cells in vitro for risk assessment, we investigated the combined effects of HF and HAL-DBPs on hepatic lipid metabolism and lipotoxicity in immortalized LO-2 human hepatocytes. Coexposure of HAL-DBPs at various multiples of environmental exposure levels with HF increased the levels of triglycerides, interfered with de novo lipogenesis, enhanced fatty acid oxidation, and inhibited the secretion of very low-density lipoproteins. Lipid accumulation caused by the coexposure of HAL-DBPs and HF also resulted in more severe lipotoxicity in these cells. Our results using an in vitro NAM-based method provide novel insights into metabolic reprogramming in hepatocytes due to coexposure of HF and HAL-DBPs and strongly suggest that the risk of NAFLD in sensitive populations due to HAL-DBPs and poor lifestyle deserves further investigation both with laboratory and epidemiological tools. We also discuss how results from our studies could be used in health risk assessments for HAL-DBPs.

Development and validation of a GC-MS/MS method for the determination of iodoacetic acid in biological samples.

Iodoacetic acid (IAA) is a halogenated disinfection by-product of growing concern due to its high cytotoxicity, genotoxicity, endocrine disruptor effects, and potential carcinogenicity. However, the data on distribution and excretion of IAA after ingestion by mammals are still scarce. Here, we developed a reliable and validated method for detecting IAA in biological specimens (plasma, urine, feces, liver, kidney, and tissues) based on modified QuEChERS sample preparation combined with gas chromatography-tandem triple quadrupole mass spectrometry (GC-MS/MS). The detection method for IAA exhibited satisfactory recovery rates (62.6-108.0%) with low relative standard deviations (RSD < 12.3%) and a low detection limit for all biological matrices ranging from 0.007 to 0.032 ng/g. The study showed that the proposed method was reliable and reproducible for analyzing IAA in biological specimens. It was successfully used to detect IAA levels in biological samples from rats given gavage administration. The results indicated that IAA was found in various tissues and organs, including plasma, thyroid, the liver, the kidney, the spleen, gastrointestinal tract, and others, 6 h after exposure. This study provides the first data on the in vivo distribution in and excretion of IAA by mammals following oral exposure.

Thyroid-Disrupting Effects of Exposure to Fipronil and Its Metabolites from Drinking Water Based on Human Thyroid Follicular Epithelial Nthy-ori 3-1 Cell Lines.

Fipronil is a broad-spectrum insecticide used for plants and poultry. Owing to its widespread use, fipronil and its metabolites (fipronil sulfone, fipronil desulfinyl, and fipronil sulfide), termed FPM, can be frequently detected in drinking water and food. Fipronil can affect the thyroid function of animals, but the effects of FPM on the human thyroid remain unclear. We employed human thyroid follicular epithelial Nthy-ori 3-1 cells to examine combined cytotoxic responses, thyroid-related functional proteins including the sodium-iodide symporter (NIS), thyroid peroxidase (TPO), deiodinases I-III (DIO I-III), and the nuclear factor erythroid-derived factor 2-related factor 2 (NRF2) pathway induced by FPM of 1-1000-fold concentrations detected in school drinking water collected from a heavily contaminated area of the Huai River Basin. Thyroid-disrupting effects of FPM were evaluated by examining biomarkers of oxidative stress and thyroid function and tetraiodothyronine (T4) levels secreted by Nthy-ori 3-1 cells after FPM treatment. FPM activated the expression of NRF2, HO-1 (heme oxygenase 1), TPO, DIO I, and DIO II but inhibited NIS expression and increased the T4 level of thyrocytes, indicating that FPM can disrupt the function of human thyrocytes through oxidative pathways. Given the adverse impact of low FPM concentrations on human thyrocytes, supportive evidence from rodent studies, and the critical importance of thyroid hormones on development, the effects of FPM on the neurodevelopment and growth of children warrant priority attention.

Application of ARE-reporter systems in drug discovery and safety assessment.

The human body is continuously exposed to xenobiotics and internal or external oxidants. The health risk assessment of exogenous chemicals remains a complex and challenging issue. Alternative toxicological test methods have become an essential strategy for health risk assessment. As a core regulator of constitutive and inducible expression of antioxidant response element (ARE)-dependent genes, nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role in maintaining cellular redox homeostasis. Consistent with the properties of Nrf2-mediated antioxidant response, Nrf2-ARE activity is a direct indicator of oxidative stress and thus has been used to identify and characterize oxidative stressors and redox modulators. To screen and distinguish chemicals or environmental insults that affect the cellular antioxidant activity and/or induce oxidative stress, various in vitro cell models expressing distinct ARE reporters with high-throughput and high-content properties have been developed. These ARE-reporter systems are currently widely applied in drug discovery and safety assessment. In the present review, we provide an overview of the basic structures and applications of various ARE-reporter systems employed for discovering Nrf2-ARE modulators and characterizing oxidative stressors.

NRF2-ARE signaling is responsive to haloacetonitrile-induced oxidative stress in human keratinocytes.

Humans are exposed to disinfection by-products through oral, inhalation, and dermal routes, during bathing and swimming, potentially causing skin lesions, asthma, and bladder cancer. Nuclear factor E2-related factor 2 (NRF2) is a master regulator of the adaptive antioxidant response via the antioxidant reaction elements (ARE) orchestrating the transcription of a large group of antioxidant and detoxification genes. Here we used an immortalized human keratinocyte model HaCaT cells to investigate NRF2-ARE as a responder and protector in the acute cytotoxicity of seven haloacetonitriles (HANs), including chloroacetonitrile (CAN), bromoacetonitrile (BAN), iodoacetonitrile (IAN), bromochloroacetonitrile (BCAN), dichloroacetonitrile (DCAN), dibromoacetonitrile (DBAN), and trichloroacetonitrile (TCAN) found in drinking water and swimming pools. The rank order of cytotoxicity among the HANs tested was IAN ≈ BAN Ëƒ DBAN Ëƒ BCAN ˃ CAN Ëƒ TCAN Ëƒ DCAN based on their LC50. The HANs induced intracellular reactive oxygen species accumulation and activated cellular antioxidant responses in concentration- and time-dependent fashions, showing elevated NRF2 protein levels and ARE activity, induction of antioxidant genes, and increased glutathione levels. Additionally, knockdown of NRF2 by lentiviral shRNAs sensitized the HaCaT cells to HANs-induced cytotoxicity, emphasizing a protective role of NRF2 against the cytotoxicity of HANs. These results indicate that HANs cause oxidative stress and activate NRF2-ARE-mediated antioxidant response, which in turn protects the cells from HANs-induced cytotoxicity, highlighting that NRF2-ARE activity could be a sensitive indicator to identify and characterize the oxidative stress induced by HANs and other environmental pollutants.

Cadmium exposure reprograms energy metabolism of hematopoietic stem cells to promote myelopoiesis at the expense of lymphopoiesis in mice.

Cadmium (Cd) is a highly toxic heavy metal in our living environment. Hematopoietic stem cells (HSC) are ancestors for all blood cells. Therefore understanding the impact of Cd on HSC is significant for public health. The aim of this study was to investigate the impact of Cd2+ on energy metabolism of HSC and its involvement in hematopoiesis. Wild-type C57BL/6 mice were treated with 10 ppm of Cd2+ via drinking water for 3 months, and thereafter glycolysis and mitochondrial (MT) oxidative phosphorylation (OXPHOS) of HSC in the bone marrow (BM) and their impact on hematopoiesis were evaluated. After Cd2+ treatment, HSC had reduced lactate dehydrogenase (LDH) activity and lactate production while having increased pyruvate dehydrogenase (PDH) activity, MT membrane potential, ATP production, oxygen (O2) consumption and reactive oxygen species (ROS), indicating that Cd2+ switched the pattern of energy metabolism from glycolysis to OXPHOS in HSC. Moreover, Cd2+ switch of HSC energy metabolism was critically dependent on Wnt5a/Cdc42/calcium (Ca2+) signaling triggered by a direct action of Cd2+ on HSC. To test the biological significance of Cd2+ impact on HSC energy metabolism, HSC were intervened for Ca2+, OXPHOS, or ROS in vitro, and thereafter the HSC were transplanted into lethally irradiated recipients to reconstitute the immune system; the transplantation assay indicated that Ca2+-dependent MT OXPHOS dominated the skewed myelopoiesis of HSC by Cd2+ exposure. Collectively, we revealed that Cd2+ exposure activated Wnt5a/Cdc42/Ca2+ signaling to reprogram the energy metabolism of HSC to drive myelopoiesis at the expense of lymphopoiesis.

Lead suppresses interferon γ to induce splenomegaly via modification on splenic endothelial cells and lymphoid tissue organizer cells in mice.

Splenomegaly is a symptom characterized by the presence of an enlarged spleen. The impact of environmental factors on splenomegaly is largely unknown. In this study, C57BL/6 mice were treated with 125 ppm or 1250 ppm lead (Pb) via drinking water for 8 wk, and the process of splenomegaly was evaluated. Treatment with 1250 ppm Pb, but not 125 ppm Pb, caused splenomegaly, which was associated with increased capacity for erythrocyte clearance. Intriguingly, Pb-caused splenomegaly was independent of lymphoid tissue inducer (LTi) cells, which produce lymphotoxins α and ß (LTα/ß) to activate endothelial cells and LT organizer (LTo) cells and drive the development of spleen physiologically. A direct action of Pb on endothelial cells and LTo cells did not impact their proliferation. On the other hand, during steady state, a tonic level of interferon (IFN)γ acted on endothelial cells and LTo cells to suppress splenomegaly, as IFNγ receptor (IFNγR)-deficient mice had enlarged spleens relative to wild-type mice; during Pb exposure, splenic IFNγ production was suppressed, thus leading to a loss of the inhibitory effect of IFNγ on splenomegaly. Mechanically, Pb acted on splenic CD4+ T cells to suppress IFNγ production, which impaired the Janus kinase (Jak)1/ signal transducer and activator of transcription (STAT)1 signaling in endothelial cells and LTo cells; the weakened Jak1/STAT1 signaling resulted in the enhanced nuclear factor-κB (NF-κB) signaling in endothelial cells and LTo cells, which drove their proliferation and caused splenomegaly. The present study reveals a previously unrecognized mechanism for the immunotoxicity of Pb, which may extend our current understanding for Pb toxicology.

COVID-19, Diabetes, and Associated Health Outcomes in China: Results from a Nationwide Survey of 10 545 Adults.

This study examined the associations between diabetes and self-reported/familial COVID-19 infection and investigated health-related outcomes among those with diabetes during China's nationwide quarantine. The 2020 China COVID-19 Survey was administered anonymously via social media (WeChat). It was completed by 10 545 adults in all of mainland China's 31 provinces. The survey consisted of 74 items covering sociodemographic characteristics, preventive measures for COVID-19, lifestyle behaviors, and health-related outcomes during the period of quarantine. Regression models examined associations among study variables. Diabetes was associated with a six-fold increased risk of reporting COVID-19 infection among respondents or their family members. Among people with diabetes, individuals who rarely wore masks had double the risk of suspected COVID-19 infection compared with those who always wore masks, with an inverse J-shaped relationship between face mask wearing and suspected COVID-19 infection. People with diabetes tended to have both poor knowledge of COVID-19 and poor compliance with preventive measures, despite perceiving a high risk of personal infection (40.0% among respondents reporting diabetes and 8.0% without diabetes). Only 54-55% of these respondents claimed to consistently practice preventive measures, including wearing face masks. Almost 60% of those with diabetes experienced food or medication shortages during the quarantine period, which was much higher than those without diabetes. Importantly, respondents who experienced medication shortages reported a 63% higher COVID-19 infection rate. Diabetes was associated with an increased risk of self-reported personal and family member COVID-19 infection, which is mitigated by consistent use of face masks.

Blood lead levels and their associated risk factors in Chinese adults from 1980 to 2018.

In China, studies on lead exposure to grownup are scarce compared to children, although relevant disease burdens for adults are much severe than that in developed countries. The present study evaluated blood lead levels (BLLs) in Chinese adults by data mining using Monte Carlo simulation. A total of 115 scientific studies published between January 1980 and March 2021 reflecting 45,514 Chinese adults were included in the study. After a continuous increase in Chinese adult BLLs from 1980-1983 (GM 74.84 µg/L) to 1994-1996 (GM 92.27 µg/L), BLLs began to decline from 2000--2002 (GM 80.32 µg/L) to 2016-2018 (GM 21.57 µg/L). This decline implied that the lead phase-out policy in gasoline was effective over the past two decades. The study indicated that North, South, and Southwest China were still relatively high compared to other regions in the past decade. Statistical analysis showed that BLLs of males (GM 68.45 µg/L) were higher than females (GM 56.51 µg/L), smokers (GM 80.96 µg/L) higher than nonsmokers (GM 58.95 µg/L), and populations over 40 (GM 40.43 µg/L) higher than younger populations (GM 40.37 µg/L). The significantly positive correlation between the concentrations of PM2.5 and topsoil lead and BLLs in Chinese adults indicated that air and soil pollution affect adult BLLs. Taken together, our results showed that strict lead control strategies and regular bio-monitoring are needed to maintain low BLLs in the population.

Comparative Study on the Treatment of Ankyloglossia by Using Er:YAG Laser or Traditional Scalpel.

ABSTRACT: The aim of this study was to compare, respectively, postoperative pain, wound healing, and patient satisfaction following lingual frenum extension treated with the Erbium Yttrium aluminum garnet. (Er:YAG) laser or the conventional scalpel. Twenty-eight patients receiving lingual frenectomy were randomly assigned to the Er:YAG laser group (n = 15) or the traditional scalpel group (n = 13). The surgical parameters were set to 3W or 4W basing on types of the lingual frenum when the Er:YAG laser was working. The same procedure was applied to the traditional scalpel group with transverse incision and longitudinal suture. The postoperative pain, wound healing and patient satisfaction were evaluated at 3 hours, 3, 7, and 30 days after operation. The visual analog scale score of postoperative pain in Er:YAG laser group was lower than that in traditional scalpel group at each time point. The wound healing score of the laser group were significantly lower than that of the traditional scalpel group at 3 and 7 days after surgery. There was no significant difference in mental, diet, and language satisfaction between the 2 groups at different time points after operation. In conclusion, Er:YAG laser was superior to the scalpel regarding minor soft-tissue surgery, and it could relieve the pain and discomfort of patients in the early stage of wound.

[Determination of halogenated carboxylic acids in drinking water by ion chromatography-orbitrap mass spectrometry method].

OBJECTIVE: To establish a method for determination of the common and emerging halogenated carboxylic acids(HCAs) in drinking water by ion chromatography(IC) and quadrupole-orbitrap(Q-Orbitrap) high resolution mass spectrometry(HRMS) combined the traditional quantitative detection with semi-target analysis. METHODS: Effects on the type of chromatographic column, the composition of mobile phase, the flow rate of acetonitrile added post column, the column temperature, and the injection volume were studied in detail for IC-HRMS method, also for HRMS conditions. Drinking water sample was directly injected into IC-HRMS for analysis after filtration. The chromatography separation was performed on an AS21 anion exchange chromatography column(2 mm×250 mm) with the gradient elution using 800 mmol/L methylamine-water as mobile phase, and acetonitrile was added after column. The detection was conducted on HRMS with the electrospray ionization negative mode. And the quantitative analysis of 8 haloacetic acids(HAAs) and semi-target screening of 19 HCAs were achieved by full MS/dd-MS~2 mode. RESULTS: Good linearity(r>0.996) was obtained for each of 8 HAAs for IC-HRMS. The method detection limits(MDLs) and method quantification limits(MQLs) were in the range of 0.50-2.5 µg/L and 1.7-8.3 µg/L, respectively. Intra-and inter-day relative standard deviations(RSDs) were in the range of 1.50%-11.0% and 4.58%-10.9%, respectively. The recoveries were in the range of 61.3%-117%(n=6). The proposed method was applied to analyze 39 drinking water samples, and dichloroacetic acid and trichloroacetic acid were detected and quantified, with concentrations ranging from 1.35 to 48.0 µg/L. Besides, five HCAs(difluoroacetic acid, trifluoroacetic acid, bromochloroacetic acid, monochloropropionic acid and dichloropropionic acid) were preliminary identified with semi-target screening method. CONCLUSION: The developed method was simple, rapid, no sample preparation except filtration and low reagent cosumption, which could meet the need of drinking water monitoring and achieve comprehensive screening of HCAs in drinking water. In addition, full MS/dd-MS~2 data acquisition mode could provide retrospective analysis of existing data by adding the emerging or interesting HCAs into the screening compound database.

Correction: Camptothecin suppresses NRF2-ARE activity and sensitises hepatocellular carcinoma cells to anticancer drugs.

The original version of this article contained an error in Figure 6A. The volumes of the tumour xenografts were incorrectly calculated. The correct figure and figure legend are provided, where the volume has been calculated using V = length × width2×π/6. The interpretation of the data and conclusions are not affected.

Developmental exposure to mercury chloride impairs social behavior in male offspring dependent on genetic background and maternal autoimmune environment.

To date, the connection between inorganic mercury (Hg) and social behavior remains incompletely understood. The aim of this study was to investigate the influence of maternal autoimmunity by inorganic Hg (Hg2+) exposure on social behavior of offspring. Wild-type (WT) and immunoglobulin deficient (Ig-/-) B10.S dams fertilized by male WT B10.S or SJL mice were treated with 50 µM Hg chloride (HgCl2). Non-pregnant female WT B10.S mice were used to investigate factors regulating HgCl2-induced autoimmunity to brain. HgCl2 selectively impaired social behavior in male offspring, but not female offspring from WT B10.S dams × male SJL, in that only male offspring displayed reduced time distribution with the stranger mouse, decreased sniffing to the stranger mouse and increased self-grooming. HgCl2 did not disrupt social behavior of male or female offspring from WT B10.S dams × male WT B10.S or Ig-/- B10.S dams × male SJL. The offspring from WT and Ig-/- B10.S dams × male SJL had equivalent autoimmunity to brain antigens during HgCl2 exposure, indicating that maternal, but not offspring-derived anti-brain antibodies (Ab) impaired social behavior of the offspring. Non-pregnant WT B10.S mice treated with HgCl2 had increased anti-brain Ab dependent on increase in CD4 T cell activation and IFNγ signaling to macrophages. IFNγ interaction with macrophages drove B cells and plasma cells to produce IgG. Therefore, HgCl2 selectively impaired social behavior in males with certain genetic background via maternally derived anti-brain Ab production, thus providing a novel insight into our current understanding of Hg toxicity.

Carcinogenic risk of N-Nitrosamines in Shanghai Drinking Water: Indications for the Use of Ozone Pretreatment.

N-Nitrosamines are drinking water disinfection byproducts that pose a high carcinogenic risk. We hypothesized that raw water treatment processes influence the types and concentrations of nitrosamines in drinking water, thereby posing differential health risks. We compared the finished water of two water treatment plants (WTP-A, WTP-B) serving Shanghai, China. Both plants use the Qingcaosha reservoir as a water source to generate drinking water with conventional but distinct treatment processes, namely preoxidation with sodium hypochlorite (WTP-A) vs ozone (WTP-B). Average nitrosamine concentrations, especially that of the probable human carcinogen (2A) N-nitrosodimethylamine, were higher in finished (drinking) water from WTP-A (35.83 ng/L) than from WTP-B (5.07 ng/L). Other differences in mean nitrosamines in drinking water included N-nitrosodipropylamine (42.62 ng/L) and N-nitrosomethylethylamine (26.73 ng/L) in WTP-A in contrast to N-nitrosodiethylamine (7.26 ng/L) and N-nitrosopyrrolidine (59.12 ng/L) in WTP-B. The estimated adult cancer risk from exposure to mixed nitrosamines was 1.83 times higher from WTP-A than from WTP-B drinking water. Children exposed to nitrosamines had a significantly higher cancer risk than adults ( p < 0.05). Disease burden exceeded 106 person-years. Taken together, these data suggest that use of ozone in the preoxidation step can reduce nitrosamine formation in drinking water and thereby lower the population cancer health risk.

Heavy Exposure of Waste Collectors to Polycyclic Aromatic Hydrocarbons in a Poor Rural Area of Middle China.

Manual collection and open-air incineration of waste materials is a common practice in rural regions of China and beyond. Low-temperature combustion of rubber and plastic waste generates high levels of airborne polycyclic aromatic hydrocarbons (PAHs). We investigated ten urinary hydroxylated PAH metabolites (OH-PAHs), the oxidative damage biomarker (8-hydroxy-deoxyguanosine, 8-OHdG), and four serum biomarkers including gamma-glutamyl transferase (GGT) and alanine aminotransferase (ALT) in 41 waste collectors and 122 control subjects residing in the same or a distant rural village in Henan Province. The level of PAH metabolites in urine (median: 17.24 µg/g Cre) was twice that of controls living in the same area without an occupational history involving waste collection (median: 8.16 µg/g Cre) and thrice that of controls living 30 km away (median: 6.07 µg/g Cre). The concentrations of OH-PAHs were positively associated with urinary 8-OHdG levels (ß = 0.283, p < 0.05). Serum GGT and ALT were slightly increased in waste collectors. Urinary 8-OHdG levels were similar in one-year and longer-term workers, suggesting that rubber and plastic waste collection/incineration carries a high PAH exposure risk. These data provide solid baseline information, emphasizing the importance of monitoring the long-term health outcomes of waste collectors and changes in exposure patterns associated with rural development and regulation of waste disposal.

Rapid and sensitive determination of nine bisphenol analogues, three amphenicol antibiotics, and six phthalate metabolites in human urine samples using UHPLC-MS/MS.

Bisphenol analogues, amphenicol antibiotics, and phthalate have widely aroused public concerns due to their adverse effects on human health. In this study, a rapid and sensitive method for determination of nine bisphenol analogues, three amphenicol antibiotics, and six phthalate metabolites in the urine based on ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry was developed and validated. The sample pretreatment condition on the base of mixed-mode anion-exchange (Oasis MAX) SPE was optimized to separate bisphenol analogues and amphenicol antibiotics from phthalate metabolites: the former were detected with a mobile phase of 0.1% ammonium water solution/methanol containing 0.1% ammonium water solution in negative mode, whereas the latter were determined with a mobile phase of 0.1% acetic acid solution/acetonitrile containing 0.1% acetic acid in negative mode. The limits of detection were less than 0.26 ng/mL for bisphenol analogues, 0.12 ng/mL for amphenicol antibiotics, and 0.14 ng/mL for phathalate metabolites. The recoveries of all target analytes in three fortification levels ranged from 72.02 to 117.64% with the relative standard deviations of no larger than 14.51%. The matrix effect was adjusted by isotopically labeled internal standards. This proposed method was successfully applied to analyze 40 actual urines and 13 out of 18 studied compounds were detected. Graphical abstract Simultaneous determination of nine bisphenol analogues, three amphenicol antibiotics, and six phthalate metabolites in human urine samples.

Comparative study on the incision healing of the palatal mucosa by using Er:YAG laser or traditional scalpel in the SD rats.

The aim of this study was to compare the histology of wound healing following incisions with the scalpel or the Er:YAG laser in the palatal mucosa of SD rats. Two types of wounds were performed with the stainless steel scalpel or the Er:YAG laser in the palatal mucosa of SD rats, while the adjacent untreated palatal mucosa was chosen as control. Rats were sacrificed on day 1, day 3, day 7, and day 30 post-surgery. Biopsy samples from each wound were examined and the expression of IL-1ß and TGF-ß1 was determined by enzyme-linked immunosorbent assay (ELISA). The early postoperative incision of the scalpel group had obvious bleeding and swelling, while the laser wound mainly covered the surface of white pseudomembrane. The infiltration of neutrophils and lymphocytes in the stroma of the scalpel incision was more than that of the laser group. Compared to the laser group, 1 and 3 days after operation, the TGF-ß1 content of the scalpel group were significantly increased (P = 0.032 and 0.019). Seven days after operation, the TGF-ß1 content of two groups was decreased. TGF-ß1 expression of control group was obviously increased (P > 0.05); 1, 3, and 7 days after operation, the traditional scalpel amount of IL-1ß expression was significantly higher than that of control group (P = 0.000, 0.000, and 0.001). Postoperative day 1, IL-1ß expression of laser group and control group had no significant difference (P = 0.572). Three days after operation, IL-1ß expression of laser incision was increased and was significantly higher than that in control group (P = 0.032), however lower than the scalpel group (P = 0.03). Seven days after operation, the IL-1ß expression of two groups had no significant difference (P = 0.333); however, the IL-1ß expression of two groups were significantly higher than that of the control group (P = 0.02 and 0.001). Compared to the traditional scalpel, the incision of Er:YAG laser has smaller inflammation reaction, more pseudomembrane coverage, and minimal damage of the mucoperiosteal tissue.

A Study on Environmental Factors for Nonsyndromic Cleft Lip and/or Palate.

The aim of the study was to investigate the association between environmental factors and nonsyndromic cleft of the lip and/or palate (NSCL/P) in Yantai District, China. A retrospective case-control study was carried out. A total of 236 NSCL/P children were selected from Department of Oral and Maxillofacial Surgery of Yantai Stomatological Hospital between September 2013 and December 2016 as cases; 209 controls were chosen from other diagnosis in the same department during the same period. The 2 groups matched age and sex. The parents of participants were inquired regarding the risk factors, and the answers were filled in a questionnaire by physicians. Chi-square and multivariate logistic regression analysis were used to analysis the data. There was significantly increased NSCL/P risk with high maternal age (P =0.002), family history (P = 0.001), abortion history (P = 0.033), poor parental education level (P = 0.008), maternal smoking (P = 0.044), maternal alcohol (P = 0.039), common cold or fever (P = 0.035), drug use (P = 0.006), and maternal stress (P = 0.049). Reduced NSCL/P risk was found with folic acid supplementation (P = 0.005), adequate maternal age (P = 0.002), and high parental education (P = 0.001). The proper amount of folic acid, the appropriate age of childbearing, and the high education were the protective factors of NSCL/P, whereas family history, abortion history, drug use during pregnancy, maternal tobacco and alcohol, and maternal stress were the risk factors for NSCL/P in Yantai District, China.

Camptothecin suppresses NRF2-ARE activity and sensitises hepatocellular carcinoma cells to anticancer drugs.

BACKGROUND: Resistance to chemotherapy is a major obstacle in the treatment of human hepatocellular carcinoma (HCC). Despite playing an important role in chemoprevention, nuclear factor erythroid 2-related factor 2 (NRF2) also contributes to chemo- and radio-resistance. The current study focusses on camptothecin as a novel NRF2 inhibitor to sensitise HCC to chemotherapy. METHODS: The expression and transcriptional activity of NRF2 in human HCC biopsies and camptothecin-treated culture cells were determined using immunostaining, western blot, reverse-transcription quantitative real-time PCR (RT-qPCR) and luciferase reporter assay. The effect of camptothecin on chemosensitivity of cancer cells was assessed in vitro and in xenografts. RESULTS: The expression and transcriptional activity of NRF2 were substantially elevated in HCC biopsies compared with corresponding adjacent tissues, and positively correlated with serum α-fetoprotein, a clinical indicator of pathological progression. In searching chemicals targeting NRF2 for chemotherapy, we discovered that camptothecin is a potent NRF2 inhibitor. Camptothecin markedly suppressed NRF2 expression and transcriptional activity in different types of cancer cells including HepG2, SMMC-7721 and A549. As a result, camptothecin sensitised these cells to chemotherapeutic drugs in vitro and in xenografts. CONCLUSIONS: Camptothecin is a novel NRF2 inhibitor that may be repurposed in combination with other chemotherapeutics to enhance their efficacy in treating high NRF2-expressing cancers.