Broadband and Spectrally Selective Photothermal Conversion through Nanocluster Assembly of Disordered Plasmonic Metasurfaces.

Plasmonic metasurfaces have been realized for efficient light absorption, thereby leading to photothermal conversion through nonradiative decay of plasmonic modes. However, current plasmonic metasurfaces suffer from inaccessible spectral ranges, costly and time-consuming nanolithographic top-down techniques for fabrication, and difficulty of scale-up. Here, we demonstrate a new type of disordered metasurface created by densely packing plasmonic nanoclusters of ultrasmall size on a planar optical cavity. The system either operates as a broadband absorber or offers a reconfigurable absorption band right across the visible region, resulting in continuous wavelength-tunable photothermal conversion. We further present a method to measure the temperature of plasmonic metasurfaces via surface-enhanced Raman spectroscopy (SERS), by incorporating single-walled carbon nanotubes (SWCNTs) as an SERS probe within the metasurfaces. Our disordered plasmonic system, generated by a bottom-up process, offers excellent performance and compatibility with efficient photothermal conversion. Moreover, it also provides a novel platform for various hot-electron and energy-harvesting functionalities.

Microwave ablation versus laparoscopic resection as first-line therapy for solitary 3-5-cm HCC.

BACKGROUND AND AIMS: The study objective was to compare the effectiveness of microwave ablation (MWA) and laparoscopic liver resection (LLR) on solitary 3-5-cm HCC over time. APPROACH AND RESULTS: From 2008 to 2019, 1289 patients from 12 hospitals were enrolled in this retrospective study. Diagnosis of all lesions were based on histopathology. Propensity score matching was used to balance all baseline variables between the two groups in 2008-2019 (n = 335 in each group) and 2014-2019 (n = 257 in each group) cohorts, respectively. For cohort 2008-2019, during a median follow-up of 35.8 months, there were no differences in overall survival (OS) between MWA and LLR (HR: 0.88, 95% CI 0.65-1.19, p = 0.420), and MWA was inferior to LLR regarding disease-free survival (DFS) (HR 1.36, 95% CI 1.05-1.75, p = 0.017). For cohort 2014-2019, there was comparable OS (HR 0.85, 95% CI 0.56-1.30, p = 0.460) and approached statistical significance for DFS (HR 1.33, 95% CI 0.98-1.82, p = 0.071) between MWA and LLR. Subgroup analyses showed comparable OS in 3.1-4.0-cm HCCs (HR 0.88, 95% CI 0.53-1.47, p = 0.630) and 4.1-5.0-cm HCCs (HR 0.77, 95% CI 0.37-1.60, p = 0.483) between two modalities. For both cohorts, MWA shared comparable major complications (both p > 0.05), shorter hospitalization, and lower cost to LLR (all p < 0.001). CONCLUSIONS: MWA might be a first-line alternative to LLR for solitary 3-5-cm HCC in selected patients with technical advances, especially for patients unsuitable for LLR.

The effect of health literacy, self-efficacy, social support and fear of disease progression on the health-related quality of life of patients with cancer in China: a structural equation model.

BACKGROUND: Health literacy (HL), self-efficacy (SE), social support (SS) and fear of disease progression (FOP) are all important factors affecting health-related quality of life (HRQoL) in cancer patients. However, their synergistic effects and underlying mechanisms on HRQoL in cancer patients remain unclear. Therefore, the purpose of this study was to construct a structural equation model (SEM) to explore the underlying mechanism of factors affecting HRQoL. It is hoped that this study will provide a theoretical basis for future interventions. METHODS: A cross-sectional design and convenience sampling method were used to investigate cancer inpatients in two general hospitals in Chongqing and Chengdu. Data were collected using structured scales, including HL, SE, SS, FOP and HRQoL. Finally, the SEM was constructed, and P ≤ 0.05 was considered significant. RESULTS: There were 1749 participants included in this study. Correlation analysis showed that all variables were significantly correlated with one another except for symptoms, physical health (PD) and social family (SF) (p < 0.01). The SEM of the HRQoL had a good overall fit (GFI = 0.943, AGFI = 0.917, NFI = 0.950, RFI = 0.936, CFI = 0.955, IFI = 0.955, RMSEA = 0.072). The model indicated that HL had the strongest correlation with HRQoL (ß = 0.398, p < 0.01), followed by FOP (ß = -0.364, p < 0.01), SE (ß = 0.347, p < 0.01) and SS (ß = 0.184, p < 0.01). CONCLUSIONS: The HRQoL of cancer patients is correlated with HL, SS, SE and FOP. HL can directly affect HRQoL and mediate HRQoL through SS and SE. Future programs should consider HL promotion, SE improvement and SS expansion as the breakthrough point when designing targeted intervention strategies. At the same time, the importance of the impact of FOP on the HRQoL of patients with cancer should not be ignored.

Investigation of health literacy status and related influencing factors in military health providers of Chinese People's liberation Army, a cross-sectional study.

OBJECTIVE: The aim of this study was to investigate health literacy and analyze its influencing factors in military health providers of the Chinese People's Liberation Army (PLA Army). METHODS: From November to December 2018, cluster sampling was used to select 1512 military health providers from the Army Medical University. Health literacy was measured by using the Chinese Citizen Health Literacy Questionnaire (HLQ) (2015 edition). Influencing factors that may affect health literacy were assessed using the chi-square test and multivariate logistic regression models. RESULTS: The knowledge rate of health literacy was relatively low (21.6%). The knowledge rate of health-related skills (HRS, 18.7%) was the lowest of the three aspects of health literacy, and the knowledge rate of chronic diseases (CD, 19.6%) was the lowest of the six dimensions of health literacy. Participants who were older, were female, were of Han ethnicity, were the only child in their families, came from urban areas, never used tobacco, and had higher household income were likely to have higher health literacy. CONCLUSION: The health literacy levels of military health providers of the PLA Army are relatively low. Further research and health education are necessary to improve health literacy.

A One-Size-Fits-All Approach to Pressure Ulcers: Whole-Buttock Fasciocutaneous Advancement Flap.

BACKGROUND: Buttock pressure injuries can be difficult to treat. There are many choices of flaps to reconstruct these wounds, but few are large, technically simple, and easily recycled. AIM AND OBJECTIVE: We are presenting our experience on surgical reconstruction of buttock pressure injuries using large whole-buttock fasciocutaneous flaps that are easily designed for ulcers regardless of location and size and are easily recycled for treatment of recurrences. MATERIAL AND METHODS: We conducted a retrospective review of all patients who received reconstruction with fasciocutaneous rotational flaps for buttock region pressure injuries from January 2013 to December 2018. The key steps of this one-size-fits-all flap include elevation of a large, oversized flap to achieve tension-free closure, avoiding fascial incisions over bony prominences, placing the V-Y type closure wound in the posteromedial thigh, and the use of closed incisional negative wound therapy postoperatively. RESULTS: Fifty patients underwent 54 flaps reconstruction for coverage of stage 4 gluteal pressure injuries between January 2013 and December 2018. Seventy-four percent healed without the need for further operation. The average size of the defect was 90 cm2 (maximum = 300 cm2). The average follow-up period was 31 months. Four of the 54 flaps were "recycled" flaps, 3 were performed for the coverage of recurrent ulcers and 1 flap was performed for treatment of a postoperative wound dehiscence. CONCLUSIONS: We recommend this simple, one-size-fits-all approach, whole-buttock fasciocutaneous flap when surgically treating gluteal pressure injuries for selected patients.

Involvement of Aquaporins in the Intense Pulsed Light-Enhanced Wound Healing in Diabetic Rats.

BACKGROUND AND OBJECTIVES: We previously demonstrated that intense pulsed light (IPL) irradiation prior to wounding improved the wound healing in rats with diabetes mellitus (DM). Also, we found that IPL upregulated the expression of aquaporin 3 (AQP3), a protein that is crucial for wound healing, in normal rats. This present study aimed to examine the involvement of AQPs in the IPL-enhanced wound healing in diabetic rats. STUDY DESIGN/MATERIALS AND METHODS: Streptozotocin was used to induce diabetes in Sprague-Dawley rats. Animals were divided into four groups: normal group, DM only group, DM rats with IPL treatment 2 weeks before wounding (DM + IPL-Pre group), and DM rats with concurrent IPL irradiation and wounding (DM + IPL-Con group). Wounds were created on the dorsal skin of rats. The expressions of AQP1, 3, 4, 7, and 9 in the pre-injured skin, periwound, and wound were determined. RESULTS: Among all the AQPs analyzed, only the expressions of AQP3 and AQP7 were significantly altered. Unirradiated diabetic rats showed much higher expression level of AQP3 in the regenerating skin compared with normal rats. IPL pretreatment, but not concurrent treatment, attenuated the expression toward the level detected in the normal wounds. In contrast, a lower expression level of AQP7 was noted in the regenerating skin of DM only rats and IPL pretreatment upregulated the expression to a level similar to that in the normal rats. CONCLUSION: The beneficial effect of IPL pretreatment on the wound healing in diabetic rats might involve a mechanism by which the expression of AQPs is regulated. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Association of serum microcystin levels with neurobehavior of school-age children in rural area of Southwest China: A cross-sectional study.

To investigate whether microcystin-LR (MC-LR) influences children's cognitive function and memory ability, we measured serum MC-LR and whole blood lead levels in 697 primary students, and collected their academic and neurobehavioral test scores. The median of serum MC-LR levels was 0.80 µg/L (the value below the limit of detection to 1.67 µg/L). The shapes of the associations of serum MC-LR levels (cut-point: 0.95 µg/L) with scores on academic achievements, digit symbol substitution test and long-term memory test were parabolic curves. Logistic regression analysis showed that MC-LR at concentrations of 0.80-0.95 µg/L was associated with the increased probability of higher achievements on academic achievements [odds ratio (OR) = 2.20, 95% confidence interval (CI): 1.28-3.79], and also with scores on digit symbol substitution test (OR = 1.73, 95% CI: 1.05-2.86), overall memory quotient (OR = 2.27, 95% CI: 1.21-4.26), long-term memory (OR = 1.85, 95% CI: 1.01-3.38) and short-term memory (OR = 2.13, 95% CI: 1.14-3.98) after adjustment for confounding factors. Antagonism of MC-LR and lead on long-term memory was observed (synergism index = 0.15, 95% CI: 0.03-0.74). In conclusion, serum MC-LR at concentrations of 0.80-0.95 µg/L was positively associated with higher scores on cognitive and neurobehavioral tests, and antagonism between MC-LR at concentrations of 0.80-1.67 µg/L and lead exposure was obviously observed on long-term memory in children. Concerning that MC-LR is a neurotoxin at high doses, our observation is interesting and need further investigation.

In Vivo Imaging of Senescent Vascular Cells in Atherosclerotic Mice Using a ß-Galactosidase-Activatable Nanoprobe.

Senescence-associated diseases have severely diminished the quality of life and health of patients. However, a sensitive assay of these diseases remains limited due to a lack of straightforward methods. Considering that senescence-associated ß-galactosidase (SA-ß-Gal) is overexpressed in senescent cells, the detection of SA-ß-Gal in senescent cells and tissues might be a feasible strategy for the early diagnosis of SA diseases. In this study, a ß-galactosidase-activatable nanoprobe BOD-L-ßGal-NPs was developed for the imaging of senescent cells and vasculature in atherosclerotic mice via real-time monitoring of ß-Gal. BOD-L-ßGal-NPs was fabricated by encapsulating a newly designed NIR ratiometric probe BOD-L-ßGal within a poly(lactic-co-glycolic) acid (PLGA) core. Nanoprobe BOD-L-ßGal-NPs showed good accumulation in arteries, thus successfully visualizing senescent cells and vasculature in atherosclerotic mice by tail vein injection. Our findings indicated that nanoprobe BOD-L-ßGal-NPs holds great potential for the early diagnosis and therapy of atherosclerosis and other aging-associated diseases.

Preparation of Highly Swelling/Antibacterial Cross-Linked N-Maleoyl-Functional Chitosan/Polyethylene Oxide Nanofiber Meshes for Controlled Antibiotic Release.

Due to the cell affinity of chitosan (CS) and the hydrophilicity of polyethylene oxide (PEO), CS/PEO composited nanofiber meshes (NFMs) have been extensively used as wound healing dressings for skin tissue regeneration. Nonetheless, numerous innate drawbacks of the NFM system such as the use of toxic spinning solvents and cross-linkers, moderate water regain capacity, and lack of triggered release function significantly hampered their biomedical applications. In order to enhance their performances in promoting cell growth and preventing bacterial infection, highly swelling cross-linked N-maleoyl-functional chitosan (MCS)/PEO NFMs have been developed as the next-generation CS/PEO NFM system through an acid-free electrospinning process and a UV-irradiated cross-linked treatment without the use of aldehyde-containing cross-linkers. With the simultaneous introduction of ethylene oxide chains and disulfide bonds in the cross-linkages, this new NFM system displays enhanced swelling capability, antibacterial ability, triggered antibiotic release, and high biocompatibility. These biomedical merits enable the new NFM systems to be utilized as tissue scaffolds, especially for functional wound healing dressings.

Rational design of fluorescent probes for targeted in vivo nitroreductase visualization.

Nitroreductase (NTR) has been recognized as a biomarker for identifying the hypoxic status of cancers. Therefore, it is of high scientific interest to design effective fluorescent probes for tracking NTR activity. However, studies on elucidation of the structure-performance relationship of fluorescent probes and those providing valuable insight into optimized probe design have rarely been reported. Three BODIPY based fluorescent probes were made by conjugation of para-, ortho-, and meta-nitrobenzene to the BODIPY core via a thiolether bond, respectively. Our study revealed that the linkage and nitro substituent position significantly influence the capability of nitroreductase detection.

Beneficial Effect of Intense Pulsed Light on the Wound Healing in Diabetic Rats.

BACKGROUND AND OBJECTIVE: Wound healing in diabetes mellitus (DM) patients is one of the major health concerns globally. Intense pulsed light (IPL) has been widely used in cosmetic dermatology via mechanisms involving fibroblast stimulation, collagen synthesis, and dermal remodeling, which are events that also occur during the process of wound healing. This present study was aimed to evaluate the possible beneficial effect of IPL on the wound healing in diabetic rats. MATERIALS AND METHODS: Diabetes was induced in Sprague-Dawley rats using streptozotocin. The rats were randomly divided into four groups: normal group, DM only group, DM rats with IPL treatment 2 weeks before wounding (DM + IPL-Pre group), and DM rats with concurrent IPL exposure and wounding (DM + IPL-Con group). The wounds were created on the dorsal skin of rats. Wound closure rate, collagen deposition, and angiogenesis were assessed. RESULTS: There were no significant differences in the wound closure rate and mean time to wound closure between IPL-treated diabetic rats and normal rats. By contrast, delayed wound closure and prolonged mean time to wound closure were both noticed in DM only group. Enhanced collagen deposition and angiogenesis were observed in IPL-Pre, but not IPL-Con diabetic rats, as compared with untreated DM rats. CONCLUSION: Results of this study may provide novel insight into future preventive strategies using IPL for the management of wounds in diabetic patients. Lasers Surg Med. © 2019 Wiley Periodicals, Inc.

Low microRNA-139 expression associates with poor prognosis in patients with tumors: A meta-analysis.

BACKGROUND: microRNA-139 (miR-139) is dysregulated in various types of tumors and plays a key role in carcinogenesis. miR-139 may be used as a diagnostic and prognostic biomarker of cancers. However, the data from the literature are not consistent. The present study aimed to verify the prognostic and diagnostic values of miR-139 in solid tumors. DATA SOURCES: PubMed, Web of Science and Embase databases were searched and publications from January 2011 to August 2017 were included. We used Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database to further validate this meta-analysis. RESULTS: Eight individual studies from seven articles were included. Pooled analyses showed that low miR-139 expression was related to worse overall survival (OS) [hazard ratio (HR) = 2.27; 95% confidence intervals (CI): 1.74-2.95; P < 0.001] in solid tumors, including hepatocellular carcinoma (HCC) and glioblastoma multiforme (GBM), consisting with the results of TCGA. However, our results of CRC showed that low miR-139 expression was associated with poor OS which was contradictory with the results in TCGA database and need larger samples to validate the phenomenon; whereas for CRC patients, high miR-139 expression predicted poor RFS, which was in good accordance with TCGA results. The results of 27 microarrays from GEO database showed that miR-139 expression levels were lower in tumor tissues compared to adjacent non-tumor tissues or healthy tissues. Decreased miR-139 expression was also significantly correlated with poor differentiation grade (OR = 3.57; 95% CI: 1.44-8.85; P = 0.006). However, the combined data indicated that no associations between miR-139 expression and the following parameters such as age (pooled OR = 1.50; 95% CI: 0.69-3.24; P = 0.304), gender (pooled OR = 0.92; 95% CI: 0.56-1.51; P = 0.738), tumor size (pooled OR = 1.51; 95% CI: 0.69-3.31; P = 0.298), late tumor-node-metastasis stage (pooled OR = 1.63; 95% CI: 0.99-2.68; P = 0.057) and lymph-node-metastasis (pooled OR = 0.66; 95% CI: 0.34-1.28; P = 0.222). CONCLUSIONS: Low miR-139 expression was related to poor prognosis in HCC and GBM, which could be regarded as a potential prognostic biomarker. However, its precise functional role in CRC still need to be further investigated through larger samples and multicenter studies.

Chronic Microcystin-LR Exposure Induces Hepatocarcinogenesis via Increased Gankyrin in Vitro and in Vivo.

BACKGROUND/AIMS: Our recent study indicated that the serum microcystin-LR (MC-LR) level is positively linked to the risk of human hepatocellular carcinoma (HCC). Gankyrin is over-expressed in cancers and mediates oncogenesis; however, whether MC-LR induces tumor formation and the role of gankyrin in this process is unclear. METHODS: We induced malignant transformation of L02 liver cells via 35 passages with exposure to 1, 10, or 100 nM MC-LR. Wound healing, plate and soft agar colony counts, and nude mice tumor formation were used to evaluate the tumorigenic phenotype of MC-LR-treated cells. Silencing gankyrin was used to confirm its function. We established a 35-week MC-LR exposure rat model by twice weekly intraperitoneal injection with 10 µg/kg body weight. In addition, 96 HCC patients were tested for tumor tissue gankyrin expression and serum MC-LR levels. RESULTS: Chronic low-dose MC-LR exposure increased proliferation, mobility, clone and tumor formation abilities of L02 cells as a result of gankyrin activation, while silencing gankyrin inhibited the carcinogenic phenotype of MC-LR-treated cells. MC-LR also induced neoplastic liver lesions in Sprague-Dawley rats due to up-regulated gankyrin. Furthermore, a trend of increased gankyrin was observed in humans exposed to MC-LR. CONCLUSION: These results suggest that MC-LR induces hepatocarcinogenesis in vitro and in vivo by increasing gankyrin levels, providing new insight into MC-LR carcinogenicity studies.

Serum microcystin levels positively linked with risk of hepatocellular carcinoma: A case-control study in southwest China.

Microcystins have been reported to be carcinogenic by animal and cell experimentation, but there are no data on the linkage between serum microcystins and hepatocellular carcinoma (HCC) risk in humans. We conducted a clinical case-control study to investigate the association between serum microcystins and HCC risk after controlling several known risk factors, such as hepatitis B virus, alcohol, and aflatoxin. From December 2013 to May 2016, 214 patients newly diagnosed with HCC along with 214 controls (frequency-matched by age and sex) were recruited from three hospitals in Chongqing, southwest China. Basic information on lifestyle and history of disease was obtained by questionnaire. Blood samples were collected and analyzed for serum microcystin-LR (MC-LR) and aflatoxin-albumin adduct by enzyme-linked immunosorbent assay and for hepatitis B surface antigen status by chemiluminescence assay. Binary logistic regression analyses were performed to assess the independent effects of MC-LR and its joint effects with other factors on HCC risk. The adjusted odds ratio for HCC risk by serum MC-LR was 2.9 (95% confidence interval [CI], 1.5-5.5) in all patients. Notably, a clear relationship between increased MC-LR level (Q2, Q3, and Q4) and HCC risk was observed with elevated adjusted odds ratios (1.3, 2.6, and 4.0, respectively). Positive interactions with the additive model were investigated between MC-LR and hepatitis B virus infection (synergism index = 3.0; 95% CI, 2.0-4.5) and between MC-LR and alcohol (synergism index = 4.0; 95% CI, 1.7-9.5), while a negative interaction was found between MC-LR and aflatoxin (synergism index = 0.4; 95% CI, 0.3-0.7). Additionally, serum MC-LR was significantly associated with tumor differentiation (r = -0.228, P < 0.001). CONCLUSION: We provide evidence that serum MC-LR was an independent risk factor for HCC in humans, with an obvious positive interaction with hepatitis B virus and alcohol but a negative interaction with aflatoxin. (Hepatology 2017;66:1519-1528).

Crystallographic structure of recombinant Lactococcus lactis prolidase to support proposed structure-function relationships.

Lactococcus lactis prolidase (Xaa-Pro dipeptidase; EC.3.4.13.9) is unique from other prolidases by showing allosteric behaviour, substrate inhibition, and metal-dependent substrate specificity. We have previously shown several critical residues for these characteristics using site-directed mutagenesis and amino acid sequence-based models. In this present study, the three-dimensional structure of recombinant L. lactis prolidase was determined by X-ray crystallography at 2.25Å resolution in order to provide evidences of the proposed mechanism. Three molecules are located in the crystal asymmetric unit where molecule A forms a dimer with molecule B, while molecule C forms a dimer with molecule C' in the adjacent asymmetric unit. Of all the three molecules, molecule C is less defined and incomplete. While this fact compromises the overall quality of the refined model, the functional interpretation of the structure is not compromised since the biologically-functional homodimeric configuration of L. lactis prolidase is represented by well-defined molecules A and B. The refined model confirmed that there is a twelve-residue (residues 32-43) loop structure from one subunit over the active site of the other subunit, proving the existence of the putative loop structure in our previous study. This loop is three amino acids longer than the loops of prolidases of Pyrococcus furious (1pv9) and Pyrococcus horikoshii OT3 (1wy2). The crystal structure shows the loop structure can form two states ("open" and "closed" states) through interaction between the loop and active site proximity. It supports the proposed formation of allosteric site by the loop and Arg 293.

Environmental Microcystin Exposure Increases Liver Injury Risk Induced by Hepatitis B Virus Combined with Aflatoxin: A Cross-Sectional Study in Southwest China.

Three liver hazards, two confirmed-hepatitis B virus (HBV) and aflatoxin (AFB), and one rarely studied in populations-microcystin (MC), simultaneously exist in tropical and humid areas; however, there are no epidemiological data on their risks in the same population. We conducted a community-based cross-sectional survey among 5493 adults in two rural towns and statistically analyzed the comparative and combinative effects of the three factors after detecting HBsAg and HBV DNA titers, determining estimated daily intakes (EDIs) of AFB1 and MC-LR and testing serum AST and ALT as liver injury markers for each participant. We observed a HBsAg(+) rate of 7.6%, a relatively high AFB1 exposure level (mean EDIAFB1 = 471.30 ng/d), and a relatively low MC-LR exposure level (mean EDIMC-LR = 228.25 ng/d). ORs for abnormal AST (2.42, 95%CI = 1.69-3.45) and ALT (2.87, 95%CI = 1.91-4.29) increased in HBV infections compared with HBV-unexposed participants but did not increase in participants with separate or combined exposure to AFB1 and MC-LR (EDIs ≥ mean). Meanwhile, after adjustment for confounding factors, means of AST and ALT and ORs of abnormal AST and ALT were successively elevated after exposure to HBV, HBV&AFB1 (or HBV&MC-LR), and HBV&AFB1&MC-LR, especially in the group with detectable HBV DNA (AST: OR = 11.38, 95%CI = 3.91-33.17; ALT: OR = 17.09, 95%CI = 5.36-54.53). Notably, ORs for abnormal AST and ALT in the HBV exposed group were not significantly different from those in HBV&AFB1 or in the HBV&MC-LR exposed group but were significantly higher in the HBV&AFB1&MC-LR exposed group (P = 0.029 and P = 0.037, respectively). Our study indicated that microcystin may have the potential to increase the risk of liver injury induced by combined exposure to HBV and aflatoxin. However, in consideration of the uncertainties in the detection of the toxins and evaluation of the EDIs, more epidemiological data are expected to determine the increasing toxic effects of microcystins.

Determination of Environmental Exposure to Microcystin and Aflatoxin as a Risk for Renal Function Based on 5493 Rural People in Southwest China.

Although the nephrotoxicity of microcystin and aflatoxin has been observed in animal and clinical cases, few population data are available. We conducted a cross-sectional study in Southwest China to investigate the association of renal function indicators (RFIs, including BUN, SCr, and eGFR) with exposure to microcystin and aflatoxin in 5493 members of the general population. Microcystin-LR levels in water and aquatic products and aflatoxin B1 levels in daily foods were measured by ELISA, and individual estimated daily intake (EDI) was assessed on the basis of the measurement and questionnaire. We found that participants with abnormal RFIs had a much higher mean level of microcystin-LR EDI than those with normal RFIs and that there was a significant increasing trend for abnormal rates and odds ratios of RFIs with increasing microcystin-LR EDI quartiles (p for trend = 0.000). Compared with the lowest quartile of microcystin-LR exposure, those in the highest quartile had significantly higher risks of abnormal BUN (OR = 1.80, 95% CI = 1.34-2.42), SCr (OR = 4.58, 95% CI = 2.92-7.21), and eGFR (OR = 4.41, 95% CI = 2.55-7.63), respectively, but no higher risk was found in subjects with higher AFB1 exposure. After adjustment for confounding factors, risk associations with microcystin-LR persisted. Consequently, our results suggest that microcystin, rather than aflatoxin, might be one important risk of renal-function impairment.

Ghrelin Prevents Cisplatin-Induced Testicular Damage by Facilitating Repair of DNA Double Strand Breaks Through Activation of p53 in Mice.

Cisplatin administration induces DNA damage resulting in germ cell apoptosis and subsequent testicular atrophy. Although 50 percent of male cancer patients receiving cisplatin-based chemotherapy develop long-term secondary infertility, medical treatment to prevent spermatogenic failure after chemotherapy is not available. Under normal conditions, testicular p53 promotes cell cycle arrest, which allows time for DNA repair and reshuffling during meiosis. However, its role in the setting of cisplatin-induced infertility has not been studied. Ghrelin administration ameliorates the spermatogenic failure that follows cisplatin administration in mice, but the mechanisms mediating these effects have not been well established. The aim of the current study was to characterize the mechanisms of ghrelin and p53 action in the testis after cisplatin-induced testicular damage. Here we show that cisplatin induces germ cell damage through inhibition of p53-dependent DNA repair mechanisms involving gamma-H2AX and ataxia telangiectasia mutated protein kinase. As a result, testicular weight and sperm count and motility were decreased with an associated increase in sperm DNA damage. Ghrelin administration prevented these sequelae by restoring the normal expression of gamma-H2AX, ataxia telangiectasia mutated, and p53, which in turn allows repair of DNA double stranded breaks. In conclusion, these findings indicate that ghrelin has the potential to prevent or diminish infertility caused by cisplatin and other chemotherapeutic agents by restoring p53-dependent DNA repair mechanisms.

Gut microbiota and clinical response to immune checkpoint inhibitor therapy in patients with advanced cancer.

BACKGROUND: There is currently no well-accepted consensus on the association between gut microbiota and the response to treatment of immune checkpoint inhibitors (ICIs) in patients with advanced cancer. METHODS: Fecal samples were collected before ICI treatment. Gut microbiota was analyzed using 16 S ribosomal RNA sequencing. We investigated the relationship between the α-diversity of fecal microbiota and patients' clinical outcomes. Microbiota profiles from patients and healthy controls were determined. Pre-treatment serum was examined by cytokine array. RESULTS: We analyzed 74 patients, including 42 with melanoma, 8 with kidney cancer, 13 with lung cancer, and 11 with other cancers. Combination therapy of anti-PD1 and anti-CTLA-4 was used in 14 patients, and monotherapy in the rest. Clinical benefit was observed in 35 (47.3 %) cases, including 2 complete responses, 16 partial responses, and 17 stable diseases according to RECIST criteria. No significant difference in α-diversity was found between the benefiter and non-benefiter groups. However, patients with α-diversity within the range of our healthy control had a significantly longer median overall survival (18.9 months), compared to the abnormal group (8.2 months) (p = 0.041, hazard ratio = 0.546) for all patients. The microbiota composition of the benefiters was similar to that of healthy individuals. Furthermore, specific bacteria, such as Prevotella copri and Faecalibacterium prausnitzii, were associated with a favorable outcome. We also observed that serum IL-18 before treatment was significantly lower in the benefiters, compared to non-benefiters. CONCLUSIONS: The α-diversity of gut microbiota is positively correlated with more prolonged overall survival in cancer patients following ICI therapy.

Fiber Bragg grating-based plane strain monitoring of aerostat envelope structures.

A theoretical analysis of fiber Bragg grating (FBG)-based plane strain monitoring of aerostat envelope structures is presented. Plane strain analysis of FBG-based aerostat envelope structures is much more complex than the case along the axis of the optical fiber because the effect of transverse stress on the FBG should be taken into consideration. To achieve accurate strain measurement of the aerostat envelope, a theoretical model is set up by using two perpendicular fibers in the monitoring. An analytical formula that evaluates the relationship between the strain measured by FBG sensors and the real one in the aerostat envelope is established. On the other hand, the real strain of aerostat envelope strain is affected by two unknown parameters, axial transfer rate K(L) and the radial transfer rate K(R). An equation is derived to calculate the axial transfer rate K(L). Then, the finite element method results show that K(R) is a very small value, but it cannot be ignored in accurate measurement. This paper would lay a theoretical groundwork for the research and design of FBG sensors in the structural health monitoring of aerostat envelope structures.