Association of chronic inflammation, primary tumor sidedness, adjuvant therapy and survival of metastatic colorectal cancer (mCRC) remains unclear. Circulating inflammatory cell, fibrinogen (Fib), albumin (Alb), pre-albumin (pAlb), Alb/Fib (AFR) and Fib/pAlb (FPR) were detected, and clinical outcome was obtained to determine the predictive, prognostic and monitoring roles of them in discovery and validation cohort. We found that elevated FPR, low AFR and poor survival was observed in right-sided mCRC comparing to the left-sided disease, elevated FPR harbored the highest areas under curve to independently predict poor progression-free survival and overall survival in overall and left-sided mCRC case in two cohorts. No survival difference was examined between the two-sided patients in subgroups stratified by FPR. Radiochemoresistance was observed in high FPR case. However, the patient could benefit from bevacizumab plus radiochemotherapy. Low FPR patient showed the best survival with treatment of palliative resection plus radiochemotherapy. Moreover, circulating FPR was significantly increased ahead imaging confirmed progression and it reached up to the highest value within three months before death. Additionally, c-indexes of the prognostic nomograms including FPR were significantly higher than those without it. These findings indicated that FPR was an effective and independent factor to predict progression, prognosis and to precisely identify the patient to receive optimal therapeutic regimen. Colorectal cancer (CRC) is a kind of molecular heterogeneous disease that undergo a variety of clinical courses and possess diverse therapeutic responses –3. It haKRAS wild-type metastatic CRC (mCRC) patient, whereas the left-sided individual was reported more responsive to the therapeutic regimen [In recent decades, a continued rightward of CRC was reported by several population-based epidemiological studies ,11, and  regimen ,17, and  regimen ,18. HoweSystematic inflammation has been reported as an obvious hallmark within CRC ,20. It cIn present study, we investigated the association between FPR, AFR, localization of the primary tumor, clinical therapy and survival within discovery (302 left-sided and 128 right-sided mCRC patients) and validation cohort (46 left-sided and 31 right-sided mCRC patients). We found that significant severe chronic inflammation and malnutrition represented by FPR in right- and left-sided mCRC contributed to radiochemoresistance, resulting in poor response and survival in both sides of mCRC patient. Circulating FPR was an effective, economical and practice indicator to stratify the patient to receive the optimal therapeutic regimen, and to predict progression and survival of left-sided mCRC patient.Overall, a total of 990 firstly diagnosed mCRC patients from November 2011 to May 2015 were prospectively identified in present study, discovery cohort including 430 mCRC patients who didn’t receive targeted therapy and validation cohort containing 77 mCRC cases undergoing bevacizumab plus radiochemotherapy were enrolled as eligible patients according to the inclusion and exclusion criteria. The detail screening flow diagram of eligible patients and the baseline characteristics as well as laboratory detection were described in p=0.014), Fib (p=0.002), PLR (p<0.001) and low AFR (p<0.001), pAlb (p=0.019), Alb (p=0.003) and LMR (p=0.040) were observed in right-sided mCRC in comparison with the left-sided cancer. However, there was no significant difference of NLR, dNLR, CEA and CA199 between the two-sided diseases. Comparing to left-sided mCRC, the number of dead patient  was obviously increased in right-sided mCRC and OS  within left-sided mCRC was extremely longer than that within the right-sided patient, but not PFS  was significantly short comparing to those with low FPR, respectively  was obviously worse than the cases harbored low PLR, and there were significant differences of OS within high and low subgroup stratified by dNLR , Fib  and pAlb , respectively , PLR , dNLR , Fib , and low AFR , Alb  and pAlb  were associated with poor survival in Kaplain-Meier curve and Cox regression  in right-sided mCRC individuals. However, there was no significant association between them when it was adjusted by the other factors. The other inflammatory indicators were not related to the survival of right-sided mCRC patients  and OS  within high FPR mCRC patient were obviously worse than the low FPR patient   . However-15.015) .Time-dependent ROC curve was used to evaluate the predicted efficacy of FPR in mCRC patient, and area under the curve (AUC) was selected as the common tool to compare the difference between them. The AUCs of FPR were 0.749 for PFS and 0.740 for OS in overall discovery cohort , and allIn validation cohort, AUC of FPR was 0.884 for predicting PFS and it was the same to Fib and AFR, but it was significantly higher than the other indicators . Even movs. 78.57%, p=0.040; left-sided mCRC: 95.65% vs. 75.76%, p=0.047) and death  within high FPR subgroup were significant higher than the low group only in overall and left-sided mCRC in discovery cohort  in validation cohort. However, no obvious association was examined between FPR and the other characteristics in two cohorts.The association between FPR and the baseline characteristics was examined in the two cohorts. The numbers of mCRC case with disease progression . Moreover, the median OS of left-sided mCRC patient with high FPR was obviously worse than right-sided patients harbored low FPR in discovery (plog-rank test=0.017) and validation (plog-rank test=0.016) cohort (plog-rank test=0.002) and palliative resection plus radiochemotherapy subgroup (plog-rank test=0.001)  or high FPR  in the two cohorts  . However cohorts .plog-rank test<0.001) and non-surgery subgroup (plog-rank test<0.001) (plog-rank test=0.064). However, no survival difference was observed between palliative resection plus radiochemotherapy treated mCRC patients and the patients undergoing bevacizumab plus radiochemotherapy log-rank testp=0.899  . In the st=0.899 .log-rank testp =0.020) . Whereas, the significant survival difference was observed between bevacizumab plus radiochemotherapy and radiochemotherapy treated mCRC patient (log-rank testp =0.049)  . The sur =0.049) .p<0.05). Furthermore, it was significantly increased in the time of one month before clinical imaging confirmed progression compared with the lowest point (p<0.05), and it reached up to the highest value within three months before death (p<0.01).According to the inclusion criteria and willing of the patient, seventeen palliative resection and thirty-four radiochemotherapy treated mCRC patients were included to investigate the role of FPR in predicting progression of mCRC patients. Each of them provided detected sample in each time point, and all of them were progressed and dead in the follow-up period. As shown from p<0.05) and death (p<0.01).Using the significant characteristics and FPR, we established the prognostic nomograms and evaluated progression and death risk of overall mCRC patients within three years. The prognostic nomograms with or without FPR were showed in Despite high risk of disease progression triggered by chronic inflammation and malnutrition –28, the It has been well known that Fib, Alb and pAlb are not only commonly recognized as a vital factor in coagulation cascade reaction and as a useful indicator to imply nutrition status, respectively, but also can effectively respond to para-inflammation and systematic inflammation in cancer –32. HypeNowadays, left- and right-sided CRC have been known as two distinct diseases, for significant differences in mutation spectrum of oncogene and anti-oncogene and prognosis of the two-sided diseases ,40–42. IOur previous study also showed that FPR could stratify the eligible surgical cases who can benefit from adjuvant radiochemotherapy . In pres+ colonic myofibroblast, fibroblast, endothelial cell could secret interleukin-6(IL-6), IL-21 and IL-33 to activate NF-κB and JAK/STAT pathway to promote systematic inflammation of mCRC by regulating differentiation of T helper 17 cell and regulatory T cell [As we known, the interaction between stromal cell, inflammation-related cells such as neutrophil, macrophage and monocyte, inflammatory cytokine and cancer cell remodeled an adapted microenvironment not only to promote progression of the disease but also to involve in resistance to anticancer therapy –45. C-tey T cell –49. Fib,y T cell , IL-6 sey T cell . Moreovey T cell . On the y T cell . Consequy T cell ,55, resuThe prospective study is the first time for us to evaluate the predictive, prognostic and monitoring role of FPR in left- and right-sided mCRC patients. It is also the first time for us to illustrate that severe systematic inflammation involving in radiochemoresistance is the main reason for the survival difference between left- and right-sided mCRC cases. Additionally, dynamic monitoring FPR can predict the disease progression ahead clinical imaging detection, and prognostic nomogram including FPR can efficiently predict the progression and death outcome of mCRC patients. However, the cases in our study are from the single center, and the sample size isn’t large enough. Thus our findings needed to be validated by other prospective study with large sample size from multiple centers. Moreover, in vivo and in vitro experiments are not carried out to furtherly confirm the association between high FPR, radiochemoresistance and poor survival in the mCRC patient.In summary, our findings have demonstrated that significant difference of chronic inflammation represented by FPR has an impact on radiochemotherapy sensitivity, resulting in significant survival difference in right- and left-sided mCRC. Elevated FPR is an efficient and independent prognostic factor to predict poor survival of left-sided mCRC patients and to improve the efficacy of its prognostic nomogram. It serves as a readily valuable indicator for monitoring progression and can be considered as a precise stratification factor in future clinical trials aiming to optimize common treatment strategies for the disease.In our study, a total of 990 firstly diagnosed mCRC patients in the Second Affiliated Hospital of Nanchang University were prospectively identified from November 2011 to May 2015. We screened the eligible case according to the following inclusion and exclusion criteria: 1) the patient should be firstly diagnosed as mCRC by X-ray, CT, MRI or pathological detection; 2) all patients should be free of hereditary polyposis and nonpolyposis CRC, emergency surgery, palliative operation, neoadjuvant chemoradiotherapy, ulcerative colitis-associated cancer ahead the clinical confirmation; 3) the eligible cases were not suffered from other malignancies, recent bacterium and virus infection, autoimmune and hematologic as well as cardiovascular and cerebrovascular disease; 4) liver and kidney function should be normal in all the included patients; 5) all included patients didn’t intake either drugs such as antibacterial agent, non-steroidal anti-inflammatory drug, antiplatelet or anticoagulant drug nor intravenous albumin supplement in recent three months; 6) the eligible patient could provide complete clinical characteristics, and contact information for three years’ follow-up; 7) the patient signed the informed consent and they agreed to collect pre-treatment peripheral, serum, and plasma samples for late-stage detection. The study was approved by the Medical Ethics Committee of the local hospital.The baseline characteristics such as demographic and clinicopathological data and clinical therapeutic regimen were extracted from the medical record. The tumor location from ileocecal section to the splenic flexure (without it) and the splenic flexure to rectum were considered as right- and left-sided CRC, respectively. Routine three years’ follow-up  were performed by means of email, telephone, and medical record in all eligible patients after the first time treatment and the follow-up deadline was July 2018. Three years’ progression-free survival (PFS) and overall survival (OS) were the main endpoints in present study, the two of them were measured from the first clinical confirmation until the date of local progression or new distant-site metastasis and death from any cause, respectively.In order to investigate the relationship of systematic inflammation, primary tumor location with clinical efficacy and outcome of mCRC patient, the respective two milliliters pre-treatment peripheral blood, serum, and plasma samples were collected from all eligible patients for detection. All the samples were collected at 7:00 to 9:00 am ahead the first clinical confirmed time. Moreover, mCRC patients with both progression and death event were selected to collect these samples in the following each time point  and all the detections were completed within two hours after the sample collection.SYSMEX XE-2100 machine  with nucleic acid fluorescence staining and laser flow analysis method was used to detect differential white cell count. Plasma Fib was measured by clauss method using SYSMEX CA-7000 machine . Bromcresol green dye method, immunoturbidimetric assay and electrochemiluminescence immunoassay were selected to examine serum Alb, pAlb, carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) with machines of OLYMPUS AU5400  and SIEMENS ADVIA Centaur CP machine , respectively. The inter- and intra-batch coefficients of variation of immune cell count, Fib, Alb, pAlb, CEA and CA199 kits were less than 5%. According to the detection result, we calculated the following ratios: Alb to Fib ratio (AFR), Fib to pAlb ratio (FPR), neutrophil to lymphocyte ratio (NLR),  to lymphocyte ratio , platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR).p<0.05 was recognized as a statistical significance.Continuous variables with normal and skewed distribution were expressed as mean±standard deviation, median and inter-quartile ranger (IQR), respectively. Chi-square or Fisher’s exact test was used to compare the difference of categorical variable, and continuous variable with skewed distribution was compared by Mann-Whitney U test. The optimal cut-off points of Fib, Alb and pAlb and the ratios replying on three years’ OS were determined by X-tile 3.6.1 software . The difference of survival rate was calculated using Kaplan-Meier curve with log-rank test. Cox proportional regression with hazard ratio (HR) and 95% confidential interval (CI) was applied to examine the prognostic role of clinical baseline characteristics and laboratory detected indicators in overall, left- and right-sided mCRC patient. Prognostic predictive efficacy of the significant factor was assessed and compared by time-dependent receiver operating characteristic (ROC) curve. The significant characteristics and laboratory markers were used to establish PFS and OS prognostic nomograms, and Harrell’s concordance index (c-index) were selected to evaluate their predicted efficacy. All the statistics were analyzed using SPSS. 22.0  and R 3.5.1. All analyses were two-sided, and The study was approved by the institutional ethics committees of the Second Affiliated Hospital of Nanchang University and all procedures were conducted in accordance with ethical principles.The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.Supplementary FiguresSupplementary Tables


Giorgia Sulis and Madhukar Pai discuss the global distribution, and approaches to diagnosis and treatment, of isoniazid-resistant tuberculosis, For decades, people working in tuberculosis (TB) knew that monoresistance to isoniazid (INH) was common. INH has been in clinical use since the 1950s, and drug resistance was expected because its use became widespread. But this knowledge did not necessarily lead to testing for INH-resistant, rifampicin-susceptible TB (Hr-TB) or to the use of special drug regimens for this form of TB. Indeed, for decades, no drug-susceptibility testing (DST) for any drug was done unless patients failed first-line therapy or had risk factors for drug-resistant TB (DR-TB). Simply put, we chose to ignore the problem.When the TB world woke up to the need for universal DST and included it as a key goal in the End TB Strategy released in 2015, the focus became rapid testing for rifampicin resistance (RR) as a means of achieving universal DST. Novel technologies such as Xpert MTB/RIF  were rolled out in 2010, but the technology did not include INH-resistance testing [PLOS Medicine, showing that—on average—7.4% (95% CI 6.5–8.4) of new cases and 11.4% (9.4–13.4) of previously treated patients have Hr-TB [In 2020, we can no longer hide from this worrisome problem because Hr-TB is much more common than RR and could seriously jeopardize progress in the fight against TB. This is confirmed by an analysis of aggregated drug resistance data from 2003 to 2017 across 156 countries presented in the accompanying research study by Anna Dean and colleagues in The analysis by Dean and colleagues highlights major flaws in national surveillance systems, which go hand in hand with limited laboratory capacity. The small sample sizes available from some countries make national prevalence estimates imprecise. Furthermore, the diversity of detection methods employed across settings along with the widespread lack of quality control underscores the need for improved surveillance by countries.From a clinical standpoint, if INH resistance is not detected, new patients are managed as if they had pansusceptible TB, with a substantially increased risk of treatment failure or relapse and a greater propensity to acquire further resistance . Yet, moThankfully, some progress has been made in the last couple of years. In 2018, the World Health Organization (WHO) issued new treatment recommendations for Hr-TB, replacing the previous 9-month course of rifampicin, pyrazinamide, and ethambutol (RZE) with a 6-month regimen based on levofloxacin plus RZE ,6. This However, high-TB-burden countries will struggle to routinely implement these new guidelines for Hr-TB because easy access to INH-resistance testing is a challenge. Although there are WHO-endorsed technologies (such as line-probe assays and liquid cultures) that can detect INH resistance, these tools are limited to centralized or reference laboratories . Also, eThe year 2020 might bring some hope, as the Xpert MTB/XDR cartridge  is expected to be released and will include resistance testing for INH, fluoroquinolones, and second-line injectables . The TB katG and inhA mutations [Whole-genome sequencing (WGS) data continue to shed light on the wide range of mutations associated with drug resistance, thus not only improving our understanding of transmission dynamics but also helping to refine therapeutic choices for the individual patient . Importautations ,14. Receutations .Beyond technologies and guidelines, we need to acknowledge the human impact of DR-TB, which imposes a tremendous physical, mental, financial, and social burden on patients. In addition to the 3 million TB patients who fail to get diagnosed or notified , there a


The increasing demand for high food quality and safety, and concerns of environment sustainable development have been encouraging researchers in the food industry to exploit the robust and green biodegradable nanocomposites, which provide new opportunities and challenges for the development of nanomaterials in the food industry. This review paper aims at summarizing the recent three years of research findings on the new development of nanomaterials for food packaging. Two categories of nanomaterials  are included. The synthetic methods, physical and chemical properties, biological activity, and applications in food systems and safety assessments of each nanomaterial are presented. This review also highlights the possible mechanisms of antimicrobial activity against bacteria of certain active nanomaterials and their health concerns. It concludes with an outlook of the nanomaterials functionalized in food packaging. Nanoscience and nanotechnology have become exciting fields of research and development since its introduction by Richard Feynman in 1959 . These mIn recent years, owing to the unique properties of nanomaterials other than their bulk counterparts mainly covering physical, chemical and biological properties, studies on the synthesis, characterization, applications and assessments of these materials have promoted the scientific advancement to grow and alter the entire agrifood area ,8. SpeciPackaging is a key component of each stage in the food industry; however, its permeable nature is the major defect in conventional food packaging materials. There are no packaging materials fully resisting water-vapors and atmospheric gases . MoreoveFurthermore, the enormous potential of nanotechnology has received attention from researchers in multi-disciplinary areas to develop promising and desirable materials in food packaging systems. On the whole, the applications of nanocomposite materials for food packaging reported in the recent three years are divided into three main functions, i.e., improved, smart and active food packaging . FirstlyThis review references more than 170 articles published in the recent three years and summaries the up-to-date developments of nanomaterials applied in the food packaging field, presenting a comprehensive review of various nanostructures and related technologies used to construct functional food packaging systems. The contents of this article mainly concentrate on synthesis methods, physical and chemical properties and biological activity, applications in food systems and safety assessments of different types of nanomaterials. This review also highlights the possible mechanism of some characteristics, such as antimicrobial activity against bacteria and improved reduction and stabilization properties of certain active nanomaterials. In the last part, an outlook of the nanomaterials functionalized in food packaging is included.2, MgO and Fe3O4, have attracted great interest due to their resistance to the rough processing conditions and enhancement of strong inhibition against foodborne pathogens. As for the other materials like various clays, they could offer resistance to gases and water vapor, and improve the mechanical strength of biopolymers [Generally, nanomaterials applied in food packaging can be classified into two categories: inorganic and organic materials. For the former materials, metals and metal oxides and clay nanoparticles incorporated into bionanocomposite films and nanofibers can be considered ,26. Besipolymers . The secpolymers ,29.So far, in all kinds of nanoparticles developed and characterized, silver-based nanoparticles (NPs) have taken an important place due to their inherent feature of antimicrobial activity even in solid-state samples, and have therefore been used as bacteriostatic agents from ancient times. Silver-salts materials also have an inhibition effect on the growth of diverse pathogens affecting human health, such as those in films, catheters, burns, cuts and wounds to protect them from infection . Silver-AgNPs is one of the most studied and applied antimicrobial agents because of its broad-spectrum antimicrobial activity against microorganisms. The traditional solvothermal synthesis methods of AgNPs-functionalized packaging materials which usually require physical and chemical preparations of synthesizing and immobilizing, however, seem to be very expensive and hazardous and not environmentally friendly. This method has been gradually discarded for the tedious and complicated procedure. Interestingly, AgNPs prepared through biological synthesis exhibit high solubility, yield and stability. Additionally, it is simpler, faster, more environmentally friendly and dependable, and is recognized as a green approach to produce AgNPs with well-defined morphology and size under optimal conditions in favor of application in food packaging . Chu et The physical and chemical properties of nanoparticles are important for their action, efficacy, bio-distribution and safety. Accordingly, characterizations of nanomaterial are crucial to evaluate functions of the developed particles . CharactBecause of the aforementioned unique properties, AgNPs have been widely used in the health care industry, house-hold utensils, food storage, environmental and biomedical applications. Herein, it is interesting to emphasize the applications of AgNPs in food systems, including antibacterial, antifungal, antioxidant, anti-inflammatory, antiviral, anti-angiogenic and anti-cancer. Heli et al. reported that the exposure of corrosive vapor (ammonia) remarkably reduced the population density of AgNPs embedded into bacterial cellulose, causing a large distance between the residual nanoparticles and a decrease in the UV-Vis absorbance related to the plasmonic properties of AgNPs . This ma2) into Penaeus semisulcatus by a titration comparison within the other migrations, and found that titration had a superior sensitivity compared to the other migration methods in determining the residues of nanoparticles (p < 0.05) [Lactobacillus acidophilus LA-5, Bifidobacterium animalis subsp. lactis BB-12 and Streptococcus thermophilus ST-Y31, which deserves great public attention.On account of gaps in understanding toxicology of nanomaterials, the development of their applications is related to safety concerns. In case of food contact bio-nanocomposite materials, the first steps of consumers’ exposures are the migrations of nanoparticles from packaging to food products. Thus, in order to estimate the risk, we need to know the possibilities of nanoparticles released from food contact materials . Gallocc < 0.05) . Hannon  < 0.05) . The tes < 0.05) . The rel < 0.05) . These bZinc oxide (ZnO) has attracted great interest worldwide because of its excellent properties, particularly resulting from the realization of the development of nanomaterials. Considerable studies of ZnO-NPs have been triggered on the production of nanoparticles using different synthesis methods and on their future applications, attributed to their high luminescent efficiency with a large exciton binding energy (60 meV) and a wide band gap (3.36 eV) . ZnO-NPsSynthesis methods of zinc oxide have been developing rapidly. Because the synthesis approach determines the properties of nanomaterial, the selection of synthetic methods is a crucial step in the engineering of ZnO-NPs for a decided utilization. In recent decades, three main approaches have been used for forming ZnO-NPs: physical, chemical and biological methods. Among them, the casting method followed by solvent evaporation is the most common method used in preparation of ZnO nanocomposites with different morphologies. Rokbani et al. reported a synthesis method using a combination of ultrasound stimulations and autoclaving to prepare electrospun nanofibers of mesoporous silica doped with ZnO-NPs . JafarzaB. cereus, whereas Q-UV and UV-A irradiation showed no effect on the mechanical properties of developed nanomaterial. Kotharangannagari and Krishnan studied the shape memory properties of novel biodegradable nanocomposites made of starch, polypropylene glycol (PPG), lysine and ZnO-NPs [Compared with traditional antimicrobial agents, metal oxide nanoparticles show higher stability under extreme conditions with antimicrobial activity at low concentrations, and are considered to be non-toxic for humans . Among t ZnO-NPs . The res ZnO-NPs . The ten ZnO-NPs . The res ZnO-NPs .L. monocytogenes contamination on spinach but with no effect on its quality, mainly including color and vitamin C content [Nigella sativa seed extract-zinc nanostructures (NS-ZnNPs) material and found that NS-ZnNPs showed inhibition effects on the biofilm formation of four food pathogens including C. violaceum 12472, L. monocytogenes, E. coli, PAO1, at their sub-inhibitory concentrations [ZnO-NPs are recognized as inexpensive with potential antimicrobial properties. So the applications of ZnO-NPs packaging in food systems concentrate on its antibacterial effect, and they are used to prolong the fresh food products’ shelf-life. Youssef et al. used an innovative carboxymethyl cellulose/chitosan/ZnO bionanocomposite film to enhance the shelf-life of Egyptian soft white cheese . Mizieli content . Suo et  content . Al-Shabtrations .ZnO-NPs are utilized as active materials in food packaging, which might bring a potential risk for consumers contacting with this material. This nanoparticle has been demonstrated in in vivo studies that they can access organs through different pathways such as ingestion, inhalation, and parenteral routes . Ansar eCopper-based nanoparticles mainly include copper nanoparticles (CuNPs) and copper oxide nanoparticles (CuO-NPs). Most studies focusing on CuO NPs suggest that this material is one of the most-extensively studied metal oxide nanoparticles. The antimicrobial activity is its important feature, thus this material can be used to reduce the growth of bacteria, viruses and fungi. The nano-sized CuO-NPs were allowed to interact with the cell membrane due to their enormous surface area, and then showed an increased antimicrobial effect . CuO-NPsCystoseira trinodis as an eco-friendly material [4 treated methods to form a heat-sealable casein protein layer laminated with sodium alginate-pectin.CuO-NPs have potentials for forming antimicrobial nanohybrids. Almasi et al. claimed that whether the polymer substrate has already exhibited antimicrobial activity or not, the incorporated CuO-NPs could further increase the activity of the two components contained in the nanocomposite . They hamaterial . Eivazihmaterial . No morematerial . This bimaterial  synthesiListeria monocytogenes and E. coli.The properties of the CuO-NPs depend on the synthesis method and they are very important for their applications in various areas, such as food packaging research, which rely on their biological activity. Although the specific mechanism of the antimicrobial effect of CuO nanoparticles is little known, their antimicrobial actions on bacterial cells have been proposed . Beigmoh4-treated NPs film against the growth of E. coli. Li et al. prepared chitosan/soy protein isolates nanocomposite film reinforced by Cu nanoclusters, and this material showed the improved elongation at break and tensile strength, and higher water contact angle and degradation temperature and decreased water vapor permeation [Nanomaterials with various characteristics generated from many polymers constructing copper-based nanocomposites can be used in a variety of applications. The antimicrobial activity of copper-based nanocomposites reveals applications in engineering food packaging, textile industry, medical devices and water decontamination. Some applications in food packaging over the recent three years are presented in rmeation . Lomate rmeation .Although copper-based nanocomposites have been applied for diverse purposes, CuO-NPs and copper ions can be released from the packaging materials into the food systems. Little is known on the toxicity of copper-based nanocomposites and more attentions have been concentrated on CuO NPs .2-NPs), as among the most explored materials, are considered as valuable metal oxide nanomaterials with thermostability and inertia. The material also has the ability to modify the properties of biodegradable films. Besides, this material has many advantages such as being cheap, nontoxic, and photo-stable. It has been emerging as a superior photo-catalyst material for energy and environmental fields, such as air and water purification, antimicrobial, self-cleaning surfaces and water splitting [2-NPs and their applications in the food packaging area have attracted extensive attentions attributed to their antimicrobial activity.Titanium dioxide nanoparticles  nanofibers at different temperatures to obtain antibacterial nanostructures with a relative high selective area [2 nanocomposite aerogels by a sol-gel process and followed by drying under the supercritical conditions [2 colloid was added; then crosslinking reaction was induced in the presence of zinc ions and tert-butanol [2 drying.TiObehavior . He et an method . Li et aadsorbed . Lopez dive area . Nesic enditions . Firstly-butanol . Finally2-NPs had promoted the suitability of developed films applied in food packaging. The functional properties of these nanomaterials can be tailored by synthesizing composites that combine the properties of the individual component to achieve synergistic effects. Xing et al. investigated the impact of TiO2-NPs on the physical and antimicrobial capabilities of polyethylene (PE)-based films. They found that the antimicrobial activity of the films was attributed to the biocidal action of TiO2-NPs against bacteria [2-NPs on PLA substrates, cellulose nanofibers and nanocomposite coatings, and found that the addition of TiO2-NPs reduced the penetrant diffusivity but did not affect gas barrier performances, as well as slightly decreased the optical transparency [2-NPs  incorporated into potato starch films [2-NPs enhanced the optical transparency, and slightly increased the tensile strength and contact angle, and significantly declined the water vapor permeability properties, and decreased the elongation at break of the film. Goudarzi et al. produced the eco-friendly starch and TiO2-NPs bio-composites at different TiO2-NPs contents , and investigated the mechanical, physical, water-vapor permeability (WVP), thermal properties and as well as UV transmittance of the synthesized nanomaterial [2 content. Abdel Rehim et al. prepared the photo-catalytic paper sheets by adding different ratios of TiO2-NPs/sodium alginate nanocomposite [2-NPs to them.Considerable studies indicated that addition of TiObacteria . Roilo esparency . Oleyaeich films . It was material . They foomposite . It was 2-NPs are antimicrobial agents. When they are irradiated with UV light, many reactive oxygen species are produced that have the ability to kill microorganisms. Moreover, as nano-additives, TiO2 can improve the mechanical properties of polymer nanocomposites [2, Ag-TiO2 and Ag-TiO2-zeolite nanocomposites , which aimed at being applied in bread packaging [2-LDPE (NT-LDPE) packaging. They investigated the effects of NT-LDPE material packaging on the antioxidant activity and quality of strawberries [TiOmposites . Mihaly-ackaging . The effwberries .2-NPs have been explored basically on their uptake by inhalation. It was concluded by the International Agency for Research on Cancer (IARC) that decided based epidemiological studies to assess whether TiO2 dust causing human cancers was inadequate. Evidence for carcinogenicity in experimental animals was sufficient, which was conducted on account of the induction of respiratory tract tumors in rats after prolonged inhalation. Accordingly, TiO2-NPs is classified as a Group 2B carcinogen by the IARC [2-NPs applied in food packaging. Ozgur et al. evaluated the effect of different amounts of TiO2-NPs  in vitro at 4 °C for 3 h on sperm cell kinematics with the velocities of Rainbow trout [2-NPs. The results revealed that a statistical significance (p < 0.05) presented in the velocities of sperm cells. When concentration of TiO2-NPs reached at 10 mg/L, an increased activity of TGSH and SOD (p < 0.05) levels were found. Salarbashi et al. prepared biodegradable SSPS nanocomposites consisting of varying ratios of SSPS and TiO2-NPs, and found that TiO2-NPs existed in plasma membranes of epithelial cell lines after a 10-day exposure to a number of free nanomaterials [2-NPs and biomolecules including albumin and glucose [2-NPs under physiological conditions. It was found that oral absorption of food grade TiO2-NPs was slightly higher compared to general grade TiO2-NPs; however, these nanoparticles were excreted through the feces. Besides, the biokinetics of food grade TiO2-NPs were extremely relied on their interaction with biomolecules.Nanoparticles exhibited an increased surface-to-mass ratio enhancing the reactivity. Moreover, nanoparticles displayed an increased tendency to penetrate the cell membranes and consequently having the potential to transfer through the biological barriers. So far, the health effects of TiOthe IARC . Based oow trout . Additioaterials . However glucose . They in3O4-NPs and iron-based nanoparticles, as well as SiO2-NPs [In addition to the metal oxides mentioned above, several other metal oxide and nonmetal oxide nanomaterials also showed an increased potential using as packaging materials, such as MgO-NPs, FeSiO2-NPs ,104,105.MgO naturally exists as a renewable, colorless, crystalline mineral and is economically produced on a large scale. The use of MgO has been recognized as generally safe even in the food applications by the U.S. Food and Drug Administration (FDA). Swaroop and Shukla produced films by incorporating MgO-NPs in PLA polymer through a solvent casting method, and found 2 wt% amount of MgO-NPs in PLA films exhibited the most observed improvement in the oxygen barrier and tensile strength properties, as well as a superior antibacterial efficacy; whereas, nearly a 25% negative effect was found on water vapor barrier properties .3O4@GO) as fillers and then were used to fabricate a PVA nanocomposite film [3O4-NPs [Ren et al. synthesized inorganic materials of magnetic ferroferric oxide nano-particles in-situ coating on graphene oxide nanosheets  using a casting method assisted by sonication [2-NP on gastrointestinal function and health, based on an in vitro model composed of HT29-MTX and Caco-2 co-cultures representing goblet and absorptive cells, respectively [2-NPs was harmful to the brush border membrane and that exposure to the physiologically relevant doses of well-characterized SiO2-NP for acute (4 hours) and chronic (5 days) time periods eventually led to adverse effects in cells.The activities of SiOsulation . Mallakpnication . Guo et ectively . The resAt the present time, nano-clay has approximately 70% market value all over the world, meaning that it is the most commercially applied nanomaterial. There are various kinds of clay minerals according to their structures and chemistries as well as sources. Based on the layered structures, these materials are categorized into four major classes, i.e., chlorite, montmorillonite (MMT)/smectite, illite and kaolinite . MMT is Halloysite nanotubes (HNTs), as a kind of natural nanomaterials belonging to kaolinite, have a hollow tubular-like structure within the inner and outer diameters of 15 nm and 50 nm, respectively. Due to this tubular shape, HNTs have a capability of being loaded by various materials, which have been developed as functional nanocapsules . Biddeciv/v, 1% v/v and 1.5% v/v) and MMT  [Nano-clays, especially MMT, act as crucial fillers in the biodegradation of nanomaterials when incorporated with a polymer, because they are toxin-free, environmentally friendly and safe to be used in food packaging. Besides, their activities to reduce permeability of gases and improve mechanical properties have been confirmed for polymer nanomaterials. Kim et al. investigated a potential application of multilayer packaging films for packing food containing waterborne content, which were prepared by dry laminating commercially available PVA/vermiculite nanocomposites . They fohitosan) . The reshitosan) ,17,118. hitosan) . Furtherhitosan) . They re2-SiO2-NPs [2 and 50% N2 and air, and both stored at 4 °C for 90 days. It was found that the moisture content and hardness showed no significant changes during storage. The sliced salami stored under vacuum and high CO2 using the multilayer material displayed the longest storage time of 75 days. Kim et al. developed insect-proof HNTs material, which were applied to a LDPE-based film to control Plodia interpunctella  from infesting the food [Pseudomonas spp.) and enhancing antioxidant activity. There were no observed metals (Si and Al) of clay diffused to the muscle of fish. Guimaraes et al. evaluated fresh-cut carrots (FCC) coated by MMT-NPs subjected to packaging of passive modified atmosphere [Generally, clays are low-cost, naturally occurring and eco-friendly agents and used in various applications. Clay minerals are used in the fields of agriculture, geology, engineering, construction and process industries . Peter eSiO2-NPs . The resSiO2-NPs . They tethe food . Peighamthe food . The devthe food . They fumosphere . The usemosphere . They fo+ and their thermally degraded byproducts and then induced toxicity in the model of lung epithelial cells of human [With nano-clay or MMT-NPs materials attracting more and more attentions worldwide, analyses of risks of these nanomaterials to the lung health of exposed workers have been emerging. Besides, present studies aiming to demonstrate the toxicological actions of nano-clay showed that the structure had resulted in the promotion of cellular uptake and interactions . Han et of human . Analysiof human . The resThe concept of a bio-based economy is gradually receiving attentions from scientific, societal, and economic aspects, and there is a great deal of driving force to develop strategies for this purpose . The insTraditionally, most plastic packaging materials are made from petroleum-based polymers, mainly containing the commodity polystyrene (PS) and polyethylene (PE), which are recognized as not being environmentally friendly. With the development of new polymer materials, the biodegradable polymer-based plastics can provide a viable alternative, such as PVA ,133,134,E. coli  and S. aureus (MRSA). Furthermore, the films showed no cytotoxicity effect on HepG2 and the cell viability was above 90%.PVA, basically made from polyvinyl acetate through hydrolysis, is easily degraded by biological organisms in water. It has been extensively incorporated into other polymer-based compounds to increase the mechanical properties attributed to its hydrophilic properties and compatible structure, including mechanical performance, solvent resistance, biocompatibility and high hydrophilicity . Yang et3) nanoparticles on the biodegradability and barrier properties of PLA [3-NPs increasing to 5 wt%. It was also found that the gas permeability of CO2, O2 and N2 were enhanced by increasing temperature but decreased by increasing feeding pressure. Vasile et al. prepared the Cu-doped ZnO powder embedded into PLA samples functionalized with Ag-NPs composites by a melt blending process [PLA has drawn more attention resulting from the good biodegradability and being a candidate of substitution for traditional polymers. PLA is mainly produced by condensation polymerization from lactic acid, derived from fermentation of corn, sugars, tapioca or sugarcane. Among the various biopolymers investigated, PLA exhibits key properties, including biodegradability, renewability and superior mechanical properties, crystallinity and process ability ,145. Afrs of PLA . The res process . The resPolyhydroxyalkanoates (PHAs) have been gradually paid attention recently as biodegradable and biocompatible thermoplastics in packaging applications. The most extensively studied polymer from the PHAs is the poly(3-hydroxybutyrate), PHB, which is partially crystalline with a high rigidity and melting temperature. To decrease the crystallinity, the copolymer obtained with the insertion of 3-hydroxyvalerate (HV) units, named as PHBV, is usually employed with improved handling properties of PHB films . Zemboua2 and montmorillonite on potato starch nanocomposite films [2. The visible, UVA, UVB and UVC lights transmittance and water vapor permeability decreased with the increasing amounts of TiO2 and MMT.Aqlil et al. investigated a graphene oxide (GO)-filled starch/lignin polymer bionanocomposite . They fote films . The resE. coli and Gram-positive S. aureus bacterial strains. Liu et al. prepared starch-based nanocomposite films improved by cellulose nanocrystals to control d-limonene permeability [Shankar and Rhim prepared nanocellulose material and tested the effects on the properties of agar-based composite films . The cryeability . They foeability .Postnova et al. studied approaches in which monolithic hydrogels were prepared through mineralization of polysaccharide by a method of green sol-gel chemistry, compared with a method through the formation of polyelectrolyte complex . It was Zein, a group of prolamins from corn, is a Generally Recognized as Safe (GRAS) food-grade ingredient. With the hydrophobicity of three quarters of the amino acid residues in zein, zein-based nanomaterials have low WVP compared to many other bio-based films. Moreover, zein-based nanomaterials embedded with inorganic AgNC may have advantages such as low toxicity . Aytac e2 (NS) using a casting method [2-NPs and found that the nanoparticles improved the compatibility of WPI and chitosan [Qazanfarzadeh and Kadivar prepared WPI-based composite films with different proportions of oat husk nanocellulose (ONC) obtained from acid sulfuric hydrolysis by a solution casting method . They fog method . The reschitosan . Nanopar2 and MgO have attracted much interest because of their resistance to the rough processing conditions and enhancement of strong biocidal impacts against foodborne pathogens [Preventing microbial growth in foods is known as a critical function of packaging to meet the challenge of preserving the quality of food products. Accordingly, antimicrobial materials in food packaging are emerging as a promising technology to fulfill the demands. With the applications of antimicrobial agents in food packaging materials, the growth of bacteria is inhibited and thus the shelf-life of food products is prolonged considerably. Antimicrobial materials are grouped into two classes: organic and inorganic materials. Chitosan-based nanoparticles and chitin-based nanoparticles are typical examples of organic materials, which have lately been widely studied. In respect to the organic antimicrobial materials, some noble metals such as Ag-NPs, Cu-NPs and Au-NPs, as well as the oxidized nanomaterials including ZnO, TiOathogens .An illustration of reported biocidal mechanisms induced by these nanoparticles is shown in 2+ ions regarding accumulation of ZnO-NPs into bacteria cells; (3) ROS formation. Shao et al. tested the electronegativity on S. aureus and E. coli surfaces after AgNPs treatment, and found a possible change in bacterial surface properties [Fardioui et al. reviewed the antimicrobial mechanisms of ZnO-NPs . They fooperties . Furtheroperties . It alsooperties .In the past decades, nanomaterials in food packaging applications have been developed to enhance the barrier and mechanical properties of traditional and bio-based packaging materials, and/or to provide novel active and smart functionalities. Active and smart packaging materials deliberately incorporate active or smart components, which are intended to release or absorb substances into, onto, or from the packaged food or the surrounding environment, or to provide the intended information of their use conditions . DevelopJokar et al. summarized six main questions during the process of migration of NPs from polymer-based food contact materials to consumers in Briefly, through the investigation, Jokar et al. found that many experimental studies had not given a conclusive answer on the possibility of migration of NPs from food packaging materials to the food products . They asIn addition to the technical aspects, no regulations on nanotechnology applications have been yet established in a global context mainly because of lack of sufficient and reliable fundamental researches in regard to the safety assessment and migration characters of nanomaterials from packaging to the food system. The FDA considered that evaluations of safety, effectiveness, public health impact, or regulatory status of nanotechnology products should consider any unique properties and behaviors imparted by the application of nanotechnology . The EurThe innovation of nanomaterials in the food packaging science has brought many changes in food preservation, storage, distribution and consumption. Thanks to preventing microbial growth in foods by antimicrobial activity of nanomaterials, these changes have extended the shelf-life of foods to certain degrees with better management of spoilage in food products. Furthermore, the nanotechnology provides numerous choices for cost-effective, eco-friendly, degradable and renewable packaging materials, which have been gaining more attention and acceptance to solve the ecological environment pollutions and food shortage crises by ensuring food reaches the masses. It is pertinent to note that there are some fundamental studies on toxicity and ecotoxicity, migration assays and risk assessment of nanocomposite materials still needed. In this way, it could allow nanomaterials to work better in the food packaging field.


Risk-taking amongst veterans has severe consequences, yet few studies have examined factors that may predict risk-taking in help-seeking veteran populations. This paper presents a cross-sectional study involving a random sample of 667 UK help-seeking veterans, investigating the role of demographics, mental health and physical health presentations on the propensity for risk-taking. Out of 403 (73.4%) veterans, 350 (86.8%) reported risk-taking in the past month. We found that younger age, being in a relationship, probable PTSD, common mental health difficulties and traumatic brain injury were significantly associated with risk-taking. Additionally, a direct association was found between increased risk-taking and PTSD symptom clusters, including higher hyperarousal, elevated negative alterations in mood and cognition. Our findings provide initial evidence for demographic and mental health presentations as predictors of risk-taking in help-seeking veterans. Further research and longitudinal studies are needed to facilitate valid risk assessments, and early intervention for veteran services.  Nowadays, risk-taking in military populations is often a substantial public health concern and a leading cause of preventable deaths among military personnel . ReportsDespite consistent reports on the impact of risk-taking among military personnel, few studies have investigated help-seeking populations. Help-seeking veterans are outlined as a specific high-risk group for risk-taking due to their elevated health difficulties . A longiStrong theoretical frameworks for elevated risk-taking in help-seeking veterans, however, remain ambiguous. By nature, military personnel are exposed to situations of uncertainty and violence, with shooting, fighting, and inter-unit competitions forming core components of basic training . Some frWhilst these initial findings provide relevance to inform prevention for US personnel, corresponding research into risk-taking among UK veterans remains scarce. In comparison to the US, UK personnel often differ in terms of military service, socio-demographics, and health difficulties, and the availability of post-deployment care shadows the US . InsightThis study received approval from the Combat Stress Ethics Committee. Participants gave informed consent and all data were anonymized to ensure no identifiable participant information was reported. The current study employed a cross-sectional design to explore the predictors of risk-taking in help-seeking veterans. The primary outcome variable was a composite variable of risk-taking, aligning with previous epidemiological methods . Potentin = 667) randomly selected sample was obtained via random number generation. 403 participants completed the study and 51 opted out. After removing any participants who were deceased (n = 4) or had invalid contact details (n = 63), the final adjusted response rate was 67.2% (n = 403). Participants were required to be UK veterans, defined as having served a minimum of one day in the UK military and have contacted Combat Stress (CS) between January 2015 and January 2016. CS is a national UK charity providing clinical mental health services for veterans with PTSD and is commissioned by the National Health Service. To create a representative sample of UK help-seeking veterans, no exclusion criteria were applied. The total number of veterans meeting our criteria was 3335. From this, a 20% , age, relationship status (single/in a relationship), employment status (employed/unemployed), whether the participant had left the Armed Forces early  and the length of time taken to contact Combat Stress . Age was grouped into four categories: less than 35, 35 to 44, 45 to 54 and 55 years and over to aid clinicians in identifying the age bracket most at risk. PTSD was assessed using the Posttraumatic Checklist for the DSM-5 , which Common mental health difficulties were assessed using the General Health Questionnaire (GHQ-12) due to the high validity  in clinical populations . The GHQTraumatic Brain Injury (TBI) was assessed using the Brain Injury Screening Index . The BIFinally, physical health problems were measured using the self-reported question “do you have any problems relating to the following physical health areas? Tick all that apply”. A list of 13 problems was taken from an NHS screening tool used within a South East Hospital in England. These included; diabetes, cardiovascular problems, blood pressure, respiratory problems, liver or kidney problems, amputation, neurological problems, digestive problems, chronic pain, poor mobility, hearing impairment, sight impairment, communication problems. The total number of problems was summed and scores were then evenly split into either a ‘high-risk’ or ‘low-risk’ group for physical health problems, as informed by the sample median post-hoc . The primary outcome ‘risk-taking behavior’ was a composite variable based on previously established military risk-taking behaviors, including; heavy smoking , alcoholSurvey items regarding smoking asked participants whether or not they smoked and if so, how many cigarettes they smoked a day. If participants smoked ≥20 cigarettes a day, they were classed as risky smokers .Risky alcohol consumption was measured using the Alcohol Use Disorders Identification Test (AUDIT) to identify high drinking levels due to the high reliability and validity  showed in clinical and military populations ,30. The Risky driving was assessed using a measure adapted from a King’s College study on risk-taking in military personnel . ParticiFighting was examined through the Walter Reed Aggression Scale (WRA-4). This measure was chosen due to it being specifically designed for military populations and used in a range of previous veteran studies ,32,33. TThe data collection for this study was conducted at Combat Stress in Leatherhead from January to September 2016. The questionnaire was first mailed to participants three times and then remaining non-responders were phoned by the researcher to minimize response and selection bias. After three calls, no additional contact attempts were made. The data was cleaned using frequency lists to check for invalid characters, numbers outside of the valid range and missing values, to minimize human errors. A multiple imputation protocol was put in place where a mean score would only be calculated to replace a missing value when less than 20% of the questionnaire data were missing; otherwise, data were excluded .A risk variable was created from the total scores of each measure  which were coded according to their clinical cutoff scores. Scores above the clinical cut-off point were coded as ‘high-risk’ as they met criteria for caseness indicating risky behavior, and scores below the cut-off were coded as ‘low-risk’. Once binary variables for each variable were created, the risk-taking variables were combined to create a continuous composite primary outcome variable of ‘risk-taking behavior’ as guided by the additive model by Pickett et al. (2002) .First, unadjusted linear regressions were employed to explore the relationship between each demographic variables  and the composite risk-taking behavior. The same analyses were repeated adjusting for these demographics.Second, separate linear regression models were fitted to each health outcome  to explore predictors of risk-taking. A multivariate regression was conducted adjusting for each of the other health outcomes. For example, if PTSD was examined, common mental health difficulties, TBI, and physical health were adjusted for. In addition, all analyses adjusted for age and relationship status.Finally, a linear regression model was independently fitted to each PTSD symptom cluster, with risk-taking as the primary outcome. To minimize the influence of common confounders, subsequent analyses adjusted for the other symptom clusters, age and relationship status. All analyses were conducted in 2017 using STATA Version 13.0 .Of the 403 participants completing the study, 386 were male (96%) with an average age of 50.9 years . In total, 68% were in a relationship and 69% were employed. Only 11% of the sample had left the UK Armed Forces early and 48% had taken longer than 5 years to seek help from CS. In terms of health, 82% of the sample met criteria for probable PTSD, 73% for common mental health difficulties, 48% for TBI and 28% for high-risk physical health problems. No differences were found between responders and non-responders . p < 0.0001). Similarly, a negative relationship was established in those aged 35 to 44 compared to those under 35 . In contrast, a positive association was found between participants who were in a relationship exhibiting greater risk-taking behaviors compared to those without a partner . These findings are presented in Following adjustment for demographics, a negative relationship was found between those aged above 55 engaging in lower risk-taking relative to those under 35 years . TBI was also found to be significantly associated with greater risk-taking compared to those without a TBI . Finally, a positive relationship was found between those with common mental health difficulties and greater risk-taking . No association was found between physical health problems and risk-taking , with a small increase in risky behaviors per each increase of one in the score. Additionally, moderate evidence for a positive relationship between negative alterations and risk-taking were found . This was the first study to explore demographics and health as predictors of risk-taking in UK help-seeking veterans. Veterans who were younger, in a relationship, met criteria for probable PTSD, common mental health difficulties, and TBI were more likely to engage in risk-taking behaviors. For PTSD symptom clusters, higher hyperarousal and negative alterations in mood and cognition were significant predictors of risk-taking.The majority of help-seeking veterans engaged in risk-taking behaviors, of which fighting was the most common, followed by heavy drinking, smoking and, risky driving. These findings support the theory that veterans tend to use alcohol and smoking as emotional numbing strategies for health difficulties . As highFinally, a previous study found that individuals who engaged in one type of risk-taking behavior were more likely to engage in others , whereasVeterans aged 35–44 and over the age of 55 were significantly less likely to engage in risk-taking compared to those under 35. Studies have suggested that aging leads to decreased levels of testosterone and neurotransmitters such as dopamine and serotonin . As thesWhile previous studies have determined that males have a greater biological propensity for risk-taking due to higher testosterone , no sex Veterans who met criteria for common mental health problems, TBI and PTSD were more likely to engage in risk-taking. Aligning with the emotional regulation theory in compassion-focused therapy , trauma Conversely, no differences were found in risk-taking between high and low physical health groups. Ben-Zur and Zeidner (2009) proposed that physical health difficulties resulting from trauma may reduce an individual’s attention span . An indiFinally, findings illustrated a significant dose-response effect between risk-taking and PTSD symptoms of hyperarousal and negative alterations of mood. Previous examinations of symptom clusters and risk propensity have provided mixed associations. However, these findings parallel that of a US study showing hyperarousal to be linked to aggression in treatment-seeking veterans and can be explained in terms of increased dopamine and serotonin impairing decision-making . ConversGiven the high response rate and homogeneity between responders and non-responders , this stWhile the current study measures  are widely used in clinical practice, a clinical interview with a trained professional is required to establish an accurate mental health diagnosis. As such, the current case criteria only provide an indicative screening that the individual may have the mental health difficulty. Moreover, the use of screening tools may have introduced bias or over-reported symptoms . A further limitation was the use of the WRA-4 to assess fighting. The scoring of the WRA-4 does not distinguish between verbal and physical violence which may have led to an overestimation of physically violent behavior. Nevertheless, verbal aggression can have a profound effect on the psychological well-being of the victim, so must be acknowledged as a form of violence .Finally, the dichotomization of variables could have led to the loss of rich data, increasing the risk of type two errors . VariablThe findings of this study have a range of clinical implications. As several predictors were found for risk-taking, it is important these individuals are identified early-on through additional risk assessments on risk-taking behaviors, are prioritized for treatment and continually monitored upon discharge. Specifically, veterans who are younger, in a relationship, screen positive for probable PTSD, common mental health difficulties and TBI should undertake an additional risk assessment regarding risk-taking behaviors. Currently, standard protocols target suicidal behaviors and additional assessments are needed for other behaviors such as alcohol misuse, smoking, risky driving and fighting. Specific psycho-education sessions could be provided focusing on the consequences of risky behavior, the biological and psychological mechanisms, identifying triggers and developing alternative coping strategies which may increase awareness and reduce these behaviors amongst veterans .Future longitudinal research is required to examine how factors such as demographics and health presentations affect veteran risk-taking over time as well as examining military characteristics. As interventions targeting risk-taking are currently limited, clinical research is needed to develop an evidence-based intervention to reduce risk-taking in help-seeking veterans. One pilot study in the US has begun to investigate the effect of a group-based Cognitive Behavioral Therapy intervention on risky driving but is limited to a small sample size, no control group and a short one-month follow-up . Future This was the first study to explore demographics and health as predictors of risk-taking in a sample of UK help-seeking veterans. 87% of our sample had engaged in risk-taking in the past month, with fighting (77.9%) and heavy drinking (40.2%) most common. Veterans who were younger and in a relationship were more likely to engage in greater risk-taking, alongside those who met case criteria for probable common mental health difficulties, PTSD and TBI. Finally, a direct association was found between higher hyperarousal, more negative alterations in mood and cognition and increased risk-taking. The development of additional screening and focused interventions for risk-taking is vital to lessen morbidity rates and preventable deaths among veterans.


Understanding help-seeking among victims of elder abuse is a critical challenge in the field. The vast majority of elder abuse victims remain hidden from formal support/protective response systems, such as adult protective services, legal/justice, law enforcement, or other agencies responsible for addressing this issue in the community. Guided by the Behavioral Model of Health Services Use, this study examined factors that facilitate or impede formal help-seeking among victims of elder emotional, physical and sexual abuse, represented by a call for help in the form of a report to police or other authorities. Data came from a national, population-based elder abuse study in the U.S. with a representative sample (n=304) of victims reporting abuse in the past year. Gold-standard measurement strategies were used to assess each elder abuse subtype. Multivariable logistic regression was conducted to identify help-seeking facilitators/barriers. Help-seeking through reporting to police or other authorities occurred among only 15.4% of elder abuse victims nationwide. Help-seeking was predicted by factors attached to the victim , perpetrator , and victim-perpetrator relationship (victim dependence on perpetrator). This study highlights the extremely hidden nature of elder abuse in our society, as well as the need to develop strategies that incorporate victim, perpetrator, and victim-perpetrator relationship factors to promote greater help-seeking among victims.


Chitosan-based nanomaterials have attracted significant attention in the biomedical field because of their unique biodegradable, biocompatible, non-toxic, and antimicrobial nature. Multiple perspectives of the proposed antibacterial effect and mode of action of chitosan-based nanomaterials are reviewed. Chitosan is presented as an ideal biomaterial for antimicrobial wound dressings that can either be fabricated alone in its native form or upgraded and incorporated with antibiotics, metallic antimicrobial particles, natural compounds and extracts in order to increase the antimicrobial effect. Since chitosan and its derivatives can enhance drug permeability across the blood-brain barrier, they can be also used as effective brain drug delivery carriers. Some of the recent chitosan formulations for brain uptake of various drugs are presented. The use of chitosan and its derivatives in other biomedical applications is also briefly discussed. It is considered to be the second largest renewable biomaterial after cellulose in terms of utilization and distribution . In recemonomers . Chitosamonomers , interrumonomers , and actmonomers . It is smonomers . Chitosamonomers . Chitosamonomers , in drugmonomers , for genmonomers , hemodiamonomers  and dentmonomers  as well monomers . In this article, we present several emerging biomedical applications including chitosan-based biomaterials, where two of most commonly investigated by the scientific community are highlighted: antimicrobial wound dressing and drug delivery including formulations for brain uptake. Firstly, insights about the antibacterial effects and mode of action of chitosan-based nanomaterials and their role as carriers for drug delivery are presented. Chitosan is proposed as an excellent antimicrobial wound dressing nanomaterial, either in its native form or formulated with antimicrobial substances to additionally increase its antimicrobial effect. Since chitosan and its derivatives can enhance drug permeability across the blood-brain barrier, they can also be used as excellent brain drug delivery carriers. Some of the recent chitosan formulations for brain uptake of various drugs are presented. The use of chitosan and its derivatives in other biomedical applications is also briefly discussed.3+) of glucosamine interact with the negatively charged surface of bacteria, causing leakage of intracellular constituents that results in cell death [Echerichia coli using a confocal laser microscope suggests that chitooligomers were present within the cell and probably prevent DNA transcription [2+ and Mg2+ present in the microorganism cell wall prevents the production of toxins and inhibits bacterial growth. The fourth hypothesis presents chitosan as a blocking agent that blocks nutrients and oxygen from entering the cell.Although the exact antimicrobial mechanism of chitosan and its derivatives is not yet fully understood, several hypotheses about the mode of action have recently been proposed and accepted . The mosll death . Other pcription . Anothercription . The intSeveral factors are recognized to affect the antimicrobial activity of chitosan and can be divided into three main categories: environmental factors, fundamental factors of chitosan and factors affecting different types of microorganism.Listeria monocotgenes, Salmonella enterica, Staphylococcus aureus and E. coli, compared to one stored at 25 °C [Environmental pH is one of the most important factors affecting the antimicrobial activity of chitosan and its derivatives. Chitosan shows its antimicrobial effect only in an acidic medium, since it possesses poor solubility at high pH (pH ≥ 6.5). The reason for that may lie in the fact that the majority of amino groups become uncharged near pH 7 . To overat 25 °C .E. coli, the opposite effect was found [S. aureus. A lower degree of deacetylation more successfully inhibited the growth of bacteria. In contrast, Byun et al. reported that the activity of chitosan, prepared from the ground shell with a degree of deacetylation of 81.6% is greater than that of chitosan prepared from the entire shell with a degree of deacetylation of 62% [In the case of lower molecular weight, the size and conformation of chitosan appear to be fundamental, since mobility, attraction and ionic interaction are easier with small chains than with larger ones, resulting in effective binding to the membrane surface . Howeveras found . In the as found . In the as found . In a stas found  using man of 62% . The reaCandida albicans and Fusarium solani compared to chitosan in the solution form [Candida, chitosan obtained from Pleurotus spp. showed promising results. With regard to chitosan biofilms, important for biomedical applications, it was found that reduced biomass and metabolic activity in both the adhesion phase and in the mature biofilms display no significant difference for the strains of Candida parapsilosis sensu stricto and Candida tropicalis [It was found that chitosan exhibits diverse inhibitory efficiency against different bacteria and fungi. The mode of antibacterial activity is a very complex process that varies between Gram-positive and Gram-negative bacteria, based on differences in cell structure . Gram-neion form . In the opicalis , using dopicalis . Influence of environmental, fundamental factors of chitosan and factors affecting different types of microorganism are presented in In many studies, the assay conditions for determination of chitosan minimal inhibitory concentration (MIC) have not been standardized; it is therefore difficult to make effective comparisons between studies. Chitosan-based nanomaterials have attracted significant attention in a wide variety of biomedical fields because of their unique chemical properties, including desired biodegradability, compatibility and non-toxicity. In tissue engineering, chitosan is a suitable biomaterial to construct extracellular tissue matrixes . It can 2) and natural compounds and extracts  ® [The healing process of a wound comprises a cascade synchronized events: hemostasis, inflammation, migration, proliferation and remodeling . To ensu etc.) ® ,57,58,59®, Chitpack®, Patch®, Tegasorb® and KytoCel® [E. coli, S. aureus, methicillin-resistant S. aureus (MRSA), P. aeruginosa and Klebsiella pneumoniae. Sponges containing higher nAg  concentrations showed antibacterial activity against drug-resistant bacteria. In a recent survey, metallic composites were united with natural products to increase their antibacterial nature and biocompatibility [A. vera is a natural compound that has been extensively studied in combination with chitosan for antimicrobial dressing applications [A. vera membranes as active wound dressing materials useful for skin repair. Nguyen et al. [in vivo study indicated better wound closure in wounds treated with curcumin-composite sponge than those with composite sponge without curcumin and an untreated group. Honey is one of the natural products that displays high bactericidal activity [In the native form, many commercial wound dressings are available on the market, including HidroKiKytoCel® . In ordeKytoCel® , block kKytoCel® , or inteKytoCel® . RecentlKytoCel® . The maiKytoCel® . HoweverKytoCel® . Among tKytoCel® . AnishiaKytoCel®  presentetibility . An incrtibility ,75. A. vications . Silva eications  highlighn et al.  preparedactivity . A rangeactivity , Actilitactivity  and Algiactivity . Honey factivity . To dateThree-dimensional porous scaffolds for bone tissue engineering must be biocompatible and allow osteogenesis. A variety of techniques have been developed to mimic the microstructure and properties of natural mineralized materials. Still, facile and rapid fabrication of large-size bulk materials with high calcium content under ambient conditions remains a major challenge. During gelation, a controllable inorganic gradient distribution forms, along with mineralization, where urea was used, and spontaneously hierarchically ordered hydrogel microstructures were formed. This fabrication route takes only hours to complete the gelation and mineralization processes . Composite scaffolds have been fabricated using a coaxial electrospinning technique to prepare gelatin-chitosan core-shell structured nanofibers. An arginine-glycine-aspartic acid (RGD)-like structure was formed to mimic the organic component of the extracellular matrix of natural bone. Later, by a wet chemical method, hydroxyapatite was deposited on the surface of the prepared-shell structured nanofibers. Hydroxyapatite is the major mineral constituent of natural bone. Gelatin-chitosan core-shell structured nanofibers improved the mineralization efficiency of hydroxyapatite compared to chitosan nanofibers . The desE. coli and S. aureus. In another study, scaffolds were made of poly-ε-caprolactone (50 kDa), containing chitosan and vancomycin as an antimicrobial agent for bone regeneration purposes. The scaffolds sustained vancomycin release for more than 2 weeks. The scaffolds were tested against Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria after 24 h of incubation with full growth inhibition for S. aureus [From the perspective of antibacterial effects, Zhou et al.  synthesi. aureus . AlthougPeptide and protein drug delivery systems could be improved by chitosan and its derivatives . The molThe first nasal formulations with a chitosan absorption enhancer to induce the brain’s uptake of neuroactive agents were proposed in 2008 . Nasal fThe N,N,N-trimethyl chitosan (TMC) is a positively charged, quaternized hydrophilic derivative of chitosan. It has excellent solubility over the entire pH range compared to chitosan and is completely biodegradable and biocompatible, while possessing greater bioadhesivity than chitosan . It alsoRopinirole-dextran sulfate (ROPI-DS) nanocomplex-loaded, flaxseed oil-based NNEs and TMC-modified mNNEs have been developed for direct nose-to-brain drug delivery, with the objective of providing controlled drug release for the treatment of Parkinson’s disease (PD). Direct nose-to-brain drug delivery in a mouse model has achieved significantly high drug concentrations in the brain compartment . FurtherFor treatment of PD, pramipexole dihydrochloride-loaded chitosan nanoparticles (P-CNs) were developed in another study for effective brain targeting via the non-invasive nasal route. Nanoparticles were prepared using chitosan and sodium tripolyphosphate by the ionic gelation method. P-CNs significantly enhanced antioxidant status in the form of increased superoxide dismutase and catalase activity, along with increased dopamine levels in the brain . RopinirIn vivo application of the formulation resulted in enhanced drug delivery in the brain compared to the suspension of SAX, which showed no detectable amount even after 24 h [The most common neurodegenerative disorder to cause dementia is Alzheimer’s disease (AD). Type-2 diabetes (T2D) is one of the major risk factors associated with AD. Similarities have been found in the molecular mechanisms that underlie the respective degenerative development in the two diseases. Saxagliptin (SAX) is a dipeptidyl peptidase-4 enzyme inhibitor molecule explored for its activity in AD therapy. The dipeptidyl peptidase-4 enzyme increases the level of glucagon-like peptide-1 (GLP-1) and ameliorates T2D . Becauseter 24 h . in vivo studies showed that recovery was significantly improved after intranasal administration of NP-355 and NP-647 NPs, as compared to un-encapsulated NP-355 and NP-647 [in vivo results showed that both encapsulation of CBZ in nanoparticles and the nasal route resulted in enhanced drug bioavailability and brain targeting characteristics [A biodegradable chitosan-poly(lactide-co-glycolide) (PLGA) drug was synthesized in the form of a nanoformulation as a therapeutic approach for the delivery of neuroprotective drugs to the brain in the treatment of epilepsy , which hd NP-647 . Also, cd NP-647 . CBZ is eristics . In vivo studies were performed on rats. Such an LMs system attained complete targeting of resveratrol to the CNS via a direct nose-to-CSF route, resveratrol being undetectable in the bloodstream of rats after nasal administration of the chitosan-coated resveratrol-loaded LMs [Another possibility is to produce lipid microparticles (LMs), coated with chitosan and containing the polyphenol resveratrol. Specifically, for central nervous system diseases, resveratrol has been reported to be effective against neurologic disorders such as AD and PD, brain ischemia and epilepsy. aded LMs . Recent Chitosan formulations as drug delivery carriers are not limited to delivering active agents to the brain, but can be used for many other delivery purposes in biomedicine. As mentioned before, the low solubility of chitosan in biological systems limits its use as a drug delivery carrier . Therefoin vitro and in vivo. In vitro, the most commonly used cell lines that have been transfected using chitosan-pDNA complexes are HEK293, A549, HeLa and COS-1 [To improve the protein-sponging ability of chitosan, a variety of methods has been used—e.g., incorporation of different moieties propyl-3-trimethylammonium chitosan chloride NP-conjugated anion membrane biosensor showed good sensitivity, reproducibility, reusability, low cost and an easy-to-operate system for quantification of glucose in the system [−1 cm−2) and fast response times. Palladium nanoparticles modified with chitosan oligosaccharide (COS) were functionalized with RGD peptide, which improves particle accumulation in MDA-MB-231 breast cancer cells and results in enhanced photothermal therapeutic effects under an 808-nm laser. The RGD peptide-linked, COS-coated palladium nanoparticles (Pd@COS-RGD) destroyed the tumor effectively under 808-nm laser illumination at a power density of 2 W cm−2. They act as an ideal nanotheranostic agent for enhanced imaging of and therapy for tumors using a non-invasive near-infrared laser [Chitosan and chitosan nanocomposites have also been used in bioimaging, biomedical devices, sensors, etc. Darder at al.  reportediosensor . A GOx- e system . Shakya e system  prepareded laser . Karagozed laser  reporteded laser . Many of3+) of glucosamine interact with the negatively charged surface of bacteria, causing leakage of intracellular constituents that results in cell death. Chitosan is one of the most abundant polysaccharide polymers, and is capable of significant antimicrobial activity against a wide variety of fungi and bacteria. Despite many proposed hypotheses and contributing effects, there is no consensus on the mechanism of action for its antimicrobial activity. This could be explained by the fact that, in most studies, the assay conditions have not been standardized and it is thus difficult to make a good comparison between them. The most widely accepted hypothesis is that positively-charged amine groups (NHin vivo, the toxicity of nanoparticles still needs to be solved. There has been no effort made to fully evaluate its efficiency in an infectious area in vivo and in vitro. Similarly, there are many opportunities for future studies of chitosan use in combination with natural compounds and extracts. Further improvement to chitosan-based wound dressings are also needed. These include development of new smart dressings containing sensors and therapeutic molecules that are released at the same time as the microbial growth. In this concept, a wound dressing system releases bioactive compounds when any change in the medium occurs, including pH, temperature or UV due to initial bacterial activity.In the present review, chitosan has been presented as an ideal renewable agent for the fabrication of antimicrobial wound dressings, either alone in its native form or upgraded and incorporated with antibiotics, metallic antimicrobial particles, natural compounds and extracts. The incorporation of metallic nanoparticles into chitosan-based matrices has been reported as a novel idea to increase and sustain antimicrobial effect. Prior to clinical application Brain drug delivery is another biomedical application where chitosan and its derivatives as nano-biodegradable carriers play an important role. A wide variety of chitosan-based nanoparticles has proven to improve the therapeutic efficacy in various brain diseases, owing to its fine biological properties, modifiability and effective uptake by intranasal mucosal cells to tumor cells. There are still challenges to solve regarding the toxicity of some chitosan derivatives, which could serve as carriers of material for nose-to-brain drug delivery. Moreover, in the case of chitosan and protein complexes, the interaction between polysaccharides and proteins, the phase behavior and colloidal properties of complexes between chitosan, a positively-charged polysaccharide, and proteins still need to be investigated. In acidic pH, chitosan is highly protonated, which stabilizes the complexes. Furthermore, the addition of NaCl leads to a reduction in both size and zeta-potential and facilitates complex aggregation. In conclusion, chitosan-based nanomaterials are often present in today’s clinical applications and are expected to have an even greater impact on emerging biomedical applications.


Background: Self-regulated learning refers to the monitoring and controlling of one's own cognitive performance before, during, and after a learning episode. Previous literature suggested that self-regulated learning had a significant relationship with academic achievement, but not all self-regulated learning strategies exerted the same influences. Using an invalid strategy may waste the limited psychological resources, which will cause the ego depletion effect. The present meta-analysis study intended to search for the best self-regulated learning strategies and inefficient strategies for Chinese students in elementary and secondary school, and analyzed the critical phases of self-regulated learning according to Zimmerman's theory. The moderating effects of gender, grade, and publication year were also analyzed.Methods: Empirical studies which conducted in real teaching situations of elementary and secondary education were systematically searched using Chinese academic databases. Studies focused on undergraduate students, students of special education, or online learning environments were excluded. Fifty-five cross-sectional studies and four intervention studies (which generated 264 independent samples) were included with a total sample size of 23,497 participants. Random effects model was chosen in the current meta-analysis, and publication bias was also examined.Results: The results indicated that the overall effect size of self-regulated learning on academic achievement was small for primary and secondary school students in China. The effect sizes of self-efficacy, task strategies, and self-evaluation were relatively higher than other strategies. Self-regulated learning strategies have the largest effect size on science disciplines (including mathematics and physics). Performance phase and self-reflection phase are key phases of self-regulated learning. From 1998 to 2016, the effect size between self-regulated learning and academic achievement was gradually decreasing.Conclusions: The main findings of the current study showed that self-efficacy, task strategies, and self-evaluation were key self-regulated learning strategies for Chinese students. Performance phase and self-reflection phase played significant roles in the process of self-regulated learning. Future studies need to include more intervention studies with rigorous treatment fidelity control and provide more empirical evidence from online learning, so as to compare the different effects of self-regulated learning between traditional education and online education. Professional learners are good at using strategies to help their study and holding openness view to difficult tasks, and they are willing to accept challenges until they reach the goal. Using effective learning strategies, having strong self-efficacy and will power are significant characteristics of professional learners  on the relationship between SRL and academic achievement. Thus, it is intriguing to examine if publication year would be a moderator in the meta-analysis.Although researchers have provided critical reviews of existing self-regulated learning studies , Wanfang Database, and Vip Paper Check System. The following key words were used: “Self-regulated learning,” “self-monitoring,” “self-management,” “time management,” “learning strategies,” “metacognition,” “goal orientation,” “goal setting,” “self-efficacy,” “self-reflection,” “self-evaluation”; “academic achievement,” “interim/final grade,” “academic performance,” “grades,” and “academic success.” Then, we also searched through the reference lists of systematic review articles of SRL.After literature searching, all the authors discussed the following inclusion and exclusion criteria: 1) In order to ensure ecological validity, empirical studies should be conducted in real teaching situations. (2) Participants in the empirical studies must be elementary, junior high, or senior high school students in China. Undergraduate students and students of special education were excluded. (3) Empirical studies based on the online learning environments were excluded. (4) Empirical studies should report the correlation coefficients, sample sizes, means, and standard deviations. After literature screening /(59+59) = 0.763. Because the two authors had different opinions about the classification of SRL strategies, they did not reach a consensus on 14 of the 59 studies. In cases where classification was not in agreement, the two authors discussed and came to a consensus.All articles were separately coded by the first author and the second author. Inter-rater agreement CA = 2Although most studies in the current meta-analysis were cross-sectional studies, 4 out of the 59 studies were based on intervention. It is necessary to report treatment fidelity of these intervention studies to ensure that study outcomes were due to treatment rather than factors incidental to the intervention . A few studies reported the means, sample sizes, and standard deviations of experimental group and control group, we also transformed these number into Cohen's d. In interpreting the effect size, we followed Rosenthal . The current meta-analysis was conducted with a random effects model, because accumulated evidence suggested heterogeneity in effect sizes  = 3,766.115, p < 0.001, I2 = 93.0%], suggesting the presence of moderators.Two hundred and sixty-three independent samples reported the correlations between specific SRL strategies  and academic achievement. Five independent samples viewed SRL as an integrated conception and reported the correlations between SRL and academic performance. Table Table QB(3) = 22.025, pB = 0.000]. The effect sizes of forethought phase, performance phase and self-reflection phase were 0.316, 0.525, and 0.465.According to Zimmerman's theory, we classified SRL strategies into forethought phase, performance phase, and self-reflection phase. Concretely, attention focus, goal orientation, goal setting, and task interest/value were classified into the forethought phase. Task strategies, metacognitive monitoring, and attention focus were classified into the performance phase. Attribution, self-satisfaction/affect, and self-evaluation were classified into the self-reflection phase. Table QB(2) = 38.623, pB < 0.001, See Table d = 0.629) was higher than that of senior high school students (Cohen's d = 0.303) and elementary school students (Cohen's d = 0.164).All independent samples were classified into three groups: elementary school, junior high school, and senior high school. Some independent samples included both elementary school students and junior high school students, or junior high school students and senior high school students, but did not specify the educational stage. These independent samples were not included in this moderator analysis. It was found that educational stage significantly moderated the relationship between SRL and academic performance .The time span of the present meta-analysis ranged from 1998 to 2016. We examined the moderating effects of publication year and the proportion of female using meta-regression. From 1998 to 2016, the effect size of SRL gradually declined [N of the present study was 9,558. According to Rosenthal's , covering 23,497 Chinese students, and tried to understand the relationship between SRL strategies and academic achievement in education in China. We examined the moderating effects of gender, grade, and year of publication. According to Rosenthal 's guidelWe found that the effect sizes of self-efficacy, self-evaluation, and task strategies were relatively large, suggesting that these were important SRL strategies for Chinese students. Similar to the present study, Richardson et al.  conducteIn addition, the present study found different effect sizes for the different academic fields (higher effects for science performance than for language), suggesting that SRL strategies were more effective for improving science performance. Lucangeli and Cornold  suggesteAccording to the phases and sub-processes of SRL, we classified all SRL strategies in empirical studies into forethought phase, performance phase, and self-reflection phase. The effect size of forethought phase  was lower than that of performance phase (medium) and self-reflection phase (medium), but there was no difference between performance phase and self-reflection phase.From a theoretical perspective, researchers have different views in terms of whether SRL should contain the forethought phase . For example, social cognitive view suggested that SRL is acquired through a triadic interaction between three characteristics: (1) self-observation (monitoring one's actions); (2) self-judgement ; (3) self-reactions (one's response to performance outcomes), which did not involve the elements of motivation or planning , which might be an important potential moderator  on the relationship between SRL and academic achievement. For example, the research design  and fidelity of data collection may be different in the included studies. In addition, most empirical studies in the current meta-analysis were cross-sectional studies, whereas only four studies were based on intervention, which limited the generalizability of the current study to some extents. We evaluated the treatment fidelity of these intervention studies but found that few studies provided a rigorous treatment fidelity control. Despite these limitations, the current study provided an insight from Chinese scientific community to the field of SRL.Future studies could examine the moderating effect of SES or other interesting variables. More SRL empirical studies in online learning are needed in China, so researchers could compare the difference effects between traditional learning and online learning on the relationship between SRL and academic performance. For example, Broadbent and Poon  suggesteThe conclusions emerging from the present study are as follows: First, for Chinese elementary school students and high school students, self-efficacy, task strategies, and self-reflection turned to be better SRL strategies. Second, SRL strategies were more effective for science disciplines than for linguistics disciplines. Third, the performance phase and the self-reflection phase are critical phases of SRL in that they have a larger effect on academic achievement. Fourth, the effect size of junior high school was larger than that of senior high school and elementary school. Junior high school is probably the critical period of SRL development. Fifth, from 1998 to 2016, the effect size of SRL was gradually decreasing. Lastly, most empirical studies in the present meta-analysis were cross-sectional studies, whereas only four were intervention studies. More empirical-based intervention studies may be necessary before generalizing the current conclusions to educational practice.According to the present study, educators should improve students' self-efficacy, and teach them some sample task strategies. Teachers could encourage students to evaluate their own performance and to reflect their learning actions. It could be beneficial for teachers to know how to teach SRL at different educational levels and disciplines, because SRL works better at different educational levels and disciplines. At the same time, teachers need to receive training on SRL theory and models to understand how they can maximize their students' learning (Panadero, JL searched for references, coded and analyzed the data, and prepared the manuscript. HY coded the data and helped prepare the manuscript. YT designed the study and prepared the manuscript. ZZ and XH supervised the whole research process and proofread the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Escherichia coli Hfq, or more precisely its amyloid-like C-terminal region (CTR), induces DNA compaction into a condensed form. In this paper, we evidence a new property for Hfq; precisely we show that its CTR influences double helix structure and base tilting, resulting in a strong local alignment of nucleoprotein Hfq:DNA fibers. The significance of this alignment is discussed in terms of chromatin structuration and possible functional consequences on evolutionary processes and adaptation to environment.The Hfq protein is reported to be involved in environmental adaptation and virulence of several bacteria. In Gram-negative bacteria, Hfq mediates the interaction between regulatory noncoding RNAs and their target mRNAs. Besides these RNA-related functions, Hfq is also associated with DNA and is a part of the bacterial chromatin. Its precise role in DNA structuration is, however, unclear and whether Hfq plays a direct role in DNA-related processes such as replication or recombination is controversial. In previous works, we showed that  These include changes in growth and mutagenesis rates, stress resistance, or plasmid supercoiling -poly[d(T)] long polymer, may be inclined differently by a few degrees when bound to the protein, similar to the base tilt observed for free poly[d(AT)]-poly[d(AT)]  . This chy[d(AT)] . Here wey[d(AT)] . Neverthy[d(AT)] ), we sus59 dsDNA along the strand axis versus in an orthogonal arrangement, the approximate 1:1 dsDNA:Hfq-CTR association suggests an out-of-axis organization of the two elongated molecular architectures, permitting an optimal packing. This is indeed confirmed by SRLD measurements on the dsDNA:Hfq-CTR complex, where the β-strand is found to be perpendicular to the dsDNA helical axis. This would, for example, be the case if the peptide arranges in the DNA grooves or associates in an orthogonal orientation to the dsDNA, assuming an amyloid arrangement angement .Functionally, such a property could generate short-range chromosomal contacts and could be of major importance for some DNA-related processes such as homologous recombination, site-specific recombination or DNA repair, with an impact on evolutionary processes and adaptation to environment ,58,59. Hin vivo and the structural and mechanistic background in vitro, our results definitively evidence that Hfq and precisely its CTR has an important role to be considered as bacterial chromatin organizer and in DNA-related regulative processes. Different reports based on hfq gene-disrupted cells revealed the important regulatory role of Hfq in various cellular processes, with major impact on environmental adaptation. Most of these effects were attributed to sRNA-Hfq-based regulation [Although a lot of work remains to be done to decipher the various Hfq mechanisms at stake gulation ,18,64, b