The present study aimed to develop Nursing Stretch Break (NSB) application to relieve work-related musculoskeletal complications and fatigue among hospital nurses.  This interventional study was conducted among 71 nurses (15 men and 56 women with a mean age of 33.32 ± 6.42) employed in Shiraz governmental hospitals, Southwest Iran, for four months. In this study, NSB was developed; it includes eight main menus for the user, including (1) Registration, (2) Stretches, (3) User panel, (4) Questions from the researcher, (5) About us, (6) Contact us, (7) Reports, and (8) Answers to questions. Data were collected pre and post-intervention via the Persian version of the Nordic Musculoskeletal Questionnaire (P-NMQ), the Persian version of the Multidimensional Assessment of Fatigue (P-MAF) Scale, the Persian version of the Numeric Rating Scale (P-NRS), and the Persian version of the Usefulness, Satisfaction, and Ease of use (P-USE) questionnaire.  NSB application usability testing showed that the mean scores of P-USE subscales were high. The prevalence of work-related musculoskeletal symptoms (WMSs) in the last 7 days in nurses' body parts, except the elbows and knees, was significantly lower after the intervention than before. In addition, the intensity of work-related musculoskeletal pain/discomfort in all body parts, except the knees, was significant relief after the intervention compared to before. The results demonstrated that the difference in the mean score of the total fatigue and its subscales, except “degree of interference with activities of daily living,” was significant after the intervention compared to before.  NSB could be a low-cost and feasible ergonomic solution to improve the nurses' musculoskeletal health. Work-related musculoskeletal disorders (WMSDs) are a worldwide concern that develop in the soft tissue structures in the body, such as the muscles, tendons, joints, nerves, ligaments, cartilage, spinal discs, and blood vessels due to repeated or prolonged ergonomic exposures. Such exposures may include awkward or static postures, repetitive motions, forceful exertion, manual materials handling (MMH), contact stresses, vibration, temperature extremes, and lack of rest break, which may be exacerbated or modified by psychosocial and organizational issues and individual/personal characteristics . WMSDs aA systematic review among African workers demonstrated that WMSD was a problem in many African countries, with the prevalence ranging from 15.0% to 93.6%. This study revealed that the highest reported symptoms were related to the “health professional cadres” .Krishnan et al. reported that 97.3% of the nurses complained of having work-related pain during the last 12 months. The highest prevalence of WMSs was linked to the lower back 86.7%), ankles (86.7%), neck (86.0%), shoulders 85.0%), lower legs (84.7%), and upper back (84.3%). In addition, the participants complained of severe pain in the lower back (19.7%), right shoulder (29.7%), and left shoulder (30.3%). It is revealed that 73.1% of the nurses sustained WMSDs for the past 12 months [.0%, lowe.7%, anklYao et al., in their study, demonstrated that the prevalence of WMSDs among study nurses was 84% in all body regions in the previous year, with the highest prevalence in the neck (68.2%), followed by the waist (67.6%) and shoulder (54.6%). Statistical analyses showed that physical exercise was associated with WMSDs in nurses. Therefore, the lack of exercise significantly increased the risk of WMSDs [Nurses, as a vital working group in the health care industry, are prone to WMSs. They are encountered with various risk factors, including a high volume of work, awkward postures, highly dynamic repetitive activities, and patient handling for long hours. In these situations, a high prevalence of WMSs and a high level of fatigue are expected among hospital nurses. In a previous study, we found out that the prevalence of WMSs and the amount of fatigue among Iranian nurses were high. The highest prevalence of the reported WMSs in the last 12 months was linked to the ankles/feet (81.8%), lower back (80.2%), knees (63.2%), upper back (62.8%), and shoulders (62.4%). In addition, the mean ± standard deviation of total fatigue related to the last 7 days was 32.46 ± 5.59, indicating moderate to high level of fatigue . Recent Therefore, to relieve work-related musculoskeletal complications and fatigue, we decided to design an application, so that hospital nurses can use it easily in the workplace.This study is “Phase II” from a comprehensive study among Iranian nurses. In Phase I, 500 Iranian nurses, employed in Shiraz governmental hospitals, Southwest Iran, were examined via the Persian version of the Nordic Musculoskeletal Questionnaire (P-NMQ) to determine the prevalence of WMSs and the Persian version of the Multidimensional Assessment of Fatigue (P-MAF) Scale to determine the amount of fatigue. This phase (Phase I) revealed that the prevalence of WMSs and the amount of fatigue among the study population was high .n = 74). Three nurses were excluded from the study for various reasons, including acute musculoskeletal injury during the study (one person) and changing the job (two people). Finally, 71 individuals were included in the study (response rate = 96%).n: sample size, N: statistical population size = 500, z: 1.96, p=0.94, q = 0.06, and d = 0.05.Therefore, in Phase II, we decided to design and use an application to relieve work-related musculoskeletal complications and fatigue among Iranian hospital nurses. Phase II was an interventional study carried out on 71 hospital nurses. The subjects were selected from 500 participants in “Phase I” via simple random sampling. The sample size was calculated by Cochran's equation . In addition, this study was conducted according to the Helsinki Declaration and its later amendments . All nurIn the current study, data were gathered using self-reporting as follows.This questionnaire included age, height, weight, job tenure, working h/day, gender, marital status, number of children, education level, smoking, and shift work.The NMQ initially developed by Kuorinka et al. provides reports of discomfort in body regions. It includes the neck, upper and lower back, and upper and lower limbs and determines if symptoms were present during the last 12 months and the last 7 days . The psyNRS is a unidimensional measure of pain/discomfort intensity . The psyThe MAF scale was developed by Belza et al. It contains 16 items that assess various aspects of fatigue. This tool is a self-administered questionnaire on four dimensions of fatigue, including “degree and severity,” “amount of distress it causes,” “its timing,” and “the degree to which fatigue interferes with daily living activities.” For rating items, a numerical rating scale (1–10) is used for items 1–14, and a categorical scale (1–4) is used for timing items 15 and 16. Finally, a Global Fatigue Index (GFI) was calculated. For GFI, the scores range from 1 to 50 (1 = no fatigue to 50 = severe fatigue) . The parThe USE questionnaire initially developed by Lund measures the subjective usability of a product or service. The USE contains 30 items on a 7-point Likert scale (1 = strongly disagree to 7 = strongly agree) with a “N/A” option. The items belong to four dimensions: usefulness, ease of use, ease of learning, and satisfaction . The psyThe current study was conducted in two stages, as follows.In this stage, we developed and reviewed the Nursing Stretch Break (NSB) application. The research team included medical informatics and health information management specialists, software engineers, physiotherapists, occupational therapists, ergonomics specialists, and sport sciences specialists. To this aim, first, after the search in scientific databases, including Science Direct, PubMed/Medline, Scopus, ProQuest, Google Scholar, Clinical Key, Cochrane, IranDoc (Iranian database), MagIran (Iranian database), and also textbooks in the field of physiotherapy, occupational therapy, ergonomics, and sport sciences, related exercise stretches were extracted by the research team. Then, an expert panel was held to discuss and determine the stretch type. Finally, 24 exercise stretches related to different body regions, including the upper limbs, trunk, and lower limbs, were found to be proper for hospital nurses. The expert panel also discussed application modules and appearance features such as icon size and color.It is worth mentioning that the NSB stretches were planned based on the FITT principle . In addition, it was also adjusted based on SMART  goals. The panel of experts consisted of an ergonomist, two physiotherapists, an occupational therapist, three experts in health information technology, and two nurses.In the next step, a prototype of the NSB was constructed. It includes eight main menus for the user, including (1) Registration, (2) Stretches, (3) User panel, (4) Questions from the researcher, (5) About us, (6) Contact us, (7) Reports, and (8) Answers to questions. The expert panel reviewed the constructed prototype (as mentioned above), discussed pitfalls, and presented solutions. Then, the defects of the NSB were fixed, and the final version was developed. After designing the NSB application, we examined its usability from the experts' point of view via the P-USE questionnaire.The prototype of the NSB was beta-tested two times among 10 nurses with smartphones (5 smartphones with the android operating system and 5 smartphones with IOS operating system). For the first time, the application was successfully installed for 8 out of the 10 enrolled nurses (80%); it was not successfully installed for 2/10 nurses (20%) due to incompatibility of their android version of the smartphone. In the second time, the smartphone operating system version was updated. In this step, the NSB was successfully installed for 10 nurses, and we asked them to test the app during the next two weeks.Stage II of the study consisted of three steps, as follows.(1) Step I: Before Intervention. In this step, the participants completed the questionnaires mentioned above  in their workplace. Each subject filled out the questionnaire in his/her workplace.Demographic/occupational questionnaire, P-NMQ, and P-MAF scales were filled out during the work shift. For assessing the musculoskeletal pain/discomfort intensity, the participants were required to rate P-NRS on Saturday, Monday, and Wednesday at the beginning and end of the work shift. Then, the difference between the P-NRS scores at the beginning and end of the shift during the three working days was calculated. The mean of differences was considered as work-related musculoskeletal pain/discomfort.(2) Step II: Intervention. In the intervention step, the participants installed the NSB application on their smartphones. The NSB provided stretches to the study nurses every hour. They performed various stretches for 5 to 10 minutes. Individuals were asked to hold the stretches for 30 seconds at a moderate intensity [ntensity . The strntensity .To ensure that nurses performed the stretches, one of the researchers regularly monitored them through NSB reporting, presence at the hospital, phone calls, and virtual networks.(3) Step III: After the Intervention. After the intervention, the participants completed the questionnaires as mentioned in Step I at their workplace. Besides, the usability of the NSB from the nurses' point of view was examined using the P-USE questionnaire.All evaluations were done in the same work shifts before and after the intervention to prevent the impact of “work shift” (as a confounding variable) on the study findings.t-test, and Wilcoxon signed-rank test. The Kolmogorov–Smirnov and Shapiro–Wilk tests were used to test the data normality. A p value <0.05 was considered to be statistically significant.Data were analyzed through the IBM SPSS version 21, using descriptive statistics, McNemar's test, paired sample The findings of the stages of the study were presented as follows.Because the previous study results showed that the prevalence of WMSs and the amount of fatigue were high among hospital nurses, we were encouraged to take an intervention to relieve work-related musculoskeletal complications and fatigue in this working group.This study aimed to design and use an application to relieve work-related musculoskeletal complications and fatigue among Iranian hospital nurses. The means ± standard deviations of the subjects' age and job tenure were 33.32 ± 6.42 years and 9.70 ± 6.70 years, respectively.The discussion is presented in two sections as follows.After developing the final version of NSB, we tested the usability of the application. User-centered design considers end users' needs and limitations in each stage of the design process by using methods . ExaminiThe findings of the study showed that the highest prevalence of WMSs in the last 7 days among the study nurses was related to the ankles/feet (80.3%), lower back (77.5%), and knees 59.2%), respectively. The prevalence of WMSs in different body regions of the study population was almost similar to that reported among other Iranian working groups, including hospital nurses .2%, resp, healthcBased on observation and interviews with hospital nurses, the high prevalence of WMSs among the study nurses can be attributed to the predisposing risk factors, including awkward/static working postures for prolonged periods during patient transfer, strenuous physical demands of the nursing profession, and their poor health and fitness conditioning status.Our findings demonstrated a significant reduction in the prevalence of WMSs in the last 7 days in different body regions, except for the elbows and knees after the intervention as compared to before it. In addition, it was revealed that the intensity of work-related musculoskeletal pain/discomfort in all body regions, except the knees, was significant before and after the intervention. Although work-related musculoskeletal complications in the elbows and knees decreased after the intervention compared to before, this reduction was not statistically significant.The comparison of the study groups in the total fatigue and its subscales before and after the intervention showed that the mean score of the total fatigue and its subscales, except “degree of interference with activities of daily living,” were significant before and after the intervention. These findings indicate that using NSB to provide appropriate stretch could effectively relieve musculoskeletal complications in almost all body regions and reduce fatigue among hospital nurses.Abdelall et al. in their study showed that the web-application microbreak stretches helped to reduce physical pain, discomfort/pain, and fatigue and improve mental focus with minimal disruption among the surgeons . In addiZayed et al., in their study, stated that warming up and stretching before performing their nursing duties were a coping strategy for reducing WMSs among the nursing staff . In a stIn the current study, there was no control group. Given the data collection by self-report, the findings should be interpreted cautiously. Moreover, this study was performed among governmental hospital nurses in Shiraz. Therefore, the results might not be generalizable to other working groups.The findings of the current study demonstrated that NSB could be an effective and practical approach to relieve work-related musculoskeletal complications and fatigue among hospital nurses. In addition, the usability testing of the NSB showed that it was a useful, easy to use, easy to learn, and satisfactory application.Finally, we recommend that the newly designed application (NSB) should be used to reduce musculoskeletal pain and fatigue among hospital nurses. A practical recommendation for nurses is to install NSB on their smartphones and perform various stretches for 5 to 10 minutes every hour. They are also advised to hold stretches for 30 seconds at an intensity sufficient to elicit a feeling of strong stretch, not pain.


Growing evidence suggests that alcohol consumption is a risk factor for hearing loss; however, the evidence has been inconsistent. This systematic review and meta-analysis aimed to evaluate the effect of alcohol consumption on hearing loss.Q statistic and I2 statistic), a fixed- or random-effects model was used to calculate the pooled odds ratios (ORs). Subgroup and sensitivity analyses were performed to assess the potential sources of heterogeneity and robustness of the pooled estimation. Publication bias in the literature was evaluated using Egger’s test.We searched several databases up to November 2021, for published articles using the keywords “alcohol drinking” and “hearing loss”. Two investigators independently conducted the study selection and data extraction. Based on the results of the heterogeneity analysis  observational studies were identified in this search; 27,849 participants were included. Compared with non-drinkers, the pooled OR of drinkers was 1.22 .Evidence suggests a positive association between alcohol consumption and hearing loss. Drinkers were at a higher risk than non-drinkers. Drinking limitations may be useful for preventing hearing loss. Hearing loss is a chronic and disabling sensory disorder and a major public health concern worldwide. The latest estimates reveal that hearing loss currently affects 1.59 billion people worldwide, which is 20.3% of the global population, of whom 430 million (5.5%) have moderate or severe hearing loss . At the CAT, HSP70, CDH23, CASP, NOX3, and NRN1) [The occurrence and development of hearing loss is multifactorial and is a long-term and chronic process. In addition to noise exposure, other factors such as genes (nd NRN1) –12, envind NRN1) , 14, andnd NRN1) , 16  cohort-based, case-control, or cross-sectional study; (2) studies that investigated the risk of hearing loss in drinkers; (3) studies that identified hearing loss by pure-tone average; and (4) studies that provided odds ratio (OR) or relative risk (RR) with the corresponding 95% confidence interval (CI).The exclusion criteria were as follows: (1) studies in the format of reviews, editorials, master and doctoral dissertations, and abstracts; (2) studies with a small sample size (n <30); (3) studies whose subjects were children (<15 years old); (4) studies in which the outcome was sudden deafness; (5) studies that middle ear disease was identified by a test of tympanometry or bone conduction.The following information from the selected studies was independently extracted by two investigators: principal author, year of publication, study design, number of subjects, sex and age of participants, country, information about the alcohol consumption, diagnostic criteria of hearing loss, adjusted OR/RR with 95% CIs, adjusting or matching variables, and statistical analyses. Noise-Induced Hearing Loss (NIHL)  is causeThe methodological quality of the included cross-sectional studies was assessed using the 11-item checklist recommended by the Agency for Healthcare Research and Quality. The article quality was assessed as follows: low quality = 0–3, moderate quality = 4–7, and high quality = 8–11. The quality of the included cohort and case-control studies was assessed using the Newcastle-Ottawa Scale (NOS); the rating criteria for the NOS were as follows: Low quality = 1–5, medium quality = 6–7, and high quality = 8–9 .I2 test were performed to evaluate heterogeneity. When the Q test P-value was more than 0.10 or the I2 value was less than 50%, the ORs were pooled according to the fixed-effects model. Otherwise, a random effects model was applied [P values were two-sided, and P<0.05 was considered statistically significant for all included studies. Statistical analyses were performed using Stata/MP version 16.0 .OR was used to measure the association between alcohol consumption and hearing loss. Owing to the low incidence of hearing loss, the reported RR was approximately considered as an OR. When the OR was reported separately at different drinking levels, we extracted the highest level of results. One study separately estimated the OR and 95% CI in men and women, and it was treated as a different study in the analysis. Prior to merging the overall pooled ORs, the Q test and  applied . Forest The main characteristics of the 18 selected studies, comprising 27,849 participants, are presented in P = 0.032. I2 = 41.2%).In total, 19 studies (18 plus one article that separately estimated OR and 95% CI in men and women) assessed the association between alcohol consumption and the risk of hearing loss. Among the 19 studies, nine reported a positive relationship between alcohol consumption and the risk of hearing loss, while 10 found no association. A sensitivity analysis was performed to investigate the source of heterogeneity. Sensitivity analysis showed that the pooled effect sizes obtained for the association of alcohol consumption with the risk of hearing loss did not depend on the individual study.P = 0.144).The funnel plot was used to examine publication bias in the association between alcohol consumption and hearing loss. The graph appears to be symmetrical, and a few studies fall outside the dotted line, suggesting the absence of publication bias. Moreover, we found no publication bias according to Egger’s regression test , subgroup analysis was conducted to explore the sources of heterogeneity. The results for most subgroups indicated a positive relationship between alcohol consumption and the risk of hearing loss, and heterogeneity was reduced across these seven subgroups analyses. Sensitivity analysis showed that our results were robust, and there was no publication bias according to funnel plot and Egger’s analysis. In summary, these results suggest that alcohol consumption is an independent risk factor for hearing loss.A meta-analysis of 18 studies published over the past 25 years showed a significant relationship between alcohol consumption and hearing loss. Compared to non-drinkers, the risk of developing hearing loss increased 1.22-fold among drinkers. Although heterogeneity was moderate in our analysis  than the combination of the two independent variables: alcohol and noise (7.996), indicating that there may be synergistic effects of noise and alcohol consumption . HoweverTo properly interpret the results of the present study, it is necessary to consider several limitations. First, there was no standard definition of alcohol consumption, which was generally a subjective answer to the questionnaire. Some articles were classified by the type of alcohol consumed, others by the amount of alcohol consumed (and in different units of measurement), or simply as two categories, drinking and non-drinking. Due to the limited number of articles and the mixed classification methods, this study classified drinking into two categories: drinking and non-drinking . Second, the diagnostic criteria for hearing loss were inconsistent among the included studies. Some chose the average value in the high-frequency type  as the standard hearing loss threshold, and some were based on the speech-frequency type . Moreover, the hearing thresholds varied, which might have led to more heterogeneity. Third, to measure hearing acuity precisely, control of ambient noise level, the examiners’ techniques, and the precision of the audiometer are important for good reproducibility. Although most of these studies described one or two of these important factors, the overall adjustment for these issues might not be sufficient. Finally, we did not examine the relationship between different alcohol dose levels and the risk of hearing loss because there was insufficient information about the dose-response relationship in this study.Additional rigorous mega-cohort studies or large-scale randomized trials on the association between alcohol consumption and hearing loss are urgently required. Mega-cohort studies involving alcohol consumption habits are realistic and preferable but require several improvements. First, drinking behavior requires a standardized definition that includes at least three aspects: frequency of drinking, quantity of drinking per day, and episodes of heavy drinking. Fortunately, as early as 1993, the WHO developed and released a drinking questionnaire designed to quickly and easily detect drinkers with risky drinking patterns . SubsequIn conclusion, our systematic review and meta-analysis of available epidemiological studies found a positive association between alcohol consumption and hearing loss, suggesting that alcohol consumption may increase the risk of hearing loss. As some inherent limitations in the original studies were observed, no definitive conclusion could currently be drawn. We recommend that more well-designed prospective studies are needed to confirm the relationship between intake of alcohol and risk of hearing loss.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S1 Fig(TIF)Click here for additional data file.


Nanotechnology has helped a lot in diagnosing and treating multiple illnesses, specifically cancer, and increasing the development of targeted drug delivery methods. Nanocomposites are materials with at least one component smaller than 100 nm. Therefore, this study aims to assess the anticancer effects of silver-graphene nanocomposite on MCF-7.  In this study, the rate of inhibition of cancer cell growth and production of reactive oxygen radicals, malondialdehyde, and glutathione stores in MCF7 cells were investigated. Cancer cells were exposed to nano particles for 48 hr. Silver nanoparticles and graphene both reduced the growth rate of MCF-7. Subsequently, by treating the cells with silver-graphene nanocomposite, the rate of inhibition of cell growth at the highest concentration was 84.60%. Nanoparticles also inhibited the growth of cancer cells through the oxidative stress pathway by increasing the amount of intracellular ROS, followed by increasing malondialdehyde and decreasing glutathione stores, so that at the highest combined concentration of nanoparticles, the amounts of LPO and ROS increased up to 70% and 74 %, and glutathione reserves decreased by 16%. Treatment of MCF-7 cells with silver or graphene nanoparticles and combination treatment with these two substances against cisplatin have sound effects, and by affecting oxidative stress factors, such as increased ROS and subsequent increase in lipid membrane damage, inhibit cell growth and proliferation. According to the mathematical model, silver graphene nanocomposite> silver nanoparticles> graphene has the best effect in inhibiting the growth of cancer cells, respectively. In today’s world, nanotechnology has greatly helped to diagnose and treat illnesses, specifically cancer, by using nanoparticles and developing new targeted drug delivery methods , 2. The Nanoparticles can be divided into various types. According to the morphology, physical, size, and chemical properties. Some are carbon-based nanoparticles, ceramic nanoparticles, metal nanoparticles, polymeric nanoparticles, semiconductor nanoparticles, and lipid-based nanoparticles . BesidesCancer cells use the mechanism of autophagy to cope with stress and survive. As stress increases, autophagy is activated, destroying ROS and stopping the aging mechanism , 11. TheMelissa officinalis L. (MO) is a plant of the Lamiaceae family. This plant has different names, such as lemongrass, bee mummy, and honey mummy, and in Iran, it is known as Badranjbouyeh, Warangboo, and Faranjmashk in some places. The growing regions of this plant are in southern Europe and northern Africa, the Caucasus and northern Iran, the eastern Mediterranean region, and western Asia. Ingredients of this plant include rosmarinic acid, chlorogenic acid, caffeic acids, tannins, flavonoids, and sesquiterpenes  with a maximum level of 0.5% in cooked products .One of the methods of making nanoparticles is biosynthesis. In this method, natural materials such as plants and microorganisms are used to synthesize nanoparticles. Plants are a viable option due to their compatibility with the body and environment. The biosynthesis of nanoparticles using plant extracts has its perks in pharmacology and other medical applications and is considered a simple replacement for complicated physical and chemical methods. In this technique, extracts from biological organisms are used both as stabilizers and reducers in the production of nanoparticles. In this nanoparticle production process, in contrast to physical and chemical methods that have 2 phases and require an oxidation-reduction phase and a phase of adding a stabilizer, biological methods are single-phase, and the oxidizer and stabilizers are already in biological extracts. In conclusion, this process is energy efficient .Amongst nanostructures, metallic nanoparticles are the ones with biological applications, where 56% of nanoparticles happen to be silver ones . The proGraphene is one of the carbons’ allotropes. It has a honeycomb structure consisting of single plates of carbon atoms. Its unique qualities, including lightness and thinness, electrical, optical, thermal properties, and mechanical resistance, make it useful in multiple fields such as electrical, thermal, sensitizers, refining industry, textile industry, capacitor production, and as medicine carriers for tissue engineering in pharmacology . The binM. officinalis coated with silver, graphene, and silver-graphene nanocomposite on breast cancer cell line by evaluating oxidative stress factors.Therefore, this research aims to study the anticancer effect of MaterialsIn this study, silver-graphene nanocomposite and silver nanoparticles were synthesized using the Salunke and Kim method . The MCFPreparing the extracts of melissa officinalisM. officinalis leaves . Five grams of M. officinalis leaves were put into 25 ml of the ethanolic solvent. They were pounded for 15 min, and then 90 ml of extra solvent was combined with the mashed content. The extraction was done using a mechanical stirrer for 3 hr with a 750 rpm rotational speed in a dark area. The extracted solution was filtered twice using Whatman Grade 1 filter papers. The extracts were placed in a dark tube at 4 °C  suspensionTen ml of plant extract was combined with 1 mmol/laqueous AgNo3 solution (90 ml) to reduce the Ag+. Afterward, the solution at 60 °C was stirred for 2 hr. It was centrifuged for 20 min at 15000 rpm to purify the synthesized nanoparticles with pellet re-dispersion in the deionized water. The purified powder of nanoparticles was used to aid us in further analyses . Synthesizing grapheneIn order to materialize graphene, plant extract (50 g/l) was placed in the low-power sonication of expanded graphite  for 24 hr. The temperature was lowered to less than 30 °C and stabilized there using a continuous flow of water in the ultra-sonication bath (JACUltra-sonic4020P). In order to separate large unstable graphite aggregates, the dispersion was left overnight after the sonication process. Water with the sodium cholate surfactant at 0.3 mg/ml was used to steady graphene dispersions. 46 ml of deionized water was added to the paste, and the solution was evaporated at 95 °C for 40 min. The solution was centrifuged at 1500 rpm for 90 min to obtain a stable dispersed graphene solution. The final solution was washed with distilled water to remove the sulfate ions. The solution was dried at 50 °C for two days using an air oven. The final powder was used for the subsequent analysis .Preparing nanocomposites suspensionGraphene and silver ions were reduced together so that the Ag/Graphene nanocomposites could be prepared. Firstly, 1 g of graphite was combined with 100 ml of AgNP solution and mixed with 50 ml of deionized water. The reaction mixture was sonicated for one day in the ultra-sonication bath (JAC ultrasonic 4020P) at 60 °C. 10 ml of hydrazine using magnetic stirring was slowly added to the mixture. The sonication temperature was organized by controlling the water volume in the bath and covering it with a lid. Then for one hour, the mixture’s temperature was raised to 95 °C and kept at that level. The gained powders were washed numerous times using ethanol and deionized water. After centrifugation, an air oven was used to dry the prepared samples at 50 °C for 48 hr .Characterization of nanocompositesThe amount of UV-visible and measurable nanocomposites was determined using a UV-visible spectrophotometer . The nanocomposite solution was frozen, and its structure and composition were analyzed using field emission SEM . The X-ray differentiation method was used  to analyze AgNP and graphene. A Nano Raman spectroscope  was used to discuss the structural properties of graphene sheets (single-layer or multilayer properties) (28). The particle size, the size distribution of the nanoparticles (PDI), and zeta potential were assessed using a particle size analyzer . Preparation of MCF7 cell line2. In order to execute the tests, when the cells reached 70% of cellular growth, they were separated from the bottom of the flask using Trypsin-EDTA, and the contents were centrifuged for 5 min at 1500 rpm. A suspension was created using 1 ml of the cell culture and the sedimented cells. The percentage of live cells in the cell suspension was determined using a trypan blue dye, a hemocytometer slide, and a light microscope. After ensuring that the cells in the suspension were not contaminated, cells with a higher than 90% survival rate were used for the test (The MCF-7 cell line was positioned in the culture medium containing 1% AB (penicillin/streptomycin) and 10% FBS . The culture medium containing the cells was incubated at 37 °C and 5% COthe test , 30.Assessing cell toxicity using the MTT test In order to determine cell toxicity, the breast cancer cells (from the MCF-7 line) were exposed to different concentrations of the assembled mixtures. It is a competitive metabolic test and evaluates mitochondrial function. The yellow-colored MMT, which happens to be a tetrazole, is reduced to the insoluble purple-colored formazan in the mitochondria of live cells. The reduction only happens in the presence of active mitochondrial reductase enzymes. Therefore, this reaction can be directly related to the number of live cells. Afterward, different concentrations of the suggested combination (silver nanoparticles and silver-graphene nanocomposite) were prepared. The negative control group received no stimulant, the positive control group was exposed to an IC50 dose of cisplatin (5.75 µM), and theCalculating the amount of ROSThe amount of ROS was determined using fluorometry and the DCFH-DA reagent in the control and treatment groups. 20 μl of DCFH-DA was added to the cell sample and kept at the temperature of 4 °C for 15 min. Absorption was then measured at the wavelength of 312 nm and the emission of 420 nm .Measurement of lipid peroxidationAfter incubation, the cells were assessed using the thiobarbituric acid (TBA) method. To 0.2 ml of cell suspension, 0.1 ml of TBA reagent was added. The mentioned materials were mixed well, placed in a hot water bath, and incubated for 30 min. After cooling down, 0.2 ml of n-butanol was added to the combination, shaken well, and centrifuged for 10 min at 3500 rpm. The n-butanol layer was separated at the wavelength of 532 nm, and the amount of TBARs was calculated using the standard curve  was used to cover the slides. Then, 1 ml of LMP 1% (low melting agarose) was added to the treated cells, and slides coated with 1% NMP agarose were placed in this solution so that a layer was placed on them and kept at 4 °C for ten min. The slides were immersed in an alkaline lysis buffer and placed in an alkaline electrophoretic buffer for 40 min to decompress the DNA. Then, electrophoresis was performed for 40 min (300 mA and 25 V). The slides were immersed in neutralizing Tris buffer solution for 15 min and stained with ethidium bromide for ten min. A fluorescence microscope with 400x magnification was used to examine the slides. DNA damage was measured using Comet score software and expressed as tail length, and percentage of DNA in tail and tail moment, and the results were presented as mean ± SEM .Statistical analysis50 was determined using the Sigma plot program.The statistical program Prism ver. 6 was used to analyze data. Statistical tests, ANOVA and Tukey’s post test were used for further, more complete analyses. The amount of ICMathematical models were analyzed by SPSS Software, and graphs were made by software Table Care 2D ver. 5.01.SEM images of synthesized AgNP / graphene nanocomposite on M. officinalis leaves by SEM imagesSynthetic silver nanoparticles are shown. AgNP has a diameter of about 50 to 80 nm and a spherical shape . In UV-vAssessing the antiproliferative effect of nanoparticles on MCF-7 cell line According to 50 concentration to treat cancer cells, had a growth inhibition rate of 52.20%.P<0.01), 120 μg/ ml (P<0.001), and 250 μg/ml (P<0.01) were significantly different (P<0.001), 30 μg/ ml (P<0.01), and 250 μg/ mL(P<0.01) of the graphene group were significantly different   .Amount of reactive oxygen species (ROS) produced by nanoparticles in MCF-7 cell lineP<0.0001). With an increasing concentration of the three therapeutic substances, we see an increase in intracellular ROS production, which inhibits cancer cell growth. At the highest therapeutic concentration of 250 μg/ml, this rate reached 68%, 68.40%, and 70.40%. According to Statistically, in comparison with the cisplatin group, concentrations of 15, 30, 60, and 250 μg/ml silver nanoparticles and graphene  and concMeasuring the quantity of malondialdehyde (MDA) created by nanoparticles in the MCF-7 cell lineP<0.001) and concentrations of 250 μg/ml (P<0.01) were significantly different (According to ifferent .P<0.001) and (P<0.01), respectively , 60 (P<0.05), and 250 μg/ml (P<0.001) were significantly different  created by nanoparticles in the MCF-7 cell lineGlutathione is a non-enzymatic anti-oxidant. Its role is to reduce the level of oxidants produced in the body. The cell loses its defense power and is destroyed by reducing this factor.As shown in On the other hand, exposure to cells with different concentrations of silver nanoparticles also reduced the glutathione level of MCF7 cells, which increased from 39.60% at 15 μg/ml to 76.40% at 250 μg/ml; Which has shown the effect of silver nanoparticles in reducing glutathione and cancer cell death.P<0.01), (P<0.001), (P<0.01), respectively   .Calculating the amount of tail moment created by nanoparticles in the MCF-7 cell lineIn the Tail moment graph (P<0.0001).nt graph  comparedMathematical modelMathematical equation determined for MCF-7 cell line and its treatment with silver nanoparticles, graphene, and silver-graphene nanocompositesAll three treatments describe a logarithmic nonlinear model. Based on the curve, it is shown that the use of silver-graphene nanocomposite was more effective than silver nanoparticles, and silver nanoparticles were more effective than graphene and had more lethality -9.According to Cancer is a name given to diseases caused by unstoppable tissue reproduction. Therefore, the cells spread to other tissues using the blood flow, tissues, and the lymphatic system without limiting their proliferation. The abnormal cells form gatherings in other body areas . Breast A study on the hydroalcoholic extract of MO found that its mechanism for inhibiting cell growth is due to increased ROS and induction of apoptosis in colorectal cells . AnotherNowadays, in nanotechnology, using nanoparticles has helped a lot in diagnosing and treating diseases, especially cancer , 2. This research determined the cell survival rate using the MTT method. The goal was to assess the anticancer effect of silver nanoparticles, graphene, and silver-graphene nanocomposites in breast cancer cells. For this purpose, the ROS, MDA, and intracellular glutathione levels induced by silver nanoparticles, graphene nanocomposites, and silver-graphene in the MCF-7 breast cancer cell line were measured. 50, silver nanoparticles have a higher mortality effect on cancer cells by increasing the amount of reactive oxygen species and malondialdehyde, and decreasing glutathione reserves. According to the Tables, Figures, and information provided, it was found that cytotoxicity caused by silver nanoparticles inhibited the growth of cancerous cells (positive control). Additionally, this study found that 250 μg/ml of silver nanoparticles caused an increase in the death of cancer cells compared with the cisplatin group. According to ICet al. assessed the anti-oxidant and anticancer effects of silver nanoparticles on human colon cancer cells (COLO207) and Madin-Darby Canine Kidney (MDCK) cells in 2015. Their results showed that silver nanoparticles have a concentration-dependent inhibitory effect on free radicals. They can also cause morphological changes such as chromatin density, loss of cell membrane potential, and stoppage of the G1/S cell cycle. These alterations ultimately lead to the induction of apoptosis in cancer cells. Also, a high level of reactive oxygen species significantly affects DNA fragmentation and can eventually lead to apoptosis . HePG-2 cell apoptosis was triggered by the overproduction of ROS, DNA damage-mediated p53 phosphorylation, and affecting MAPKs and AKT signaling .Comparing these results to the present shows that silver nanoparticles can stop the proliferation of cancer cells. The dose-dependent production of reactive oxygen species and malondialdehyde increases, and glutathione production decreases; these alterations cause toxicity and increase cell mortality in breast cancer cells from the MCF-7 line. The inhibitory effects of graphene, through its ability to cause cell toxicity, differed significantly from the cisplatin group. However, 250 μg/ml of graphene increases cell mortality and the number of dead cancer cells. Also, this study demonstrated that the percentage of live cells in groups exposed to 15, 30, 60, 120, and 250 μg/ml graphene was higher than in the cisplatin group. et al., in a 2010 reading, showed that graphene and single-walled carbon nanotubes induce cellular toxicity, and these effects are dose and shape-dependent. Graphene has higher metabolic activity in lower concentrations than single-walled carbon nanotubes, whereas, in higher concentrations, it is the opposite. Lactate dehydrogenase levels were significantly higher in single-walled carbon nanotube examples compared with graphene. Additionally, ROS were formed in a dose and time-dependent manner after being exposed to graphene, showing an oxidative stress mechanism. Also, after being exposed to graphene, caspase 3 is activated in a time-dependent manner which shows the ability to induce apoptosis in which shape plays a crucial part  and assessing their nanoecotoxicity in zebrafish embryos. The results of this study have reported the effects of nanoecotoxicity of GO-AgNPs in a dose-dependent manner in zebrafish embryos. Also, silver nanoparticles cause toxicity of the GO-AgNPs nanohybrid. Besides, the chorion embryo membrane critically impacts the toxicity of GO-AgNPs, and NOM is not adequate to prevent the agglomeration of GO-AgNPs in the exposure medium and mitigates the toxicity of GO-AgNPs  composites affect the structure and esterase-like activity of Human Serum Albumin (HSA) and Human Endometrial Stem Cells (hEnSCs) .Silver-graphene nanocomposites (GO-AgNPs) induced significant cytotoxicity by ROS production, loss of cell viability, increased expression of pro-apoptotic and decreasing expression of anti-apoptotic genes and DNMT3A, increased leakage of LDH, and level of MDA, GO-AgNPs incited DNA hypomethylation in CFFCs .Comparing these results demonstrates that silver-graphene nanocomposites can impede cancer cells, and this inhibitory effect increases by raising the concentration. Reactive oxygen species and malondialdehyde are produced dose-dependently, and the production of glutathione reduces, which in turn causes toxicity and ultimately leads to apoptosis in breast cancer cells.The results show that using silver nanoparticles and graphene alone or in combination can be a new solution in cancer treatment. As seen in the results, treatment of breast cancer cells with silver or graphene nanoparticles and combination treatment with these two substances against cisplatin have sound effects, and by affecting oxidative stress factors such as increased ROS and subsequent increase in lipid membrane damage, inhibit cell growth and proliferation.Treatment of MCF-7 cells with silver or graphene nanoparticles and combination treatment with these two substances against cisplatin have sound effects, and by affecting oxidative stress factors such as increased ROS and subsequent increase in lipid membrane damage, inhibit cell growth and proliferation. According to the mathematical model, silver graphene nanocomposite> silver nanoparticles> graphene has the best effect in inhibiting the growth of cancer cells. M. officinalis in other cell lines . It is possible to measure M. officinalis’s anticancer effect on a larger scale by examining different cell lines and signaling pathways associated with apoptosis.Characterization techniques were not enough; FTIR analyses of extract, Ag- NPs, and silver-graphene nanocomposites could be performed in future studies to confirm functional groups and, more precisely, the chemical structure, which will guide researchers to discover the molecular mechanism of the mentioned anticancer effects. Also, we could not evaluate the anticancer effects ofMS and MG Contributed to conception, study design, and management. BK Contributed to the mathematical model. FM Contributed to the analysis of data, writing the article, and drafting the manuscript. FM and PM Contributed to the preparation of the cell line, stress oxidative assay, and editing the manuscript. NGB Contributed to the comet assay and revised the manuscript. All authors read and approved the final manuscript. The authors confirm that the data supporting the findings of this study are available.This study was supported by a grant from the Research Council of Mazandaran University of Medical Sciences (grant no. 2652534).All authors declare that they have no conflicts of interest.


Q4vsQ1 = 0.62; 95% CI = 0.51–0.76; p-trend < 0.001). No modification of the estimated ORs by sex, breakfast time, and number of eating occasions per day were observed. Conclusion: Our results suggest that higher breakfast size is associated with lower prevalence of MetS in Spanish adults, supporting the importance of a high energy breakfast. Further prospective studies are necessary to confirm these findings.Background: Recent evidence suggest that energy distribution during the daytimecould be a potential determinant for the development of metabolic syndrome (MetS). Objective: To cross-sectionally assess the association between breakfast size and the prevalence of MetS in Spanish adults. Methods: Our study included a subset of 3644 participants from the European Prospective Investigation into Cancer and Nutrition Spain study recontacted between 2017–2018. Information on diet, sociodemographic, lifestyle, sleep quality, and chronotype was collected using standardized questionnaires, while anthropometric and blood pressure data were measured in a face-to-face personal interview by a nurse. MetS was defined according to the Adult Treatment Panel III (ATPIII) definition by measuring serum levels of total cholesterol, tryglycerides and glucose. Breakfast size was calculated as:  * 2000 kcal. To evaluate the association between breakfast size and MetS prevalence, a multivariable logistic regression model adjusted by potential confounders was used to estimate OR and 95% CI. Results: Prevalence of MetS in our study was 40.7%. The mean breakfast size was 306.6 * 2000 kcal , with 14 (0.4%) participants skipping breakfast. Participants in the highest quartile of breakfast size had a lower MetS prevalence compared to participants in the lowest quartile (OR Worldwide, prevalence and trends of metabolic syndrome (MetS) are rapidly increasing, along with prevalence of obesity, insulin resistance and type 2 diabetes . In SpaiSeveral factors, including genetic, sedentary lifestyle, and unhealthy diet, have been associated with the increasing prevalence of MetS . Eating Breakfast is often considered the most important meal  and manyBesides the size of breakfast, also its quality and macronutrients composition have been studied in recent years in relation to cardiometabolic health, glycemic control, and individual biomarkers of metabolism ,23,24,25According to some reports addressing the question of what percentage of total energy intake should breakfast cover, the most common proposed range is between 15% and 25% of the daily energy . Some meThis study was carried out in subjects from the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Spain). The EPIC-Spain cohort included 41,437 subjects aged 29–69 years, who were recruited between 1992 and 1996 from five regions of Spain: Asturias, Granada, Murcia, Navarra, and Gipuzkoa. Further details about the EPIC-Spain cohort can be found elsewhere ,33. The subset of participants elegible for this study were those who, by December 2015, were alive and younger than 67 years  and younger than 60 years , a total of 8000 people. The age restriction was based on evidence showing that the effect of chronotype and social jetlag diminishes in older generations .Signed informed consent forms were retrieved from all participating individuals, and approval was granted to each center from their local Ethics Committees (54/U/2016).n = 4224) was recontacted via telephone, between 2017 and 2018, and was interviewed by trained staff to obtain information related to their diet (relevant for chrono-nutrition) and sleeping patterns (relevant for defining chronotype). During the telephone interview, data on sleep quality were also collected by means of the Pittsburgh Sleep Quality Index (PSQI) questionnaire [The initial sample of this analysis  were also collected. Finally, all participants were invited to a face-to-face personal visit with a nurse for the collection of anthropometric measurements , blood pressure, and a fasting blood sample. All measurments have followed standarized measurements as we have previously described . A totaln = 3772). The samples were taken in a fasting (at least 12 h since the last intake) following standard protocols, and were stored at −80 °C. The serum samples were analyzed by standardized enzymatic laboratory techniques to obtain concentrations of specific biochemical parameters .During the personal interview a 30 mL blood sample was taken from those participants who agreed to participate in the blood collection process  and 75 (p75) were used for continuous variables. For categorical variables, bivariate analyses were performed by MetS status and by breakfast size categories, as absolute and relative frequencies. Chi-square test and Wilcoxon rank sum test were used for categorical and continuous variables, respectively overall and by components.To evaluate the association between breakfast size and MetS prevalence, a logistic regression model was used to estimate prevalence odds ratio (OR) and 95% confidence interval (95% CI). Breakfast size was evaluated using both the categorical variables based on quartiles. Furthermore, we evaluated the association between breakfast size and each of the five components used in the MetS definition. Restricted cubic splines (RCS) with 3–5 knots were used to explore linearity in the trend in the Mets prevalence with breakfast size. Since relationship was not lineal, continuous analysis was not presented. Akaike information criterion (AIC) was used to select the best representation of the relation between breakfast size and prevalence of MetS. The minimum AIC was found with a four-knot RCS  . Two models were built using logistic regression. The minimally adjusted model included sex, age (years), and center. The multivariate model was additionally adjusted for educational level , recreational Physical activity (MET-h/week), number of eating occasions per day , and breakfast time . Smoking history, PA at home, vigorous PA, sleep quality, sleep duration, chronotype, time from wake up to first meal, lunch time, dinner time, and dietary intake at full day  were not included as adjustment covariates because they were not statistically significant in the bivariate analysis. Modification of the estimated Ors by sex, breakfast time, and number of eating occasions per day was evaluated using a likelihood ratio test.All statistical tests were two-sided and evaluated at a level of 0.05. All analyses were performed using SAS v 9.4. Restricted cubic splines analysis was performed using R v 3.6.3.A total of 3644 subjects (40.7% with MetS) with biochemical and diet data (125 (3.3%) and 3 (0.08%) of the participants were excluded due to no information on diet or MetS status were available respectively) , with a Sociodemographic and dietary variables by MetS condition are presented in Finally, regarding dietary intake, a reduction in daily total energy intake across quartiles of breakfast size  was found. Specifically at breakfast, we observed a statistically significant descending gradient from the lowest to the highest quartile of breakfast size regarding the percentage of energy from proteins (Q1: 16.1% vs. Q4: 12.4%) and carbohydrates (Q1: 58.3% and Q4: 53.4%); and the opposite for fats (Q1: 23% and Q4: 33.4%). Further details on diet are shown in the Q4vsQ1 = 0.62; 95%CI = 0.51–0.76) , hypertension , and hyperglycemia . No statistically significant associations were observed with the remaining  components of Met even a similar tendency reletd to other components has been found  . The moden found .No modification of the estimated ORs were observed, by sex, breakfast time, or number of eating occasions per day (data not shown).To our knowledge, this is the first multicenter study reporting on the influence of breakfast size over the prevalence of MetS. The results arising from this cross-sectional analysis of 3644 Spanish adults showed 38% lower MetS prevalence in those participants with higher breakfast sizes, compared to those with lower breakfast sizes More specifically, our results showed lower prevalence of MetS when between 15 and 30% of the daily energy intake was covered by breakfast.Traditionally, studies on metabolic health and weight control have highlighted the effects of breakfast skipping ,13,14,15Recently, a small prospective study in Spain , which i1 = 23% vs. Q4 = 33%, p < 0.001), which seemed to lead to decreased fat consumption during the rest of the day . A recent Australian cross-sectional study [In two cross-sectional studies performed by de Castro, it was suggested that low energy density intake  in the morning could reduce the total daily energy intake ,43, De Cal study  on breakWe observed that the highest proportion of participants reporting more than five eating occasions per day and a higher daily energy intake were in the lowest quartile of energy intake from breakfast. Furthermore, we found that eating more than five meals per day increased the prevalence of MetS by 23%, probably due to frequent snacking. In regard to frequency of meals, previous studies have shown controversial results. As reflected in a 2021 literature review, including observational and intervention studies results have shown contrasting results. By one hand, some results showed that a higher number of eating occasions being associated with lower BMI, lower energy density, lower alcohol intake, and higher fruit intake. By the other hand, other authors found that a high number of eating occasions increased food stimuli, hunger and the desire to eat, while consequently also increasing BMI, abdominal fat, and the risk of developing type 2 diabetes . Our resO’Neil et al. proposed that a range between 15% and 25% energy contribution should be covered at breakfast . We obseWhereas the mechanisms involved in the effects of the breakfast size on metabolism and weight-related health remain unclear, they may include both behavioral patterns–such as increased or decreased physical activity, and food choice– and the influence of circadian rhythms on energy metabolism ,44. As fWe would like to mention that, before our study, available evidence raised from small samples, which implies very heterogenous populations and, consequently, make their results not suitable for comparison; breakfast patterns could vary across countries and age of the participants . FurtherThe main limitation of our study was that our data were obtained cross-sectionally, and so it does not allow for a determination of causality. Self-reported bias was likely for sleep duration, as well as for the individual’s chronotype despite validated questionnaires being used for the assessment of these variables. Information on medication for hypertriglyceridemia, HDL-cholesterol, hypertension, and hyperglycemia was not collected, so prevalence of MetS could be underestimated. We would like to highlight that the present study involved a large sample from five Spanish regions and included the use of diet history questionnaires, structured by eating occasion, which enabled us to collect detailed information on individual food intake, meal timing and to estimate macronutrients and breakfast size. In conclusion, our results show that high breakfast size is associated to total daily energy intake and may decrease the prevalence of MetS, as observed in a large sample of Spanish older adults. Our findings reinforce the importance of breakfast size as a potential strategy to reduce the prevalence of MetS, since in modern societies adequate meal timing and energy distribution during the day are difficult to achieve. Further research in prospective studies or randomized control trial in the general adult population are needed to confirm the role, if any, of breakfast size in relation to MetS.


Triticum aestivum L.) growth and yield under different drought levels. The plants were grown in pots under natural ecological environmental conditions and were harvested on 25th of April, 2020. The results revealed that seed priming of Si-NPs  suggestively improved, the spike length, grains per spike, 1000 grains weight, plant height, grain yield, and biological yield by 12–42%, 14–54%, 5–49%, 5–41%, 17–62%, and 21–64%, respectively, relative to the control. The Si-NPs improved the leaf gas trade ascribes and chlorophyll a and b concentrations, though decreased the oxidative pressure in leaves which was demonstrated by the diminished electrolyte leakage and upgrade in superoxide dismutase and peroxidase activities in leaf under Si-NPs remedies over the control. The outcomes proposed that Si-NPs could improve the yield of wheat under a dry spell. In this manner, the utilization of Si-NPs by seed priming technique is a practical methodology for controlling the drought stress in wheat. These findings will provide the basis for future research and helpful to improve the food security under drought and heat related challenges.Silicon nanoparticles (Si-NPs) have shown their potential for use in farming under water-deficient conditions. Thus, the experiment was accomplished to explore the impacts of seed priming of Si-NPs on wheat ( Productivity of crops is diminishing because of restricted stock of water2, less intake of nutrients, and poor photosynthesis3. Even though drought effects wheat performance at all growth stages, it is more rudimentary during the blooming and grain-filling stages , which results in considerable yield loss. The leading explanations behind these losses are the diminished rate of net photosynthesis due to metabolic limitations, oxidative impairment to chloroplasts and stomatal closing, and abandoned grain set and improvement4. Nonetheless, drought stress animates the creation of ethylene6 which delay and slow down the root growth and prolongation7. All things considered, plants have established different versatile mechanisms to acclimatize the water shortage by prompting a succession of physiological and biochemical reactions8. Among these components, antioxidants play a vital role in reducing oxidative damage caused by drought9.Drought is striking ecological stress among other abiotic stresses, which adversely influence crop growth and yield of the crops around the world10, and high risk in the future due to recent changes in climate12. Wheat is a major rabi season crop which is contributing 8.7% of the worth expansion in agribusiness and 1.7% to Pakistan’s GDP. The territory under wheat growth in Pakistan during 2019–2020 was 8825 thousand hectares with a growth of 1.7% when contrasted with the space of a year ago which was 8678 thousand hectares. Moreover, the estimated production of wheat was 24.946 million tons in 2019 which was 2.5% higher than the previous year14.Drought impact in Pakistan is more significant because of its massive reliance on agribusiness. Besides this, Pakistan become more vulnerable to drought due to a lack of stress awareness and control practices15. The rapid climate change and global warming have the worst impact on the crops in the future because it enhances the frequency and intensity of drought due to less rainfall and high temperature on earth16. Accordingly, for enhancing the yield and preserving the wheat from such stresses need to develop more understanding and approaches to overcome these issues17.Over half of the world’s wheat fields are influenced by periodic drought stress19. Sedghi et al.20 stated that the utilization of silicon nanoparticles is assuming a significant part in the plant resistance against the shortage of water over expanding amino acids, chlorophyll b contents, lipids, and proteins. Among other NPs, the Si-NPs are helpful in elevation the plant growth and photosynthesis under an intensive atmosphere22.In the last decade, nanoparticles play an imperative role in agriculture due to their unique properties, such as greater absorption ability, higher surface area, efficient delivery method for a specific spot, and such technology used in many ways like additives, plant growth enhancers, nano-fertilizers, and plant protection agents23. Between various nanoparticles, silica nanoparticles play a magnificent role by increasing the photosynthesis that enhances the yield of Cucurbita pepo L.24 and hawthorn seedlings25 under stress conditions. Many types of research indicated that plant growth, antioxidant activities, and nutrient uptake process under drought stress was faster with the application of nanoparticles because such particles enhance the resistance of plant28. Si-NPs improve photosynthesis parameters of certain plants during dry season and has a greater impact in agriculture as compared to other fertilizers31. The exogenous application of NPs provoke root endodermal silicification, and antioxidant system activity and manage the cell water stability32. Nano-silicon application has improved production and growth and enhanced plant water status with extraordinary changes in the ultrastructure of leaf organelles, initiation of plant protection and defense system and searching of unambiguous particles33. Besides, SiO2 NPs have been described as a plant growth inducer, which raises root endodermal silicification, upgrades antioxidant system under pressure, and improve resilience to abiotic stresses and the cell water balance32. The connection between SiO2 and plant cell wall has been reported in numerous monocots34.Nanoparticles application expanded the growth, chlorophyll substances, and gas trade qualities in the wheat grain and diminished the water deficiency37. Seed priming is a fruitful strategy in many ways, for example by eliminating the worst effect of abiotic stresses, stimulating the valuable physiological changes, helping at the initial stage of germination, enhancing seed germination rate, minimizing the seedling emergence time, and most importantly it is a cost-effective technique for farmers43. There is no literature regarding effect of Si-NPs on wheat morpho-physiological and biochemical attributes under drought at different growth stages. So, the objective of this study is to mitigate the catastrophic effects of drought on wheat under drought conditions by the application of silicon nanoparticles.Nano-particles can be applied in many ways under the biotic and abiotic conditions in the field of agriculture such as by seed priming, soil, and foliar application, but seed priming is the most efficient methodThe research work was carried out in the wirehouse, department of agronomy, The Islamia University of Bahawalpur, Pakistan . The experimental layout was a randomized complete block design with four replications of each treatment of silicon nanoparticles . All pots were irrigated equally till complete emergence, after that water deficient condition was executed at critical growth stages, such as tillering, flowering, and grain filling stages, while complete irrigation was considered as control.43, was mixed with deionized water and ultra-sonication of each Si-NPs treatment  for thirty minutes for proper dispersion was done. The wheat seeds were then soaked in NPs solutions for 20 h in dark under room temperature. For control treatment seeds were soaked in deionized water. Finally, dried the primed seed of the wheat crop and stored at 4 °C for further experiment.The wheat seeds (Glaxy-2013) were sterilized with a solution of sodium hypochlorite (2.6% active chlorine) for 120 s and washed thrice with distilled water. Then the measured amount of silicon nanoparticles, Sigma-Aldrich supplied spherical Si-NPs with a particle size in the 40–80 nm range2g−1 and 28.08 molecular weight. Scanning Electron Microscope was used to measure the NPs’ sizes  were obtained from Regional Agricultural Research Institute (RARI) Bahawalpur, as it is lodging and heat resistant. Wheat seeds were primed with Si-NPs and planted in plastic pots (26 × 29 cm) filled with clayey loam soil on 9th November 2019 and a physio-chemical investigation of the soil was done before planting , number of grains per spike, 1000-grain weight (g), plant height (cm), organic yield per plant (g), grain yield per plant (g), and harvest index were calculated following the standard procedures and protocols. For yield, wheat plants were manually harvested after the completion of the life cycle. Similarly, for measuring the plant height, four plants were arbitrarily selected from each pot and measured the height from soil surface to spikelet with the help of a ruler having read in millimeters and centimeters. For measuring the spike length and grains per spike, used a centimeter scale measuring the length from base to terminal spikelet from 10 plants randomly and counted the grains from randomly selected ten clusters of seeds. Besides, to quantify 1000-grain weight, the digital balance was used due to its accuracy of 0.01 g.44:For measuring the RWC, 5 mature fresh flag leaves were taken randomly from each treatment and immediately placed in polyethylene bags and taken to the laboratory. Where, firstly, get the fresh weight of taken samples quickly before any dehydration. Then, the sample was placed in distilled water for getting a turgid weight. After 3 h, the sample was taken out from distilled water and measured its turgid weight. After that sample was placed in an oven for 2 days at 65 °C and obtained its dry weight. Finally, the relative water content of each treatment was measured by utilizing the below-given formula45. SOD activities were measured by using the procedure published by Cakmak47, whereas POD was determined by the method of Zhang and Kirkham48.The superoxide dismutase and peroxidase were measured with the help of a spectrophotometer. Fresh leaf material 0.5 g from each treatment was homogenized with 50 mM phosphate buffer with 7.5 pH and 1 mM dithiothreitol (DTT) under chilled conditions after washing and drying the sample with distal watera, and Chl b) were extracted in 80% (v/v) acetone and measured spectrophotometrically  according to Metzner et al.49. Leaf Chl fluorescence was calculated utilizing a pulse amplitude modulation portable fluorometer . The leaves were dark and adapted in a leaf clip for 30 min. For all treatments, 30 measurements (three replicates of 10 leaves from various plants) were recorded. The data acquired were utilized to figure out the maximum efficiency of PS II (FV/FM) and performance index on an absorption basis (Plans)50 according to the equations reviewed by Stirbet51.The photosynthetic pigments chlorophyll  by R software  to check the association among different studied morpho-physiological attributes.STATISTIX software (version 8.1) was run on present data to determine the analysis of variance (ANOVA) and 5% LSD was used as the probability for the mean comparison of dataAll the plant experiments were in compliance with relevant institutional, national, and international guidelines and legislations.The result of the combined analysis of variance showed that Silicon nanoparticles concentration, drought intervals, and control irrigation regimes significantly affected all measured traits. There was a critical two-way connection between NPs concentration and drought on enzyme action, SOD, and POD. Additionally, the interaction among nanoparticles concentration, drought, and irrigation regimes was significant for spike length, the number of grains per spike, 1000-grain weight, plant height, grain yield, and biological yield. Besides, there was significant correlation between NPs concentration and control, besides NPs concentration and drought interaction on photosynthesis rate, transpiration rate, stomatal conductance, and RWC content. Moreover, the percentage of nitrogen, phosphorus, and potassium was affected by the triple association between the drought, control, and nanoparticles treatment.Silicon nanoparticles played a major share in plant growth under drought conditions at critical periods of wheat growth, when analyzed with control treatments. Plant height was reduced by 38.25% in DTS, 9.07% in DFS, and 6.77% in DGFS compared to control watering. When compared to the control (0 mg/L NPs), applications of 300, 600, and 900 mg/L of silicon nanoparticles mitigate the negative effects of drought and increase plant height by 2.5%, 3.2%, and 6.9%, respectively. The results showed that seed priming with 900 mg/L Si-NPs was the most effective, whereas the 0 mg/L Si-NPs treatment resulted in the shortest plant heights.The yield attributes were significantly influenced by the application of Si-NPs under water-deficient conditions shown in Table Seed preparation with silicon nanoparticles beneficially influenced the chlorophyll contents of wheat leaves grown under drought stress Fig. A,B. Comp2O2 is also affected as the crop goes to later stages  dropped by37.8, 30.0, and 29.2% under drought stress at DTS, DFS, and DGFS, respectively, compared to the control treatment. Moreover, seed preparation of 300, 600 and 900 mg/L of Si-NPs significantly improved stomatal conductance by 15.1, 31.6, and 41.6% as compared to control. In a drought condition, the highest results were achieved by seed priming with 900 mg/L of Si-NPs treatment.Si-NPs significantly affected the water use efficiency in wheat both under control and drought conditions, as indicated in Fig. 2O2 were measured and higher amounts were seen in control plants. Moreover, at a higher dose of Si-NPs values of these above-mentioned parameters were reduced  at different stages  of wheat under drought stress showed variability among the treatments and growth stages. The amount of H2O2 was boosted under drought with negative eigenvalues  was performed to analyze the variations and associations among different morpho-physiological parameters of wheat under the application of Silicon nano-particles and drought stress. The treatments were scattered in different biplots, while the parameters were represented as vectors Fig. . The fir47. It has been observed by several studies that drought stress reduces the germination rate of wheat35. Drought has been shown to reduce seed germination, growth, and wheat yield32. Seed priming of nanoparticles enhanced the germination, seedling, roots structure, nutrient uptakes, and minimized the effect of water deficient conditions41.The primary objective of this study was to determine the optimal doses of Si-NPs for seed priming in order to accelerate wheat development and mitigate the negative effects of drought. Significant enhancements in growth characteristics were seen in seed primed with 900 mg/L under stress. Seed germination and plant growth are both negatively impacted by drought stress53 Correspondingly, Aslam et al.54 observed that plant height was reduced in quinoa plants under water-limited conditions, which is parallel with our study. Liu and Lal55 stated that nano-particles are providing one more method to provide nutrients to plants under drought situations which is beneficial for plant height. Similarly, Paparella et al.56 found that seedlings become more vigorous at the early stages due to seed priming which prompts the metabolic system of wheat seed. Moreover, plant height was enhanced by the application of Si because it performed as a barrier when it was deposited in leaf apoplasts and protect the plant from stresses57. Silicon nano-particle seed priming beneficially enhanced the plant height of wheat under water-deficient conditions at critical stages of wheat growth. Because, Si may improve the protein substance, uptake of nutrients, photosynthetic rate and decrease the cell membrane in various plants59. Another plausible explanation is that plant height and morphological activities were enhanced due to the accumulation of water and nutrient in the seed during the time of priming with nanoparticles61. In this study, role of Si-NPs in wheat growth with and without drought was also studied.Under drought, the plant height of wheat decreased significantly at different critical stages reported by Raza et al.63. The Si might reduce the drought stress influence on photosynthetic pigments by increasing cytokinin endogenously, which restorative the chlorophyll formation and improve chloroplast ultrastructure64. Besides this, Asgari et al.36 stated that it might be a result of NPs enhancing the nutrients in plants that improve photosynthesis. Furthermore, Si-NPs increased the thickness of the cell wall and enhanced the transport of nutrients by the opening of the xylem which is a major cause of enhancing the photosynthesis rate65.Moreover, our outcomes exhibited photosynthesis activity enhanced positively with the application of Si-NPs Fig. . As rese66. Abaaszadeh et al.67 concluded that the production of peroxidase, phenolic, and chlorophyllase was reduced under water stress conditions due to that chlorophyll concentrations were badly effect. Additionally, reducing water use efficiency and RWC in plants under drought stress diminished turgor pressure, water retention, and plant size. Comparative outcomes related to our study were noticed by Farooq et al.68, Zhao et al.69, and Mamnouie et al.70. Contrary to this, photosynthesis rate, transpiration rate, stomatal conductance, and RWC expanded as the result of Si-NPs application in both irrigation regimes, particularly in plants under drought stress. Zhu and Gong71 stated that these increments in gas exchange parameters may be due to Si potential to preserve the water under drought. Moreover, Si is accumulated under leaves cuticle, framing a twofold layer of Si-cuticle, consequently, the accumulation of Si has diminished the transpiration72. Accordingly, it is recommended that a silica-cuticle twofold layer framed on leaf epidermal tissue is responsible for higher RWC of leaves. In agreement with our results, Gong et al.73 found that the use of Na2SiO3 enhanced LA, dry mass, RWC, and leaf thickness of wheat plants under water stress. Likewise, Silica NPs improved water use efficiency, RWC, and chlorophyll content in maize crops75.Drought stress decreased photosynthesis rate, transpiration rate, stomatal conductance, water use efficiency, and relative water contents of leaves in plants under water-deficient conditions. There was a close connection between the photosynthesis, transpiration rate, and total chlorophyll focus for wheat growth under drought stress2O2, EL, and MDA substances were decreased significantly shown in Fig. 77. Similarly, many researchers reported that nano-particles rise the activity of antioxidants in many crops79. Consequently, the application of silicon enhances the activities of SOD, glutathione reductase80, and catalase81 moderately balancing the adverse effect of drought on plants.Si-NPs application significantly enhanced the action of SOD and POD while, H78. A significant loss of nitrogen and phosphorus in plant tissues was documented by Rizwan et al.23 under situations of drought stress. The current research found that, compared to the control, Si-NPs significantly enhanced N, P, and K content under drought circumstances.The absorption of nutrients including N, P, and K by plants is also negatively impacted by drought stress. It has been shown in a number of studies that drought stress causes a decrease in both the content of N, K, and P in plant tissue and the rate of nutrient absorption from soil. It is well-documented that soybean N content drops significantly during drought stress82. Wheat yield and biomass are enhanced by enhancing the number of Si-NPs (0–900 mg/L) shown in Table 83. Such as dry matter production in plants decreases due to the limitation of photosynthesis and stomatal closure which reduced the carbon dioxide concentration under drought stress84. Moreover, Yazdanpanah et al.85 stated that under drought stress excessive accumulation of ROS which causing the oxidative damage of lipids, proteins, and DNA in plants which decreased plant growth and development. Similarly, other researchers reported that drought stress decreases the biomass, grain, and yield of wheat87.In drought conditions, wheat growth and development are diminished due to fluctuating in the balance of nutrients88. However, Si-NPs improved the destructive effect of drought on the growth, yield, and its components due to a variation in transpiration, improvement in photosynthesis rate, and plant water status89. These findings are in line with Sharifi Rad et al.90 and Shallan et al.91. Si-NPs have the potential to boost the RWC, chlorophyll contents, ROS activities, growing conditions, and yield of crops93.Furthermore, the results exhibited that utilization of some concentrations of Si-NPs increased biomass, plant height, yield, and yield components in both irrigation regimes. Generally, the positive effect of Si application in plants is not too obvious under optimum conditions, but it is most evident when the plant is under suboptimal conditionsThe results exposed that the Silicon nanoparticles (Si-NPs) seed priming under drought conditions significantly enhances the growth of wheat and reduces water stress. The biomass, plant height, and yield of the wheat crop were boosted due to Si-NPs seed priming. It can be concluded that enhancing the concentration of Si-NPs in wheat plants significantly enhanced the number of antioxidant enzymes, chlorophyll contents, and gas exchange parameters, and minimized the water stress. Moreover, seed priming Si-NPs enhanced the enzyme activities that minimized the concentrations of ROS in wheat leaves. Therefore, the results suggest that seed priming application of Si-NPs can be helpful to wheat plants either in normal irrigation or in drought stress. Though, further investigations at pot and field levels are still needed to see how nano-particles initiate this impact on drought stress in cereals by the priming application of NPs under drought conditions.


The purpose of this paper is to offer the most important epidemiological indicators of malignant neoplasms in Poland for the year 2019. In 2019, the Polish National Cancer Registry received information on almost 171.2 thousand new cancer cases and 100.3 thousand cancer deaths. The most common male cancers were prostate (20.6%), lung (16.1%), colon (6.8%), bladder (6.4%), and rectal (4.2%) cancers. Age-standardized incidence rates were at 118 per 100,000 for prostate, 89 for lung, 40 for colon, 38 for bladder, and 23 for the rectum. The most prevalent female cancers encompassed breast (22.9%), lung (9.9%), corpus uteri (7.0%), colon (5.9%), and ovary (4.3%). Age-standardized incidence rate was at 95 per 100,000 for breast cancer, 40 for lung 40, 29 for corpus uteri, 24 for colon, and 18 for ovarian cancer. The five leading causes of male cancer deaths were cancer of the lung (27.4%), prostate (10.3%), colon (8.0%), bladder (5.8%), and stomach (5.7%). Age-standardized mortality rates were 100 per 100,000 for lung, 46 for prostate, 32 for colon, 24 for urinary bladder, and 22 for stomach cancer. Most female deaths due to cancer were caused by lung (17.9%), breast (15.1%), colon (7.7%), ovary (6.0%), pancreas (5.7%), and corpus uteri (4.0%) cancers. Age-standardized mortality rates were 39 per 100,000 for lung, 33 for breast, 17 for colon, 13 for ovarian, 13 for pancreatic, and 9 for corpus uteri cancer. This problem's scale is reflected in the increasing number of incident cases and deaths globally. According to GLOBOCAN estimates, only in 2020, around 19.3 million new cancer cases were diagnosed worldwide, and almost 10.0 million individuals died due to cancer. Moreover, the global cancer burden is expected to be 28.4 million cases per year in two decades, denoting an almost 50% rise2. Noteworthy, these values did not encompass indirect costs of cancer-related absenteeism in the workplace. Finally, cancer was the second leading cause of death in Poland over the last decade, accounting for almost one-fourth of all male and female deaths3.Also, in Poland, cancer has a considerable impact on public health, influencing healthcare expenditures, burdening cancer survivors and their families, and remaining one of the leading causes of death. In 2009, Poland spent EUR 1.05 billion on oncology, in 2018—EUR 2.1 billion, and in 2019—EUR 2.3 billion. In 2020 the expenditure was estimated at EUR 2.4 billion. These amounts included services provided under the so-called oncology package, but also part of the services: clinical oncology, oncological surgery, oncological gynecology and hematology, chemotherapy, radiotherapy, and drug programs related to oncological treatmentIn 2015, the United Nations Members States adopted the 2030 Agenda for Sustainable Development, with several Sustainable Development Goals, including improving health by reducing premature mortality due to non-communicable diseases by 2030. Effective national cancer control plans must address the rising cancer burden to meet this goal. The Polish parliament adopted a new National Strategy for Oncology (NSO) 2020–2030 in 2020 to improve evidence-based prevention, population screening programs, appropriate treatment, and palliative care. The overarching goal of NSO is to increase the percentage of people surviving five years after completion of oncological therapy. The initiative also encourages cancer surveillance through cancer registries and attempts to boost cancer survivability.4, representing the most extensive cancer registry with full-population coverage in European Union. Since 1979, the PLCR has published an annual statistical bulletin entitled „Cancer in Poland”. This cyclical publication is addressed to everyone interested in the epidemiology of malignant neoplasms in Poland. The current edition of the report pertains to the cancer situation in 2019 and presents the most up-to-date data and information on cancer epidemiology in Poland5.Polish National Cancer Registry (PLCR) collects, stores, and manages the data on all cancer cases diagnosed within the Polish population. The PLCR offers important insight into cancer epidemiology in Central Europe and covers a population of 38.0 million individualsThe overarching goal of this article is to present a synopsis of the most important cancer epidemiological indicators in Poland for the year 2019.6, a non-profit national institution responsible for statistical and epidemiological cancer research in Poland (population 38.0 million in June 20194). The registry covers practically all incident cancer cases diagnosed in the Polish population since 1965. Data are actively collected from hospitals, healthcare practitioners, and palliative care centers. Reporting cancer to the PLCR is mandatory. All notifications are submitted by physicians and coded according to the International Statistical Classification of Diseases and Related Health Problems, Tenth Edition (ICD-10). At the PLCR, all cases are afterward verified by qualified coders based on histopathological/cytological/cytometry exam results and additionally coded applying the International Classification of Diseases for Oncology, Third Edition (ICD-O-3). Finally, the records are passed through specific tools to validate entries based on the valid causes of death in relation to the sex and age of the deceased. The PLCR collection system is based on a unique Polish personal identification number (PESEL), which avoids double coding for the same patient. The reported data on incident cases is still burdened with some under-registration. Hence, in this publication, the term "incidence" should be understood as a registered incidence.Data were obtained from the PLCRWe identified all Polish patients diagnosed with malignant neoplasms registered in the PLCR database between the 1st of January 2019 and the 31st of December 2019 and collected as of the 3rd of December 2021. Vital status was verified based on yearly controls of registered patients' vital status in the PESEL database. Since PLCR is a population-based registry that uses PESEL for registration and employs the PESEL database for yearly follow-up, the likelihood of loss to follow-up is minimal. Individuals who emigrated permanently from Poland and had no legal tie with the country may account for a meager portion of under-reported deaths.Crude annual incidence rates were defined as the number of new cases diagnosed per 100,000 person-years. Annual crude mortality rates were defined as the number of new deaths among cancer patients per 100,000 person-years. In the denominator, we applied the mid-year population, defined as the population's size on the 31st of June of the respective year. To enable comparison with other populations, we performed direct age-standardization of incidence and mortality for the revised European Standard Population (ESP2013). Since data are presented per annum, and the denominator is the middle-year population, we communicate the metrics per 100,000 inhabitants in the Results section for simplicity of presentation.Fifteen-year (2005–2019) incidence trends and annual percent change (APC), with 95% confidence intervals (CI), were calculated for seven cancer sites, i.e., colorectum (ICD-10 C18–C21), lung (C33–C34), female breast (C50), cervix (C53), ovary (C56), prostate (C61), and skin melanoma (C43). Joinpoint regression was applied, and the best-fitting model was selected with permutations tests, with an overall significance level at 0.05. Rates were considered to decrease if APC < 0 and 95% CI did not contain zero, and to increase if APC > 0 and 95% CI did not contain zero; otherwise, rates were considered stable.7 at the powiat level . Such a granular analyses was conducted due to the high age-standardized mortality rates in northern Poland. The identification of statistically significant hot spots  allows the identification of above-average mortality areas. The spatial neighborhood of each powiat was defined as all its neighboring powiats. The test for independence was conducted using 1000 conditional permutation simulations.Spatial cluster analysis of the age-standardized (ESP2013) incidence and mortality rates (ASR) was conducted based on the Getis-Ord local statistics Gi*Colormaps used Jenks natural breaks classification method (maximization of variance between classes and minimization within classes). Age-standardized mortality rates’ Getis-Ord local statistics Gi* colormaps were centered at 0  with high mortality spatial clusters depicted in red color and low mortality spatial clusters depicted in blue color.Joinpoint analysis and graphs were performed using the Joinpoint Regression software . Statistical and spatial analysis, choropleth maps, and age-standardized incidence and mortality maps were produced using RStudio Version 1.4.1103 .According to Polish legislation, individual-level data from the PLCR can be used for statistics in aggregate form and scientific purposes. The PLCR obeys strict regulations to secure the complete confidentiality and protection of the individuals.In 2019, in Poland, there were 171,218 incident cancer cases  and 100,324 deaths due to cancer . The age- and sex-standardized (ESP2013) incidence and mortality rates were higher in northwest than in the southeast regions of Poland, independently of sex , lung (16.1%), colon (6.8%), urinary bladder (6.4%), and rectum , prostate (10.3%), colon (8.0%), bladder (5.8%), and stomach (5.7%). Age-standardized mortality rates were 100 per 100,000 for lung cancer, 46 for prostate cancer, 32 for colon cancer, 24 for urinary bladder cancer, and 22 for stomach cancer . The second highest APC was for melanoma, with an upward trend, independent on sex . For female breast cancer, the incidence has been increasing since 2009, around + 1.2% per year (95% CI + 0.7% to + 1.6%). Lung cancer time trends differed by sex. While men presented a downward trend since 2012 , since 2014 an upward trend was observed for women . In the last ten years, colorectal cancer incidence has been decreasing in both sexes—among men since 2015, with an APC at − 1.7% (95% CI − 3.3 to − 0.1%) and among women since 2014 with APC at − 1.5% (95% CI − 2.3 to − 0.6%). For cervical cancer, the incidence has been systematically decreasing since 2005 . Ovarian cancer incidence has been stable between 2005 and 2019.In 2019, childhood (0–19 years of age) cancers were responsible for 6.6% of all deaths among boys and 7.3% among girls. The most prevalent tumors of children were leukemias, lymphomas, and brain tumors, accounting for over 60% of all cases in this age group. A similar distribution was observed in mortality, independently of sex.Among young adults (20–44 years of age), the age-standardized incidence rate of female cancers was more than double that of male cancers . The most common male cancers in this group pertained to the testicle , colorectum , and skin melanoma . Young men’s mortality was primarily from brain tumors (14%). Among young women, the most common cancer sites were breast , cervix , ovary , and colon .The age-standardized cancer incidence rate for middle-aged men (45–64 years of age) was 502 per 100,000 and for women it was 544 per 100,000. The most common male cancers in this group pertained to lung , prostate , colon , bladder , and stomach . The most prevalent female cancers affected breast , lung , colon , ovary , and corpus uteri .In the oldest age-group (> 65 years of age), the age-standardized incidence rate of female cancers was more than double that of male cancers than female cancers  incidence and mortality rates' spatial patterns concurred with the previously published PLCR annual reports, with higher rates in northwest Poland and a gradual decrease towards the southeast regions, independently of sex.5. Also, the crude number of deaths due to cancer increased in this time (from about 39 thousand to 100 thousand per year). The increase in the incidence and mortality due to cancer observed in Poland in the last 50 years can be attributed to changes in the population's age structure8 and the increase in the registered incidence by the mid-1980s, as a result of the improvement of cancer registration and coverage.The annual number of incident cases has quadrupled between 1965 and 2019 (from around 38 thousand to more than 171 thousand per year)13. In most voivodships , prostate cancer was the most common male cancer, followed by lung cancer. Lung was the leading cancer topography in the two other voivodships. Noteworthy, lung cancer mortality was almost two-folds higher than for prostate cancer. In all 16 voivodships, the highest mortality rate was attributed to lung cancer. The second most common cause of cancer-related death was colorectal (14 out of 16 voivodships) or prostate cancer (2 out of 16 voivodships).Since 2016, the structure of cancer incidence among Polish men has been similar to that observed in other countries with a very high Human Development Index, namely with the domination of prostate and lung cancerThe structure of cancer incidence among Polish women was dominated by breast cancer, with incidence twice as high as for lung cancer. In all voivodships (16 out of 16) breast was the leading cancer site. However, in 14 of the 16 voivodships, lung cancer was the leading cause of cancer-related deaths. The second and third positions were shared by breast and colorectal cancer. Although in the last 15 years, the lung cancer has become the main contributor to female cancer-related mortality (a position occupied from the mid-1970s to the mid-2000s by breast cancer), the breast cancer mortality rate trend has changed back to upward in the last decade, and breast cancer may in the future again become the leading cause of female death due to cancer.15. To assure a decrease in tobacco-related female lung cancer mortality rates, more efforts are needed. Not only must women-targeted smoking cessation services be available, but policymakers should also enforce increasing the excise duty on tobacco products and outlawing menthol and slim cigarettes. The Tobacco Products Directive (2014/40/EU) has already implemented some of these concepts. However, this regulation has only been in effect for a short time and has had no impact on mortality figures. Nonetheless, Polish policymakers should make effective implementation of the Directive a priority because it has the potential to reduce lung cancer mortality among Polish women further.The most obvious finding to emerge from this report is that, since the beginning of the twenty-first century, the mortality due to male lung cancer has been decreasing, and female lung cancer has been increasing. These changes can be attributed to changes in smoking patterns over time—decline in smoking rates by men and increase by women16). The pandemia has compelled temporary limitations in admittance to planned therapies, delayed diagnosis, and cancer screening routines18. As presented in several previous international studies, the lower affluence on cancer screening programs has increased the incidence of advanced-stage cancers, mortality rates, and years of life lost20. This scenario is also expected to be observed in Poland from 2020 onwards. Future works should also investigate the influence of the COVID-19 pandemics on national cancer survival.The present manuscript represents a snapshot of the state of cancer in Poland in 2019, before the COVID-19 pandemic , it is expected that the national cancer incidence, prevalence, and survival will shift due to the differences in these metrics in the Ukrainian populationThe condition for a sound assessment of cancer epidemiology is the high reliability of the data, both in terms of completeness and case coding quality. In the last 30 years, the fraction of morphologically verified cancer cases reported to PLCR, for all cancers aggregated, increased from 51 to 91%. In 2019, around 91% of the reported male cancer cases and 92% of female cases were confirmed by a pathological examination. At the same time, the mortality/incidence ratio decreased from 1.0 to 0.6. Both metrics reflect a noticeable quality improvement of cancer reporting and registration in Poland.The report's key strength is the considerable study population and close-to-complete nationwide coverage, which ensures the study's representativity and generalizability. Furthermore, because the state finances the Polish healthcare system, everyone has equal access to diagnostic and treatment procedures, regardless of socioeconomic position; therefore, we do not expect underreporting owing to a lack of diagnosis caused by the high cost of healthcare.It is important to remember that cancer registries keep track of cancer cases, not patients. Because a patient may have many primary malignancies, they may appear in a registry database more than once. Two cases are included when a person has two primary malignancies in two locations, e.g., lung and breast.Our study has the constraint that, despite regulations requiring timely reporting of new cases, late reports are received for various reasons. Providers may overlook deadlines; institutions may find other cases, and death certificates reveal unreported cases. For investigators and registry staff dedicated to accurateness, precision, consistency, and timeliness, these scenarios are challenging.The results presented in this study enable an evaluation of the current oncological strategy and its effectiveness on an annual basis  and a comparison between Poland and other countries' health metrics. Following the previous reflections, the present study can affect national cancer control policies both in the near and long-term, such as predicting the extra future strain on the Polish health system by considering the effect of last years' pandemia and extraordinary migratory influx.In 2019, the Polish National Cancer Registry received information on almost 171 thousand new cancer cases and 100 thousand cancer deaths. During the last two decades, the overall age-standardized cancer incidence increased consistently, the mortality remains relatively stable.In 2019, the most common male cancers pertained to prostate, lung, colon, urinary bladder, and rectum. The leading causes of mortality in men were lung, prostate, colon, bladder, and stomach cancer. The most prevalent female cancers encompassed breast, lung, corpus uteri, colon, and ovary cancer. Most female cancer deaths were due to lung, breast, colon, ovary, pancreas, and corpus uteri cancer.Cancer constitutes a significant health problem in Poland, where its incidence and mortality trends are determined by the population pyramid and changes in the exposure to carcinogens, especially tobacco smoking. The impact of smoking prevalence is especially evident in the female population. In 2019, the number of female lung cancer deaths exceeded the number of breast cancer deaths.Supplementary Information.