To preliminarily analyze factors that affected the prevalence of anxiety in Chinese patients with cleft lip and/or palate (CL/P).The Generalized Anxiety Disorder Scale (GAD-7) was used to screen anxiety in Chinese CL/P patients. Non-CL/P individuals were also included as the control group. Sociodemographic and clinical data consisting of diagnosis, gender, only child or not, monthly household income, and current family location were collected to analyze possible factors that could affect the anxiety of this patient population.One hundred forty-two and 78 valid questionnaires were collected from the study and control groups, respectively. The mean GAD-7 score of the study group (3.092 ± 3.381) was significantly lower than the control (3.987 ± 2.505). Moreover, the proportion of patients presenting with moderate-severe anxiety was larger in the study group than in the control group (6.6 vs. 0.0%). Statistically significant differences in GAD-7 scores were observed between the study and control groups when the patient was the only child, living in an urban area, or the monthly household income was between 1,000 and 5,000 yuan.Although the severity of anxiety in Chinese CL/P patients was not severer than those without CL/P, there was a relatively high incidence of moderate-severe anxiety in CL/P patients, while the only child, current family location and the monthly household income played significant roles in affecting anxiety psychology. Cleft lip and palate (CL/P) is one of the most common congenital craniofacial abnormalities, characterized by failure of normal fusion of the palate and lip at the midline during embryonic development, resulting in a clinically obvious deformity of the newborn , bringinAs a common mental illness, anxiety refers to a feeling of nervousness, impatience, and restlessness about things, accompanied by physical symptoms such as palpitation, chest distress, and hyperventilation . It has Patients with complete or incomplete unilateral or bilateral non-syndromic cleft lip and (or) palate.Patients who underwent cleft lip repair and (or) palatoplasty.Patients aged 10 years or above .Chinese Patients with a history of cleft lip and (or) cleft palate who visited West China Hospital of Stomatology, Sichuan University, between July 2019 and January 2021 were enrolled in the study group. Inclusion criteria of the study group were as follows:Through the distribution of questionnaires in the general population, inclusion criteria of the control group were as follows:(1). Individuals with no significant facial defects or other major diseases.(2). Individuals aged 10 years or above .Sociodemographic and clinical data were collected for analysis, including diagnosis, gender, only child or not, monthly household income, and current family location.The research protocol was reviewed and approved by the Ethics Committee of West China Hospital of Stomatology, Sichuan University (No. WCHSIRB-D-2016-084R1). Written informed consents were acquired from all the patients or their parents.The Generalized Anxiety Disorder 7-Item Scale (GAD-7) was used to assess patient anxiety status. Seven items were used to assess the frequency of anxiety symptoms over 2 weeks on a 4-point Likert scale ranging from 0 (never) to 3 (nearly every day). The total score of GAD-7 ranged from 0 to 21, with increasing scores indicating more severe functional impairments due to anxiety. The total score was calculated for each patient and interpreted as follows: normal (0–4), mild (5–9), moderate (10–14), and severe (15–21).As one of the most widely used assessment scales applied for screening, diagnosis, and severity assessment of anxiety disorders , GAD-7 hIn present study, all subjects were given questionnaires in Chinese version and guided by trained volunteers to make sure every item was fully understood. Each subject completed the questionnaire independently.P-values < 0.05 were statistically significant, while P-values < 0.01 were highly statistically significant.SPSS 23.0  is used for statistical analyses, and the count data was represented by mean ± standard deviation (SD). Independent samples-T test was used to compare the two independent variables within groups and the independent variables between groups, while one-way ANOVA was used to compare more-than-two independent variables within groups when the compliance with normal distribution is tested by Shapiro-Wilk. The Kruskal-Wallis test was typically used when the normality assumption was violated. A total of 145 GAD-7  questionnaires were collected from the study group (Mean age: 17.2 ± 5.8 years), while a total of 78 questionnaires were collected from the control group (Mean age: 18.5 ± 5.2 years). No significant difference in age was found between the two groups. The demographic characteristics of both groups were shown in The mean GAD-7 scores in the study and control groups were 3.092 and 3.987 points, respectively, and the scores difference was statistically significant . MoreoveSociodemographic and clinical data consisting of diagnosis, gender, only child or not, monthly household income, and current family location did not influence the anxiety status between subgroups in both study and control groups. However, analysis between groups showed a statistically significant difference in subjects that were an only child and lived in an urban location, while a highly statistically significant difference was demonstrated in subjects with a total family income between 1,000 and 5,000 yuan .It has always been assumed that facial appearance is vital for healthy psychosocial development . Given tInterestingly, we found that the average GAD-7 score of Chinese CL/P patients was lower than that of the control group. Possible explanations were as follows: There were studies that claimed CL/P patients reported better emotional wellbeing and overall self-worth than healthy people, and the impact of CL/P was not worse than having other concerns around appearance , 15, givThe heterogeneity of cleft types could explain the differences observed in our study. Although the difference was not statistically significant, higher GAD-7 scores were found in patients diagnosed with cleft palate (CP) or cleft lip and palate (CLP) than those with cleft lip (CL), consistent with previous studies. As for CLP patients, they faced more significant challenges in social interactions and communications than other types of CL/P resulting from significant speech difficulties and language delays , potentiWe also found that female patients scored slightly higher in GAD-7 than males while the difference was not statistically significant, indicating the possibility that female patients experienced relatively worse psychological conditions to some extent. As gender differences have been frequently studied when it came to psychology, it has been demonstrated that females were more likely to experience appearance dissatisfaction  and moreMoreover, a statistical difference in patients who were an only child was found between CL/P patients and the general. For the sake of reasonable explanation, we found that as parents with children or children with siblings suffering from severe diseases such as cancer were more likely to break the family's normal function and dynamic balance , dysfuncIn terms of household income, CL/P patients with a monthly household income between 5,000 and 10,000 yuan were documented to have the highest GAD-7 scores, followed by a monthly household income lower than 1,000 yuan. A statistically significant difference in scores was found between groups in subjects with monthly household income between 1,000 and 5,000 yuan, as the control group scored higher than the study group. Given that the general consensus from most published studies was that the severity of anxiety and depression was negatively associated with the household income , 27, socHigher GAD-7 scores were obtained between groups in subjects from rural areas, which could be partly explained by the negative role of their residential location that could influence their self-worth and self-knowledge . It is tSeveral limitations need to be noted in our study. The participants of our study were recruited from a limited geographic area and the study was conducted in only one specialized hospital of stomatology in western China. Also, the sample size of our study was not large enough. In addition, there was the outbreak of The 2019 Coronavirus Disease (COVID-19) epidemic during our collection of data, posing a challenge to psychological resilience upon both Chinese society and the international community. Our results might be influenced by the outbreak and prevalence of COVID-19.Herein, given the limitations of this study, we preliminarily provided some evidence on the significance of various causes of anxiety in Chinese CL/P patients. Most importantly, we found that the severity of anxiety in Chinese CL/P patients was not severer than those without CL/P.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.The studies involving human participants were reviewed and approved by the Ethics Committee of West China Hospital of Stomatology, Sichuan University (No. WCHSIRB-D-2016-084R1). Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin. Written informed consent was obtained from the individual(s), and minor(s)' legal guardian/next of kin, for the publication of any potentially identifiable images or data included in this article.ZX and CY contributed equally to this work. ZX, CY, YZ, YY, WX, and YZ contributed to the collection of data. ZX, CY, YZ, and TC analyzed the data. ZX, CY, BS, HH, and CG contributed to writing and revising the paper. BS, HH, and CG supervised the research. All authors contributed to the article and approved the submitted version.This work was supported by the Research and Develop Program, West China Hospital of Stomatology Sichuan University (RD-02-202107), granted to HH.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Neoadjuvant therapy is recommended as standard care for patients with locally advanced resectable esophageal cancer. Neoadjuvant chemotherapy (nCT) and chemoradiotherapy (nCRT) have convincingly been shown to improve the survival rate compared with surgery alone based on the results of several randomized clinical trials. Immunotherapy has become a new research direction in the field of EC research due to its great curative effects. However, controversies still remain in regard to identifying the most appropriate combination of nCT, nCRT, immunotherapy, and surgery, optimizing more effective neoadjuvant treatment protocols and surveillance strategies. This review comprehensively summarizes the research progress and describes and discusses the outcomes, pros, and cons of current trials. We believe our work has great academic value and will be of great help for researchers to understand the domestic and foreign research status in the field of neoadjuvant therapy in EC.Neoadjuvant therapies, primarily chemotherapy and chemoradiotherapy, are able to improve the overall survival (OS) in patients with locally advanced resectable esophageal cancer (EC) based on the results of several randomized clinical trials. The advantage of neoadjuvant therapy is chiefly attributed to the decreased risk of local–regional recurrence and distant metastasis. Thus, it has been recommended as standard treatment for patients with resectable EC. However, several fundamental problems remain. First, the combination of neoadjuvant chemotherapy (nCT), neoadjuvant chemoradiotherapy (nCRT), and surgery for EC patients with different histological types remain controversial. Furthermore, to reduce the toxicity of preoperative chemotherapy and the risk of complications caused by preoperative radiation therapy, the treatment protocols of nCT and nCRT still need to be investigated and optimized by prospective trials. Moreover, for patients with complete clinical response following neoadjuvant therapy, it is worth ascertaining whether a “watch and wait” surveillance plus surgery-as-needed policy is more favorable, as well as, in addition to preoperative chemoradiotherapy, whether immunotherapy, especially when combined with the traditional neoadjuvant therapy regimens, brings new prospects for EC treatment. In this review, we summarize the recent insights into the research progress and existing problems of neoadjuvant therapy for locally advanced resectable EC. Esophageal cancer (EC) is the seventh most commonly diagnosed cancer and the sixth-leading cause of cancer-related death globally according to the statistics in 2020 from the American Cancer Society . Even thChemotherapy works locally and systematically by downgrading the primary tumor to increase the chance of radical resection and elimination of  micrometastases, thereby reducing the risk of distant metastases . The saf2, fluorouracil: 1000 mg/m2) and immediate surgery alone. It was the first trial to identify a significant OS benefit in nCT group compared with surgery alone. Both histological subgroups showed a survival benefit, with a 5-year OS of 23% for AC and 26% for SCC (p for interaction = 0.81). The OS benefit can be attributed to the large sample size of the trial and the significant improvement in R0 resections in the nCT group (60% vs. 54%). However, this study found no difference in distant metastasis rates between the two groups, suggesting a comparatively modest systematic benefit of this chemotherapy regimen [2) and continuous infusion of fluorouracil (1000 mg/m2) for four days, followed by surgery. Inconsistent with the results of the OEO2-trial, the RTOG trial showed no improvement in local control and OS rate. A possible explanation may be due to the toxicity of the RTOG-trial’s nCT regimen related to a larger amount of cisplatin [As early as 2002, a large randomized controlled multicenter study was conducted by England Medical Research Council (MRC) with a sample of 802 patients with resectable EC  . The cheisplatin . Thus, tisplatin . To further improve survival outcomes, several large RCTs have studied a combination of neoadjuvant and adjuvant chemotherapy, i.e., perioperative chemotherapy. As for the MAGIC trial, 503 patients from 1994 to 2002 were randomized into perioperative chemotherapy and surgery alone. These patients were diagnosed with resectable gastric adenocarcinoma, GEJ, and lower esophageal adenocarcinoma. The chemotherapy regimens included epirubicin, cisplatin, and 5-FU (ECF) for three preoperative and postoperative cycles. The results showed that perioperative chemotherapy significantly increased the 3- and 5-year OS from 31% to 44% and 23% to 36.3%, and decreased distant metastases from 37% to 24%, respectively. Preoperative chemotherapy reduced the tumor size in all patients but had limited effects on R0 resection rates .2 on day 1, cisplatin 75 mg/m2 on day 1, 5-FU 750 mg/m2/day on continuous perfusion for 5 days) every 3 weeks. In contrast with the surgery group, the chemotherapy group had a better survival rate, higher 3-year OS rate and pathological complete response (pCR), but the improvement of R0 resection rate was not statistically significant. More extensive randomized phase III trials are still needed in the future to explore the potential survival benefit of docetaxel in the perioperative period of resectable GEA. The latest Korean PRODIGY trial and the German NEO-FLOT trial are under way to see whether an updated combination regimen for nCT can bring superior clinical efficacy.In recent years, the combined chemotherapy using docetaxel, cisplatin, and 5-FU (DCF) has been consistently proven to bring more favorable outcomes in EC. Ojima et al.  reportedIn Japan, esophagectomy followed by two courses of neoadjuvant chemotherapy with CF is considered to be the standard strategy for the treatment of patients with advanced or recurrent EC. Although the results from the subgroup analysis of the JCOG9907 trial showed that CF regimens were able to benefit patients with clinical stage III SCC, patients’ survival was limited, indicating the need for different effective regimens ,28. We hp = 0.93). In addition, DCF had significantly better histological findings on major tumor (p < 0.0001) and a much earlier pathological T stage (p = 0.008). The frequency of recurrence after operation was higher in patients treated with ACF compared with DCF (p = 0.008), indicating a better safety from DCF regimen. It is worth noting that no significant difference between DCF and ACF was found in OS; a possible reason is that the follow-up period was too short (34.5 months). Therefore, a follow-up study was conducted to assess the long-term outcomes and analyze the primary endpoint, RFS, as well as secondary endpoints such as OS and recurrence patterns [Although the nCT regimen DCF is of particular value for EC treatment, related research and trials are still ongoing. For resectable advanced SCC, the OGSG1003 Phase II trial randomly assigned 162 patients to group DCF and ACF  to make a comparison between the two chemotherapy regimens . The pripatterns . Consist2 on day 1, cisplatin 40 mg/m2 on day 1, 5-FU 2000 mg/m2 on days 1–2, leucovorin 400 mg/m2 on day 1. The results have shown that mDCF is not only effective in nMEC and AC patients (64.9% and 44.5% of OS at 3 and 5 years), but also reduces the incidence of severe neutropenia to only 13%. In addition to the impact on AC, the mDCF regimen showed promising results for local advanced SCC, with a 71.4% 2-year OS and a significant reduction in the incidence of grade 3/4 hematologic toxic events (43% for leukopenia and 14% for neutropenia) compared to the maternal DCF regimen. It is worth mentioning that elderly patients and patients with comorbidities account for a large proportion of EC patients, and the possibility of DCF causing adverse events increases. Therefore, the bDCF, a refined regimen in which docetaxel was divided and administered biweekly, was introduced to reduce serious adverse events in these frail patients. Akiyama et al. [Despite the advantages of DCF, severe grade 3/4 adverse events, especially grade 3 or 4 neutropenia in 66.2–78.2% patients and febrile neutropenia in 14.5–22.9% patients, have drawn great attention. Due to the relatively high toxicity of DCF, some clinical studies have focused on adjusting the dose and frequency of the regimen in the hope of maintaining efficacy while reducing toxicity ,37. To ia et al.  investigApart from adjusting the dosage and frequency of medication, the renewal of drugs as well as the continuous optimization of different drug combinations have also become the critical research issues of nCT for EC. Nab-paclitaxel (Nab-PC), a new generation formulation of paclitaxel, has been used with cisplatin and has shown excellent performance in terms of the down-staging rate, R0 resection, and pCR rate . S-1, dep = 0.025), which was more favorable than those of the CROSS trial [p = 0.002) and the pCR rate reached 43.2%. Therefore, the nCRT may be considered as a practical approach for patients with locally advanced SCC. However, the results of the French FFCD9901 trial, which included 195 patients (70% with SCC), showed that no significant difference between the nCRT and surgery arm regarding the R0 resection rate and 3-year survival [In most Western countries, nCRT followed by esophagectomy has become a standard of care for patients with locally advanced resectable EC . The larSS trial . Moreovesurvival . Due to survival . Moreovesurvival ,51, the survival . The resHowever, with the emerging findings regarding the neoadjuvant interventions, many controversies remain, such as optimizing more effective nCRT protocols and surveillance strategies post-nCRT, and better patient selection for nCRT and surgery. In the following paragraphs, we focus on the research progress addressing these existing problems.Based on the JCOG9204 and JCOG9907 trial results, nCT with CF regimen is a standard treatment for patients with cStage II/III SCC in Japan. In Western countries, the OEO2 RCT was carried out, in which 66% of patients with AC also showed a survival advantage in the neoadjuvant CF regimen group. In comparison, the CROSS trial has been proved to provide the maximum ever seen survival benefits for patients with esophageal or junctional cancer and has defined a new benchmark for the benefits from nRCT. Of note, using carboplatin and paclitaxel instead of the traditional CF regimen is one major innovation in the CROSS trial . In addi2, day1), oxaliplatin , and capecitabine  every 21 days for two cycles followed by nCRT with 5FU, oxaliplatin, plus concurrent daily radiation (50.4 Gy in 28 fractions). The primary endpoint of this study was the pCR rate, and secondary endpoints included OS and disease-free survival (DFS). A total of 8 of 28 (28.6%) patients that underwent induction chemotherapy had pCR versus 40.7% of patients that underwent nCRT followed by surgery (p = 0.34). Given no statistical differences between the two groups, the trial was terminated, but the patients were followed. However, after a median follow-up of 60.4 months, a separation in OS was unexpectedly observed favoring the patients treated with induction chemotherapy over no induction . Moreover, induction (versus no induction) chemotherapy was associated with longer OS and DFS, particularly among patients with well/moderately differentiated tumors. Consistently, several recent studies also indicated that the intensification of preoperative cytotoxic chemotherapy brings no benefit to unselected patients with non-metastatic EC, indicating that other approaches are supposed to be considered to improve survival outcomes [Another treatment strategy that has been a common concern is the induction of chemotherapy before nCRT and surgery. A multicenter phase II RCT (NCCTG N0849) evaluated the effect of adding induction chemotherapy prior to nCRT in EC patients . Inductioutcomes ,56. Futup < 0.001) and 30-day mortality, but with no difference in OS [Going back to the aforementioned CROSS trial, another major innovation was the use of a lower neoadjuvant radiation dose (41.4 Gy in 23 fractions) instead of the standard dose (50.4 Gy in 25–28 fractions). To our knowledge, no converse data have exhibited inferior outcomes of 41.4 Gy in the nCRT process. As we know, higher radiation doses produce potentially better tumor control, but also expose patients to increased risks according to the sigmoidal curve for cell kill versus radiation dose in principle of radiation biology. A retrospective study from the USA using the National Cancer Data Base (NCDB) showed that a high neoadjuvant radiation dose is associated with an increased pCR rate , and an equal distant dissemination rate (28%) [Given that a substantial fraction of patients receiving nCRT reached pCR ,9, it iste (28%) . Similarte (28%) ,74. In conclusion, post-nCRT surveillance and surgery as needed are feasible for patients who reach cCRs without compromising OS. Although the benefit of active surveillance strategy has been investigated via different study designs, the currently available results were based on different protocols of neoadjuvant treatment and surveillance strategies. Therefore, there is an urgent need to perform high-quality RCTs regarding an active surveillance strategy for EC.As mentioned above, nCT and nCRT have been proved to bring a more significant survival benefit than surgery alone for patients with locally advanced resectable EC. However, according to the previous evidence-based findings and current guidelines, nCRT did not show an advantage over nCT, which means the optimal treatment strategy remains controversial. As shown in p = 0.04), 5-year survival rate , pCR  and R0 resection rate , while the benefit was not associated with the risk of 30-day postoperative or in-hospital mortality [A recent meta-analysis of eight RCTs involving 1030 patients with resectable EC was published to provide clinical evidence for comparing nCRT with nCT. This study reported a benefit of nCRT over nCT in OS  is an important biomarker for predicting the outcome of SCC treatment. It has been reported that EGFR signaling pathway plays a crucial role in the growth, proliferation, invasion, and apoptosis of EC cells, and upregulated EGFR can be observed in most EC patients ,81,82,83p = 0.04) and significantly prolonged PFS  without causing grade 3 or even more serious toxicity. The cheerful results on the treatment response and survival condition of nimo will be supportive to its further clinical study. Chen et al. enrolled 195 patients with locally advanced thoracic ESCC in a retrospective study to make a comparison between nimo-nCRT, nCRT alone (CF + 40Gy RT), and nCT alone (CF). The results showed that the addition of monoclonal antibodies was safe, the R0 resection rate reached 100%, and the pCR rate reached 41.2%. Compared with nCRT and nCT alone, the R0 resection and pCR rate, respectively, increased by 4.1% and 7.4%, and 8.8% and 26.4% [Nimotuzumab (nimo) is kind of a recombinant humanized IgG monoclonal antibody, which finally inhibits the EGFR signaling pathway by effectively blocking the binding of EGF and transforming growth factor–α (TGFα) . Accordind 26.4% . In anotnd 26.4%  concludend 26.4% . With thnd 26.4%  publisheIn addition to the EGFR signaling pathway, multitudes of studies are carried out to make contributions to the diversity of molecular targeted therapies in EC. The vascular endothelial growth factor (VEGF) inhibitor bevacizumab was added to perioperative ECX chemotherapy in the ST03 trial, but the results were not optimistic enough . AnotherAntibody-based immunotherapy, adoptive cell therapy, and vaccine-based immunotherapy yielded great fruits in improving outcomes of tumors. Among them, the birth of immune checkpoint inhibitors (ICIs) opened a new era for the treatment of EC. With the increasing related research, the overexpression of programmed cell ligand-1 (PD-1) has been found to be widely involved in the process of immune evasion, which has a lot to do with EC patients’ adverse pathological response and dreadful prognosis ,100,101.This year, Shen et al.  administImmunotherapy combined with nCRT has been proven to potentiate a synergistic effect. Local radiotherapy increases T-cell infiltration and antigen presentation, sup-porting immune-mediated out-of-field  effects ,110,111.In the end, with the development of immunotherapy, several key questions remain to be taken into consideration. On the one hand, the central premise of cancer immunotherapy is patients’ certain degree of immunity to exert antitumoral properties. Consequently, the efficacy will be greatly reduced for patients with immunologic failure. On the other hand, a great many previous studies indicated that nCT and nCRT regimens could produce toxicity, which mainly leads to immunosuppression. Further studies are supposed to focus on developing more innovative ICIs and exploring how to maximize the therapeutic efficacy of immunotherapy.Neoadjuvant therapy is an essential part of multi-modality treatments in patients with EC. It has become a research hotspot due to its high efficacy and diversified combination regimens. Compared with surgery alone, nCT and nCRT consistently improved survival condi-tions for either SCC or AC patients. However, controversies still exist. In this review, we focus on the research progress in investigating innovative chemotherapy regimens to reduce the incidence of serious complications and identify more effective nCRT protocols and post-nCRT active surveillance strategies. In addition, neoadjuvant immunotherapy and targeted therapy have shown excellent efficacy and bright development prospects, which provide more options. A multitude of clinical studies are currently ongoing in search of the best combination therapy. Hence, selecting suitable chemotherapeutic agents and the optimal radiotherapy strategy, screening the target population, and avoiding severe complications and adverse reactions are still important research directions of the future work in the field of EC. We believe that substantial breakthroughs will be made through more and more pro-spective RCTs in the near future.


Schistocerca gregaria. Phase (solitary or gregarious) did not affect sperm distribution in the vas deferens and seminal vesicle, whereas sperm accumulation of the seminal vesicle in gregarious locusts was promoted more than in solitary ones. Pheromones received from neither mature adults nor nymphs affected sperm distribution in the vas deferens and seminal vesicle. However, sperm accumulation in the seminal vesicle was more promoted in the gregarious locusts which received pheromones from mature adults than those obtained from nymphs at early adult stage, especially seven days after adult emergence.We investigated male sperm storage in the desert locust Schistocerca gregaria (Forskål). In this locust, a pair of ducts, the vasa deferentia, connect the testes to a pair of the long, slender seminal vesicles that are folded approximately thirty times, and where the sperm are stored. We found that phase variation affected the level of sperm storage in the seminal vesicle. Moreover, adult males that detected pheromones emitted by mature adult males showed enhanced sperm storage compared with males that received the pheromones emitted from nymphs: The former, adult male pheromones are known to promote sexual maturation of immature adults of both sexes, whereas the latter, nymphal pheromones delay sexual maturation. Most mature adult males had much sperm in the vasa deferentia at all times examined, suggesting daily sperm movement from the testes to the seminal vesicles via the vasa deferentia. As adult males aged, sperm were accumulated from the proximal part to the distal end of the seminal vesicle. Many sperm remained in the seminal vesicle after mating. These results suggest that young or new sperm located near the proximal part of the seminal vesicle could be used for mating, whereas old sperm not used for mating are stored in the distal part of the seminal vesicle.In general, sperm produced in the testis are moved into the seminal vesicle via the vas deferens in insects, where they are stored. How this sperm movement is controlled is less well understood in locusts or grasshoppers. In this study, the effects of age, phase variation and pheromones on male sperm storage were investigated in the desert locust,  Schistocerca gregaria (Forskål) (Orthoptera: Acrididae), distributed from Africa to parts of western Asia, is a notorious pest, associated with human famines. This locust has phase variation associated with group behavior changes and long-distance migration [The desert locust, igration ,4,5,6,7.igration ,9,10,11,igration ,14,15,16igration ,18,19, tigration ,21, and igration ,24,25,26igration ,33,34,35igration ,40,41,42igration ,37,38,43igration ,45,46. PThe male desert locust has internal reproductive organs whose structure is similar to that in other locusts or grasshoppers. The locusts have large testes, a couple of vasa deferentia, 15 paired accessory glands, a pair of seminal vesicles, and an ejaculatory duct ,48,49. TSchistocerca gregaria used in the experiments were reared in an insectary at the International Centre of Insect Physiology and Ecology (ICIPE) in Nairobi, Kenya, under gregarious conditions, except for locusts in the solitary phase, using procedures described by Rai et al. [i et al. , except To examine the effects of age, phase variation, or pheromone emission on sperm storage, male locusts were dissected in 0.86% NaCl solution at the desired age, and the vas deferens and seminal vesicle were removed from other reproductive organs using a pair of forceps. As the number of intricately intertwined sperm could not be counted accurately, the quantity of sperm was estimated by the distribution of sperm in the seminal vesicle. Most sperm in the seminal vesicle occurred as bundles (spermatodesms) . The numTo compare sperm storage between locusts in the solitary and gregarious phases, solitary virgin male locusts were individually reared as mentioned above. In contrast, the gregarious virgin locusts were collectively reared in aluminum cages (15.5 × 15.5 × 31 cm height) in groups of approximately five male individuals at 30 ± 2 °C from adult emergence. Locusts were dissected at 0, 7, 14, or 28 days after adult emergence.In this experiment, three sets of observations were made. First, the presence or absence of sperm in the vasa deferentia and seminal vesicles was determined in solitary versus gregarious male locusts. Second, the folds in right side of the seminal vesicle were counted in locusts of each phase. Third, the sperm distribution among folds of right side of the seminal vesicle was also examined. For the first two experiments, the sample size differed among each point. For the last observation, the sample size was ten locusts for each point. Although the sample size was different, each of the three data were obtained from the same individual.To investigate the effect of pheromones on sperm storage, five newly molted immature gregarious virgin adult males (referred to as recipients) were exposed to five mature (yellow) gregarious virgin adult males or five gregarious nymphal (4th or 5th) males (referred to as donors) in aluminum cages (15.5 × 15.5 × 31 cm height) at 32 ± 2 °C, which allowed the insects to receive only olfactory signals from the donors. The donors were kept in the top part of the cage, whereas the recipients were maintained in the bottom part of the cage. There was an aluminum barrier with small holes between the top and bottom parts in cages, in which only olfactory signals could affect their physiology. When a donor insect died during the exposure period, it was replaced by another donor to keep their density constant. When the donor insects (nymphs) that were the source of the nymphal pheromone molted to the adult stage, they were replaced by a new nymph. Three sets of observations were made; first, the presence or absence of sperm in both sides of the vasa deferentia and seminal vesicles was examined in these two types of male locusts. Second, the number of folds in right side of the seminal vesicle were counted for each type of locust. Third, the sperm distribution in each numbered region , on right side of the seminal vesicle was examined in 10 male locusts at each age and treatment. The recipient locusts were dissected 1, 2, or 4 weeks after exposure to pheromone treatment. Sperm distribution in the vas deferens and seminal vesicle was also observed for 3-day-old locusts.Ordinary logistic regression was used to compare the indexes of levels of stored sperm due to the main effect, days after treatment (DAT), or the differences from the root or the edge from the proximal and distal ends of the seminal vesicle at the marked folds and their interactions.U-tests to compare the length of the seminal vesicle between immature and mature adult males and the number of folds in the seminal vesicle between solitary and gregarious locusts.We used Mann–Whitney’s Sperm were found in the vasa deferentia or the seminal vesicles of gregarious male locusts five days (at 30 °C) or three days (at 32 °C) after adult emergence; however, in some individuals kept at 30 °C, there were no sperm in either the vasa deferentia nor the seminal vesicles seven days after adult emergence. These findings indicate that the start of sperm movement differed among individuals and temperatures.In general, the amount of sperm in the vas deferens seemed to increase with sexual maturation, but the accumulation rate was not quantified in this study. In immature adults, there were usually limited sperm in the vas deferens; excluding adults <10 days old, most solitary (88.9%) and gregarious (94.1%) adults had sperm in their vas deferens . Phase vU1-Value = 3.0, U2-Value = 45.0, W-value = 66.0, p = 0.0047).The length of the seminal vesicle increased with age, and the length in gregarious adults <7 days of age  was significantly shorter than that in the mature gregarious adults (28 days old)   .First, in solitary locusts, the number of folds in the seminal vesicle was significantly higher than in the gregarious locusts at each of observed ages (Day 0:  0.0068) . At Day Second, we investigated spatial storage of sperm in the seminal vesicle in the solitary locusts, and we just found a few sperm in the proximal end (fold regions +1 to +3) of the seminal vesicle, at age 1 week after adult emergence A. AdditiThird, we assessed sperm storage in the gregarious locusts, and we found few or no sperm in the proximal part (+1 to +7th fold regions) of the seminal vesicle for 60–100% of males one week after adult emergence B. Additiχ2 = 0.00045826, p = 0.9829)   , it did  0.0001) , suggestSperm distribution did not differ between adults exposed to pheromones from mature adults versus from immature nymphs at any adult age except for Day 3 . AlthougAt 1 week after adult emergence, recipient males exposed to pheromones from mature adults had many sperm or sperm bundles in the proximal part (+4 to +10th fold regions) of the seminal vesicle, in 70 to 80% of individuals A. AdditiFor males exposed to nymphal pheromones, at one week after adult emergence, 30% to 70% had many sperm in the proximal part of the seminal vesicle except for the first threefold regions B, but moAs adult males aged, the quantity of sperm in their seminal vesicles increased. As sperm migration occurred from the proximal end to the center of the seminal vesicle and from the center to the distal end, the sperm quantity also increased . Sperm qDociostaurus maroccanus (Thunberg) [The formation of mature sperm in the desert locust occurs shortly after adult emergence ,52, althhunberg) . After thunberg) , similarMelanoplus sanguinipes (F.) can copulate several times on a single day, and on each occasion transfer several spermatophores [It is generally believed that male grasshoppers or locusts ejaculate only a small proportion of sperm in the seminal vesicle into females during mating, as the migratory grasshopper, tophores ,56. On ttophores ,58,59,60The present study investigated the effects of phase variation and pheromones on the pattern of sperm distribution in the seminal vesicle of the desert locust. Overall, sperm accumulation in the seminal vesicle in the solitary locusts tended to be delayed compared to gregarious locusts. Given that our solitary locusts were held singly, but our gregarious locusts were reared as groups, both physical contact and exposure to external pheromones or other factors may have been involved in this difference in the timing of sperm accumulation. This point should be examined in the future.The effects of pheromones on the patterns of sperm accumulation in the seminal vesicle were evident within one week after adult emergence . By weekM. sanguinipes. Protein synthesis in the male accessory glands is promoted by transplantation of active corpora allata or administration of juvenile hormone, but these procedures do not affect the seminal vesicle [M. sanguinipes is affected by the allatectomy, although the seminal vesicles affected only slightly [It has been thought that changes of body coloration and sexual maturation of males are regulated, at least partially, by the corpora allata juvenile hormones ,43,61,62 vesicle ,63,64. Sslightly . One mayslightly  and ecdyslightly . ConsequThe present research suggests that sexual maturation induced by the maturation accelerating pheromone appears to be related to promotion of sperm storage in the seminal vesicle of this locust. Although sperm storage increases with adult age regardless of pheromones or phase variation, the difference in sperm quantity disappeared. Adult age, temperatures, phase variation, and pheromones are essential for male sperm storage for this locust.


The metabolic response to surgical trauma is enhanced by prolonged preoperative fasting, contributing to increased insulin resistance. This manifestation is more intense on the 1To compare whether preoperative fasting abbreviation and early postoperative refeeding associated with intraoperative and postoperative fluid restriction interfere in the evolution of patients undergoing gastrojejunal bypass. Eighty patients indicated for Roux-en-Y gastrojejunal bypass were selected. They were randomly divided into two groups: Ringer Lactate (RL) group, who underwent a 6 hours solids fasting, with the administration of 50 g of maltodextrin in 100 ml of mineral water 2 hours before the beginning of anesthesia; and Physiologic Solution (PS) group, who underwent a 12 hours solids and liquids fasting. Anesthesia was standardized for both groups. During the surgical procedure, 1500 ml of ringer lactate solution was administered in the RL and 2500 ml of physiological solution (0.9% sodium chloride) in the PS. In both groups, the occurrence of bronchoaspiration was analyzed during intubation, and the residual gastric volume was measured after opening the abdominal cavity. In the postoperative period in Group RL, patients started a liquid diet 24 hours after the end of the operative procedure; whilst for PS group, fasting was maintained for the first 24 hours, it was prescripted 2000 ml of physiological solution and a restricted liquid diet after 36 hours. Each patient underwent CPK, insulin, sodium, potassium, urea, creatinine, PaCO2, pH and bicarbonate dosage in the immediate postoperative period, and 48 hours later, the exams were repeated. There were no episodes of bronchoaspiration and gastrojejunal fistulas in either group. In the analysis of the residual gastric volume of the PS and RL groups, the mean volumes were respectively 16.5 and 8.8, which shows statistical significance between the groups. In laboratory tests, there was no difference between groups in sodium; PS group showed a higher level of serum potassium (p=0.029); whilst RL group showed a higher urea and creatinine values; CPK values were even for both; PS group demonstrated a higher insulin level; pH was higher in PS group; sodium bicarbonate showed a significant difference at all times; PaCO2 values in RL group was higher than in PS. In the analysis of the incidence of nausea and flatus, no statistical significance was observed between the groups. The abbreviation of preoperative fasting and early postoperative refeeding of Roux-en-Y gastrojejunal bypass with the application of ERAS or ACERTO Project accelerated the patient’s recovery, reducing residual gastric volume and insulin level, and do not predispose to complications. Obesity is a hard-treatment chronic disease that has become a global epidemic that causes health issues for individuals and society. Although there is evidence of metabolically healthy obesityAccording to the WHO - World Health Organization - Obesity results from an individual’s positive energy balance, which leads to excessive accumulation of body fats that causes health problems, lower life quality, and decreased life expectancy,Currently, the number of surgical procedures - resection and anastomosis of stomach and small intestine - for morbid obesity has increased significantly,A six to eight hours fasting before these procedures was implemented when rudimentary anesthetic techniques were still used. This technique was recommended to prevent pulmonary complications associated with gastric contents aspiration during anesthesia (Mendelson’s syndrome). Another work from the 1950s extended the maximum limit of gastric content to 25 ml to ensure that there would be no risk of bronchoaspiration under anesthesiaAnother problem related to prolonged preoperative fasting is increased insulin resistance, which enhances the metabolic response to surgical trauma. This result is commonly observed on the first and the second day after surgery, and it is directly proportional to the operation complexityThere is no consensus on the best perioperative care in bariatric surgery. Evidence-based protocols and guidelines are mechanisms that must be implemented in the medical routine, as they reduce the morbidity and mortality of the populationInitially, the principles of the ERAS protocol were applied in colorectal operations, which contributed to a large number of studies in this area. Other surgical specialties have been adopting these concepts, and there is constant updating as researches are developedSeveral multimodal protocol guidelines, based on randomized studies and meta-analyses, showed that, even in large operations, it is possible to abbreviate preoperative fasting for two hours by ministering carbohydrate-containing liquids. Moreover, early feeding on postoperative and reduced hospitalization time is also classified as safe by these studiesIn 2005, the ACERTO Project , based on an extensive literature review on perioperative care, initiated a pioneering multimodal program in the national territory, which, from its inception, highlighted the importance of nutritional issues in the recovery of the surgical patient. Evidence-based medicine has shown that programs for accelerating postoperative recovery, along the lines of ACERTO, are safe, reduce postoperative complications and hospitalization time without increasing hospital readmission ratesThe use of the ACERTO Project or ERAS protocol has shown that they are safe in bariatric surgery and can improve intraoperative and postoperative clinical conditions by reducing hospitalization timeThis study aimed to define whether preoperative fasting abbreviation, early feeding, trans and postoperative fluid restriction interfere in the gastrojejunal bypass patient recovery.This work consists of a randomized clinical assay in which 80 patients indicated for Roux-en-Y gastrojejunal bypass (BGYR) were recruited after approval by the Research Ethics Committee of Faculdade Evangélica Mackenzie do Paraná, accordingly to Resolution 466/12 CNS under report number 1,999,670. After the selection criteria were applied, the patients were randomized and divided into two groups. The operations were performed at a single institution - Hospital do Rocio, Campo Largo, PR, Brazil.2 associated with hypertension and/or diabetes or BMI between 40 kg/m2 and 46 kg/m2, surgical time less than 120 min and procedure performed by the same surgical team.Those eligible for BGYR and who agreed to participate in the study have signed an informed consent term. Inclusion criteria to cooperate this research were: BMI >35 kg/mThis study did not include those with renal and hepatic insufficiency or dysfunction, coagulation disorders, heart disease, allergic to dipyrone or non-steroidal anti-inflammatory drugs and who require ICU monitoring.Patients were randomly divided into two groups: ringer lactate (RL) and Physiological Solution (PS) groups. Randomization was performed using the Random® program, in which the number provided would correspond to the group in which each patient would fit.Patients from the RL group underwent 6 hours of solid fasting, administering 50 g of maltodextrin in 100 ml of mineral water 2 hours before the beginning of anesthesia, whilst the PS group underwent 12 hours of solids and liquids fasting.Anesthesia was equally regulated for both groups with an anesthetic induction of propofol (1.5 mg/kg), fentanyl (3 mcg/kg) and cisatracurium (0.15 mg/kg) and monitored in a conventional way. Analgesia was multimodal with dipyrone (2 g), ketorolac (30 mg) and epidural anesthesia with ropivacaine associated with morphine. Nausea and vomiting prevention was performed with ondansetron (8 mg), dexamethasone (4 mg) and alizapride (50 mg). The same surgical technique of RYGB was used in all patients and performed by the same surgical team.During the operative procedure, 1500 ml of ringer lactate solution was administered in a closed system in the RL group, whilst 2500 ml of saline solution was in the PS group. In both groups, the occurrence of bronchoaspiration during intubation was analyzed, and the residual gastric volume after reaching the abdominal cavity was measured. For this last procedure, the anesthetist collected gastric fluid through the Fouchet tube and the surgeon assisted by manipulating the stomach, making it more effective and precise. In the surgery room and after the operation, each patient underwent exams of CPK, insulin, sodium, potassium, urea, creatinine, PaCO2, pH and bicarbonate. In the 24 hours RL group postoperative period, patients started a liquid diet and infusion of 1000 ml of ringer lactate solution, 1000 ml of glucose solution, antibiotic prophylaxis (Kefazol 1 g 8/8h), analgesics and antiemetics, when needed. Laboratory tests were redone, and the presence of nausea and flatus were monitored during this time. In the 48 hours postoperative period, patients started a restricted liquid diet 36 hours after surgery and were prescripted 500 ml of ringer lactate, 500 ml of glucose solution, analgesics and antiemetics, if necessary. Once again, laboratory tests were redone, and nausea and flatus were monitored during this time.In the 24 hours PS group postoperative period, patients maintained fasting and were prescripted 2000 ml of physiologic solution, 1000 ml of glucose solution, antibiotic prophylaxis (Kefazol 1 g 8/8 h), analgesics and antiemetics, if needed. Laboratory tests were redone, and the presence of nausea and flatus were monitored during this time. In the 48 hours postoperative period, patients from this group started a restricted liquid diet 36 hours after the surgery and were prescripted 1000 ml of physiological solution, 1000 ml of glucose solution, analgesics and antiemetics - if needed. Once again, laboratory tests were redone, and nausea and flatus were monitored during this time.This study analyzed variables like mean, median, standard deviation, minimum and maximum values. The resume of qualitative variables was performed considering frequencies and percentages. Aiming to compare the two groups concerning quantitative variables, Student’s t-test for independent samples was used. The Chi-Square test or Fisher’s exact test was used to compare the two groups concerning qualitative variables. Nausea and flatus comparisons between the groups were performed by binomial teste. Split-Plot analysis of the variance model was used to compare the time of evaluation. Bonferroni test was applied in the groups comparison within each moment and the moments comparison within each group. P values less than 0.05 indicated statistical significance.There were no episodes of bronchoaspiration, and there were no gastrojejunal fistulas in either group.For the quantitative analysis of the residual gastric volume (RGV) in the PS and RL, the means were respectively 16.5 and 8.8 p<0.001, .Sodium was higher in PS patients after the surgery compared to RL’s patients but without statistical significance. In the first 24 hours, a constant difference between them was noticed, however with statistical significance (p=0.013). After 48 hours, there was an increase in the RL group mean value - which reached 139.25 - but without significance compared to the PS, which had a mean of 138.98.By the end of the operation, the K serum level of the PS groups had a mean of 3.83, whilst for the RL group, the mean was 3.64 (p<0.029). Such a significant difference was not observed in subsequent analyses. RL showed an increase from its initial levels during the first 24h (p=0.016). In sequence, was observed a fall on these values below the initial point, again demonstrating statistical significance between values of 24 h and 48 h. PS group patients in the immediate postoperative period up to 48h had decreased levels with statistical significance (p<0.001).In the immediate postoperative period, both groups had equivalent serum levels, with no significant difference. However, in the 24 h, both had an increase and significant difference in the 48 h with a decrease in values (p<0.001).The values found in the PS were higher and presented a significant difference if compared to the RL in the first 24 hours. Afterwards, the insulin levels were reduced close to the initial ones (p=0.536) if compared to themselves, but showing a significant difference for both groups compared to the insulin values between 24 and 48 h.In the immediate postoperative period, the pH was 7.36 for the PS and 7.39 for the RL without statistical significance. In the following moments, were not observed any statistical significance for this parameter.The bicarbonate level showed a significant difference between the groups at all moments, being more expressive in the immediate postoperative period; PS was at 22.37 while 24.26 showed in RL (p<0.001). An increase was seen in the 24h period evolution of PS, with a posterior decrease in the 48h period. It has shown statistical significance if compared to the RL group (p<0.016). There was a significant difference (p<0.040) between the groups in the first 24 h, where values were 40 (RL) and 37.55 (PS). Both groups had a decrease in values between the immediate and the 48 h period, with statistical significance (p<0.001).The incidence of nausea was 17.5% in the PS and 7.5% in the RL immediately after surgery and without statistical significance in the other periods.Both groups had flatus within the first 24 h. In RL, it represents 25% of patients, whilst 12.5% in PS. Although, this difference was not statistically significant. For the following 48h, it occurred in 62.5% of both groups, also without statistical significance.,Evidence-based medicine is translated into practice in a context of integrated clinical experience, with the ability to critically analyze and rationally apply scientific information, aiming to improve the quality of medical care,Literature has shown safety in fasting abbreviation offering maltodextrin for two hours before anesthetic inductionRegarding this discussion in the literature, our work was based on a comparison between two groups. One with patients who underwent a long period of 12 hours fasting with fluid and solids restriction and a diet of 36 hours after the surgical procedure (PS group), and another did a 2 hours preoperative fasting, which consisted of a liquid carbohydrates diet and with a 24 hours diet after the surgical procedure (RL group). Patients who underwent long fasting periods (PS) had higher insulin levels in the first 24 hours  compared to those who abbreviated their fasting for 2 hours before surgery (RL), which characterized an increase in insulin resistance. Aguilar Nascimento, et al. (2011)Another study reviewed the abbreviation of preoperative fasting from the metabolic and gastric emptying points of view, clinical benefits, and current recommendationsYagci, et al. (2008)According to Yagci et al. (2008)Ruiz-Tovar J, et al (2019)Preoperative overnight fasting was introduced when anesthetic techniques used chloroform and were still very rudimentary to avoid respiratory complications resulting from vomiting and aspiration of gastric contents. In our study, patients in both prolonged and 2-hour fasting groups did not show signs of bronchoaspiration.Insulin resistance is the primary metabolic change during surgical stress, directly proportional to the magnitude of the operation and causes hyperglycemia in non-diabetic patients. As a result, various endocrine and inflammatory systems are stimulated. This results in an intensified postoperative catabolic response, which implies losing body fat and protein reserves. In addition, aggressive insulin treatment to maintain normal glycemic levels resulted in reducing organ dysfunction and mortality. Moreover, insulin resistance showed to be an independent factor influencing hospitalization timeSix clinical trials demonstrated a significant reduction in insulin resistance after using preoperative carbohydrate loading. The maximum improvement in insulin action observed was a factor of 50% (p<0.01) after the morning carbohydrate dose on the day of operationMatłok, et al. (2016),The surgical and anesthesiological practice is under constant development, which means that the recommendations in the literature need to be questioned and updatedThe abbreviation of preoperative fasting and early postoperative refeeding on Roux-en-Y gastrojejunal bypass with the application of programs such as ERAS or ACERTO Project accelerated the patient’s recovery, reducing residual gastric volume and insulin level, and it does not predispose to complications.


Because of the dilemma that the current industrial Cu enhancement methods lead to a significant decline in conductivity and ductility, Cu matrix composites reinforced by oriented multi-walled carbon nanotubes (MWCNTs) were prepared through sintering, hot extrusion, and cold drawing. Before sintering, Ni, Cu, and Ni&Cu coatings were electroless plated on MWCNTs as the intermediate transition layer, and then they were mixed with Cu powder through a nitrogen bubbling assisted ultrasonic process. By analyzing the composition, microstructure, and formation mechanism of the interface between MWCNTs and the matrix, the influence and mechanism of the interface on the mechanical properties, conductivity, and ductility of the composites were explored. The results indicated that MWCNTs maintained a highly dispersed and highly consistent orientation in the Cu matrix. The coating on Ni@CNT was the densest, continuous, and complete. The Ni@CNTs/Cu composite had the greatest effect, while the Cu composite reinforced by MWCNT without coating had the smallest reduction in elongation and conductivity. The comprehensive performance of the Cu@CNTs/Cu composite was the most balanced, with an ultimate tensile strength that reached 373 MPa, while the ductility and conductivity were not excessively reduced. The axial electrical and thermal conductivity were 79.9 IACS %  and 376 W/mK, respectively. Copper has excellent electrical and thermal conductivity, good plastic formability, and is easy to manufacture, so it has become the best candidate material for electrical, thermoelectric, and electronic applications. However, with the rapid development of high-speed electric railways, lightweight automobile body manufacturing, new MEMS/NEMS , and other fields in recent years, more stringent performance requirements have been put forward for key parts. These key parts include a high-speed railway electric contact line, resistance spot welding electrode for galvanized steel sheets, heat sink parts, and thermoelectric devices. Their conductive contact area is greatly decreased, the current density is greatly increased, and the heat emission condition deteriorates rapidly, which results in a significant decline in the stability of material parts. They are required to further enhance current-carrying or heat dissipation capacity with given sectional dimensions and structural strength or to reduce the sectional size to realize the miniaturization of components without sacrificing the intensity of texture or current-carrying and thermal conductivity. In other words, the strength, hardness, and electrical/thermal conductivity of the material need to be good, while the ductility and formability are acceptable. The following methods are commonly used to strengthen Cu in the current industry:When Cu is strengthened by alloying , its ductility or machinability will not be excessively reduced. However, the electron scattering caused by alloy elements will reduce its electrical/thermal conductivity.2O3 [2 [2O3 and carbon reinforcing phases such as carbon fiber [2O3 dispersion strengthened Cu electrodes used in body-in-white welding, which were prepared by an internal oxidation method 4–10 times longer than that of ordinary chromium–zirconium Cu. However, the production cost of the internal oxidation method is high, and the increase in strength is accompanied by the loss of ductility and formability. The electrode is prone to cracking during extrusion forming and spot welding, and the welding performance is unstable. In addition, there are also surface strengthening methods, including brush plating, laser surface cladding, ion implantation, metal infiltration, and electrical discharge deposition [The most mature method of reinforcing Cu is dispersion strengthening by reinforcements. The second phase mainly consists of ceramic reinforcing phases such as Al2O3 , TiB2 [2on fiber , graphiton fiber , and graon fiber . For exaposition . HoweverAs mentioned above, the current industrial methods of reinforcing Cu have the contradiction of a significant decrease in conductivity and ductility. Considering the superior designability and comprehensive performance of composites, one of the effective approaches to solve the problem is to prepare Cu composites with balanced mechanical properties, conductivity, and ductility by selecting appropriate reinforcements and controlling the composite structure and interface.The physical basis of the composite effect is the property difference between the metal matrix and reinforcement. To generate obvious benefits through reinforcement, the performance of the selected reinforcements must be far superior to that of the Cu matrix. Carbon nanotubes (CNTs) have a near-perfect bonding structure and high thermal stability . Their m3), and van der Waals’s force and the electrostatic attraction between them result in their easy entanglement. Agglomeration of CNTs significantly reduces their strengthening effect [Firstly, the aspect ratio of CNTs is very high  by a chemical plating process as intermediate layers to improve the interface adhesion between CNTs and the Cu matrix. Then, Cu matrix composites were prepared by hot extrusion and cold drawing after nitrogen bubbling-assisted ultrasonic dispersion. The effects of the spatially distributed and aligned orientation of MWCNTs and the composition and microstructure of the interface on the macroscopic anisotropy of composites such as mechanical properties, conductivity, and ductility were investigated. This study can provide new insights for balancing the mechanical and conductive properties of CNTs/Cu composites by controlling microstructure and interface.3 density, 10–20 nm diameter, 10–30 μm length) were prepared by the vapor deposition method from the Chinese Academy of Sciences Chengdu Organic Chemistry Co, Ltd. . Electrolytic Cu powder was commercially purchased with a purity of 99.8% and a size of 50–75 μm.Highly conductive MWCNTs  was performed in deionized water for 10 min using a probe ultrasonic generator . Subsequently, MWCNTs were added to nitric acid solution (6 mol/L) and refluxed at 115 °C–120 °C for 60 min. They were then filtered and washed until the pH value was 7. Sodium hydroxide solution (6 mol/L) and hydrochloric acid solution (6 mol/L) were added in turn and refluxed at 115 °C–120 °C for 40 min. They were then filtered and washed until the pH value was 7. The purified MWCNTs were sensitized and activated , followeIn the following sections, B-CNT, Ni@CNT, Cu@CNT and Ni&Cu@CNT denote uncoated CNT, Ni-plated CNT, Cu-plated CNT, and Ni&Cu-plated CNT, respectively. B-CNTs/Cu composite, Ni@CNTs/Cu composite, Cu@CNTs/Cu composite, and Ni&Cu@CNTs/Cu composite denote the uncoated MWCNT-reinforced Cu matrix composite, Ni-plated CNT-reinforced Cu matrix composite, Cu-plated CNT-reinforced Cu matrix composite, and Ni&Cu-plated CNT-reinforced Cu matrix composite.After electroless plating, B-CNTs, Cu@CNTs, Ni@CNTs, and Ni&Cu@CNTs were mixed with pure Cu powder (the content of MWCNTs was 3 vol.%), and Ф16 rods were prepared by cold pressing, sintering, hot extrusion, cold drawing, and turning using a previously reported process . Pure CuThe microstructure was characterized by field emission scanning electron microscopy ) and transmission electron microscopy . Silicon carbide  and diamond spray polishes (W1.0 μm and W0.25 μm) were used to polish the sample surface for SEM detection. The samples were thinned to less than 100 nm using a dual-beam microscope  and a focused ion beam (FIB) to fabricate foils for TEM detection. The surface microstructure of the samples was characterized by an electron backscatter diffraction (EBSD) detector mounted on a field emission SEM. The sample surface was electroplated at room temperature after mechanical polishing.The tensile and compressive properties at room temperature were tested using a microcomputer-controlled electronic universal material testing machine  respectively. The tensile direction of specimens was parallel to the drawing direction. Specimens were processed by electrical discharge machining into a dog bone shape (16.5 mm × 6 mm × 2 mm). Compression specimens were cylindrical with a standard size of Ф18 × 25 mm and surface roughness of Ra < 0.8. Tensile tests were performed at a crosshead speed of 2 mm/min. The results are the average of five measurements.The Keithley-2400 current source meter  and Keithley-2182 voltmeter  were used to test the electrical conductivity. The sample size was Φ18 mm × 5 mm. The thermal conductivity test was performed using a laser thermal conductivity analyzer  at 10–15 mbar vacuum. The sample size was Φ10 mm × 3 mm. The results are the average of five measurements.terature ,36,37,38The elongation of composite samples decreased. The elongation from high to low was as follows: B-CNTs/Cu composite, Cu@CNTs/Cu composite, Ni@CNTs/Cu composite, and Ni&Cu@CNTs/Cu composite. Among them, Ni&Cu@CNTs/Cu decreased from 18.5% of the pure Cu sample to 7.5%.Compared to pure Cu samples, the conductivity of composite samples also decreased, as can be seen in ∥ and C∥ directions . The experimental data demonstrated that the comprehensive performance of the Cu@CNTs/Cu composite was better, and its enhancement was high, while the ductility and conductivity were not excessively reduced.It can be seen from 4, and the NiSO4 content was much lower than that of the Ni-plating bath, which was not enough to form a complete coating.Furthermore, EDS elemental analysis in To further understand the microstructure of the orientation, EBSD analysis was carried out on four composite samples. Taking the EBSD images of the Ni@CNTs/Cu composite in the plane parallel to the drawing direction and that vertical to the drawing direction shown in The results of EBSD analysis in lattices . The aboIn this work, a highly oriented arrangement of CNTs in the Cu matrix was achieved. In practical applications, it is beneficial to give full play to the excellent axial performance of CNTs to make the working load direction consistent with this direction.There were some darker colored regions to the right of the yellow dotted line where clear Moire fringes were visible, as shown in region b in 2O(111) plane. In addition, on the lower side of the yellow dashed line, region b, and region c in 2O(200) plane, Cu(2O(200) plane, respectively, and (0002)MWCNT// oxidation of the electroless Cu coating. The oxidation may occur during the composite preparation process, such as storage, powder mixing, and sintering. (2) Cu reacted with oxygen-containing functional groups to form Cu2O. The acid treatment used in this work may have introduced oxygen-containing functional groups, e.g., carboxyl and hydroxyl groups on MWCNTs [2O-Cu interface is shown in 2O is a gradual transition from the helical lattice plane of Cu2O to the C(0002) lattice of MWCNT, and Cu2O at the Cu@CNTs/Cu interface plays an important role in regulating the transition medium between MWCNTs and Cu matrix [2O nanocrystals that formed in situ at interfaces can tightly connect MWCNTs and matrix, forming strong chemical bonding, which is beneficial to improve the interfacial combining strength and load transfer efficiency [n MWCNTs , which au matrix . Therefoficiency ,49,50,512O plane, Ni3C, planar Cu(111) plane, and Cu2O(111) plane were identified according to the FFT patterns of amorphous transition regions in 3C in the amorphous transition zones was the same as described before. Cu2O in the amorphous transition regions was also associated with defective sites of oxygen-containing functional groups on MWCNTs. The oxygen-mediated bonding of Cu-O-C contributed to the formation of Cu2O, which is consistent with Zhao’s s report [Similar to the Cu@CNTs/Cu composite, a 6–8-nm-thick amorphous transition zone along the sidewalls of MWCNTs was formed at the interface, as shown in the regions between the red and yellow dashed lines in 3C1, planar s report , which ss report  demonstrThe slip bands are visible in the lower right of region d of 3C(113) plane, and Cu2O(200) plane were identified on MWCNTs, as shown in 3C and Cu2O were the same as above.2O(200) plane, and Cu2O(111) plane was identified from the FFT images of the amorphous transition regions in 2O-Cu interface. The Ni&Cu@CNTs/Cu interface had the characteristics of both Ni @CNTs/Cu and Cu@CNTs/Cu interfaces. In addition to the formation of Ni and Cu solid solutions, there were also CNT-Cu2O-Cu interfaces at the interface. Nevertheless, since most of the plating was Cu, the content of Ni atoms was too small, and the influence of Cu on the interface played a dominant role.Similar to the first two composites, -6-nm-thick amorphous transition regions formed along the MWCNT side walls at the interface, as shown in the zone between the red and yellow dotted lines in There were also some darker areas in the matrix in It was found in our previous study  that theK is the constant for Cu  is the Burgers value of the matrix; S is the cross-sectional area [G is the shear modulus of the matrix; −5 K−1 [To explore the strengthening mechanism of CNTs on composites, the reinforcement effect of CNTs was quantitatively analyzed. It mainly consists of the following aspects: (a) refinement of grains by the pinning effect of CNTs , (b) OroMPa/m1/2 ), and dcequation ,62:(4)σO6 for Cu ); λ is tquations :(5)σL.T=equation :(7)σT.M=10−5 K−1 ,67) is t−5 k−1 [−6 k−1 [−5 k−1 , Cu is 1 [−6 k−1 ). Many nThe results of this study showed that the tensile strength of composites from high to low was the Ni@CNTs/Cu composite, Ni&Cu@CNTs/Cu composite, Cu@CNTs/Cu composite, and B-CNTs/Cu composite. Nevertheless, the enhancement of the Cu matrix by B-CNTs was far less than that by coated MWCNTs, and the tensile strength increased slightly. This is because the poor wettability of Cu and MWCNTs (wettability angle 145°)  determin3C, as shown in 2O. The small amount of Cu2O at the interface had a pinning effect on GBs, thus creating resistance to their movement and reducing the interfacial migration rate, which strengthened the coated MWCNT-reinforced Cu matrix composites.The Ni@CNTs/Cu composite was the strongest due to the following reasons: (1) Ni plating was the densest, continuous, and complete. In contrast, the Cu and Ni&Cu coatings were looser and incomplete, as shown in Although B-CNTs slightly affected the tensile strength of the matrix, the compressive strength improved significantly. This is because the compressive load did not cause the MWCNTs to slip out of the Cu matrix, allowing more MWCNTs to bear the load. The inherent properties of the MWCNTs (Young’s modulus reached 270–950 GPa) and the metal coating on MWCNTs can resist deformation. The force effectively was shifted from the Cu matrix to MWCNTs during the compressive strength test. The composites exhibited significant differences in orthogonal directions because the aligned MWCNTs had a larger contact area with the metal indenter in the parallel direction, which made for a more efficacious load transfer.The elongation of the composite samples decreased. The elongation from high to low was the B-CNTs/Cu composite, Cu@CNTs/Cu composite, Ni@CNTs/Cu composite, and Ni&Cu@CNTs/Cu composite. The reduced elongation was attributed to the deformation during extrusion and drawing and the blocking effect of CNTs embedded in the matrix on dislocation slip . The B-MThe mechanical properties of the composite samples were orthogonal anisotropic. The strength parallel to the drawing direction was higher than that perpendicular to the drawing direction. Here, coated MWCNTs were straight, long, uniform dispersion, and unidirectionally aligned along a uniform direction in the Cu composite as shown in ρint can be determined by the following equation:h is the reduced Planck constant; e is the charge of an electron; p is the probability of elastic scattering at the interface; n is the concentration of electron in Cu, and d is the diameter of CNTs.Good interfacial bonding enables the good transfer of electrons between CNTs and the matrix. The electron–phonon coupling is promoted, and the scattering of electrons and phonons at the interface is reduced, thereby improving the conduction properties of the overall composites . Howeverp). To mitigate the effect of interfacial scattering, improving interface wettability is considered to be an efficacious method. Here, the interface between MWCNTs and the Cu matrix was bonded closely without gaps through the process of electroless plating, sintering, extrusion, and drawing, which reduced the resistivity of interfacial scattering and thus improved the overall conductivity of the MWCNTs/Cu composites.The elastic scattering of electrons can be lessened by optimizing the interfacial structure, and the resistivity of interfacial scattering increases with wettability  the larger size of MWCNTs caused disturbance of Cu lattice periods, causing the scattering of electrons in the local elastic strain regions, thereby reducing the conductivity. (2) High-density dislocations were generated in and around the interfacial regions after hot extrusion and cold drawing, and the heterogeneous interfaces increased, which led to the decrease in conductivity. As shown in The composite samples exhibited orthogonal anisotropy in conductivity, and the conductivity parallel to the tensile direction was obviously higher. This was attributed to the good axial conductivity of MWCNTs and the fact that MWCNTs remained straight, long, monodispersed, and had unidirectional arrangement in a uniform direction in the matrix. The bending degree of MWCNTs in the matrix had a strong influence on the properties of composites, and bending and torsion increased the scattering during the conduction of heat flow and current. The contact modes between CNTs and matrix could be divided into end contact and side contact . The conWe investigated the effect of Ni, Cu, and Ni&Cu electroless coatings on the interface between CNTs and the matrix and revealed the mechanism of interface composition and microstructure on the mechanical properties, conductivity, and ductility of MWCNTs/Cu composites.The wettability of MWCNTs with respect to the Cu matrix as limited, resulting in weak mechanical bonding between CNTs and the Cu matrix in the B-MWCNTs/Cu composite. Therefore, its strengthening effect on the matrix was much lower than that of coated MWCNTs. However, the conduction performance of the B-MWCNTs/Cu composite had the minimum reduction, which may be ascribed to the reduction of the energy loss of electron–phonon conversion by the tightly bonded interface. In addition, the low-density dislocation near the interface also reduced the lattice disorder of Cu in amorphous regions.2O and Ni3C, solid solutions of Cu and Ni, transitional amorphous areas, and high-density dislocations at interfacial regions in-plated CNT-reinforced Cu composites, forming tight interface bonding, which effectively strengthened the composites. However, these factors also caused the scattering of electrons and phonons, increasing the electrical/thermal resistance of the interface and leading to a decrease in the conductivity of composites. The ductility of the composites decreased, which was attributed to the blocking effect of MWCNTs on the dislocation slip.There were interfacial products such as CuThe Ni plating was the most dense, continuous, and complete. The strengthening effect of Ni@CNT with respect to the Cu matrix is the greatest, but its elongation and conductivity decreased greatly. The Cu@CNTs/Cu composite achieved the balance of mechanical properties, ductility, and conductivity/thermal conductivity. Its ultimate tensile strength was 373 MPa, the elongation was 12.1%, and the axial conductivity and thermal conductivity were 79.9 IACS% and 376 W/mK, respectively.MWCNTs in the prepared Cu composites remained straight, long, monodispersed, and unidirectionally arranged, which enabled the excellent axial conductivity and mechanical properties of MWCNTs to be exerted, exhibiting orthotropic anisotropy.Even if the outermost tubes were damaged by acid treatment, MWCNTs with multilayer nested tube structures could still transmit electrons/phonons axially through inner tubes, which prevented the influence of outer tube damage on the conductivity.


Between t0 and t1, a statistically significant improvement was observed for all three outcomes, while the intended behaviour outcome was no longer significant between t1 and t2 . Females and who participated live at the seminar maintained a significant knowledge of mental illness and a better attitude toward community mental health care. The effects of the seminar focused on reducing stigma tended to diminish over time at one year follow-up, particular in relation to intended behaviour.The primary aim is to describe the changes in the knowledge of mental health conditions, the attitudes toward the mentally ill, and the intended behaviour towards people with mental illness among the entire student population of the third year of a degree course in Psychology. A total of 570 students attended a seminar on stigma towards mental illness and were invited to complete an online survey which collected data on sociodemographic characteristics and three validated questionnaires evaluating different aspects of stigma at three different time points . A total of 253 students (44.39%) completed the questionnaires at t0, t1, and t2. The mean age of the sample was 23.7 (SD = ±5.89), and 86.96% ( In 1963, the American sociologist Goffman used the term “stigma” to indicate those attributes  that connoted those who owned them as “... tainted, discounted one” ,3. Lack of knowledge generates stereotypes that are assimilated and considered as truthful by the general population . Agreement with the stereotype can result in a particular attitude, for example, fear of whether people with a mental illness are considered dangerous or capable of violent actions. The emotional experience ultimately leads to discriminatory behaviours, such as requiring that people with mental illness be locked up in institutions (asylums) that isolate them from society ,5,6.Besides the already mentioned public stigma, other types of stigma related to mental illness have been described in the literature: structural stigma, self-stigma, felt or perceived stigma, experienced stigma, label avoidance, courtesy stigma, and spiritual stigma ,7,8. The phenomenon of stigma towards mental illness generates dramatic consequences made evident by a number of studies. For example, stigma is the first obstacle to seeking help from mental health professionals ,10,11,12Healthcare professionals and especially mental health workers can be both victims and perpetrators of stigmatizing attitudes. An interesting paper by Bhugra and colleagues  describeIn order to define the presence and to fight stigmatizing attitudes in health professionals, several studies were conducted with the involvement of undergraduate students in health degree courses: psychology students ,26,27, nThe first aim of this longitudinal study was to describe the changes over time in the knowledge of mental disorders, the attitudes toward people who are mentally ill, and the intended behaviour towards people with mental illness in the entire student population of the third year of the degree course in Psychology of the Inter-University of Parma with Modena and Reggio Emilia after attending a Clinical Psychology course including a seminar on stigma towards mental illness. Secondly, we investigated whether changes in stigma outcomes differed for certain subpopulations: males and females, students who attended lessons in person vs. those who attended virtually, and students who had/did not have a first- or second-degree relative with a mental illness. Based on previous studies ,33,34 thn = 300 in 2018/2019; n = 270 in 2019/2020) were invited to complete an online survey that collected data on sociodemographic characteristics and validated stigma outcomes related to knowledge, attitudes, and intended stigmatising behaviour. For two consecutive academic years (A.Y.) (2018/2019 and 2019/2020), the students in the third year of the inter-university degree course in Psychology (University of Parma and University of Modena and Reggio Emilia) . Our sample size calculation suggested that we needed 230 participants to complete the study based on a total population of 570 students and considering 5% as margin of error (confidence level: 95%).Students who agreed to fill in the questionnaires were asked for the following socio-demographic information: gender, age, class participation (face to face or remotely), having already participated in stigma awareness events, and having first- and second-degree relatives who have/had a mental illness.The online survey comprised three validated psychometric questionnaires. The Italian version of the Mental Health Knowledge Schedule (MAKS-I) ,36 is a The CAMI Scale  refers to attitudes towards people who are mentally ill. Participants rate the 27 statements from 1, “Strongly Disagree”, to 5, “Strongly Agree”, and a high score corresponds with positive attitude ,38,39. The Italian version of the Reported and Intended Behaviour Scale (RIBS) is a self-administered questionnaire composed of eight items evaluating reported and intended behaviours across four different domains: (1) living with, (2) working with, (3) living nearby, and (4) continuing a relationship with someone with a mental health problem. The total intended behaviour score is calculated by summing the answers for items five through eight. A higher score indicates a higher level of intended behaviour and/or contact with someone with a mental health problem ,41. The interval variables were described using means and standard deviations (SDs), and the categorical and ordinal variables were described using frequencies and percentages. Homogeneity test between students of the two A.Y. were carried out through Mann–Whitney U test for interval variables and chi-square test for ordinal, categorial, and nominal variables . The Shapiro–Wilk Test was used to verify if the scores obtained on the questionnaires have a normal distribution . To verin = 220) was female. Only 40 students (15.81%) had already participated in stigma awareness events, while 25.30% (64) have/had a first- or second-degree relative with a psychiatric disorder . The homogeneity test failed only for the age variable . The sociodemographic characteristics of the sample and the test of homogeneity are described in Of the 570 students contacted, 302 (52.98%) agreed to be involved in the study, and 253 (44.39%) completed the questionnaires at t0, t1, and t2. The mean age of the sample was 23.74 (SD = ±5.89), and 86.96% : the percentage of those who obtained a higher score and those who obtained the same score with respect to t0 are almost the same . Through the Friedman test, a statistically significant improvement was highlighted for all questionnaire scores in repeated measurements at t0, t1, and t2. .p < 0.001) and attitudes (CAMI) . For both subpopulations, there was a statistically significant improvement for all questionnaires considering the repeated measures at t0, t1, and t2. Both the male and female subpopulations  had a stp = 0.47; Distance learning: Z = −0.14, p = 0.89). Students who attended the remote frequency (RF) course did not experience a statistically significant improvement between t1 and t2 in the stigma-related knowledge of mental disorders  or attitudes . Trends over time of MAKS-I, CAMI, and RIBS-I for students who attended in the classroom and those in distance learning are described in Both students attending face-to-face lectures in the classroom and those attending virtual lectures had a statistically significant improvement between t0 and t1 in all three stigma outcomes. There was no statistically significant improvement between t1 and t2 among those attending in person or virtually and regarding intended behaviour towards people with mental illness  considering the repeated measures at t0, t1, and t2.Before proceeding with the discussion of the results obtained, we describe the limitations that characterize this study. First, the homogeneity test failed by comparing the gender of the student population of the two academic years (A.Y. 2018/2019 and 2019/2020): the percentage of female students is slightly higher in the A.Y. 2019/2020 (89.51% vs. 92.64%). Furthermore, the number of males and females is very different; therefore, the results obtained must be compared with those in the literature with caution. The questionnaires validated in the Italian language used in this study provided decidedly good psychometric qualities in the previous validation processes ,41; howeWe found that, for the entire students’ populations, intended stigmatising behaviour improved statistically significantly only between t0 and t1. Several studies in the literature have shown that non-stigmatizing effects on behaviour of anti-stigma interventions reduce over time: Evans-Lacko and colleagues, evaluating a brief anti-stigma campaign , described how there were not evident improvements for attitudinal or behavioural elements . Even inIn the results of the trend over time in subpopulations  with an increasing involvement of peer-workers and with increasing accessibility .