Detecting Alzheimer's disease (AD) and disease progression based on the patient's speech not the patient's speech data can aid non-invasive, cost-effective, real-time early diagnostic and repetitive monitoring in minimum time and effort using machine learning (ML) classification approaches. This paper aims to predict early AD diagnosis and evaluate stages of AD through exploratory analysis of acoustic features, non-stationarity, and non-linearity testing, and applying data augmentation techniques on spontaneous speech signals collected from AD and cognitively normal (CN) subjects. Evaluation of the proposed AD prediction and AD stages classification models using Random Forest classifier yielded accuracy rates of 82.2% and 71.5%. This will enrich the Alzheimer's research community with further understanding of methods to improve models for AD classification and addressing non-stationarity and non-linearity properties on audio features to determine the best-suited acoustic features for AD monitoring. Alzheimer's disease (AD) is a neurodegenerative disease that affects cognitive functions such as speech and language. AD is a progressive kind of dementia that gets worse over time. Dementia is a broad term that refers to conditions that affect memory, thinking, and behavior because of brain damage or diseases –3, and iData augmentation techniques were used to increase the amount of training data, avoiding overfitting, and improving the model's robustness. There is a need for cost-effective and repetitive monitoring methods for early detection of AD and prediction of disease progression. Classification based on acoustic features only was attempted in  and subjects suffering from Alzheimer's (“AD”), all of whom were asked to participate in a standard cognitive test for dementia known as the Cookie Theft picture test from the Boston Diagnostic Aphasia Exam . On an aThe proposed system was divided into seven main parts: Non-Linearity and Non-Stationarity Testing, Data Representation and Feature Analysis, Cross-Validation, Data Augmentation and ML Classification. Classifiers were evaluated using data set partitioning during a 10-fold cross-validation process. The first task involved AD classification with 2 classes (cn and ad), and the second task involved AD stages classification with 4 classes  that were separated based on observation only. The number of samples per class are as follows: {“cn”:76, “ad”:81 }. The number of samples for the AD stages classification was divided based on auditory observations. For the early stage (ad1) class, audio files were chosen from the 81 “ad” class based on the level of participants' rich vocabulary, and clarity, and participated in a meaningful conversation with the interviewer. They had an easier time expanding on the description of the cookie theft picture. In some cases, participants were challenged to find the right words and answered slower than normal (cn) participants. Participants in the intermediate (ad2) and advanced (ad3) stages were characterized based on the following criteria: Had more difficulty finding the right word, used familiar words repeatedly, described familiar objects rather than calling them by name, lost their train of thoughts easily, and had difficulty organizing words logically. Subjects who had longer pauses, slurred and unclear speech with a higher frustration were classified as advanced . See Figp-values of less than 0.05 suggest that the data does not follow the normal distribution. It indicates convincing evidence to reject the null hypothesis, and p-value below 0.05 indicates significant non-linearity  with a model order of 25. Larger detection ratio values (>2) indicate that a significant nonlinearity was detected, smaller values (0.5) indicate that no significant nonlinearity was detected and that any error not explained by the linear model is mostly noise, and values close to 1 indicate that the nonlinearity detection test is unreliable and that a weak nonlinearity may exist  and second-order statistics  of a signal do not change over time, it is said to be stationary , 25. Likinearity . It was ay exist . An ordeIn the data representation and visualization stage, spectrograms, and MFCCs were implemented. Small peaks are evident in the AD speech spectrogram shown in In the feature extraction stage, acoustical features were extracted from both training and testing speeches. Three classifiers that were trained on the audio features are Logistic Regression, SVM and Random Forest. Acoustic features with linear and non-linear expressions were derived directly from the training data's speech. The acoustic analysis parameters offer the advantage of objectively describing the voice. The sub laryngeal and laryngeal systems are finely controlled by phonation and voice quality. Features in  include Cross-validation is a method for evaluating a predictive model that divides the original sample into a training set and a validation/test set for training and evaluating the model. It is also a good strategy to avoid model overfitting . The oriData augmentation is a standard approach for increasing the amount of training data, helping avoid overfitting, and improving the model's robustness. For training, speech signal systems require a large database, and data augmentation can be extremely valuable when starting out with small data sets. Exposing the classifiers to alternative representations of the training samples makes the model less biased, more invariant, and robust to such transformations when attempting to generalize the model to new datasets –32. To oFor both AD/CN and Stages AD/CN classifications, three classification models were considered: Logistic Regression, SVM, and Random Forest. The audio files were divided into two categories: 70% for training, and 30% for testing and validation. For the first and second tasks, the best performing classifier in cross-validation was Random Forest.Three classifiers ) were evaluated in this study. For the first task, the best performing classifier in cross-validation was Random Forest, followed by SVM, and finally, Logistic Regression, achieving 82.2%, 78.6%, and 66.2% accuracy respectively for models containing the combination of acoustic features and data augmentation methods, respectively. For the second task, the best performing classifier in cross-validation was Random Forest, followed by SVM, and finally, Logistic Regression, achieving 71.5%, 65.2% and 56.2% accuracy respectively for a model containing the combination of acoustic features and data augmentation methods, respectively. For Tasks 1 and 2, Random Forest classifier model evaluation metrics (Accuracy (%), AUC (%), Recall (%), Precision (%)) before and after applying data augmentation methods are shown inTable 1.The results for AD vs. CN and AD Stages vs. CN classification tasks are summarized in Based on the confusion matrix of the RandomForest model for AD classification in This study involves exploratory data analysis to understand why machine learning models make the decisions they do, and why it matters. It was found that typically speech signals have a non-linear and a non-stationarity property. Signal segmentation was applied as a pre-processing step for non-stationarity signal analysis. Non-linearity property was handled by applying a large portion of acoustic features with a non-linear expression. As well, unlike traditional machine learning models, deep learning models require a lot of training data. We found that the most noticeable linguistic changes in recordings of AD patients from the ADReSS Challenge dataset are longer hesitations and a decreased speech rate in spontaneous speech by listening intently to the recordings of AD patients. Articulation, fluency , semantic fluency, and repetition were noted as linguistic measurements. Most AD patients had problems detecting and naming things when asked to describe the “Cookie Theft” image, and they used the same terminology to describe the image. According to , 35, theAccording to , in modeThe model can be used to screen and successfully distinguish between sick and healthy individuals and can further be applied to distinguish the stage of the disease. This framework can also accommodate any future changes, such as improvement to the generality of the classification results by using larger speech databases with a greater number of speakers. Implementing this diagnostic model to a telemedicine platform would provide patients with limited mobility and/or geographic limits access to specialists, making medical consultations and diagnostics more affordable and convenient . Further


Accurate evaluation of the risk of papillary thyroid microcarcinoma (PTMC) is the key to treatment. However, the maximum diameter (MD), which is currently used in various staging systems, may not truly reflect the aggressiveness of multifocal tumors.Clinical and pathological data for 1001 patients with papillary thyroid carcinoma who underwent surgery at the Hangzhou First People’s Hospital were retrospectively analyzed. First, the relationship between total tumor diameter (TTD) and clinicopathological features in multifocal PTMC was explored. Then, patients were divided into subgroups according to the TTD. The baseline was consistent after using the propensity score matching method, and the differences between groups were compared. In addition, the effectiveness of TTD and MD in evaluating central lymph node metastasis (CLNM) was analyzed and compared.TTD is associated with a range of clinicopathological features, including lymph node metastasis, extrathyroidal extension, and risk stratification. Assuming the same MD and number of foci, the invasiveness of multifocal PTMC with TTD >1 cm was significantly higher than that with TTD <1 cm, and even higher than unifocal non-PTMC. Moreover, the efficiency of TTD in predicting CLNM was also significantly higher than that of MD.For multifocal PTMC, TTD is a more realistic indicator of tumor biological characteristics than MD. The aggressiveness of PTMC with TTD >1 cm was significantly enhanced, and surgical treatment should be actively sought in such cases. Papillary thyroid microcarcinoma (PTMC) is defined as papillary thyroid carcinoma with the largest diameter ≤1 cm. In recent years, due to its high incidence rate but relatively benign biological behavior, concerns have been raised about overdiagnosis and overtreatment of PTMC. There is a growing debate about whether active surveillance (AS) or immediate surgery are the best approaches for PTMC treatment . The 201Multifocality is common in PTMC, with an incidence of 26.8–36.9% according to different sources –7. It haHowever, previous studies were retrospective studies under natural conditions, and related confounding factors, such as MD and number of foci, were not excluded. The present study sought to evaluate the relationship between TTD and PTMC using the propensity score matching (PSM) method in order to provide an updated and more comprehensive perspective for assessing the risk of PTMC.Data for pathologically confirmed PTC patients who underwent thyroid surgery in the Department of Surgical Oncology of Hangzhou First People’s Hospital between 2009 and 2020 were collected and reviewed. The exclusion criteria were as follows: 1. lack of pathological data; 2. combination with other malignant tumors; 3. second operation; 4. mixed PTC; and 5. prior non-curative surgery. The collected patient data included age, gender, MD, number of tumor foci, central lymph node metastasis (CLNM), lateral lymph node metastasis (LLNM), capsular invasion, and ETE. All of the above pathological data were independently reviewed by two experienced pathologists. In addition, all patients were assigned into low-, intermediate-, and high-risk groups based on tumor size, multifocal characteristic, lymph node involvement, and degree of ETE according to the 2015 ATA risk stratification system.In the present study, MD was defined as the diameter of the largest tumor focus for multifocal PTC or the primary tumor focus for unifocal PTC. Papillary thyroid carcinoma with MD >1 cm was termed non-PTMC. The multifocality was defined as two or more tumor foci within the unilateral thyroid. For multifocal PTC, TTD was defined as the total combined diameter of each tumor lesion within a lobe, and both lobes were counted separately. CLNM was defined as tumor metastasis in lymph nodes of level VI of the neck region after postoperative pathological diagnosis. LLNM was defined as tumor metastasis in lymph nodes of levels II, III, IV, and V of the neck region after postoperative pathological diagnosis. Capsular invasion was defined as the tumor involving the capsule but not breaking through after the diagnosis of postoperative pathology. ETE was defined as the tumor breaking through the thyroid capsule and invading surrounding tissues or organs. It was stratified into two levels: minimal extension  and gross extension .The above data were further screened and divided into three groups according to the tumor diameter and tumor multifocality as follows: Group A: multifocal PTMC with TTD ≤1 cm, Group B: multifocal PTMC with TTD >1 cm, and Group C: unifocal non-PTMC. A total of 1001 patients participated in the study, including 172 in group A, 388 in group B, and 441 in group C. The relationship between TTD and other clinicopathological features was explored first. PSM was performed based on age, sex, TTD, and number of foci between groups A and B to minimize the effect of confounders on the outcomes between these groups. In addition, PSM was also performed based on age, sex and TTD/MD between groups A and C. After reducing the impact of potential confounding factors, the clinicopathological features were compared between the groups.Preoperative diagnosis of CLNM is a challenge for clinical decision making. The present study performed univariate logistic regression analysis on CLNM, calculated the predictive efficacy of TTD and MD, plotted receiver operating characteristic (ROC) curve, and compared the area under the curve (AUC) values.via fine-needle aspiration biopsy or preoperative imaging and confirmed by the intraoperative frozen sections.All patients enrolled in the study underwent radical surgery. Thyroidectomy and cervical lymph node dissection were performed simultaneously. Ipsilateral lobe and isthmus resection were performed for unilateral lesions. Total thyroidectomy was carried out for unilateral lesions requiring iodine-131 and bilateral lesions. Central lymph node dissection was performed routinely. Lateral lymph node dissection was done in patients with cervical lymph node metastasis diagnosed Categorical variables were described using frequencies and percentages. Continuous variables were expressed as the mean ± standard deviation (mean ± SD). The chi-square test or Fisher’s exact test was used to analyze categorical variables, while the t-test was applied to compare continuous variables. The “matchit” package was used to perform PSM analysis. The nearest neighbor algorithm was used as the matching method, with the ratio set to 1:1 and the caliper value set to 0.02. R software  and MedCalc software  were used for all data analysis in the study. Bilateral P < 0.05 served as the significance threshold.The clinical and pathological features were analyzed and compared between each group before PSM. First, significant differences were present in all characteristics except age  for the publication of any potentially identifiable images or data included in this article. K-cJ, conception and design, provision of study materials or patients, data analysis and interpretation, and manuscript writing. BL, conception and design, provision of study materials or patients, data analysis and interpretation, and manuscript writing. L-qZ, provision of study materials or patients and manuscript writing. YZ, provision of study materials or patients and manuscript writing. D-cL, conception and design, administrative support, provision of study materials or patients, and manuscript writing. All authors contributed to the article and approved the submitted version.This work was supported by the Science and Technology Department of Zhejiang Province (Grant numbers GF22H165705), the Medical and Health Technology Project of Hangzhou (Grant number Z20210025), and the Zhejiang Provincial Medical and Health Technology Project (Grant number 2022KY939).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.


Exploratory factor analysis was used to identify dietary patterns. The relationship between dietary patterns and the risk of depression after four years was examined using logistic regression, and subgroup analysis was carried out to determine whether the association differed by gender. (3) Results: A total of 2873 older adults were included in our cohort study. Three dietary patterns were identified: vegetable–egg–bean–milk pattern, meat–fish pattern, and salt-preserved vegetable–garlic pattern. The vegetable–egg–beans–milk pattern was negatively correlated with the risk of geriatric depression development (adjusted OR = 0.65 (95%CI: 0.49–0.87)), and the salt-preserved vegetable–garlic pattern was positively associated with aged depression risk (adjusted OR = 1.33 (95CI: 1.00–1.77)). The meat–fish pattern was not associated with the risk of depression in older adults. These associations were consistent in both men and women. (4) Conclusions: In this cohort study, the vegetable–egg–beans–milk dietary pattern was associated with lower risk of depression, while the salt-preserved vegetable–garlic dietary pattern was associated with higher risk of depression, and there were no gender differences in these associations. Population aging has become a key social issue in China. According to the seventh National Census statistics, China’s population aged 60 and above has reached 260 million, accounting for 18.7% of the total population, with 190 million aged 65 and above accounting for 13.5% of the total population [Depression refers to emotional disorders centered on low mood, mainly manifesting as sadness, emptiness or irritability, accompanied by various cognitive and physical symptoms, and it is one of the common mental disorders in the elderly . In ChinCompared with young people, the condition of depression in the elderly is more likely to be modified by lifestyle factors ,7. As a Many studies have shown the association of certain foods or nutrients with depression ,12,13,14Due to the limited studies, we explored the longitudinal association between dietary patterns and the risk of depression in Chinese older adults based on the Chinese Longitudinal Health and Longevity Survey (CLHLS) cohort data from 2011 to 2014.The data in this cohort study were derived from the Chinese Longitudinal Healthy Longevity Survey . The CLHLS is an ongoing prospective cohort study of the elderly aged 60 years and above. A multi-stage cluster random sampling method was used to survey the elderly aged 60 and above and their adult children in 23 provinces of China. The baseline survey was conducted in 1998, followed by follow-up surveys in 2000, 2002, 2005, 2008–2009, 2011–2012, 2014 and 2017–2018.To reflect the latest dietary patterns and depression situation of Chinese older adults in CLHLS, our cohort study utilized the data from 2011 to 2014 due to the modification of the depression scale in the 2018 CLHLS questionnaire, which resulted in the inconsistency between the 2014 and 2018 depression scales. The study included dietary-related data, depression, sociodemographic information, physical health, and some chronic disease history of the subjects in the 2011–2014 cohort . After sAll subjects signed informed consent for baseline and follow-up surveys. The project was approved by the Biomedical Ethics Committee of Peking University, China (IRB00001052-13074).To determine the main dietary patterns, based on the 13 food groups in CLHLS research, we used the principal component analysis method of exploratory factor analysis, according to Kaiser’ criterion, factors with eigenvalues greater >1 were extracted, and an orthogonal transformation was performed to rotate the factors (varimax rotation) to simplify the structure and to obtain greater interpretability. The naming of dietary patterns was based on the characteristics of the food groups in each factor combined with the interpretation of previous studies.The factor scores for each pattern (dietary pattern score) were calculated by weighting the intake of food groups by their factor loadings. Higher dietary pattern scores indicated a higher preference for a specific dietary pattern. The subjects were divided into low-to high-tertile groups  based on their dietary pattern score in 2011.The PhenX (consensus measures for Phenotypes and eXposures) Toolkit was employed by CLHLS to assess depression (PhenX code: 120500). PhenX utilized the Composite International Diagnostic Interview Screening Scales (CIDI-SC), which was developed by the criteria of the Diagnostic and Statistical Manual of Mental Disorders . PhenX is a two-item, short self-report screening tool, which includes two levels of indicators, with a “yes” answer to any question indicating a representation of depression. This measurement has been applied to some previous studies ,27. The Question 1: Have you had a time in last 12 months when you felt sad, blue, or depressed for two weeks or more? Question 2: Have you had a time in last 12 months lasting two weeks or more when you lost interest in most things like hobbies, work, or activities that usually give you pleasure? We used the Spearman–Brown coefficient instead of using Cronbach’s alpha to assess the reliability of the Phen X . The SpeAccording to the previous studies, we included sociodemographic information , physical health, living habits (body mass index (BMI), alcohol consumption, smoking status, exercise), and the number of chronic diseases , arthritis, rheumatism or rheumatoid disease, dyslipidemia, etc.) at baseline as covariates of this study.The initial fundamental characteristics of the groups, including gender, age, region of residence, marital status, family income, living conditions, BMI, alcohol consumption status, smoking status, exercise and the number of chronic diseases, were examined using independent chi-square testing.OR) and their 95% confidence interval (CI) obtained from logistic regression. Two logistic models were built: the first one was adjusted for gender, age, marital status, region residence, family income and living conditions, and the second model was additionally adjusted for the rest of the variables described above. Adherence to the empirically derived dietary pattern was classified into tertiles, and the lowest tertile was used as the reference group. Because the conclusions of previous studies on male–female differences between dietary patterns and depression were inconsistent [The association between dietary patterns and risk of depression was summarized with odds ratios , indicating that the 13 food groups were not independent and were strongly correlated so that principal component analysis could be performed. Kaiser’ criterion finally identified three factors. The eigenvalues of the three factors after maximum rotation were 2.068, 1.708 and 1.627, respectively, and they explained 15.906%, 13.135% and 12.515% of the total variance; the cumulative contribution rate was 41.555% , meat–fish pattern (meat and fish), and salt-preserved vegetable–garlic pattern  .2. For the vegetable–egg–beans–milk pattern, there were differences in the distribution of age, region of residence, family income, living conditions, BMI, smoking status, alcohol consumption status, exercise and the number of chronic diseases. For the meat–fish pattern, there were differences in the distribution of gender, age, marital status, region of residence, family income, living conditions, BMI, smoking status, alcohol consumption status and exercise. For the salt-preserved vegetable–garlic pattern, there were differences in the distribution of gender, age, marital status, region of residence, family income (except for Tertile 1), living conditions, BMI, smoking status, alcohol consumption status and exercise , 46.26% were female, 82.25% were rural residents, and the mean BMI was 22.05 kg/mexercise .p < 0.001) . Subjects with the second tertile of the salt-preserved vegetable–garlic pattern score in 2014 had a higher risk of depression after 4 years than those in the lowest tertile . No association was observed between meat-fish pattern and depression.  and full (model 2) adjustments were rather similar. After controlling all the covariates, subjects in the second and third tertile of the vegetable–egg–beans–milk pattern score had a reduced risk of depression compared to subjects in the lowest tertile . As shown in p = 0.170).Subgroup analysis showed that the protective effect of the vegetable-egg-beans-milk pattern on depression was consistent in both men and women  and the risk of depression in women . It is wPrevious studies of the relationship between dietary patterns and depression have yielded inconsistent results regarding differences between men and women. A Japanese cross-sectional study reported that the plant-based food–fish product pattern and meat pattern were significantly associated with depression in men, but no association was observed in women . A crossMore randomized controlled trials are needed to further prove the validity of the dietary patterns explored in observational studies. Previous clinical trials have confirmed the effectiveness of the Mediterranean dietary pattern and nutritional supplements in improving depression ,55, but The strength of this study was that it was a 4-year cohort study rather than focusing only on cross-sectional dietary intake, which allowed us to investigate the impact of long-term dietary patterns on the risk of sensitivity to depression. Second, the CLHLS, which covers 23 provinces or municipalities, provided the data. These regions varied in geography, economic development, public resources and health indicators and were more representative of Chinese residents.Several limitations also existed in this study. First, all the answers to the questionnaire were self-reported by the subjects, which were prone to recall bias. Second, the questionnaire included only the frequency of food intake without the amount of food intake. The frequency may not completely match the total intake, but intake frequency may be more important than the intake amount . Third, In conclusion, our longitudinal study revealed that the vegetable–egg–beans–milk dietary pattern was associated with a lower risk of depression among Chinese older adults, as well as the salt-preserved vegetable–garlic dietary pattern was associated with a higher risk of depression. The meat–fish pattern was not found to associate with depression in the elderly. Moreover, there were no gender differences in these findings. This study provided evidence that a diet was conducive to preventing depression in the elderly.


Ultrasound has been confirmed as the propagation process of mechanical vibrations in a medium, with a frequency significantly higher than 20 kHz. Moreover, it has an effect of sterilization on foods. In general, ultrasonic sterilization medium is manifested as a liquid. Ultrasonic treatment technology has certain advantages in aquatic product processing. It is noteworthy that this technology will have better effects of sterilization if used in combination with other treatment methods. Slightly acidic electrolyzed water (SAEW) is characterized by high-efficiency broad-spectrum sterilization operation, low cost, and environmental protection, among other properties, and has a positive effect on aquatic product sterilization and preservation. Selecting acidic electrolyzed water with a low concentration coupled with low-power ultrasonic waves for combined sterilization exerts a more potent sterilization effect, and acidic electrolyzed water combined with ultrasonic sterilization is expected to be a potentially environment-friendly alternative. In this study, the sterilization mechanisms of ultrasonic and SAEW methods used both individually and as a synergistic treatment, the effect on microbial growth, and the research progress of the application of the combined effect in the sterilization and refrigeration of aquatic products are reviewed. Furthermore, this study looks forward to the future development trend, with a view to its application in aquatic products, while providing a reference for research and application in the field of processing and safety. Nutrients  abound in aquatic products . The actUltrasound refers to a mechanical wave with a significantly small wavelength, which is almost always less than 0.02 m (meters) in the air. It cannot exist in a vacuum , and its existence and reproduction are dependent on a medium. Ultrasound travels farther in water than in air, whereas it is very easy to lose and disperse in the air due to its small wavelength . Althoug2) residues in food, it is not required to be rinsed with clean water to save water, and there is little need to worry about mistakes in its usage as problems will not be caused. SAEW has been proved to be effective in destroying MRSA (Staphylococcus aureus), Escherichia coli, norovirus, and influenza virus.SAEW was electrolyzed with dilute hydrochloric acid of 2~6%, and its pH value was 5.0~6.5. It contained a concentration of accessible chlorine (HClO) of 10,000 to 30,000 mg/L, was colorless and odorless, and had a high bactericidal action. In the food field, compared with the currently commonly used bactericides such as sodium hypochlorite or alcohol, it can ensure safety, and has the characteristics of reducing cost and reducing environmental load ,12. CompIn this study, the sterilization mechanism of ultrasonic waves and SAEW used both separately and synergistically was investigated regarding its effect on microbial growth and the application of the combined effect in the sterilization of aquatic products was reviewed. In addition, the development trend for the foreseeable future was forecasted. The research and application in aquatic product processing and safety provide a reference, and also novel ideas for the expansion of sterilization and refrigeration technology.Ultrasonic refers to sound waves with a frequency greater than 20 kHz. It has a short wavelength and a high frequency. In addition to its good directionality and penetrating force, it has the potential to cause cavitation and several specific effects  . The cavWhen ultrasound acts on food, four effects are exerted: cavitation effect, mechanical effect, thermal effect, and free radical effect. To be specific, the first three effects are physical effects, and the free radical effect is a chemical effect ,18.The cavitation effect is explained as follows: a considerable number of small bubbles are produced when the ultrasonic wave is acting on the liquid . One reaThe mechanical effect of ultrasound is the most basic primary effect of ultrasound, regardless of the intensity of such effects. The mechanical effect of an ultrasonic wave comes from the wave moving forward in the medium, which is called the mechanical effect in the traveling wave field. In addition, the mechanical effect caused by the reflection of ultrasonic waves in the medium is called the mechanical effect in the standing wave field . The theThe cavitation effect primarily accounts for the ultrasonic sterilization effect. Factors affecting the inactivation of microorganisms by ultrasonic waves include ultrasonic parameters , the medium in which the bacteria are located, the time of ultrasonic action, and the types of microorganisms. Most microorganisms are completely or selectively eliminated ,32,33.Escherichia coli O157:H7 reaches 68.91% under the condition of ultrasonic power of 100 W and the power density of 50 W/cm2 for 420 s, and the ultrasonic treatment makes the E. coli O157:H7 cell membrane permeable. As a result, the antibacterial activity is significantly increased, the integrity of the cell membrane is destroyed, and proteins and DNA are leaked, and thus the metabolism-related enzyme activities are reduced. An in-depth study on the antibacterial mechanism has suggested that ultrasound is capable of producing free radicals, thus increasing intracellular oxidative stress, blocking the hexose phosphoric acid pathway, and inhibiting energy metabolism [LIN et al.  have sugtabolism .2). Some researchers have suggested that at moderate acoustic intensities (10 W/cm2), the release of cell wall polysaccharides is faster than that of intracellular proteins, with a reversed result at higher sonic levels (24 and 39 W/cm2). The above results reveal that the ultrasonic damage target shifted when the ultrasonic treatment intensity shifted between low and high [Wu et al.  investigand high . The coland high . The samEnterobacter aerogenes and Bacillus subtilis are destroyed through ultrasonic treatment (up to log 4.5 reduction). However, strains of Staphylococcus spp. do not change in any way. Furthermore, E. aerogenes suspension is more responsive to ultrasonic waves at the exponential development stage than at later stages. The existing study has suggested that microbes with larger, softer capsules are more resistant to ultrasonic inactivation methods. The structure of bacterial cells fundamentally accounts for their resistance to ultrasonic deactivation.Pedrós-Garrido et al.  treated Clostridium perfringens spores in beef slurry using power ultrasound. Spore thermal resistance in beef pulp remained unchanged at 353.15 K for 600 s. The same heat shock, paired with a 60 s ultrasound treatment, reduced C. perfringens spores in beef slurry by half. On that basis, they proposed a method of promoting C. perfringens spore heat inactivation, thus leading to shortened food processing times and improved food quality.Evelyn and Silva  increaseHowever, existing research has suggested that ultrasonic treatment under certain conditions is capable of reducing the growth of microorganisms in food, prolonging the food’s shelf life, without affecting, and in some cases improving, the quality of food . HoweverAs a novel type of bactericide, SAEW has the characteristics of low pH, high redox potential, and effective chlorine, which can kill bacteria quickly and widely . In the SAEW is a potential alternative to antibacterial detergents and is considered an environmentally beneficial disinfection method with the advantage of reducing the impact of residual chlorine on human health and safety compared with other disinfectants . The antS. putrefaciens and S. saprophyticus reaches 96% and 85%, respectively, at the ACC value of mildly acid electrolytic water of 60.0 mg/L. The results of scanning electron microscopy (SEM) indicated that SAEW disrupts cell morphology and structure. Furthermore, the formation of ROS is influenced by SAEW. Ultimately, the accumulation of ROS causes a cascade of physiological abnormalities within the cell, leading to bacterial death. Hao et al. [Escherichia coli, Staphylococcus aureus, and Bacillus subtilis). The result of experiments has suggested that the disinfection effect on the three studied strains rapidly diminished with increasing dilution of AEW and SAEW, as indicated by the existing research. When AEW is diluted 17 times, the number of live E. coli, Staphylococcus aureus, and Bacillus subtilis fell to 7.84, 7.34, and 7.90 log10 CFU / ml, respectively. Survival rates for E. coli, S. aureus, and Bacillus subtilis decreased to 7.96, 6.45, and 7.89 log10 CFU /mL, respectively, at the dilution of 47 times. In addition, the results demonstrate that SAEW is more effective against the above strains than AEW in terms of antibacterial efficacy. However, even when SAEW is diluted more than AEW, its disinfection efficiency is the same. Xuan et al. [Liu et al.  have sugo et al.  studied n et al.  suggesten et al.  investign et al. . FurtherEscherichia coli and Salmonella, are significantly reduced by SAEW treatment. Spores of botrytis cinerea, Botrytis cinerea, Bacillus anthracis, and Phytophthora capsicum cannot be cultured following treatment. Therefore, SAEW has strong broad-spectrum antibacterial and fungal activities.Through the above studies, it is found that microorganisms, such as 2), chlorine gas (Cl2), hypochlorite ion (ClO-), hypochlorous acid (HClO), and hydrochloric acid (HCl). Furthermore, positively charged ions (hydrogen and sodium) move to the cathode where they gain electrons to form hydrogen gas (H2) and sodium hydroxide (NaOH).The physicochemical properties of fungicides  affect the actual effect of fungicides ,55. PureThe chemical reactions:+ + Cl−, which in turn reacts with OH- to form hypochlorous acid (HOCI) and hydrochloric acid (HCl). Slightly acidic electrolytic water occurs after the REDOX reaction to generate water. The raw materials do not contain salt; thus, even after drying, the water will not cause harm related to the concentration and crystallization of salt.2), hypochlorite ion (−OCl), and hypochlorous acid (HClO). The strongest effect, the bactericidal ability of HClO, is about 80 times that of −OCl [Escherichia coli, Staphylococcus aureus, Salmonella, vibrio parahaemolyticus and Bacillus cereus) all exhibit the effects of considerable antibacterial activity [In a membraneless chamber, electrolyzing 2–6% dilute hydrochloric acid produces somewhat acidic electrolyzed water with a pH of 5.0–6.5. There are three forms of chlorine in SAEW: chlorine gas  has been shown to be inefficient for inactivating several bacterial species . High poExisting research has reported the combined use of ultrasound (US) and slightly acidic electrolyzed water (SAEW) to reduce targeted pathogens over the past few years. Under the mechanical, cavitation, and chemical effects of ultrasonic waves, micro-cracks can be generated in the cell membrane of microorganisms, and the cell membrane permeability can be changed. Cell necrosis or apoptosis is efficiently induced when SAEW is capable of easily reaching the inside of microorganism cells, thus resulting in the increased release of intracellular chemicals . In otheThe sterilization mechanism of ultrasonic waves combined with SAEW treatment can be preliminarily studied by comparing sterilization effects, determining sterilization targets, observing bacterial morphological changes under a scanning electron microscope, and observing bacterial biological characteristics through flow cytometry ,74. The In brief, the lethality rate is higher than that of ultrasonic or acidic electrolyzed water alone in the combination of acidic electrolyzed water with ultrasonic sterilization. Ultrasound may enhance the microbial sterilization mechanism of acidic electrolyzed water, thus making it easier for acidic electrolyzed water to penetrate and kill bacteria during ultrasonication. The schematic diagram is shown in Pseudomonas and Shewanella, are the most common spoilage germs in marine fish (mainly H2S-producing bacteria). Lan et al. [2S-producing bacteria and Pseudomonas increased during cold storage, following a similar growth pattern to TVC. The quantity of microorganisms grows as storage duration increases. On day 10, the Pseudomonas levels in the distilled water group had 7.0 log10 CFU/g, whereas the ultrasound, SAEW, and ultrasound + SAEW groups had 6.43, 5.49, and 4.89 log10 CFU/g, respectively. Park et al. [Escherichia coli and Vibrio parahaemolyticus in fresh-cut herring fillets, but did not affect their sensory quality. The synergistic effect exhibited by the combined treatment of ultrasonic waves and SAEW helps to ensure its sterilization and preservation effect on food, and helps to expand its application range in food sterilization and preservation.Gram-negative bacteria, particularly n et al.  discoverk et al.  found thIn brief, the synergistic treatment of ultrasonic waves and SAEW and the independent action of the two cause more serious damage to microorganisms, so as to achieve a better sterilization effect.From the above content, it can be seen that both ultrasonic waves and SAEW have a sterilization effect .Li et al.  researchAccordingly, combined ultrasonic and SAEW treatment has a powerful and efficient bactericidal impact on microorganisms, and the findings support the therapy’s antibacterial mechanism, ability to keep fish fresh, and prolong the shelf life of food.Ultrasonic treatment technology is capable of fully retaining the nutrients of aquatic products, and it shows the advantages of high efficiency and low energy consumption, consistent with consumers’ pursuit of a pollution-free, high-quality food consumption concept. SAEW is one of the most promising microbial control fungicides in the food industry, with strong broad-spectrum antibacterial and fungal activity. The synergistic treatment of ultrasonic waves and SAEW can exert a stronger sterilization effect than either treatment alone. Thus, this technology has promising prospects for development in the field of aquatic product processing.However, the ultrasonic sterilization technology is not mature at present, and faces numerous challenges in terms of large-scale promotion and application. There is a lack of relevant standards and technical parameters for ultrasonic treatment of different aquatic products. When low-intensity ultrasound is employed alone, the killing effect on microorganisms is limited. Moreover, slightly acid electrolyzed water, as a broad-spectrum and efficient bactericide, has been extensively employed to sterilize and disinfect of aquatic products. However, the bactericidal effect of SAEW is correlated with a wide variety of factors (e.g., the mass concentration of available chlorine and treatment time. Relevant parameters should be determined in accordance with the characteristics of different types of aquatic products.The combination of ultrasonic waves and SAEW with other physical, chemical, and biological technologies will be the future development trend of food sterilization and refrigeration technology to achieve rapid and effective sterilization, environmental protection, food quality improvement, and other purposes. Studying how to optimize the combination of sterilization and refrigeration technologies for different aquatic products and building the sterilization effect data can be beneficial to ensuring food safety and preventing adverse effects on aquatic product quality, while accelerating its industrialization and application.


Significance was set at p ≤ 0.001. A significant negative correlation of FA with age was observed in posterior thalamic radiation (PTR) (p< 0.001). A significant positive correlation between age and MD was observed in sagittal stratum (SS) (p< 0.001), between age and RD in PTR, SS, and retrolenticular internal capsule (p< 0.001), and between age and AD in the body of the corpus callosum (p< 0.001). There were no significant correlations of DTI parameters with educational level. According to our study, RD showed the richest correlations with age, out of all DTI metrics. FA, MD, and RD showed significant changes in the diffusivity of projection fibers, while AD presented diffusivity changes in the commissural fibers. The observed heterogeneity in diffusivity changes across the brain cannot be explained by a single aging gradient pattern, since it seems that different patterns of degradation are true for different fiber tracts that no currently available theory can globally explain age-related changes in the brain. Additional factors, such as the effect of somatosensory decline, should be included as one of the important covariables to the existing patterns.The current concept of brain aging proposes three gradient patterns of changes in white matter that occur during healthy brain aging: antero-posterior, supero-inferior, and the myelodegeneration-retrogenesis (or the “last-in-first-out”) concept. The aim of this study was to correlate white matter diffusivity measures  in healthy volunteers with chronological age and education level, in order to potentially incorporate the findings with proposed patterns of physiological brain aging. The study was performed on 75 healthy participants of both sexes, with an average age of 37.32 ± 11.91 years underwent brain magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI). DTI was performed using tract-based spatial statistics (TBSS), with the analysis of four parameters: FA, MD, RD, and AD. Skeletonized measures were averaged in 29 regions of interest in white matter. Correlations between age and DTI measures and between education-level and DTI measures were performed using Pearson's correlation test. To correct for multiple comparisons, we applied a Bonferroni correction to the  Healthy brain aging occurs as a result of numerous interconnected structural, chemical, and functional brain changes, and, in turn, can lead to a decline in cognitive function. Brain aging is associated with a decline in concentration, attention, and other executive functions, as well as global cognitive information processing . OptimalOver the years, many novel techniques of magnetic resonance imaging (MRI) were introduced in order to clarify the neuropathological process that lies behind neurological and psychiatric disorders. One of the most revolutionary techniques is diffusion-weighted imaging (DWI) which provides tissue contrast based on the magnitude of diffusion differences between water molecules . DiffusiThe concept of cortical disconnections has been confirmed in healthy brain aging , using this technique in previous studies –8. GivenThere are three proposed gradient patterns of white matter changes during healthy brain aging. The first is the antero-posterior pattern, with more extensive changes in the anterior/frontal parts of the brain preceding the posterior lobes . The secThe aim of this study was to correlate white matter DTI anisotropy and diffusivity measures  using TBSS in healthy volunteers, with chronological age and formal education level (expressed in years of education). The second aim was to determine whether the gradient pattern of white matter associations was consistent with any proposed patterns of physiological brain aging.p-value), β = 0.2 (correspondent to the ower of 80%), and r > 0.30, the required sample was 79), 75 participants, average age 37.32 ± 11.91 years  were included into analyses after undergoing whole brain magnetic resonance imaging (MRI) from July 2011 to April 2017 at the University of Novi Sad. Six data sets were excluded from the initial sample of 81 subjects due to technically inadequate quality. All the patients were cognitively screened using Mini-Mental State Examination (MMSE)  .Inclusion criteria were over 18 years of age, MMSE score over 24 , and right-handed. MMSE is a 30-point screening test for the global cognitive assessment, used for quick exclusion of subjects with signs of cognitive impairment. Right-handedness was based on the self-report of the preferred hand and on the results of the Waterloo Handedness Questionnaire (WHQ) . CriteriAll participants underwent an MRI of the brain on a 3T clinical scanner , using an 8-channel head array. Conventional MRI of the brain consisted of T1W sagittal spin echo , T2W transversal turbo spin echo , Fluid Attenuation Inversion Recovery (FLAIR) transversal , diffusion-weighted imaging (DWI) , T2W coronal turbo spin echo , and 3D T1W MPRAGE sagittal tomograms .Conventional MRI was necessary for obtaining anatomic information and detection of potential focal or diffuse brain lesions.2 and 1,500 s/mm2) from 64 diffusion-weighted directions each and two non-diffusion weighted volumes (at b0). The data were acquired at 2 mm isotropic resolution; the fold over direction was A-P with a P shift. Field-of-view was 230. DWI images were denoised using the LPCA filter and corrected for motion by linearly aligning all DWI volumes to the b 0 image. T1-weighted images were denoised using the non-local means filter and underwent N3 intensity inhomogeneity normalization, and brain extraction. Data sets that did not fulfill the quality control criteria were excluded from the analyses (three due to extreme EPI distortion and three due to skeleton misregistration). T1 images were linearly aligned to diffusion images, and diffusion images were then non-linearly warped to their respective T1-weighted scans to correct for echo-planar imaging (EPI) induced susceptibility artifacts.Diffusion tensor imaging was performed using MDDWI sequence  with two diffusion shells , mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) scalar maps were generated from corrected images .http://enigma.usc.edu/protocols/dti-protocols/)  technique from the FSL software package  and publtocols/) . Each sutocols/)  and the tocols/)  . Methods of descriptive and comparative statistics were used . After confirmation of normal distribution, correlations between age and DTI measures and between education-level and DTI measures were performed using Pearson's correlation test. Additionally, a partial correlation was performed between age and diffusivity changes in observed DTI parameters, with education as a control variable. Permutation tests for Pearson's correlations were performed for age and localization, education and localization, and for partial correlation, using education as a control variable. Gender differences were also explored using the p-values. Significance was set at p ≤ 0.001 .To correct for multiple comparisons, we applied a Bonferroni correction to the A total of 75 participants were included in the study, 53 men (70.7%) and 22 women (29.3%). No significant gender-related differences in white matter diffusivity metrics were observed. The average age of the participants was 37.32 ± 11.91 years (range 22–62). The average education level was 13.87 ± 2.38 years of formal education. MMSE scoring was 28.87 ± 1.14 points, no person scored lower than 26.p< 0.001 and on the right p = 0.001) (= 0.001) . All corp = 0.001) (= 0.001) . There wp< 0.001 and on the right p = 0.001, p< 0.001, and on the right p< 0.001, p = 0.001). There were no significant correlations of this parameter with the level of formal education or the MMSE score  in healthy volunteers with chronological age and formal education level. Additionally, we aimed to determine whether the gradient pattern of these associations was consistent with any of the proposed physiological brain aging patterns.via the retrolenticular part of the IC toward the parietal and occipital cortices. The function of this tract is primarily somatosensory    tracts) , 29. The tracts) . The dec tracts) , patient tracts) , methamp tracts) , and chi tracts) . An inte tracts) , supportA significant increase in MD with advancing age was observed in the SS on the left side. This tract is positioned in the deep lateral aspect of the cerebral hemisphere and organized into three layers: superficial , middle , and deep (fibers of optic radiation) . It is iA significant increase in RD with advanced age was detected in the PTR, SS, and RLIC. RLIC is positioned dorsally to the corticospinal and corticopontineus tracts but represents a functionally separate entity because it carries parts of optic radiation, proximal part of PTR, and occipito-tectal and occipito-pontine fibers. Since the increase in this parameter was observed in the PTR and RLIC, it is clear that, along with the close anatomic relationship, there is also a functional connection between these two structures, mainly in the somatosensory information transmission. SS is also functionally associated with the latter two tracts. Disturbances in the diffusivity of RLIC have been priorly observed in depression , bipolarA significant increase in AD with advancing age was detected in BCC. The corpus callosum is the biggest commissural tract that connects corresponding regions of cerebral hemispheres. Different parts of CC are included in the transmission of various information, with premotor and supplementary motor fibers of the cortex located in the body 409. Madden et al. did not show differences in AD with advanced age . HoweverIt is interesting to note that FA, MD, and RD were associated with the diffusivity changes in projection tracts . On the contrary, the AD was associated with diffusivity changes in commissural tracts, connecting two hemispheres. In a recent longitudinal study, that followed healthy participants aged 50–84 years  during the follow-up period of 7 years, showed the most prominent changes in the FA and RD in commissural and projection tracts . It is pLittle is known about the oligodendrocyte dynamics and myelin sheath remodeling in the mature brain. However, recent studies confirmed that sensory enrichment could induce experience-dependent myelination and robustly increase the integration of oligodendrocytes . ReverseIt is interesting to see the overlap in the DTI metrics changes observed in specific tracts, which could potentially clear the etiology of age-related changes. We tried to group the differences in DTI metrics in the following patterns, as shown in Finally, no significant gender differences related to white matter diffusivity metrics were detected . HoweverHeterogeneity in findings in diffusivity changes across the brain, in our opinion, cannot be explained by one single gradient of physiological brain aging. It seems that different patterns of degradation are true for different fiber tracts in the brain and that no currently available theory can globally explain age-related changes in the brain. Furthermore, the effect of somatosensory decline should be included as one of the important covariables in the existing patterns.In addition, a recent study by Behler et al. showed that diffusion properties of most white matter tracts in a healthy aging brain followed a triphasic pattern , so that non-linear age correction should be applied to most of the tracts. Cerebellar tracts (superior and middle cerebellar pedunculi) showed basically no change over time ; optic radiation and anterior limb of the internal capsule showed linear regression with age, meaning that non-linear age correction is not necessary .There are some limitations to the study performed. Even though the number of participants was justified by the power analysis, it is possible that some correlations would have shown to be significant if the study sample were larger, and this might be resolved in a future study. However, it is important to highlight that the exclusion criterion for our study sample was the presence of white matter lesions including white matter hyperintensities (WMH) which represents a pertinent factor for the assessment of the changes in the white matter related to aging.The second limitation of the study was the lack of a detailed neurocognitive assessment of our participants (only a screening cognitive test was performed as a part of the exclusion criteria). MMSE scoring test represents a screening test, of high clinical importance, but is not sensitive enough for the cases of early cognitive impairment, thus, in our opinion, suitable for the exclusion of cognitively challenged persons, but not suitable for detailed correlations. Some of the tracts we analyzed are known to be associated with affect and personality features, which means that additional assessment of depression and anxiety would be recommendable.An additional limitation is a cross-sectional evaluation and the lack of longitudinal design, since the changes in diffusivity measurements may follow certain trajectories during chronological aging in an individual.It is necessary to point out that the maturation of the fibers does not follow the identical dynamics in all observed tracts. Some of the tracts  reach the full maturity  between 20 and 40 years of age . In one The final  limitation of the study is the lack of information on prematurity, which could also influence the changes in tract diffusivity (CC in the first place) .Even though there were no significant comorbidities noted in the study sample, it will be reasonable to include additional information on metabolic function  and lifestyle in the future studies , 53.It is also worth mentioning that advanced techniques for evaluation of DWI data could provide more detailed information than the DTI option  and addeAll four DTI metrics showed significant correlations with the advancing age of healthy participants . According to our study, RD showed the richest correlations with age, out of all DTI metrics. FA, MD, and RD showed significant changes in the diffusivity of projection fibers, while AD presented diffusivity changes in the commissural fibers.It is important to realize that all four DTI metrics are necessary for the assessment of healthy brain aging effect on white matter integrity, given that routinely analyzed parameters (FA and MD) do not allow complete insight into diffusivity changes. Since the changes in the white matter integrity that we observed during healthy aging also overlap with changes observed in several pathological conditions—psychiatric disorders, traumatic lesions, and dementia/MCI—caution is necessary when interpreting these differences in a healthy individual. In such cases, a longitudinal follow-up is necessary to track the trajectories of degenerative changes associated with the aging brain.Finally, the observed heterogeneity in diffusivity changes across the brain, in our opinion, cannot be explained by a single aging pattern . It seems that different patterns of degradation are true for different fiber tracts in the brain and that no currently available theory can globally explain age-related changes in the brain. Some additional factors, such as the effect of somatosensory decline, should be included as one of the important covariables in the existing patterns.The raw data supporting the conclusions of this article will be made available by the authors, withoutundue reservation.The studies involving human participants were reviewed and approved by Ethical Committee of Faculty of Medicine University of Novi Sad. The patients/participants provided their written informed consent to participate in this study.JB drafted the article. JB, MT, NB, DL, NJ, and TN were involved in acquisition, collection, and analysis of the data. DK, MT, and ML performed critical revision of intellectual content. All authors saw and approved the final version of drafted manuscript.TN and NJ were funded, in part, by NIH grants: R01 AG059874, U54 EB020403, T32 AG058507, and U01 AG068057. The authors also received partial grant support from Biogen, Inc., for research unrelated to this work. JB, DK, and DL were funded by Provincial Secretariat for Higher Education and scientific Research, grant No. 142-451-2600/2021-01.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.


Family functioning has been found to significantly impact each family member’s health mentally, physically, and socially. A number of the research has focused on the impact of impaired family functioning in general, but limited studies explore family functioning in the vulnerable period, early pregnancy. Therefore, the study aimed to investigate the characteristics and related factors in Chinese females and partners during early pregnancy.The cross-sectional study enrolled 226 pregnant women and 166 partners. Assessment tools included the McMaster Family Assessment Device (FAD), Edinburgh Postnatal Depression Scale, Patient Health Questionnaire-9, Generalized Anxiety Disorder 7-Item, Social Support Rating Scale, and Quality of Life Enjoyment and Satisfaction Questionnaire, Short Form. Correlation analysis was applied to investigate the related factors.In the present study, FAD-Behavior Control (BC) was the only dysfunctional dimension and had the highest dysfunctional rates than other dimensions. Length of time living with a partner, depressive and anxious symptoms, and quality of life were all associated with the dysfunctional family functioning of BC.The study reinforced the important clues of family functioning during early pregnancy. Also, it provided new entry points for the general population and healthcare providers to minimize the negative impact that impaired family function might bring to a family. Of particular note is that contextual theory suggests that personal development and family functioning are viewed as adaptive processes to external challenges in biological, perceptual, cognitive, behavioral, and interpersonal perspectives . PregnanGenerally, family functioning is found to influence people’s health mentally and socially and is associated with mood disorders. According to previous research, impaired family functioning is likely to increase the risk of depression and is associated with anxiety . Not onlFurthermore, earlier studies have identified the importance of dimensions in family functioning. CM and GF of family functioning could directly predict anxiety in the general population , and fouHowever, limited research has been conducted in early pregnancy groups. Thus, this study aimed to explore the characteristics of family functioning in early pregnancy among Chinese women and partners and to examine the associated factors simultaneously. Recognizing and promoting an understanding of the underlying characteristics of family functioning during pregnancy will facilitate the development of more effective family interventions for early pregnant families.2.2.1.+6 weeks. Subjects with a current or any history of mental disorders , psychoactive substance dependence, and organic brain disease or severe physical illness  were excluded from this study. Each participant signed an informed consent form, and the ethics committee approved the study.Pregnant females and partners were recruited from the outpatient clinic from December 2020 to July 2021. Except for 37 females who were excluded based on the exclusion criteria and 20 females with incomplete information, the current study sample comprised 226 pregnant women in total. One hundred and sixty-six partners participated in the study, except the 25 partners excluded based on the exclusion criteria and 6 partners with incomplete information. Following the inclusion criteria, we included participants who were ethnic Han, right-handed, received junior high school education or above, and lived with a partner. For pregnant females, we only included those aged 18–40 who were pregnant within 132.2.2.2.1.Compared to the other scales used to assess family functioning, such as the Family Intimacy and Adaptability Scale, Family Environment Scale, Family Adaptation, Partnership, Growth, Affection, Resolve Questionnaire, and so on, the McMaster Family Assessment Device (FAD) is widely used and allows for a more comprehensive assessment of family functioning. Therefore, in the current study, the FAD was used to assess pregnant females’ and male partners’ family functioning. The scale was developed by Epstein et al. in 1983 based on the MMFF theory , which iFamily assessment device-problem solving (FAD-PS) includes six items evaluating the family’s ability to resolve problems and effective functioning . FAD-CM focuses on the effectiveness of verbal information exchange within the family , which is consistent with nine items that measure whether they understand each other’s concerns and talk about their emotions and thoughts directly. In addition, FAD-RL is defined as repetitive patterns of behavior in which individuals performed family functions . FAD-AR evaluates family members’ responses to emotional stimuli with appropriate quality and quantity in feelings  and focuses on whether family members express their emotions in front of everyone and if the family’s intimate and attentive connection is essential. FAD-AI evaluates the extent to which families show interest in and value the activities and interests of family members . FAD-BC dimension evaluates the behavior pattern from three perspectives: situations involved in physical danger, psychobiological needs, and social behavior , precisely, the sub-scale asks people to assess whether or not they felt helpless when an accident happened, whether there is a rigorous principle that could not be disobeyed, and if family members had their regulations in life to obey. Lastly, FAD-GF focuses on 12 items , which includes whether family members support and trust each other and whether they have been supported to be who they are original and make decisions together in a harmonious environment.The score for each subscale is equal to the average for each item, ranging from 1.0 to 4.0 points, with higher scores indicating poorer family functioning. The cut-off scores include FAD-PS > 2.20, FAD-CM > 2.20, FAD-RL > 2.30, FAD-AR > 2.20, FAD-AI>2.10, FAD-BC > 1.90, and FAD-GF > 2.00. In the present study, a higher subscale score than the cut-off score was defined as dysfunctional family functioning for that dimension .2.2.2.Considering the potential relationship between family functioning and anxious and depressive symptoms based on previous research, the Edinburgh Postnatal Depression Scale (EPDS) and Patient Health Questionnaire-9 (PHQ-9) were used to evaluate pregnant females’ and male partners’ depressive symptoms, respectively. Generalized Anxiety Disorder-7 (GAD-7) was used to assess anxious symptoms. Those three scales are commonly used in clinical practice and show good reliability and validity.2.2.3.Psychosocial factors such as social support and quality of life may be associated with family functioning according to previous research. In the present study, pregnant females have been assessed by the Social Support Rating Scale (SSRS) to measure self-reported social support , and Qua2.3.n (%) in different categories. One sample t-test, two independent samples t-test, Chi-square test, Mann–Whitney U test, Spearman correlation and partial correlation analysis were used to investigate participants’ family functioning characteristics and related factors. Statistical significance was set as a two-tailed p < 0.05.The statistical analyses were performed on IBM SPSS for Windows, version 20.0 . Data are presented in mean , median , or 3.3.1.As shown in In clinical characteristics, we found that 5.3% of females and 54.2% of males were involved in a drinking history, defined as consuming an alcoholic beverage at least once per month on average, 3 months before pregnancy. Meanwhile, 4.9% of females and 47.6% of males involved a smoking history, defined as smoking tobacco products at least once a day for a month or longer before pregnancy. More than half of females (63.3%) and male partners (60.8%) consider current pregnancy as planned. Additionally, median scores of EPDS, PHQ-9, and GAD-7 in participants were all less than 10 points.3.2.p < 0.01). The mean scores of FAD-BC were higher than the cut-off scores . Meanwhile, we analyzed the proportion of pregnant females with healthy and dysfunctional FAD subscales, and data was presented in In pregnant females, as shown in p < 0.01) were also below the cut-off scores. Mean scores of FAD-BC  were higher than the cut-off score, too. However, scores of FAD-AI showed no statistical difference with the cut-off score . Meanwhile, data on the proportion of partners with healthy and dysfunctional FAD subscales were presented in In males, the mean scores of FAD-PS, CM, RL, AR, and GF .Differences in demographic and clinical characteristics between healthy and dysfunctional FAD-BC groups in participants were presented in r = −0.165, 0.195, 0.148, and − 0.231, respectively; all p < 0.05). In male partners, the total scores of PHQ-9 and GAD-7 were both positively associated with the scores of dysfunctional FAD-BC .Factors related to dysfunctional FAD-BC in participants were shown in 4.Numerous studies have acknowledged the negative impact of family dysfunction on the general population or individuals with mental disorders, but the understanding of family functioning in early pregnancy remains unclear. Based on the established knowledge of the special family functioning problems, this study focused on the characteristics of family functioning in early pregnancy and associated factors with promoting a basic understanding of family functioning in pregnant women and their partners.In this study, BC was the only dimension of family functioning that was dysfunctional in participants. In particular, the rate of dysfunctional BC was the highest and prominently exceeded that of healthy BC both in pregnant women and partners compared to other dimensions. According to the MMFF theory, family functioning of BC refers to family patterns that deal with family members’ behaviors to meet and express needs and motivations in risky situations or social environments, including “We do not know what to do when an emergency comes up” “If the rules are broken, we do not know what to expect” “There are rules about dealing with dangerous situations” and so on . FindingImproving the quality of family functioning are likely to promote mental health among family members. In the present study, early-pregnancy females and males with poor family functioning of BC showed more severe depressive and anxious symptoms. Available evidence supported the finding, as researchers revealed that family dysfunction is an accompaniment of an acute depressive episode commonly, and consistently impaired family functioning might influence the course and severity of depression . Family Additionally, dysfunctional BC was negatively associated with the time lived with a partner and the quality of life in females. It indicates that the longer females and their partners live together, the better the family functioning of BC might have. Traditionally, Chinese culture values the continuity of ethnicity and bloodline. Newly married couples are likely expected to have a pregnancy at an early stage after marriage . Even thIn sum, the results of the present study highlighted that maintaining good family functioning in BC might be a challenge for women and partners during early pregnancy, which requires more clinical attention and health education. It also provided insight into improving family wellness and pinpointing guidelines to promote family functioning during early pregnancy.5.Although this study found some clinically significant results, it still had the following shortcomings. Firstly, it was a cross-sectional study that could not reveal the characteristics of changes in family functioning during pregnancy. Secondly, there might be some differences and correlations in family functioning between pregnant females and partners generally. For example, in the current study, the mean score of FAD-AI in females was significantly below the cut-off score while there was no statistical significance in partners. Considering some partners of pregnant women failed to participate in the present study, we could not examine the themes mentioned above in the form of maternal-partner pairs because this paired format may better facilitate the exploration of differences and correlations. Thirdly, the data collection from partners in this study was primarily conducted online, given the relative complexity of completing the SSRS and Q-LES-Q-SF scales that may require on-site instruction, so in this case, partners’ social support and quality of life were not assessed. Additionally, factors related to family functioning included in this paper were not comprehensive. In general, the maternal pressures and opinions are different from their partners, especially in caring baby, and these may also further impact the family function, which was not explored in this study and needed to be included in the future.6.Early pregnancy is a vulnerable period of dysfunctional family functioning. The current study revealed that the dysfunctional family functioning of BC was most prominent both in females and partners in early pregnancy. Length of time living with a partner, depressive and anxious symptoms, and quality of life were associated with dysfunctional family functioning of BC in this period. The findings in this research highlighted the need for public and clinical awareness of family functioning during early pregnancy and underlined a possible guideline for family education for this period.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by The Second Xiangya Hospital of Central South University. The patients/participants provided their written informed consent to participate in this study.LL, YZ, BL, and XQ contributed to the study’s conception and design. XQ, SX, MM, XF, XN, JL, YJ, LZ, and BL are responsible for participant recruitment and data collection. XQ and WZ did the data analysis and wrote the first draft of the manuscript and revisions. BL, XQ, YZ, and HL contributed substantial revisions to the manuscript. All authors contributed to the article and approved the submitted version.The work has been supported by The National Natural Science Foundation of China (82001437 and 82171518); and the Key Program of Hunan Health Commission (202205033887). The funding sources had no role in the study design, data collection and analysis, interpretation of the data, preparation and approval of the manuscript, and decision to submit the manuscript for publication.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.


Heavy metal pollution creates environmental health concerns. Among these, iron (Fe), copper (Cu) and manganese (Mn) are commonly found in aquatic environments due to the release of wastewaters. Phytoremediation in hydroponics uses macrophytes to treat contaminated environments, and this is influenced by environmental factors. However, the relationship between these factors and the removal of Fe, Cu and Mn by macrophytes is not known. Therefore, a meta-analysis serves to determine the correlations between environmental factors and the removal of these metals in real wastewater by macrophytes, as well as to identify the role of different aquatic forms of macrophytes in phytoremediation. Emergent macrophytes had higher concentrations of manganese in their tissues, and higher bioconcentrations factor of iron and manganese than floating plants. Regardless of the biotope, higher concentrations of Fe and Cu decreased the ability of plants to bioconcentrate them. The correlations among exposure time, pH, dissolved oxygen, nitrogen, phosphorus, photoperiod and metal phytoremediation by plants were also found. It can be concluded that the emergent macrophytes showed better performance in terms of the removal of Fe, Cu and Mn, and that the significant correlations between environmental factors and removal vary with the type of metal and the environmental factor analyzed. Urbanization, industrialization and increased extension of agricultural practices have been proportional to the increase in surface and/or groundwater pollution through the release of wastewater . Heavy mIron (Fe), copper (Cu) and manganese (Mn) are metals commonly found in aquatic environments. In proper concentrations, these metals play an essential role in plant metabolism ,8,9,10. Some heavy metals, as they are not part of metabolism, are non-essential in living beings  . Thus, iDaphnia magna wastewater, N, P, photoperiod, DO and exposure time.Furthermore, we excluded studies that involved the biomonitoring of streams or lakes; those that did not provide or in which it was not possible to calculate the bioconcentration factor (BCF); those that studied, in association, two or more macrophytes in the same hydroponic tank; and those that used nonhydroponic constructed wetlands (CWs). The information extracted from the studies were BCF, [HM]For the analysis of data integration, it was assumed that the studies conducted in different locations with different plant growth habits were independent . Studiesroot) and the aerial parts , the sum of BCFroot and BCFaerial was considered to be the plant’s BCF d points . The datce level ,45.The normality of the distribution  was checked beforehand. Correlations were examined when there were at least seven pairs of interactions and were always for the entire plant regardless of the type of structural habitat . Fisher’plant for the same metal according to the nonparametric Mann–Whitney test (α = 0.05). Data in graphs and figures were extracted using Image J software “https://imagej.nih.gov/ij/ (accessed on 11 July 2022)”, and statistical analyses were performed with GraphPrism v.6 .The species were categorized into emergent and floating biotopes, and differences in their Fe, Cu, and Mn uptake were verified. For this purpose, comparisons were made between the two biotopes in terms of the uptake, ln(BCF) and ln[HM]In total, 225 publications were selected from Scopus (72 publications) and Web of Science (153 publications). Of this total, 13 studies met the selection criteria . All stuThe wastewaters studied were domestic  and industrial . In addition, 13 families  and 16 sLemna minor (Lemnaceae) and Pistia stratiotes (Araceae) were the most frequently studied, with four studies each. In addition, the concentrations of the three metals in the wastewaters ranged across 0.104–22.91, 0.032–4.64 and 0.007–230 mg L−1 for iron, copper and manganese, respectively. Some studies performed phytoremediation in more than one type of wastewater but independently plant and ln(BCF), respectively, all the others showed high CVs, some higher than 300%, as in the case of ln[HM]plant for the floating macrophytes used for phytoremediation of copper-contaminated waters. Despite this, all statistical analyses were performed with all data, without excluding the outliers.Overall, the bioconcentration factors, expressed as ln(BCF), and the concentrations of metals in plant tissues, expressed as ln[HM]plant values among roots, aerial parts (leaves/stems) and whole plants for each metal, according to the Kruskal–Wallis nonparametric test at 5% significance (data not shown).The most and least frequently reported metals were copper and manganese, respectively . The lna,b. In gn = 21, median = 2.756, minimum = −0.555, maximum = 9.998), 2.008  and 2.122 , respectively.The ln(BCF) data for iron, copper and manganese showed, regardless of the family type or biotope, means (µ) of 3.462 (Acorus gramineus), Cyperaceae  and Apiaceae (Centella asiatica), which were reported only once, in works that studied the removal of these metals in wastewaters from the pulp and paper industry plant < 0) and mainly among the floating macrophytes , Cyperaceae  and Apiaceae (Centella asiatica) in studies on the removal of these metals in wastewaters from the pulp and paper industry plant: −2.068) [The species were subgrouped into floating and emergent biotopes and showed differences between the two biotopes in the ranked mean comparison values (mean rank) of ln(BCF) and ln[HM]ificance . The sub −2.068) .p ≤ 0.05) between the two biotopes for iron and manganese  only for manganese when compared with the floating species.To sum up, emergent macrophytes had the highest ranked mean ln(BCF) values relative to floating macrophytes, with significant differences , N, P and DO concentrations, and the photoperiod were correlated with the responses ln(BCF), ln[HM]plant and %R (s) (p ≤ 0.05), with positive values of 0.727 (ln(BCF)) and 0.649 (ln[HM]plant) for iron and 0.462 (ln[HM]plant) for copper. On the other hand, for the photoperiod, there was a strong negative correlation with at least one of the three measured responses for all three metals, with rs values between −0.437 and −0.760 for Fe, Cu and Mn , reported by the parameters [HM]t and %R . The expu and Mn . Spearmap ≤ 0.05) for copper, which correlated positively or negatively with all factors except for nitrogen in terms of ln(BCF), ln[HM]plant or %R. Furthermore, for iron, only the exposure time and the concentration of the metal in the wastewater influenced the values of %R, ln(BCF) and ln[HM]plants. For manganese, only pH, exposure time and photoperiod correlated significantly with at least one of the measured responses ln(BCF), ln[HM]plant or %R. In this case, the smaller number of environmental factors with significant correlations for Fe and especially for Mn can be attributed to the smaller sample sizes plant. The same behavior was obtained for dissolved oxygen, with coefficients of 0.506 for ln(BCF) and 0.526 for the correlation with ln[HM]plant. There were no correlations between the parameter of nitrogen concentration with ln(BCF), ln[HM]plant or %R for any of the metals.For the macronutrients nitrogen and phosphorus, only the concentration of phosphorus and copper correlated (p ≤ 0.05) was obtained between [HM]wastewater and %R for iron, with rs = 0.876. On the other hand, the strongest negative correlation (p ≤ 0.05) was obtained between photoperiod and ln(BCF) for manganese with rs = −0.760. Comparisons of the order of magnitude between the significant coefficients indicated differences between the coefficients of photoperiod (−0.437) and [HM]wastewater (0.876) and %R for the metal Fe (p ≤ 0.05). On the other hand, for ln[HM]plant of the metal Cu, there were differences (p ≤ 0.05) between the correlation coefficients of DO (0.526), photoperiod (−0.627) and time (0.462) (A strong positive correlation ( (0.462) .plant, indicates how much of the metal was present in the plant tissue at harvest time est time . Howeverest time . A plantest time .plant for all three metals, as shown in Overall, among the families, emergent macrophytes showed the highest mean values of ln(BCF) and ln[HM]However, the individual performance of a macrophyte in the phytoremediation of contaminated water may vary depending on the type of wastewater and the environmental conditions of the experiments . When weFurthermore, among the metals, copper and manganese presented the lowest mobility from the wastewater to the plant tissues, with the lowest mean values of ln(BCF). Except for the macrophytes with emergent habits, all floating macrophytes presented ln(BCF) values lower than 6.9, indicating the low uptake capacity of these two metals by these macrophytes. An ln(BCF) value of less than 6.9, which corresponds to a BCF value of <1000, indicates the low capacity of plants to bioconcentrate an element in their tissues .2+), in which plants require it, is sensitively dependent on the optimal supply regulated by Mn transporters in the rhizosphere plant of copper. On the other hand, in none of the metals were there any correlations (p ≤ 0.05) of N with the variables of ln(BCF), ln[HM]plant and (%R), which indicates that nitrogen does not seem to affect the removal and/or uptake of Fe, Cu and Mn from real wastewater treated by macrophytes.Phosphorus and dissolved oxygen correlated significantly , which might makes them more able to remove pollutants .p ≤ 0.05) were found  affected the removal and uptake of Fe, Cu and Mn, but with significant correlations that varied with the type of metal and the parameter analyzed. However, it is important to verify the magnitude of the coefficient to the correlated variable. The magnitude does not depend on the correlation’s sign but on the sample size (n) used for the correlation [It was observed in the meta-analysis that the environmental factors ([HM]relation .p ≤ 0.05). For example, for the ln(BCF) of iron, there were no differences between the coefficients of time (0.727) and [HM]wastewater (−0.703) regarding the ability of macrophytes to bioconcentrate this metal in their tissues  and DO (0.526) even though they were coefficients with strong correlations.For this purpose, comparisons were made between the significant coefficients of the environmental factors with the same correlated variable. In almost all of them, there were no significant differences according to Fisher’s Z-test of transformation  on the relationship between factors in the physical and aqueous environments and the removal of Fe, Cu, and Mn from real wastewater through phytoremediation using hydroponically grown floating, emergent and submerged macrophytes. Emergent macrophytes, although less often reported, showed higher mean ln(BCF) values for iron and manganese, and higher ln[HM]In addition, Cu and Mn showed less mobility from the wastewater to plant tissues, regardless of the biotope. There were significant correlations between the factors of the physical medium (exposure time and photoperiod) and the wastewater , but in different ways: Regardless of the aquatic form of the macrophytes, higher initial concentrations of Fe and Cu in the effluent decreased the ability of plants to bioconcentrate them in their plant tissues.(i)Shorter exposure times or test durations increased the removal of Fe, Cu and Mn from the wastewater, but hindered the uptake of Fe and Cu.(ii)Shorter daylengths increased the plants’ ability to absorb the three metals and remove them from the wastewater.(iii)Lower pH increased the removal of Cu and Mn from the wastewater, but decreased the uptake of Mn.(iv)Higher concentrations of P and DO increased the uptake and concentration of Cu in plant tissues.


However, neither giving touch nor resting HRV was a significant predictor of loneliness. The current study highlights specific psychosocial factors in healthy adults that should be considered as promising pathways in order to reduce or work toward preventing loneliness, thus promoting better health and well-being.Loneliness has emerged as a public health concern. Previous research has reported its deleterious effects on physical and mental health; however, some specific psychophysiological mechanisms in healthy adults remain to be elucidated. The aim of the current study is to investigate whether self-reported social support and social touch , as well as resting heart rate variability (HRV), are significant negative predictors of loneliness in healthy adults. The study sample consists of 120 healthy students  with a mean age of 21.85 years old (DP= 2.21). The students were asked to complete a psychiatric screening questionnaire utilizing loneliness, social support, and social touch scales. HRV was derived from an electrocardiographic signal recorded for 15 min, with the participant relaxed in a supine position. Linear regression analyses were conducted to evaluate loneliness as a function of social support, social touch (giving or receiving touch), and resting HRV. The results show that social support ( Many years of research have revealed the potential consequences of social isolation for human beings  to study social engagement Porges, . HRV is Solving the question of loneliness is a major challenge, especially considering the occurrence of social isolation during the COVID-19 pandemic and the possibility of future pandemics. Cacioppo and Cacioppo  argue thThe sample comprised of 120 undergraduate students  with a mean age of 21.85 years old (DP = 2.21). Participants were recruited according to the following criteria: age ranging from 18 to 30 years, being an undergraduate or graduate student, not being under medication (except for contraceptives), not having a diagnosis of psychiatric or heart disease, being a non-smoker, and not using alcohol or drugs with daily or almost daily frequency. The study protocol was approved by the Research Ethics Committee of the local institution and all participants provided written informed consent. Data were collected prior to the COVID-19 outbreak.Initially, participants completed a health and lifestyle questionnaire to evaluate data on age, sex, exercise practice, medication use, caffeine ingestion, and physical health. The mental health status of the participants was assessed using the Psychiatric Screening Questionnaire (PSQ)  signal processing. One PC-compatible computer was used for ECG acquisition using the Acknowledge  software program. The signal recording was performed using reusable 8 mm electrodes (Ag/AgCl) in the 1st cardiac lead through an electrocardiograph ECG100C module coupled to the MP100 system  at a sampling frequency of 1000 Hz with the participant relaxed in the supine position. We decided to measure HRV in the supine position because our record lasted 15 min, and we believed that it would be more comfortable and relaxing for the participant.Data processing followed the recommendations of the Task Force of the European Society of Cardiology and the North American Society of Pacing Electrophysiology  was used to estimate the R-wave fiducial points, after which the series was screened manually and corrected for artifacts. Standard deviation of normal to normal of all intervals (SDNN) and root mean square of successive RR interval differences (RMSSD) were extracted using a time-domain analysis, whereas high-frequency (HF) and low-frequency (LF) components were extracted using a frequency-domain analysis, as recommended . The alpha level for statistical significance was set at 0.05. All tests were corrected for multiple comparisons using Bonferroni adjusted alpha levels of 0.007 per test.Statistical analyses were made using Statistica version 7.0 . Normality of data was evaluated using the Kolmogorov-Smirnov test. The HRV components were logarithm-transformed to fit data on a parametric distribution. In order to test the associations between loneliness and social variables, linear regression analyses were conducted in separate models. In each model, loneliness was entered as the dependent variable and other measures as predictors . For HRV analyses, 17 individuals were excluded because of technical problems in the recording or signal processing. Thus, the final HRV analyses were performed using the data from 103 participants  where loneliness was entered as the dependent variable and other measures as predictors , all controlled by age and sex = 25.42, Β= −0.42, SE B= 0.08, t= −5.04, p< 0.001) (model 1) = 9.55, Β= − 0.27, SE B= 0.08, t= − 3.09, p= 0.002) (model 2) = 4.31, Β= −0.18, SE B= 0.09, t= −2.07, p=0.04) (model 3)  is a predictor of greater loneliness. Several studies have documented the beneficial effects of social touch in humans in experimental designs different from ours. For example, Coan et al.  showed aFrom an ethological perspective, the conscious perception of receiving touch may have interesting outcomes. For example, in some primate species, where allo-grooming plays a crucial role in communication, engagement in social activities depends on the amount of touch received Dunbar, . In humaThe present results indicate that touch is marginally significant as a predictor of loneliness. Of importance for the current discussion, a previous study showed that visual social stimuli promoted an accelerated reaction time in the flexion of the fingers, a motor task that bears resemblance with the social touch (Souza et al., In this study, we did not find any evidence of resting HRV as a predictor of loneliness. Several studies have shown that a low HRV at rest is associated with a wide range of disorders and risk factors for several diseases (Beauchaine & Thayer, Loneliness is a relevant topic that has increased in interest over the last decade and to an even greater extent following the outbreak of the coronavirus pandemic. In fact, an emerging body of research has reported the impact of imposed social distancing and loneliness on well-being and overall health (Bao et al., It is important to note that there were some limitations in this study. Firstly, we recorded the ECG in a supine position which could change the influence of sympathetic and parasympathetic control to the heart. Secondly, we recorded the ECG for a long period of time, in which some participants could fall asleep. Thirdly, we did not record respiration as a variable. In turn, these limitations may affect the interpretability of the findings.The current study provides evidence that decreased self-reported social support and receiving of touch are important predictors of loneliness. These results highlight the effects of specific psychosocial factors that should be considered a promising pathway for reducing, or even preventing, loneliness, thus promoting better health and well-being.