The gut microbiome promotes locomotion of Drosophila larvae via octopamine signaling.

The gut microbiome is a key partner of animals, influencing various aspects of their physiology and behaviors. Among the diverse behaviors regulated by the gut microbiome, locomotion is vital for survival and reproduction, although the underlying mechanisms remain unclear. Here, we reveal that the gut microbiome modulates the locomotor behavior of Drosophila larvae via a specific neuronal type in the brain. The crawling speed of germ-free (GF) larvae was significantly reduced compared to the conventionally reared larvae, while feeding and excretion behaviors were unaffected. Recolonization with Acetobacter and Lactobacillus can fully and partially rescue the locomotor defects in GF larvae, respectively, probably due to the highest abundance of Acetobacter as a symbiotic bacterium in the larval gut, followed by Lactobacillus. Moreover, the gut microbiome promoted larval locomotion, not by nutrition, but rather by enhancing the brain levels of tyrosine decarboxylase 2 (Tdc2), which is an enzyme that synthesizes octopamine (OA). Overexpression of Tdc2 rescued locomotion ability in GF larvae. These findings together demonstrate that the gut microbiome specifically modulates larval locomotor behavior through the OA signaling pathway, revealing a new mechanism underlying larval locomotion regulated by the gut microbiome.

The lysine methyltransferase SMYD2 facilitates neointimal hyperplasia by regulating the HDAC3-SRF axis.

Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.

A Self-Adaptive Dual-ILRO Clock-Recovery Technique for Two-Tone Battery-Free Crystal-Free Neural-Recording SoC.

Wireless implantable devices are widely used in medical treatment, which should meet clinical constraints such as longevity, miniaturization, and reliable communication. Wireless power transfer (WPT) can eliminate the battery to reduce system size and prolong device life, while it's challenging to generate a reliable clock without a crystal. In this work, we propose a self-adaptive dual-injection-locked-ring-oscillator (dual-ILRO) clock-recovery technique based on two-tone WPT and integrate it into a battery-free neural-recording SoC. The 2[Formula: see text]-order inter-modulation (IM2) component of the two WPT tones is extracted as a low-frequency reference for battery-free SoC, and the proposed self-adaptive dual-ILRO technique extends the lock range to ensure an anti-interference PVT-robust clock generation. The neural-recording SoC includes a low-noise signal acquisition unit, a power management unit, and a backscatter circuit to perform neural signal recording, wireless power harvesting, and neural data transmission. Benefiting from the 6.4 µW low power of the clock recovery circuit, the overall SoC power is cut down to 49.8 µW. In addition, the proposed clock-recovery technique enables both signal acquisition and uplink communication to perform as well as that synchronized by an ideal clock, i.e., an effective number of 9.6 bits and a bit error rate (BER) less than 4.8 × 10-7 in chip measurement. The SoC takes a die area of 2.05 mm 2, and an animal test is conducted in a Sprague-Dawley rat to validate the wireless neural-recording performance, compared to a crystal-synchronized commercial chip.

Enhanced reproductive toxicity of photodegraded polylactic acid microplastics in zebrafish.

Microplastics are widely used due to their numerous advantages. However, they can have detrimental effects on marine ecosystems. When microplastics enter the ocean, they can be absorbed by marine organisms, leading to toxic effects. Additionally, the transformation of microplastics during natural degradation can alter their toxicity, necessitating further investigation. Polylactic acid (PLA) biodegradable plastics are commonly used, yet research on their toxicity, particularly their reproductive effects on aquatic organisms, remains limited. In this study, we conducted photodegradation of PLA using potassium persulfate as a catalyst to simulate natural degradation conditions. Our objective was to assess the reproductive toxicity of photodegraded PLA microplastics on zebrafish. The results revealed that photodegraded PLA exhibited elevated reproductive toxicity, resulting in abnormal oocyte differentiation, disruption of sexual hormone levels, and alterations in ovarian tissue metabolism. Metabolomics analysis indicated that both unphotodegraded PLA (UPLA) and photodegraded PLA (DPLA) disrupted oxidative stress homeostasis in zebrafish ovarian tissue by influencing pathways such as purine metabolism, phenylalanine metabolism, glutathione metabolism, and riboflavin metabolism. Furthermore, the DPLA treatment induced abnormal biosynthesis of taurocholic acid, which was not observed in the UPLA treatment group. Importantly, the DPLA treatment group exhibited more pronounced effects on offspring development compared to the UPLA treatment group, characterized by higher mortality rates, inhibition of embryo hatching, accelerated heart rates, and reduced larval body length. These findings underscore the varying levels of toxicity to zebrafish ovaries before and after PLA photodegradation, along with evidence of intergenerational toxicity.

Exploring a multi-output temporal convolutional network driven encoder-decoder framework for ammonia nitrogen forecasting.

Artificial neural networks exhibit significant advantages in terms of learning capability and generalizability, and have been increasingly applied in water quality prediction. Through learning a compressed representation of the input data, the Encoder-Decoder (ED) structure not only could remove noise and redundancies, but also could efficiently capture the complex nonlinear relationships of meteorological and water quality factors. The novelty of this study lies in proposing a multi-output Temporal Convolutional Network based ED model (TCN-ED) to make ammonia nitrogen forecasts for the first time. The contribution of our study is indebted to systematically assessing the significance of combining the ED structure with advanced neural networks for making accurate and reliable water quality forecasts. The water quality gauge station located at Haihong village of an island in Shanghai City of China constituted the case study. The model input contained one hourly water quality factor and hourly meteorological factors of 32 observed stations, where each factor was traced back to the previous 24 h and each meteorological factor of 32 gauge stations was aggregated into one areal average factor. A total of 13,128 hourly water quality and meteorological data were divided into two datasets corresponding to model training and testing stages. The Long Short-Term Memory based ED (LSTM-ED), LSTM and TCN models were constructed for comparison purposes. The results demonstrated that the developed TCN-ED model can succeed in mimicking the complex dependence between ammonia nitrogen and water quality and meteorological factors, and provide more accurate ammonia nitrogen forecasts (1- up to 6-h-ahead) than the LSTM-ED, LSTM and TCN models. The TCN-ED model, in general, achieved higher accuracy, stability and reliability compared with the other models. Consequently, the improvement can facilitate river water quality forecasting and early warning, as well as benefit water pollution prevention in the interest of river environmental restoration and sustainability.

The combined toxic effects of polystyrene microplastics and different forms of arsenic on the zebrafish embryos (Danio rerio).

Microplastics have been widely studied for their ability to adsorb heavy metals. In the natural environment, arsenic exists in different forms and its toxicity depends mainly on its form and concentration. However, different forms of arsenic combined with microplastics have yet to be explored for their biological hazards. This study was conducted to reveal the adsorption mechanism of different forms of arsenic onto PSMP and to study the effects of PSMP on the tissue accumulation and developmental toxicity of different forms of arsenic in zebrafish larvae. As a result, the absorbing ability of PSMP for As(III) was 35 times higher than that of DMAs, in which hydrogen bonding plays an important role in the adsorption process. In addition, the adsorption kinetics of As(III) and DMAs on PSMP were in good agreement with the pseudo-second-order kinetic model. Furthermore, PSMP reduced the accumulation of As(III) early in zebrafish larvae development, thereby increasing hatching rates compared with the As(III)-treated group, whereas PSMP had no significant effect on DMAs accumulation in zebrafish larvae, but decreased hatching rates compared with the DMAs-treated group. In addition, except for the microplastic exposure group, the other treatment groups could lead to a decrease in the heart rate of zebrafish larvae. Both PSMP+As(III) and PSMP+DMAs exhibited aggravated oxidative stress compared with PSMP-treated group, but PSMP+As(III) caused more severe oxidative stress at later stages of zebrafish larvae development. Moreover, specific metabolic differences (e.g., AMP, IMP, and guanosine) were produced in the PSMP+As(III) exposure group, which would mainly affect purine metabolism and promoted specific metabolic disturbances. However, PSMP+DMAs exposure shared metabolic pathways altered by PSMP and DMAs, indicating an independent effect of these two chemicals. Taken together, our findings emphasized that the combined toxicity of PSMP and different forms of arsenic posed a health risk that cannot be ignored.

Design, Synthesis, and Antitumor Activities of Isomers of Artemisinin Dimer Derivatives.

In recent years, numerous studies have reported on the anti-tumor properties of artemisinin and its derivatives. However, the relationship between their artemisinin chirality and activity remains unknown. In this study, we synthesized a series of artemisinin dimer derivatives with three different chiral structures and tested their antiproliferative activity in MCF-7 and HepG2 cells using the CCK-8 assay. Interestingly, we discovered that artemisinin dimer derivatives with ß, ß and α, ß conformations at C-10 exhibited stronger anti-tumor activity than those with an α, α configuration in MCF-7 and HepG2 cells. Notably, compound 4 showed an activity of 0.06 µM in MCF-7 cells. This study demonstrates the relationship between the conformation and activity of artemisinin dimer derivatives, and these derivatives have the potential to be developed into anti-cancer drugs.

Exploring a similarity search-based data-driven framework for multi-step-ahead flood forecasting.

Due to a small proportion of observations, reliable and accurate flood forecasts for large floods present a fundamental challenge to artificial neural network models, especially when the forecast horizons exceed the flood concentration time of a river basin. This study proposed for the first time a Similarity search-based data-driven framework, and takes the advanced Temporal Convolutional Network based Encoder-Decoder model (S-TCNED) as an example for multi-step-ahead flood forecasting. A total of 5232 hourly hydrological data were divided into two datasets for model training and testing. The input sequence of the model included hourly flood flows of a hydrological station and rainfall data (traced back to the previous 32 h) of 15 gauge stations, and the output sequence stepped into 1- up to 16-hour-ahead flood forecasts. A conventional TCNED model was also built for comparison purposes. The results demonstrated that both TCNED and S-TCNED could make suitable multi-step-ahead flood forecasts, while the proposed S-TCNED model not only could effectively mimic the long-term rainfall-runoff relationship but also could provide more reliable and accurate forecasts of large floods than the TCNED model even in extreme weather conditions. There is a significant positive correlation between the mean sample label density improvement and the mean Nash-Sutcliffe Efficiency (NSE) improvement of the S-TCNED over the TCNED at the long forecast horizons (13 h up to 16 h). Based on the analysis of the sample label density, it is found that the similarity search largely improves the model performance by enabling the S-TCNED model to learn the development process of similar historical floods in a targeted manner. We conclude that the proposed S-TCNED model that converts and associates the previous rainfall-runoff sequence with the forecasting runoff sequence under a similar scenario can enhance the reliability and accuracy of flood forecasts while extending the length of forecast horizons.

Apple puree as a natural fructose source provides an effective alternative carbohydrate source for fuelling half-marathon running performance.

Carbohydrate supplementation during endurance exercise is known to improve performance, but the effects of food-based approaches in running exercise are understudied. Therefore, this study investigated the performance and gastrointestinal (GI) effects of a carbohydrate supplement containing a natural fructose source compared with a highly processed fructose source in a combined glucose-fructose supplement, during a half-marathon. Eleven trained runners (9 males, 2 females; age 32 ± 8 y, 89:53 ± 13:28 min half-marathon personal record) completed a familiarisation (8 miles) and two experimental trials (13.1 miles) on an outdoor running course, with blood and urine samples collected before and after the run. Subjective GI measures were made throughout the run. Carbohydrate was provided as a natural fructose source in the form of apple puree (AP) or highly processed crystalline fructose (GF) in a 2:1 glucose-to-fructose ratio (additional required glucose was provided through maltodextrin). Half-marathon performance was not different between carbohydrate sources (AP 89:52 ± 09:33 min, GF 88:44 ± 10:09 min; P = 0.684). There were no interaction effects for GI comfort (P = 0.305) or other GI symptoms (P ≥ 0.211). There were no differences between carbohydrate sources in ad libitum fluid intake (AP 409 ± 206 mL; GF 294 ± 149 mL; P = 0.094) or any other urinary (P ≥ 0.724), blood-based (P ≥ 0.215) or subjective (P ≥ 0.421) measures. Apple puree as a natural fructose source was equivalent to crystalline fructose in supporting half-marathon running performance without increasing GI symptoms.HighlightsResearch examining food-first and food-based approaches to carbohydrate supplementation and endurance running performance are limited. Therefore, this study aimed to compare carbohydrate supplements either containing a natural or highly processed fructose source as part of a glucose-fructose supplement on half-marathon running performance and gastrointestinal comfort in trained runners.Running performance (apple puree 89:52 ± 09:33 min vs. crystalline fructose 88:44 ± 10:09 min), gastrointestinal comfort and symptoms were not different between the two fructose sources.Apple puree can be effectively used as a carbohydrate source to fuel half-marathon running performance.

Nanoparticle-Based Photodynamic Inhibition of Candida albicans Biofilms with Interfering Quorum Sensing.

Biofilm formation is a critical event in the pathogenesis and virulence of fungal infections caused by Candida albicans, giving rise to about a 1000-fold increase in the resistance to antifungal agents. Although photodynamic treatment (PDT) has been excellently implicated in bacterial infections, studies on its potential against fungal infection through the clearance of fungal biofilm formation remain at its infancy stage. Here, we have designed photodynamic nanoparticles with different sizes, modifications, and the ability of generating reactive oxygen species (ROS) to examine their effects on inhibiting biofilm formation and destructing mature biofilms of C. albicans. We found that the nanoparticles modified with oligo-chitosan exhibited a better binding efficiency for planktonic cells, leading to stronger inhibitory efficacy of the filamentation and the early-stage biofilm formation. However, for mature biofilms, the nanoparticles with the smallest size (∼15 nm) showed the fastest penetration speed and a pronounced destructing effect albeit conferring the lowest ROS-producing capability. The inhibitory effect of photodynamic nanoparticles was dependent on the disruption of fungal quorum sensing (QS) by the upregulation of QS molecules, farnesol and tyrosol, mediated through the upregulation of ARO 8 and DPP 3 expression. Our findings provide a powerful strategy of nanoparticulate PDT to combat fungal infections through the inhibition of both hyphal and biofilm formation by disrupting QS.

Artificial Intelligence in the Prediction of Gastrointestinal Stromal Tumors on Endoscopic Ultrasonography Images: Development, Validation and Comparison with Endosonographers.

Background/Aims: The accuracy of endosonographers in diagnosing gastric subepithelial lesions (SELs) using endoscopic ultrasonography (EUS) is influenced by experience and subjectivity. Artificial intelligence (AI) has achieved remarkable development in this field. This study aimed to develop an AI-based EUS diagnostic model for the diagnosis of SELs, and evaluated its efficacy with external validation. Methods: We developed the EUS-AI model with ResNeSt50 using EUS images from two hospitals to predict the histopathology of the gastric SELs originating from muscularis propria. The diagnostic performance of the model was also validated using EUS images obtained from four other hospitals. Results: A total of 2,057 images from 367 patients (375 SELs) were chosen to build the models, and 914 images from 106 patients (108 SELs) were chosen for external validation. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the model for differentiating gastrointestinal stromal tumors (GISTs) and non-GISTs in the external validation sets by images were 82.01%, 68.22%, 86.77%, 59.86%, and 78.12%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in the external validation set by tumors were 83.75%, 71.43%, 89.33%, 60.61%, and 80.56%, respectively. The EUS-AI model showed better performance (especially specificity) than some endosonographers. The model helped improve the sensitivity, specificity, and accuracy of certain endosonographers. Conclusions: We developed an EUS-AI model to classify gastric SELs originating from muscularis propria into GISTs and non-GISTs with good accuracy. The model may help improve the diagnostic performance of endosonographers. Further work is required to develop a multi-modal EUS-AI system.

A Wireless Headstage System Based on Neural-Recording Chip Featuring 315 nW Kickback-Reduction SAR ADC.

Wireless neural-recording instruments eliminate the bulky cables in multi-channel signal transmission, while the system size should be reduced to mitigate the impact on freely-moving animals. As the battery usually dominates the system size, the neural-recording chip should be low power to minimize the battery in long-termly monitoring. In general, a neural-recording chip consists of an analog front end (AFE) and an 8 bit -10 bit analog-to-digital converter (ADC), while it's challenging to design an ADC with an 8 -10 effective number of bits (ENOB) and sub- µ W power consumption due to the kickback noise. In this work, we propose a kickback-reduction technique for a successive-approximation-register (SAR) ADC based on neural-recording chip. Fabricated in 65 nm CMOS process, the proposed technique reduce the ADC power to 315 nW, resulting in an 8-channel neural-recording chip with 249 µW in total. Measured results show that the chip achieves an ADC ENOB of 9.73 bits, as well as an AFE gain of 43.3 dB and input-referred noise (IRN) of 9.68 µVrms in a bandwidth of 0.9 Hz -7.2 kHz. Combined with a BLE chip and a PCB antenna, the chip is implemented into a 2.6 g wireless headstage system (w/o battery), and an in-vivo demonstration is conducted on a male Sprague-Dawley rat with Parkinson's disease. The headstage system transfers the in-vivo neural signals to a commodity smartphone through BLE, and the miniature size induces little impact on freely-moving activities.

A Review of Generalized Zero-Shot Learning Methods.

Generalized zero-shot learning (GZSL) aims to train a model for classifying data samples under the condition that some output classes are unknown during supervised learning. To address this challenging task, GZSL leverages semantic information of the seen (source) and unseen (target) classes to bridge the gap between both seen and unseen classes. Since its introduction, many GZSL models have been formulated. In this review paper, we present a comprehensive review on GZSL. First, we provide an overview of GZSL including the problems and challenges. Then, we introduce a hierarchical categorization for the GZSL methods and discuss the representative methods in each category. In addition, we discuss the available benchmark data sets and applications of GZSL, along with a discussion on the research gaps and directions for future investigations.

Mechanisms of miR-29a-5p involvement in osteogenic phenotype transformation and cellular regulation of vascular smooth muscle and thus influencing calcification in VSMCs in chronic kidney disease.

Vascular calcification is one of the major complications of chronic kidney disease (CKD), which could be further accelerated by the osteogenic transition and apoptosis of smooth muscle cells, thereby advancing the progression of renal diseases and increasing the mortality rate of cardiovascular events. MicroRNA is a kind of key regulator in the phenotypic transition of vascular smooth muscle cells (VSMCs), but its role remains unclear in VSMCs. In this study, VSMCs were stimulated by platelet-derived growth factors - BB (PDGF-BB) in varying concentrations to establish the VSMC dysfunction models. The relative expression of miR-29a-5p was quantified via the quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation of VSMCs was determined via the BrdU method, analysis of cell cycle via flow cytometry, and the migration of VSMCs via Transwell assay. Expression of γ-secretase activating protein (GSAP) and markers of VSMC differentiation, including α-SMA, SM-22α, SMMHC and Calponin, was quantified via the Western blot. The targeting relationship between the 3'-UTR of miR-29a-5p and GSAP was validated through the dual-luciferase reporter gene assay. As a result, we found that PDGF-BB could trigger a decrease of miR-29a-5p in a time- and dose-dependent manner (P < 0.05). Overexpression of miR-29a-5p could curb the effect of PDGF-BB on the proliferation and migration of VSMCs while upregulating the expression of markers of differentiation (P < 0.05). In addition, the expression of GSAP was also affected by the negative regulation of miR-29a-5p, while the restoration of GSAP eliminated the effect of miR-29a-5p on the VSMCs partially (P < 0.05). Moreover, vascular calcification models were also established in the CKD rats, suggesting that the inhibition of GSAP could prevent PTH-induced vascular calcification in CKD rats. In conclusion, miR-29a-5p could inhibit the PDGF-BB-induced proliferation, migration and phenotypic transition of VSMCs via targeting GSAP. Thus, miR-29a-5p/GSAP might be a potential target for the treatment of vascular calcification.

Mapping of lumbar multifidus stiffness Quantification in ankylosing spondylitis with shear-wave elastography.

BACKGROUND: Lower back pain and stiffness are the typical symptoms of ankylosing spondylitis (AS). In this study, muscle mass was assessed by muscle density, mechanical elasticity, and area. We investigated the characteristics of lumbar paraspinal-muscle (PSM) mass using muscle ultrasound shear-wave elastography (SWE), as well as the validity of this method for identifying patients with AS. METHODS: We recruited a representative cohort of 30 AS patients, and 27 healthy volunteers who were age- and sex-matched to the patient study group, investigated the Young's modulus (YM), cross-sectional area (CSA) and thickness of lumbar multifidus (LM) muscle using SWE. This study did not need to be randomized. Data were collected at the department of ultrasonography of Guangdong Provincial Hospital of Chinese Medicine. We analyzed the data using SPSS version 18.0 (IBM Corp, Armonk, NY, USA). Normal distribution was evaluated by the Shapiro-Wilk test and Q-Q plots. Demographic and baseline data will be analyzed with standard descriptive statistics. Data will be presented as the mean ± standard deviation (SD). Non-normally distributed data are presented as medians with interquartile ranges (IQR). RESULTS: Young's modulus (YM) of SWE in AS patients was significantly higher than that in volunteers. Percentage change in lumbar multifidus (LM) muscle cross-sectional area (CSA) and thickness were significantly lower in AS patients than in healthy volunteers on the left side of the body. Correlation analysis showed a positive correlation between percentage change in CSA and thickness in both volunteers and AS patients. In AS patients, YM was negatively correlated with percentage change of CSA and thickness on the right side, while increased disease duration in AS was associated with increased YM on the left. CONCLUSION: AS patients showed reductions in LM muscle mass and function as the disease progressed, SWE could reflect these changes well. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000031476. Registered 02/04/2020. http://www.chictr.org.cn/index.aspx .

A Power-Harvesting CGM Chiplet Featuring Silicon-Based Enzymatic Glucose Sensor.

Diabetes has become a leading cause of death and disability in the past decades. Continuous glucose monitoring (CGM) is a prevailing technique to determine the glucose level and provide in-time treatment. However, conventional CGM systems combine an electrochemical sensor with a CMOS chip, suffering from bulky size and interface issues. Integrating the CGM sensor on silicon is potential to miniaturize the CGM system and reduce the cost, while the recent silicon-based sensors show limited detection range and sensitivity. In this work, we present a silicon-based CGM chip let with wireless power transfer (WPT) and real-time wireless telemetry. Fabricated on a single silicon substrate, the chiplet consists of a silicon-based CGM sensor, a power-harvesting wireless-telemetry chip, and a silicon-based antenna. Measured results show that the chip let achieves a sensitivity of 4 µA.mM.cm-2 and a linear detection range of 0-10 mM. Based on WPT and backscattering communication, the chip let consumes 18.8 µ W power in glucose telemetry.

Relationships Between Biological Heavy Metals and Breast Cancer: A Systematic Review and Meta-Analysis.

Introduction: Heavy metals were classified as essential, probably essential, and potentially toxic in the general population. Until now, it has been reported inconsistently on the association between heavy metals and BC. In this meta-analysis, we aimed to assess the association between heavy metals and BC and review the potential mechanisms systematically. Methods: We searched for epidemiological studies in English about the association between heavy metals and BC published before September 2020 in PubMed, Web of Science, and Embase databases. In total 36 studies, comprising 4,151 individuals from five continents around the world were identified and included. Results: In all biological specimens, Cu, Cd, and Pb concentrations were higher, but Zn and Mn concentrations were lower in patients with BC than in non-BC participants [SMD (95% CIs): 0.62 (0.12, 1.12); 1.64 (0.76, 2.52); 2.03 (0.11, 3.95); -1.40 (-1.96, -0.85); -2.26 (-3.39, -1.13); p = 0.01, 0.0003, 0.04, <0.0001, <0.0001]. Specifically, higher plasma or serum Cu and Cd, as well as lower Zn and Mn, were found in cases [SMD (95% CIs): 0.98 (0.36, 1.60); 2.55 (1.16, 3.94); -1.53 (-2.28, -0.78); -2.40 (-3.69, -1.10); p = 0.002, 0.0003, <0.0001, 0.0003]; in hair, only lower Zn was observed [SMD (95% CIs): -2.12 (-3.55, -0.68); p = 0.0004]. Furthermore, the status of trace elements probably needs to be re-explored, particularly in BC. More prospective studies, randomized clinical trials, and specific pathogenic studies are needed to prevent BC. The main mechanisms underlying above-mentioned findings are comprehensively reviewed. Conclusion: For BC, this review identified the current knowledge gaps which we currently have in understanding the impact of different heavy metals on BC. Systematic Review Registration: www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020176934, identifier: CRD42020176934.

High Intensity Interval Training: A Potential Method for Treating Sarcopenia.

Sarcopenia, an age-related disease characterized by loss of muscle strength and muscle mass, has attracted the attention of medical experts due to its severe morbidity, low living quality, high expenditure of health care, and mortality. Traditionally, persistent aerobic exercise (PAE) is considered as a valid way to attenuate muscular atrophy. However, nowadays, high intensity interval training (HIIT) has emerged as a more effective and time-efficient method to replace traditional exercise modes. HIIT displays comprehensive effects on exercise capacity and skeletal muscle metabolism, and it provides a time-out for the recovery of cardiopulmonary and muscular functions without causing severe adverse effects. Studies demonstrated that compared with PAE, HIIT showed similar or even higher effects in improving muscle strength, enhancing physical performances and increasing muscle mass of elder people. Therefore, HIIT might become a promising way to cope with the age-related loss of muscle mass and muscle function. However, it is worth mentioning that no study of HIIT was conducted directly on sarcopenia patients, which is attributed to the suspicious of safety and validity. In this review, we will assess the effects of different training parameters on muscle and sarcopenia, summarize previous papers which compared the effects of HIIT and PAE in improving muscle quality and function, and evaluate the potential of HIIT to replace the status of PAE in treating old people with muscle atrophy and low modality; and point out drawbacks of temporary experiments. Our aim is to discuss the feasibility of HIIT to treat sarcopenia and provide a reference for clinical scientists who want to utilize HIIT as a new way to cope with sarcopenia.