Impact of exercise on chemotherapy-induced peripheral neuropathy in survivors with post-treatment primary breast cancer.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect of neurotoxic chemotherapy. Exercise activates neuromuscular function and may improve CIPN. We examined the association between exercise and CIPN symptoms in breast cancer survivors. METHODS: In a retrospective cross-sectional study, we included patients completing a survey assessing exercise exposure and neuropathy symptoms in a tertiary cancer center survivorship clinic. We evaluated exercise duration and intensity using a standardized questionnaire quantified in metabolic equivalent tasks (MET-h/wk). We defined exercisers as patients meeting the National Physical Activity Guidelines' criteria. We used multivariable logistic regressions to examine the relationship between exercise and CIPN and if this differed as a function of chemotherapy regimen adjusting for age, gender, and race. RESULTS: We identified 5444 breast cancer survivors post-chemotherapy (median age 62 years (interquartile range [IQR]: 55, 71); median 4.7 years post-chemotherapy (IQR: 3.3, 7.6)) from 2017 to 2022. CIPN overall prevalence was 34% (95% confidence interval [CI]: 33%, 36%), 33% for non-taxane, and 37% for taxane-based chemotherapy. CIPN prevalence was 28% (95% CI: 26%, 30%) among exercisers and 38% (95% CI: 37%, 40%) among non-exercisers (difference 11%; 95% CI: 8%, 13%; p < 0.001). Compared to patients with low (<6 MET-h/wk) levels of exercise (42%), 11% fewer patients with moderate (6-20.24 MET-h/wk) to high (>20.25 MET-h/wk) levels of exercise reported CIPN. Exercise was associated with reduced prevalence of all CIPN symptoms regardless of chemotherapy type. CONCLUSION: CIPN may persist several years following chemotherapy among patients with breast cancer but is significantly reduced by exercise in a dose-dependent manner.

Strong Protection by 4-Hydroxyestrone against Erastin-Induced Ferroptotic Cell Death in Estrogen Receptor-Negative Human Breast Cancer Cells: Evidence for Protein Disulfide Isomerase as a Mechanistic Target for Protection.

Ferroptosis is a recently identified form of regulated cell death, characterized by excessive iron-dependent lipid peroxidation. Recent studies have demonstrated that protein disulfide isomerase (PDI) is an important mediator of chemically induced ferroptosis and also a new target for protection against ferroptosis-associated cell death. In the present study, we identified that 4-hydroxyestrone (4-OH-E1), a metabolic derivative of endogenous estrogen, is a potent small-molecule inhibitor of PDI, and can strongly protect against chemically induced ferroptotic cell death in the estrogen receptor-negative MDA-MB-231 human breast cancer cells. Pull-down and CETSA assays demonstrated that 4-OH-E1 can directly bind to PDI both in vitro and in intact cells. Computational modeling analysis revealed that 4-OH-E1 forms two hydrogen bonds with PDI His256, which is essential for its binding interaction and thus inhibition of PDI's catalytic activity. Additionally, PDI knockdown attenuates the protective effect of 4-OH-E1 as well as cystamine (a known PDI inhibitor) against chemically induced ferroptosis in human breast cancer cells. Importantly, inhibition of PDI by 4-OH-E1 and cystamine or PDI knockdown by siRNAs each markedly reduces iNOS activity and NO accumulation, which has recently been demonstrated to play an important role in erastin-induced ferroptosis. In conclusion, this study demonstrates that 4-OH-E1 is a novel inhibitor of PDI and can strongly inhibit ferroptosis in human breast cancer cells in an estrogen receptor-independent manner. The mechanistic understanding gained from the present study may also aid in understanding the estrogen receptor-independent cytoprotective actions of endogenous estrogen metabolites in many noncancer cell types.

Five Dimensions of Needs for Help: The Efficacy of a Technology-Based Intervention Among Asian American Breast Cancer Survivors.

Cancer survivors including Asian American breast cancer survivors have reported their high needs for help during their survivorship process. With the COVID-19 pandemic, the necessity of technology-based programs to address their needs for help without face-to-face interactions has been highlighted. The purpose of this randomized intervention study was to determine the efficacy of a technology-based program in reducing various types of needs for help among this specific population. This was a randomized clinical trial with repeated measures. A total of 199 participants were included in the data analysis. The recruitment settings included both online and offline communities/groups for Asian Americans. The needs for help were assessed using the Support Care Needs Survey-34 Short Form (SCNS) subscales measuring psychological, information, physical, support, and communication needs. Data analysis was conducted through an intent-to-treat approach. In the mixed effect models, psychological needs, information needs, physical needs, and communication needs decreased over time (P < .001). However, there were no significant group * time effects. Social support significantly mediated the effects of a technology-based intervention on psychological, information, and support needs at the pre-test and the post-1 month. This study supported significant decreases in the needs for help of Asian American breast cancer survivors by a technology-based intervention. Further studies are needed with other racial/ethnic groups of cancer survivors to confirm the efficacy of a technology-based intervention in reducing cancer survivors' needs for help during their survivorship process.

Global, regional, and national time trends in incidence for tuberculosis, 1990-2019: An age-period-cohort analysis for the Global Burden of Disease 2019 study.

BACKGROUND: Tuberculosis (TB) represents a significant global health concern, being the leading cause of mortality from a single infectious agent worldwide. The investigation of TB incidence and epidemiological trends is critical for evaluating the effectiveness of control strategies and identifying ongoing challenges. OBJECTIVES: This study presents the trend in TB incidence across 204 countries and regions over a 30-year period. METHODS: The study utilises data sourced from the Global Burden of Disease (GBD) database. The age cohort model and gender subgroup analysis were employed to estimate the net drift (overall annual percentage change), local drift (age annual percentage change), longitudinal age curve (expected age ratio), and cycle and cohort effect (relative risk of cycle and birth cohort) of TB incidence from 1990 to 2019. This approach facilitates the examination and differentiation of age, period, and cohort effects in TB incidence trends, potentially identifying disparities in TB prevention across different countries. RESULTS: Over the past three decades, a general downward trend in TB incidence has been observed in most countries. However, in 15 of the 204 countries, the overall incidence rate is still on the rise (net drift ≥0.0 %) or stagnant decline (≥-0.5 %). From 1990 to 2019, the net drift of tuberculosis mortality ranged from -2.2 % [95 % confidence interval (CI): -2.33, -2.05] in high Socio-demographic Index (SDI) countries to -1.7 % [95 % CI: -1.81, -1.62] in low SDI countries. In some below-average SDI countries,men in the birth cohort are at a disadvantage and at risk of deterioration, necessitating comprehensive TB prevention and treatment. CONCLUSIONS: While the global incidence of TB has declined, adverse period and cohort effects have been identified in numerous countries, raising questions about the adequacy of TB healthcare provision across all age groups. Furthermore, this study reveals gender disparities in TB incidence.

LDCT screening results among eligible and ineligible screening candidates in preventive health check-ups population: a real world study in West China.

To compare the LDCT screening results between eligible and ineligible screening candidates in preventive health check-ups population. Using a real-world LDCT screening results among people who took yearly health check-up in health management center of West China Hospital between 2006 and 2017. Objects were classified according to the China National Lung Cancer Screening Guideline with Low-dose Computed Tomography (2018 version) eligibility criteria. Descriptive analysis were performed between eligible and ineligible screening candidates. The proportion of ineligible screening candidates was 64.13% (10,259), and among them there were 4005 (39.04%) subjects with positive screenings, 80 cases had a surgical lung biopsy. Pathology results from lung biopsy revealed 154 cancers (true-positive) and 26 benign results (false-positive), the surgical false-positive biopsy rate was 4.17%, and ineligible group (7.69%) was higher than eligible group (2.47%), P < 0.05. Further, in ineligible screening candidates, the proportion of current smokers was higher among males compared to females (53.85% vs. 4.88%, P < 0.05). Of the 69 lung cancer patients detected in ineligible screening candidates, lung adenocarcinoma accounts for a high proportion of lung cancers both in male (75.00%) and female (85.00%). The proportion of ineligible screening candidates and the surgical false-positive biopsy rate in ineligible candidates were both high in health check-ups population.

The association between sarcopenia and incident of depressive symptoms: a prospective cohort study.

BACKGROUND: Epidemiological studies have shown that sarcopenia was associated with depression among older adults. However, most of these investigations used a cross-sectional design, limiting the ability to establish a causal relation, the present study examined whether sarcopenia was associated with incident depressive symptoms. METHODS: This is a prospective cohort study with participants from the Western China Health and Aging Trends (WCHAT) study. Participants could complete anthropometric measurements and questionnaires were included. The exposure was sarcopenia, defined according to the Asian Working Group for Sarcopenia in 2019, the outcome was depressive symptoms, evaluated by GDS-15. We excluded depression and depressive symptoms at baseline and calculated the risk of incident depressive symptoms during the follow-up year. RESULTS: A total of 2612 participants (mean age of 62.14 ± 8.08 years) were included, of which 493 with sarcopenia. 78 (15.82%) participants with sarcopenia had onset depressive symptoms within the next year. After multivariable adjustment, sarcopenia increased the risk of depressive symptoms (RR = 1.651, 95%CI = 1.087-2.507, P = 0.0187) in overall participants. Such relationship still exists in gender and sarcopenia severity subgroups. Low muscle mass increased the risk of depressive symptoms (RR = 1.600, 95%CI = 1.150-2.228, P = 0.0053), but low muscle strength had no effect (RR = 1.250, 95%CI = 0.946-1.653, P = 0.117). CONCLUSIONS: Sarcopenia is an independent risk factor for depressive symptoms, Precautions to early detect and targeted intervene for sarcopenia should continue to be employed in adult with sarcopenia to achieve early prevention for depression and reduce the incidence of adverse clinical outcomes.

Association between the triglyceride glucose index and low skeletal muscle mass: a cross-sectional study.

OBJECTIVES: Triglyceride glucose (TyG) represents a consistent surrogate biomarker and index of insulin resistance (IR), IR has also been linked to skeletal muscle mass loss (SMM-L). Here, we evaluated the association between SMM-L and the TyG index (TyGi). DESIGN: An analytical cross-sectional study. SETTING: Tertiary care hospitals. PARTICIPANTS: 36 275 participants who underwent health checks between 1 January 2013 and 31 December 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: A bioelectrical impedance analysis was used to assess the body composition, SMM-L was defined as low ASMI (total limb lean mass/height2) and TyGi was calculated as ln(triglycerides (mg/dL)×fasting blood glucose (mg/dL)/2). RESULTS: A total of 36 275 subjects were included in the study, of which 58.46% were male, with a mean age of 43.74±12.33 years. The prevalence of low skeletal muscle mass (SMM) was 17.7% and the mean TyGi was 8.56±0.64. TyGi was found to be significantly correlated with low SMM in all subjects (OR 1.87, 95% CI 1.75 to 2.00, p<0.001), with higher correlations seen in younger subjects (OR 1.97, 95% CI 1.77 to 2.20, p<0.001), and remaining significant in middle age (OR 1.95, 95% CI 1.77 to 2.14, p<0.001), old age (OR 1.73, 95% CI 1.38 to 1.16, p<0.001), men (OR 1.60, 95% CI 1.46 to 1.76, p<0.001) and women (OR 2.59, 95% CI 2.39 to 2.87, p<0.001). CONCLUSIONS: These data demonstrated a significant independent interaction between TyGi and low SMM in all subjects regardless of sex and age subgroups in the general population.

Recent Progress in Phage-Based Nanoplatforms for Tumor Therapy.

Nanodrug delivery systems have demonstrated a great potential for tumor therapy with the development of nanotechnology. Nonetheless, traditional drug delivery systems are faced with issues such as complex synthetic procedures, low reproducibility, nonspecific distribution, impenetrability of biological barrier, systemic toxicity, etc. In recent years, phage-based nanoplatforms have attracted increasing attention in tumor treatment for their regular structure, fantastic carrying property, high transduction efficiency and biosafety. Notably, therapeutic or targeting peptides can be expressed on the surface of the phages through phage display technology, enabling the phage vectors to possess multifunctions. As a result, the drug delivery efficiency on tumor will be vastly improved, thereby enhancing the therapeutic efficacy while reducing the side effects on normal tissues. Moreover, phages can overcome the hindrance of biofilm barrier to elicit antitumor effects, which exhibit great advantages compared with traditional synthetic drug delivery systems. Herein, this review not only summarizes the structure and biology of the phages, but also presents their potential as prominent nanoplatforms against tumor in different pathways to inspire the development of effective nanomedicine.

Transistor-based immunosensor using AuNPs-Ab2-HRP enzyme nanoprobe for the detection of antigen biomarker in human blood.

Alpha-fetoprotein (AFP) is inextricably linked to various diseases, including liver cancer. Thus, detecting the content of AFP in biology has great significance in diagnosis, treatment, and intervention. Motivated by the urgent need for affordable and convenient electronic sensors in the analysis and detection of aqueous biological samples, we combined the solution-gated graphene transistor (SGGT) with the catalytic reaction of enzyme nanoprobes (HRP-AuNPs-Ab2) to accurately sense AFP. The SGGT immunosensor demonstrated high specificity and stability, excellent selectivity, and excessive linearity over a range of 4 ng/mL to 500 ng/mL, with the lower detection limit down to 1.03 ng/mL. Finally, clinical samples were successfully detected by the SGGT immunosensor, and the results were consistent with chemiluminescence methods that are popular in hospitals for detecting AFP. Notably, the SGGT immunosensor is also recyclable, so it has excellent potential for use in high-throughput detection.

Investigation of the Relationship between Apolipoprotein E Alleles and Serum Lipids in Alzheimer's Disease: A Meta-Analysis.

Prior studies have yielded mixed findings concerning the association between apolipoprotein E(APOE)-ε4 and serum lipids in patients with Alzheimer's disease (AD) and healthy individuals. Some studies suggested a relationship between APOEε4 and serum lipids in patients with AD and healthy individuals, whereas others proposed that the APOEε4 allele affects lipids only in patients with AD. Our study aimed to investigate whether APOE alleles have a distinct impact on lipids in AD. We conducted a comprehensive search of the PubMed and Embase databases for all related studies that investigate APOE and serum lipids of AD from the inception to 30 May 2022. Elevated total cholesterol (TC) and low-density lipoprotein (LDL) levels were found in APOEε4 allele carriers compared with non-carriers. No significant differences were found for high-density lipoprotein (HDL) and triglyceride (TG) levels in APOEε4 allele carriers compared to non-carriers. Notably, elevated TC and LDL levels showed considerable heterogeneity between patients with AD and healthy controls. A network meta-analysis did not find a distinct effect of carrying one or two APOEε4 alleles on lipid profiles. Higher TC and LDL levels were found in APOEε4 allele carriers compared with non-carriers, and the difference was more significant in patients with AD than in healthy controls.

Clinical characteristics, racial inequities, and outcomes in patients with breast cancer and COVID-19: A COVID-19 and cancer consortium (CCC19) cohort study.

Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. Methods: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity. Results: 1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32-1.67]); Black patients (aOR 1.74; 95 CI 1.24-2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70-6.79) and Other (aOR 2.97; 95 CI 1.71-5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83-12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63-3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20-2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66-3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89-22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status. Conclusions: Using one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients. Funding: This study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. Clinical trial number: CCC19 registry is registered on ClinicalTrials.gov, NCT04354701.

A randomized controlled trial testing a virtual program for Asian American women breast cancer survivors.

A culturally tailored virtual program could meet the survivorship needs of Asian American women breast cancer survivors (AABC). This study aims to determine the efficacy of a culturally tailored virtual information and coaching/support program (TICAA) in improving AABC's survivorship experience. A randomized clinical trial (NCT02803593) was conducted from January 2017 to June 2020 among 199 AABC. The intervention group utilized TICAA and the American Cancer Society [ACS] website while the control group used only ACS website for 12 weeks. The outcomes were measured using the SCNS-34SF (needs; primary), the MSAS-SF (symptoms; secondary), and the FACT-B (quality of life; secondary). The data were analyzed using an intent-to-treat approach. The intervention group showed significant reductions in their needs from the baseline (T0) to post 4 weeks (T1) and to post 12 weeks (T2). Although the changes were not statistically significant, the intervention group had decreased symptoms from T0 to T2 while the control group had an increase in their symptoms. The intervention group had a significant increase in their quality of life from T0 to T2. A culturally tailored virtual program could therefore improve quality of life in AABC patients. Trial Registration: To Enhance Breast Cancer Survivorship of Asian Americans (TICAA), NCT02803593, https://clinicaltrials.gov/ct2/show/NCT02803593?titles=TICAA&draw=2&rank=1.

Interest in and Barriers to Practicing Yoga among Family Caregivers of People with Cancer.

Background: Family caregivers of people with cancer report high levels of psychological distress. Yoga, with well-documented mental health benefits, could be a useful intervention to address distress in this population. However, little is known about yoga practices among cancer caregivers. The present study evaluates their interest in and barriers to yoga practice. Methods: We conducted a cross-sectional survey study of family caregivers of cancer patients at five suburban satellite locations of an academic cancer center. Survey items and statistical analyses focused on yoga usage as well as interest in and barriers to yoga practice. Results: Among 539 participants, most were females (64.8%), white (84.2%), and caring for a spouse or partner (54.7%). Interest in practicing yoga among study participants was 42.3%. Increased interest was independently associated with being females (odds ratio [OR] = 3.30, 95% confidence interval [CI] = 1.98-5.51, P < 0.001) and employed (part-time: OR = 2.58, 95% CI = 1.1-6.18, P = 0.03; full-time: OR = 1.77, 95% CI = 1.1-2.01, P = 0.02). Few participants (6.3%) were currently practicing yoga, although 31% had done so in the past. Sixty-one percent of those who had practiced before their loved one's diagnosis stopped practicing yoga afterward. Commonly cited barriers to yoga practice included time constraints (37.3%) and psychological obstacles (33.6%). About a quarter of those who had never practiced yoga lacked awareness of yoga's benefits (26.6%). Conclusion: Despite the low use of yoga, interest in practicing was moderately high, especially among women and employed caregivers. As caregivers face numerous barriers to yoga practice, strategies are needed to overcome these barriers and help them access yoga's health benefits.

Correlation between diabetic retinopathy and Helicobacter pylori infection: a cross-sectional retrospective study.

AIM: To explore the correlation between diabetic retinopathy (DR) and Helicobacter pylori (Hp) infection, based on data from a physical examination population. METHODS: This cross-sectional retrospective analysis included data of 73 824 health examination participants from December 2018 to December 2019. Participants were divided into the diabetic group and non-diabetic group, non-diabetic retinopathy (NDR) group, non-proliferative diabetic retinopathy (NPDR) group, proliferative diabetic retinopathy (PDR) group, and Hp infection group. Gender, age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), glycated hemoglobin A1c (HbA1c), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and Hp data were recorded to compare the degree of DR lesions and Hp infection. Logistic regression analysis was used to evaluate the correlation between DR and Hp infection. RESULTS: There was a statistically significant difference between the diabetic and non-diabetic group (χ2=94.17, P<0.0001). Logistic regression analysis showed that male sex, age, BMI, SBP, TG, LDL-C, and Hp infection were independent risk factors for DR. There was no correlation between the degree of DR lesions and Hp infection (ρ=-0.00339, P=0.7753). Age [odds ratio (OR)=1.035, 95%CI: 1.024, 1.046, P<0.0001] and SBP (OR=1.009, 95%CI: 1.004, 1.015, P=0.0013) were independent risk factors for the degree of DR. CONCLUSION: There is a significant correlation between DR and Hp infection in the physical examination population. Hp infection is a risk factor for DR, and there is no significant difference between Hp infection and DR of different pathological degrees. Actively eradicating Hp may be of help to prevent DR.

Electro-acupuncture versus battle field auricular acupuncture in breast cancer survivors with chronic musculoskeletal pain: subgroup analysis of a randomized clinical trial.

PURPOSE: Chronic musculoskeletal pain is common and debilitating among breast cancer survivors. The PEACE trial demonstrated that electro-acupuncture (EA) and battle field auricular acupuncture (BFAA) both reduced pain more than usual care (UC) in cancer survivors. However, the comparative effectiveness between EA and BFAA among breast cancer survivors is unknown. METHODS: EA and BFAA received ten weekly treatments. UC was offered ten EA treatments after week 12. The primary endpoint was change in mean Brief Pain Inventory (BPI) pain severity from baseline to week 12. We analyzed the subset of 165 (46%) trial participants with a breast cancer primary diagnosis. We conducted constrained linear mixed model analyses, which constrained all arms to a common pre-randomization baseline mean. Model-based mean estimates at weeks 12 and 24 were compared between arms using model contrasts. RESULTS: Among 165 breast cancer survivors, common pre-randomization mean pain severity was 5.35 [95% Confidence Interval (CI) 5.04, 5.66]. At week 12, BPI pain severity score was 2.69 (2.26. 3.13) in EA, 3.60 (3.17, 4.02) in BFAA, and 5.06 (4.47, 5.65) in UC. EA reduced pain severity significantly more than BFAA at weeks 12 [- 0.90 (- 1.45, - 0.36), p = 0.001] and 24 [- 0.82, (- 1.38, - 0.27), p = 0.004]. EA and BFAA significantly improved both Patient-Reported Outcomes Measurement Information System (PROMIS) - Global Health physical health and mental health component scores at week 12 compared to UC. Mild toxicities were reported. CONCLUSION: EA was more effective than BFAA at reducing pain severity, but both similarly improved physical and mental health scores. Breast cancer survivors with chronic musculoskeletal pain may consider EA before BFAA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02979574. https://clinicaltrials.gov/ct2/show/NCT02979574.

Long-term exposure to polystyrene microplastics triggers premature testicular aging.

BACKGROUND: Plastic pollution is greatly serious in the ocean and soil. Microplastics (MPs) degraded from plastic has threatened animals and humans health. The accumulation of MPs in the tissues and blood in animals and humans has been found. There is therefore a need to assess the toxicological effects of MPs on the reproductive system. RESULTS: In this study, we explored the effect of polystyrene microplastics (PS-MPs) on premature testicular aging in vitro and in vivo. In vitro, we found that testicular sertoli cells (TM4 cells) was prematurely senescent following PS-MPs treatment by the evaluation of a range of aging marker molecules (such as Sa-ß-gal, p16 and 21). TM4 cells were then employed for in vitro model to study the potential molecular mechanism by which PS-MPs induce the premature senescence of TM4 cells. NF-κB is identified as a key molecule for PS-MPs-induced TM4 cellular senescence. Furthermore, through eliminating reactive oxygen species (ROS), the activation of nuclear factor kappa B (NF-κB) was blocked in PS-MPs-induced senescent TM4 cells, indicating that ROS triggers NF-κB activation. Next, we analyzed the causes of mitochondrial ROS (mtROS) accumulation induced by PS-MPs, and results showed that Ca2+ overload induced the accumulation of mtROS. Further, PS-MPs exposure inhibits mitophagy, leading to the continuous accumulation of senescent cells. In vivo, 8-week-old C57 mice were used as models to assess the effect of PS-MPs on premature testicular aging. The results illustrated that PS-MPs exposure causes premature aging of testicular tissue by testing aging markers. Additionally, PS-MPs led to oxidative stress and inflammatory response in the testicular tissue. CONCLUSION: In short, our experimental results revealed that PS-MPs-caused testicular premature aging is dependent on Ca2+/ROS/NF-κB signaling axis. The current study lays the foundation for further exploration of the effects of microplastics on testicular toxicology.

The role of sclerostin in lipid and glucose metabolism disorders.

Lipid and glucose metabolism are critical for human activities, and their disorders can cause diabetes and obesity, two prevalent metabolic diseases. Studies suggest that the bone involved in lipid and glucose metabolism is emerging as an endocrine organ that regulates systemic metabolism through bone-derived molecules. Sclerostin, a protein mainly produced by osteocytes, has been therapeutically targeted by antibodies for treating osteoporosis owing to its ability to inhibit bone formation. Moreover, recent evidence indicates that sclerostin plays a role in lipid and glucose metabolism disorders. Although the effects of sclerostin on bone have been extensively examined and reviewed, its effects on systemic metabolism have not yet been well summarized. In this paper, we provide a systemic review of the effects of sclerostin on lipid and glucose metabolism based on in vitro and in vivo evidence, summarize the research progress on sclerostin, and prospect its potential manipulation for obesity and diabetes treatment.

RNA-targeted small-molecule drug discoveries: a machine-learning perspective.

In the past two decades, machine learning (ML) has been extensively adopted in protein-targeted small molecule (SM) discovery. Once trained, ML models could exert their predicting abilities on large volumes of molecules within a short time. However, applying ML approaches to discover RNA-targeted SMs is still in its early stages. This is primarily because of the intrinsic structural instability of RNA molecules that impede the structure-based screening or designing of RNA-targeted SMs. Recently, with more studies revealing RNA structures and a growing number of RNA-targeted ligands being identified, it resulted in an increased interest in the field of drugging RNA. Undeniably, intracellular RNA is much more abundant than protein and, if successfully targeted, will be a major alternative target for therapeutics. Therefore, in this context, as well as under the premise of having RNA-related research data, ML-based methods can get involved in improving the speed of traditional experimental processes. [Figure: see text].

Attenuation of amyloid-ß-induced mitochondrial dysfunction by active components of anthocyanins in HT22 neuronal cells.

Alzheimer's disease (AD) is a common form of neurodegenerative disease in the elderly. Amyloid-ß (Aß)-associated neurotoxicity is an important component of the neurodegenerative change in AD. Recent studies have revealed a beneficial effect of anthocyanins in improving learning and memory in AD animal models. Using cultured HT22 mouse hippocampal neuronal cells as an in vitro model, we examined in this study the protective effect of ten pure components of anthocyanins against Aß 42-induced cytotoxicity and also investigated the mechanism of their protective effects. We found that treatment of HT22 cells with the pure components of anthocyanins dose-dependently rescued Aß 42-induced cytotoxicity, with slightly different potencies. Using petunidin as a representative compound, we found that it enhanced mitochondrial homeostasis and function in Aß 42-treated HT22 cells. Mechanistically, petunidin facilitated ß-catenin nuclear translocation and enhanced the interaction between ß-catenin and TCF7, which subsequently upregulated mitochondrial homeostasis-related protein Mfn2, thereby promoting restoration of mitochondrial homeostasis and function in Aß 42-treated HT22 cells. Together, these results reveal that the pure components of anthocyanins have a strong protective effect in HT22 cells against Aß 42-induced cytotoxicity by ameliorating mitochondrial homeostasis and function in a ß-catenin/TCF-dependent manner.

HKDC1 Silencing Inhibits Proliferation and Glycolysis of Gastric Cancer Cells.

Gastric cancer (GC) is the third most lethal and fifth most common cancer in the world. In a variety of cancers, the hexokinase domain component 1 (HKDC1) is carcinogenic. This study was to investigate into how HKDC1 contributes to the development and progression of GC. Three different datasets (GSE103236, GSE13861, and GSE55696) were extracted from the Gene Expression Omnibus (GEO) database and then analyzed using the sva package. The R software was used to identify 411 differentially expressed genes (DEGs) in the pooled dataset. We discovered 326 glycolysis-related genes (glyGenes) in the cancer genome atlas-stomach adenocarcinoma (TCGA-STAD) cohort using gene set enrichment analysis set (GSEA). HKDC1 is one of the most prevalent glyGenes in GC tumor tissues and cells, as seen in the Venn diagram. According to the results of the Cell Count Kit-8 assay, the proliferation of AGS and MKN-45 cells decreased when HKDC1 was knocked down. Lack of HKDC1 in cells enhanced oxygen consumption and decreased glycolytic protein expression while suppressing glucose absorption, lactate production, ATP level, and extracellular acidification ratio. As an oncogene in gastric cancer development, HKDC1 influences cell proliferation and glycolysis.