[Comparison of the efficacy of phlebotomy under touch pain point and ultrasound-guided puncture decompression in the treatment of acute calcific supraspinatus tendinitis].

OBJECTIVE: To compare the efficacy of blood letting under pain point touch and ultrasound-guided puncture decompression in the treatment of acute supraspinatus muscle calcifying tendinitis. METHODS: From January 2020 to January 2023, 45 patients with acute supraspinatus muscle calcifying tendinitis were selected and divided into treatment group and control group. In the treatment group, a total of 22 patients were treated with ultrasound-guided puncture decompression, including 16 females and 6 males, aged from 20 to 64 years old(39.31±5.80) years old, 11 on the left shoulder and 11 on the right shoulder. In the control group, there were 23 cases, including 15 females and 8 males, aged from 19 to 66 years old (40.67±6.13) years old, 12 on the left shoulder and 13 on the right shoulder. The treatment was treated with pain point touch bloodletting therapy. The visual analog scale (VAS) pain score, University of California, Los Angeles(UCLA) shoulder system score and shoulder Constant-Murley score were used to evaluate the therapeutic effect before treatment, 1 weeks, 1 month and 3 months after treatment, respectively. RESULTS: One patient in the control group gave up follow-up for personal reasons after 1 week of treatment, and the other 44 patients completed all follow-up. Six months after treatment, there were no recurrence cases in both groups. After statistical analysis, VAS pain score, UCLA score and Constant-Murley score of the treatment group and the control group were significantly different from those before treatment (P<0.05), and the improvement was more obvious in the treatment group. There was no statistical significance between the two groups (P>0.05). CONCLUSION: Bloodletting under pain point touch and ultrasound-guided puncture decompression are effective in the treatment of acute calcific supraspinatus tendinitis, with simple operation and low cost, which can effectively reduce local pain and effectively improve shoulder joint function. Primary hospitals can selectively operate treatment according to their own conditions.

Trends in Mortality After Incident Hospitalization for Heart Failure Among Medicare Beneficiaries.

Importance: Despite advances in treatment and care quality for patients hospitalized with heart failure (HF), minimal improvement in mortality has been observed after HF hospitalization since 2010. Objective: To evaluate trends in mortality rates across specific intervals after hospitalization. Design, Setting, and Participants: This cohort study evaluated a random sample of Medicare fee-for-service beneficiaries with incident HF hospitalization from January 1, 2008, to December 31, 2018. Data were analyzed from February 2023 to May 2024. Main Outcomes and Measures: Unadjusted mortality rates were calculated by dividing the number of all-cause deaths by the number of patients with incident HF hospitalization for the following periods: in-hospital, 30 days (0-30 days after hospital discharge), short term (31 days to 1 year after discharge), intermediate term (1-2 years after discharge), and long term (2-3 years after discharge). Each period was considered separately (ie, patients who died during one period were not counted in subsequent periods). Annual unadjusted and risk-adjusted mortality ratios were calculated (using logistic regression to account for differences in patient characteristics), defined as observed mortality divided by expected mortality based on 2008 rates. Results: A total of 1 256 041 patients (mean [SD] age, 83.0 [7.6] years; 56.0% female; 86.0% White) were hospitalized with incident HF. There was a substantial decrease in the mortality ratio for the in-hospital period (unadjusted ratio, 0.77; 95% CI, 0.67-0.77; risk-adjusted ratio, 0.74; 95% CI, 0.71-0.76). For subsequent periods, mortality ratios increased through 2013 and then decreased through 2018, resulting in no reductions in unadjusted postdischarge mortality during the full study period (30-day mortality ratio, 0.94; 95% CI, 0.82-1.06; short-term mortality ratio, 1.02; 95% CI, 0.87-1.17; intermediate-term mortality ratio, 0.99; 95% CI, 0.79-1.19; and long-term mortality ratio, 0.96; 95% CI, 0.76-1.16) and small reductions in risk-adjusted postdischarge mortality during the full study period (30-day mortality ratio, 0.88; 95% CI, 0.86-0.90; short-term mortality ratio, 0.94; 95% CI, 0.94-0.95; intermediate-term mortality ratio, 0.94; 95% CI, 0.92-0.95; and long-term mortality ratio, 0.95; 95% CI, 0.93-0.96). Conclusions and Relevance: In this study of Medicare fee-for-service beneficiaries, there was a substantial decrease in in-hospital mortality for patients hospitalized with incident HF from 2008 to 2018, but little to no reduction in mortality for subsequent periods up to 3 years after hospitalization. These results suggest opportunities to improve longitudinal outpatient care for patients with HF after hospital discharge.

An Effective Strategy on Synthesizing a Stable SiOx-Based Anode for High Density Lithium-Ion Batteries.

Silicon oxides (SiOx) have received extensive attention as an promising anode candidate for next-generation lithium-ion batteries (LIBs). However, their commerical applications have been seriously hindered by low conductivity, large volume expansion and unstable soild-electrolyte interface (SEI) layer, which result in low intial coulombic efficiency, poor rate performance and short cycling lifepan. In this work, we demonstrate a simple way to prepare a series of SiOx materials with lithium fluoride (LiF) modified by hydrothermal method and carbothermal modification. When the mass ratio of SiOx and LiF equals 1:0.15, the long-term cycling capacity retention can be greatly improve form 30.2% to 76.7% after 200 cycles. The result is primarily because the enhancement of electrons and Li+-ions transport and the stability of SEI layer due to LiF addition. However, excess LiF addition can hinder the diffusion of Li+-ions. This study presents the great potential of LiF modified on SiOx anode materials for LIBs.

Partial response of hepatocellular carcinoma to lenalidomide following progression in response to lenvatinib: A case report.

Hepatocellular carcinoma (HCC) is one of the most aggressive types of cancer. Although it has a high mortality rate, there is currently no effective treatment for HCC. Lenvatinib has traditionally been used as the first-line treatment for advanced HCC (aHCC); however, resistance to this therapy is common. It can be difficult to select effective second-line drugs to overcome lenvatinib resistance when treating aHCC. For patients with aHCC, poor treatment efficacy can result in patients missing the optimal treatment window and can lead to an irreversible situation. Lenalidomide has begun to be used to treat HCC; however, to the best of our knowledge, its efficacy in patients with lenvatinib-resistant HCC remains to be reported on in the literature. The present case report, to the best of our knowledge, describes the first case in the literature of a patient with lenvatinib-resistant aHCC who achieved a partial response after the treatment regimen was switched to lenalidomide. The present case report provides a promising novel route for the treatment of lenvatinib-resistant HCC.

Development of novel humanized CD19/BAFFR bicistronic chimeric antigen receptor T cells with potent antitumor activity against B-cell lineage neoplasms.

Chimeric antigen receptor T cell (CAR-T) therapy has shown remarkable efficacy in treating advanced B-cell malignancies by targeting CD19, but antigen-negative relapses and immune responses triggered by murine-derived antibodies remain significant challenges, necessitating the development of novel humanized multitarget CAR-T therapies. Here, we engineered a second-generation 4-1BB-CD3ζ-based CAR construct incorporating humanized CD19 single-chain variable fragments (scFvs) and BAFFR single-variable domains on heavy chains (VHHs), also known as nanobodies. The resultant CAR-T cells, with different constructs, were functionally compared both in vitro and in vivo. We found that the optimal tandem and bicistronic (BI) structures retained respective antigen-binding abilities, and both demonstrated specific activation when stimulated with target cells. At the same time, BI CAR-T cells (BI CARs) exhibited stronger tumour-killing ability and better secretion of interleukin-2 and tumour necrosis factor-alpha than single-target CAR-T cells. Additionally, BI CARs showed less exhaustion phenotype upon repeated antigen stimulation and demonstrated more potent and persistent antitumor effects in mouse xenograft models. Overall, we developed a novel humanized CD19/BAFFR bicistronic CAR (BI CAR) based on a combination of scFv and VHH, which showed potent and sustained antitumor ability both in vitro and in vivo, including against tumours with CD19 or BAFFR deficiencies.

A novel "mix-response" biosensor for colorimetric and photothermal dual-mode detection of sulfide ions in food based on silver-doping Prussian blue nanoparticle.

Effective identification of sulfur ions (S2-) in foodstuff is crucial for food safety and human health, but it remains challenging. Traditional single-mode colorimetric sensing methods are simple and sensitive, but are prone to interference from colored substances which can lead to false positives or negatives results. Herein, we develop a novel "mix-response" biosensor for colorimetric and photothermal dual-mode detection of S2- with good simplicity, sensitivity and portability. In this biosensor, silver-doping Prussian blue nanoparticle (SPB NPs) was used as signal output component, which not only exhibits blue color characteristics, but also has photothermal conversion properties activated by near-infrared (NIR) laser. Upon increasing the S2- concentration, the prepared SPB NPs undergo etching, leading to the formation of new silver sulfide precipitation (Ag2S), along with different colorimetric and photothermal response signals. For the portable visualization of S2-, the color information was recorded by a smartphone in combination with RGB (red channel) analysis and the evolution of the photothermal signal was documented by a thermal imager. The introduction of smartphone and handheld thermal imager in this "mix-response" biosensor makes it suitable for on-site quantitative detection of S2- without sophisticated instrument. Moreover, the development of this "mix-response" biosensor does not need the use of recognition probes (e.g. aptamers and reaction intermediates), thereby simplifying the construct procedures of sensing strategies and improving the economic efficiency of detection. More importantly, the photothermal response signals can overcome the interference of colored substances in foods, thereby reducing the false positives or negatives of the detection results.

A metabolic atlas of blood cells in young and aged mice identifies uridine as a metabolite to rejuvenate aged hematopoietic stem cells.

Aging of hematopoietic stem cells (HSCs) is accompanied by impaired self-renewal ability, myeloid skewing, immunodeficiencies and increased susceptibility to malignancies. Although previous studies highlighted the pivotal roles of individual metabolites in hematopoiesis, comprehensive and high-resolution metabolomic profiles of different hematopoietic cells across ages are still lacking. In this study, we created a metabolome atlas of different blood cells across ages in mice. We reveal here that purine, pyrimidine and retinol metabolism are enriched in young hematopoietic stem and progenitor cells (HSPCs), whereas glutamate and sphingolipid metabolism are concentrated in aged HSPCs. Through metabolic screening, we identified uridine as a potential regulator to rejuvenate aged HSPCs. Mechanistically, uridine treatment upregulates the FoxO signaling pathway and enhances self-renewal while suppressing inflammation in aged HSCs. Finally, we constructed an open-source platform for public easy access and metabolomic analysis in blood cells. Collectively, we provide a resource for metabolic studies in hematopoiesis that can contribute to future anti-aging metabolite screening.

Multi-strategy cooperative scheduling for airport specialized vehicles based on digital twins.

Efficient specialized vehicle cooperative scheduling is significant for airport operations, particularly during times of high traffic, which reduces the risk of flight delays and increases customer satisfaction. In this paper,we construct a multi-type vehicles collaborative scheduling model with the objectives of minimizing vehicle travel distance and vehicle waiting time. Additionally, a three-layer genetic algorithm is designed, and the crossover and mutation operations are enhanced to address the scheduling model. Due to the numerous uncertainties and stochastic interferences in airport operations, conventional scheduling methods unable to effectively address these challenges, this paper combines improved genetic algorithm, simulation algorithm, and digital twins technology, proposing a multi-strategy scheduling framework for specialized vehicles based on digital twins. The scheduling framework utilises digital twins to capture dynamic data from the airport and continuously adjusts the scheduling plan through the scheduling strategy to ensure robust scheduling for specialized vehicles. In the event of severe delays at the airport, fast and efficient re-scheduling can be achieved. Finally, the effectiveness of the proposed scheduling framework is validated using domestic flight data, and extensive experiments and analyses are conducted in different scenarios. This research contributes to addressing the optimization problem of cooperative scheduling for multi-type vehicles at airports.

Ratiometric fluorescent determination of sulfadimethoxine in foods based on a dual-emission metal-organic framework.

Ratiometric fluorescence detection is endowed with higher accuracy than single fluorescence signal assay. In this work, we construct a ratiometric fluorescence probe for the facile quantification of sulfadimethoxine (SDM) in foods. By wrapping N-doped carbon dots (N-CDs) and gold nanoclusters (AuNCs) into zeolitic imidazolate framework-8 (ZIF-8), the nanocomposite of N-CDs/AuNCs@ZIF-8 is facilely prepared and emits two fluorescence including 475 nm from N-CDs and 650 nm from AuNCs. Since bovine serum albumin (BSA) is the stabilizer of AuNCs, SDM can form a complex with BSA, resulting in the fluorescence quenching of AuNCs at 650 nm by a static quenching mechanism. In contrast, SDM has a rare influence on the fluorescence of N-CDs (475 nm). As a result, the use of the probe of N-CDs/AuNCs@ZIF-8 for SDM detection enables simultaneous measurement of response signal and reference signal. Under the optimal condition, the SDM assay based on the probe has a good linear relationship within 10 to 2 × 106 ng/mL and the limit of detection (LOD) is low to 1.064 ng/mL. In addition, the fluorescent probe shows good reliability for the detection of SDM in practical food samples.

A laponite-based immunologically active gel delivery system for long-acting tumor vaccine.

Traditional bolus vaccines typically require multiple doses, which complicates the vaccination process and may cause missed shots, leading to sub-optimal immunity and reduced vaccine effectiveness. Herein, a gel-based long-acting vaccine system with self-adjuvant properties based on laponite was constructed to simplify vaccination procedures and improve vaccine effectiveness. Firstly, the gel system could recruit multiple types of immune cells to form immune niches. Secondly, it could achieve sustained delivery of antigens to lymph nodes by active transport and passive drainage. Then, the gel system triggered the formation of a large number of germinal centers, which elicited enhanced and durable humoral immune responses, as well as strong cellular immune responses. As a result, it eventually showed good prophylactic and therapeutic effects in a variety of tumor models including melanoma, colorectal cancer and peritoneal metastasis models. By further combining the immunoadjuvant CpG ODN and cytokine IL-12, the effect of the gel-vaccine could be further enhanced. In a murine peritoneal metastasis model of colorectal carcinoma, a single administration of the gel-vaccine resulted in complete tumor eradication in 8/9 mice. In summary, this study developed an immunologically active gel-vaccine system. And as a robust and versatile vaccine platform, by loading different antigens and adjuvants, this gel-vaccine system is expected to realize its better therapeutic potential.

Establishment of a humanized mouse model using steady-state peripheral blood-derived hematopoietic stem and progenitor cells facilitates screening of cancer-targeted T-cell repertoires.

Background: Cancer-targeted T-cell receptor T (TCR-T) cells hold promise in treating cancers such as hematological malignancies and breast cancers. However, approaches to obtain cancer-reactive TCR-T cells have been unsuccessful. Methods: Here, we developed a novel strategy to screen for cancer-targeted TCR-T cells using a special humanized mouse model with person-specific immune fingerprints. Rare steady-state circulating hematopoietic stem and progenitor cells were expanded via three-dimensional culture of steady-state peripheral blood mononuclear cells, and then the expanded cells were applied to establish humanized mice. The human immune system was evaluated according to the kinetics of dendritic cells, monocytes, T-cell subsets, and cytokines. To fully stimulate the immune response and to obtain B-cell precursor NAML-6- and triple-negative breast cancer MDA-MB-231-targeted TCR-T cells, we used the inactivated cells above to treat humanized mice twice a day every 7 days. Then, human T cells were processed for TCR ß-chain (TRB) sequencing analysis. After the repertoires had been constructed, features such as the fraction, diversity, and immune signature were investigated. Results: The results demonstrated an increase in diversity and clonality of T cells after treatment. The preferential usage and features of TRBV, TRBJ, and the V-J combination were also changed. The stress also induced highly clonal expansion. Tumor burden and survival analysis demonstrated that stress induction could significantly inhibit the growth of subsequently transfused live tumor cells and prolong the survival of the humanized mice. Conclusions: We constructed a personalized humanized mouse model to screen cancer-targeted TCR-T pools. Our platform provides an effective source of cancer-targeted TCR-T cells and allows for the design of patient-specific engineered T cells. It therefore has the potential to greatly benefit cancer treatment.

Tracking 5-Year Trends in the Workforce Prescribing Psychotropics and Medications for Opioid Use Disorder: A Cross-Sectional Study.

BACKGROUND: Although there is increased demand for behavioral health services, there is limited national data on the workforce prescribing psychotropics and/or medications for opioid use disorder (MOUD), and many current estimates are based on self-reported data or clinician rosters. OBJECTIVE: To describe trends in the workforce prescribing psychotropics (i.e., antidepressants, antipsychotics, antianxiety medications, mood stabilizers) and/or MOUD from 2017 to 2021. DESIGN: Cross-sectional analysis of 2017-2021 IQVIA Xponent retail prescription claims data. PARTICIPANTS: Clinicians who prescribed more than ten total prescriptions for psychotropics and/or MOUD in a calendar year. MAIN MEASURES: We analyzed the number of prescriptions and prescribers by year, month, drug type, specialty type, payor type, and clinician county rurality. KEY RESULTS: There was a 2.7% increase in the number of prescribers between 2017 and 2021, with the highest growth among psychiatric nurse practitioners (44.7%), nurse practitioners (25.5%), and physician assistants (6.5%). Primary care physicians (PCPs) and advanced practice clinicians (APCs) made up more than half of the workforce but prescribed 3.5 times fewer prescriptions on average compared to psychiatric and addiction medicine specialists. PCPs and APCs in rural areas wrote the most prescriptions collectively for psychotropics and MOUD per month. CONCLUSIONS: Using prescription data, a proxy for being active in the workforce, goes beyond specialty designation to identify the full workforce prescribing psychotropics and MOUD, including the growing role of APCs and PCPs.

A novel lncRNA LOC101928222 promotes colorectal cancer angiogenesis by stabilizing HMGCS2 mRNA and increasing cholesterol synthesis.

BACKGROUND: Metastasis is the leading cause of mortality in patients with colorectal cancer (CRC) and angiogenesis is a crucial factor in tumor invasion and metastasis. Long noncoding RNAs (lncRNAs) play regulatory functions in various biological processes in tumor cells, however, the roles of lncRNAs in CRC-associated angiogenesis remain to be elucidated in CRC, as do the underlying mechanisms. METHODS: We used bioinformatics to screen differentially expressed lncRNAs from TCGA database. LOC101928222 expression was assessed by qRT-PCR. The impact of LOC101928222 in CRC tumor development was assessed both in vitro and in vivo. The regulatory mechanisms of LOC101928222 in CRC were investigated by cellular fractionation, RNA-sequencing, mass spectrometric, RNA pull-down, RNA immunoprecipitation, RNA stability, and gene-specific m6A assays. RESULTS: LOC101928222 expression was upregulated in CRC and was correlated with a worse outcome. Moreover, LOC101928222 was shown to promote migration, invasion, and angiogenesis in CRC. Mechanistically, LOC101928222 synergized with IGF2BP1 to stabilize HMGCS2 mRNA through an m6A-dependent pathway, leading to increased cholesterol synthesis and, ultimately, the promotion of CRC development. CONCLUSIONS: In summary, these findings demonstrate a novel, LOC101928222-based mechanism involved in the regulation of cholesterol synthesis and the metastatic potential of CRC. The LOC101928222-HMGCS2-cholesterol synthesis pathway may be an effective target for diagnosing and managing CRC metastasis.

Organolanthanide Single-Molecule Magnets with Heterocyclic Ligands.

Lanthanide (Ln) based mononuclear single-molecule magnets (SMMs) provide probably the finest ligand regulation model for magnetic property. Recently, the development of such SMMs has witnessed a fast transition from coordination to organometallic complexes because the latter provides a fertile, yet not fully excavated soil for the development of SMMs. Especially those SMMs with heterocyclic ligands have shown the potential to reach higher blocking temperature. In this minireview, we give an overview of the design principle of SMMs and highlight those "shining stars" of heterocyclic organolanthanide SMMs based on the ring sizes of ligands, analysing how the electronic structures of those ligands and the stiffness of subsequently formed molecules affect the dynamic magnetism of SMMs. Finally, we envisaged the future development of heterocyclic Ln-SMMs.

Health care provider movement increased through COVID-19.

COVID-19 placed unprecedented strain on the health workforce, raising concerns of increasing worker turnover and attrition. This study explores the use of 2 publicly available Medicare datasets-Provider Enrollment, Chain, and Ownership System (PECOS) and Doctors and Clinicians-to track provider movement across states and organizations from 2017 to 2023. We found an increase in state-to-state movement of providers post-COVID-19, with an initial spike in physician movement in the first year (April 2020 to March 2021). Movement varied across specialties and professions. Between organizations, we saw an initial increase in movement for family physicians but not internal medicine physicians. Overall, provider movement was generally to larger organizations. Our study finds increasing movement of providers in the post-COVID-19 period through the novel use of 2 publicly available Medicare datasets. Tracking health care workforce movement closer to real time is important to understand a changing workforce-with differences across communities-and to guide policies to ensure sufficient workforce and prevent worsening disparities over time.

Synchrony or asynchrony: development of facial expression recognition from childhood to adolescence based on large-scale evidence.

The development of facial expression recognition ability in children is crucial for their emotional cognition and social interactions. In this study, 510 children aged between 6 and 15 participated in a two forced-choice task of facial expression recognition. The findings supported that recognition of the six basic facial expressions reached a relatively stable mature level around 8-9 years old. Additionally, model fitting results indicated that children showed the most significant improvement in recognizing expressions of disgust, closely followed by fear. Conversely, recognition of expressions of happiness and sadness showed slower improvement across different age groups. Regarding gender differences, girls exhibited a more pronounced advantage. Further model fitting revealed that boys showed more pronounced improvements in recognizing expressions of disgust, fear, and anger, while girls showed more pronounced improvements in recognizing expressions of surprise, sadness, and happiness. These clear findings suggested the synchronous developmental trajectory of facial expression recognition from childhood to adolescence, likely influenced by socialization processes and interactions related to brain maturation.

A more complete measure of vertical integration between physicians and hospitals.

OBJECTIVE: To develop an accurate and reproducible measure of vertical integration between physicians and hospitals (defined as hospital or health system employment of physicians), which can be used to assess the impact of integration on healthcare quality and spending. DATA SOURCES AND STUDY SETTING: We use multiple data sources including from the Internal Revenue Service, the Centers for Medicare and Medicaid Services, and others to determine the Tax Identification Numbers (TINs) that hospitals and physicians use to bill Medicare for services, and link physician billing TINs to hospital-related TINs. STUDY DESIGN: We developed a new measure of vertical integration, based on the TINs that hospitals and physicians use to bill Medicare, using a broad set of sources for hospital-related TINs. We considered physicians as hospital-employed if they bill Medicare primarily or exclusively using hospital-related TINs. We assessed integration status for all physicians who billed Medicare from 1999 to 2019. We compared this measure with others used in the existing literature. We conducted a simulation study which highlights the importance of accurately identifying integrated physicians when study the effects of integration. DATA COLLECTION/EXTRACTION METHODS: We extracted physician and hospital-related TINs from multiple sources, emphasizing specificity (a small proportion of nonintegrated physicians identified as integrated). PRINCIPAL FINDINGS: We identified 12,269 hospital-related TINs, used for billing by 546,775 physicians. We estimate that the percentage of integrated physicians rose from 19% in 1999 to 43% in 2019. Our approach identifies many additional physician practices as integrated; a simpler TIN measure, comparable with prior work, identifies only 30% (3877) of the TINs we identify. A service location measure, used in prior work, has both many false positives and false negatives. CONCLUSION: We developed a new measure of hospital-physician integration. This measure is reproducible and identifies many additional physician practices as integrated.

Programmed cell death factor 4-mediated hippocampal synaptic plasticity is involved in early life stress and susceptibility to depression.

Early life stress (ELS) increases the risk of depression later in life. Programmed cell death factor 4 (PDCD4), an apoptosis-related molecule, extensively participates in tumorigenesis and inflammatory diseases. However, its involvement in a person's susceptibility to ELS-related depression is unknown. To examine the effects and underlying mechanisms of PDCD4 on ELS vulnerability, we used a "two-hit" stress mouse model: an intraperitoneal injection of lipopolysaccharide (LPS) into neonatal mice was performed on postnatal days 7-9 (P7-P9) and inescapable foot shock (IFS) administration in adolescent was used as a later-life challenge. Our study shows that compared with mice that were only exposed to the LPS or IFS, the "two-hit" stress mice developed more severe depression/anxiety-like behaviors and social disability. We detected the levels of PDCD4 in the hippocampus of adolescent mice and found that they were significantly increased in "two-hit" stress mice. The results of immunohistochemical staining and Sholl analysis showed that the number of microglia in the hippocampus of "two-hit" stress mice significantly increased, with morphological changes, shortened branches, and decreased numbers. However, knocking down PDCD4 can prevent the number and morphological changes of microglia induced by ELS. In addition, we confirmed through the Golgi staining and immunohistochemical staining results that knocking down PDCD4 can ameliorate ELS-induced synaptic plasticity damage. Mechanically, the knockdown of PDCD4 exerts neuroprotective effects, possibly via the mediation of BDNF/AKT/CREB signaling. Combined, these results suggest that PDCD4 may play an important role in the ELS-induced susceptibility to depression and, thus, may become a therapeutic target for depressive disorders.

Aflatoxin B1 induces ROS-dependent mitophagy by modulating the PINK1/Parkin pathway in HepG2 cells.

Aflatoxin B1 (AFB1) is extremely harmful to both humans and animals. Mitophagy is a selective process of self-elimination and has an important role in controlling mitochondrial quality. The present study aimed to investigate the effect of reactive oxygen species (ROS) accumulation on AFB1-induced mitophagy in HepG2 cells to provide a new perspective from which to design novel therapeutic strategies to treat AFB1 poisoning. ROS release was induced in HepG2 cells with AFB1 (10 µmol/L). Cell autophagy activity, mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) levels, Parkin translocation and both the transcription and expression of mitophagy-related proteins were measured when N-acetyl-L-cysteine (NAC) partially decreased the ROS level, while the knockdown of nuclear factor erythroid 2-related factor 2 (Nrf2) resulted in a large accumulation of ROS. The results reveal that NAC pretreatment ameliorated the decline in both the MMP and the ATP levels while also activating phosphoglycerate mutase 5 (PGAM5)-PTEN-induced kinase 1 (PINK1)/Parkin, while the Nrf2 knockdown group exhibited the opposite trend. These results suggest that AFB1-induced mitophagy in HepG2 cells depends on ROS, and proper ROS activates mitophagy to play a protective role.