Autoimmune encephalitis followed by hemophagocytic lymph histiocytosis: a case report.

Objective: This study aims to report three cases of autoimmune encephalitis followed by hemophagocytic lymphohistiocytosis. Methods: Data of relevant patients treated between 2019 and 2022 were retrospectively collected from the Department of Neurology at the Second Affiliated Hospital of Guangzhou Medical University. Results: The age at onset of the three patients was 37, 63, and 36 years, respectively. All three patients were female and presented with cognitive dysfunction and seizures. Behavioral and psychological symptoms were also observed in two cases. All patients were positive for autoantibodies in both the cerebrospinal fluid and serum, while two showed multiple abnormal brain signals on magnetic resonance imaging. All patients exhibited hypocytosis and elevated soluble CD25 and serum ferritin levels. The final diagnoses in two cases were lymphomas, while the remaining case without tumors suffered from a severe infection. All patients received immunotherapy, and the two with lymphoma received anti-tumor treatment. The patient with infection died, and two patients with tumors improved after chemotherapy. Conclusion: Autoimmune encephalitis followed by hemophagocytic lymphohistiocytosis is a rare and severe condition. Prompt attention should be paid to the decline in blood cell counts, particularly in patients who show a slight improvement after immunotherapy or have a risk of lymphoma. Screening for potential tumors and infections and early treatment may help these patients.

REEP4 as Potential Biomarker Associated with Predictive Prognosis and Immune Response in Kidney Clear Cell Carcinoma.

Kidney clear cell carcinoma (KIRC) commonly presents with metastases upon diagnosis, highlighting the critical need to identify more precise biomarkers for early detection, intervention, and personalized treatment. Although The REEP family has been investigated in cancer development, the specific relationship between REEP4 and cancer remains unclear. In our study, we employed bioinformatics analysis and conducted fundamental experiments to evaluate the potential of REEP4 as a biomarker for predicting the prognosis and therapeutic efficacy of KIRC. Comparing KIRC tumor tissues to normal tissues, we observed a significant upregulation in REEP4 expression, with higher levels of REEP4 correlating positively with tumor malignancy. Further COX regression analysis, as well as single and multifactorial analyses, confirmed that high REEP4 expression indicated lower survival rates in KIRC. Gene function analysis also identified associations between REEP4 and critical pathways such as the cell cycle, along with its involvement in protein binding. Furthermore, our investigation of the immune response suggests that a favorable immunotherapeutic response is linked to a reduction in REEP4 expression. Subsequently, we conducted in vitro experiments to confirm the overexpression of REEP4 in KIRC tumor tissues and renal cancer cells. In summary, our study revealed a close association between REEP4 expression and KIRC, emphasizing its correlation with prognosis and the immune response. These findings suggest that REEP4 is a potential biomarker for KIRC.

Childhood exposure to polycyclic aromatic hydrocarbons is associated with emotional and behavioral problems in adolescence: a longitudinal study in China.

PURPOSE: The aim of this study was to investigate the relationship between childhood polycyclic aromatic hydrocarbon (PAH) exposure and emotional and behavioral problems in adolescence. METHODS: Participants included 998 school-age children aged 7-12 years (514 girls and 484 boys). Metabolite concentrations of four PAHs (1-hydroxypyrene [1-OHPyr], 2-hydroxynaphthalene [2-OHNap], 2-hydroxyfluorine [2-OHFlu], and 9-hydroxyphenanthrene [9-OHPhe]) were measured in urine samples at baseline (Dec 2014-Dec 2015). During adolescence, we measured emotional and behavioral problems in study participants. We used logistic regression models to assess the effects of different levels of PAH metabolite concentrations on emotional and behavioral problems for boys and girls, separately. RESULTS: Boys exposed to 1-OHPyr and 2-OHFlu had a significantly higher risk of externalizing problems (OR: 2.62, 95% CI: 1.09 ~ 6.29; OR: 2.92, 95% CI: 1.15 ~ 7.42). 2-OHNap exposure faced a higher risk of internalizing problems (OR: 3.85, 95% CI: 1.28 ~ 11.58; OR: 3.63, 95% CI: 1.13 ~ 11.63) and externalizing problems (OR: 4.27, 95% CI: 1.44 ~ 12.70; OR: 4.68, 95% CI: 1.49 ~ 14.73). Moreover, boys exposed to 9-OHPhe exhibited a significant risk of anxiety (OR: 2.84, 95% CI: 1.01 ~ 7.97; OR: 3.00, 95% CI: 1.04 ~ 8.68). Similarly, girls exposed to 9-OHPhe had a significant risk of anxiety (OR: 2.41, 95% CI: 1.25 ~ 4.64). CONCLUSION: Childhood PAH exposures are associated with emotional and behavioral problems in adolescence, and boys seem more susceptible than girls.

Effective alleviation of depressive and anxious symptoms and sleep disorders in benzodiazepine-dependent patients through repetitive transcranial magnetic stimulation.

Benzodiazepine (BZD) dependence poses a significant challenge in mental health, prompting the exploration of treatments like repetitive transcranial magnetic stimulation (rTMS). This research aims to assess the impact of rTMS on alleviating symptoms of BZD dependence. A randomized control trial was employed to study 40 BZD-dependent inpatients. Their symptoms were quantified using the Hamilton Anxiety Rating Scale (HAMA), Montgomery-Åsberg Depression Rating Scale (MADRS) and Pittsburgh Sleep Quality Index (PSQI). Participants were divided into a conventional treatment group (daily diazepam with gradual tapering) with supportive psychotherapy and another group receiving the same treatment supplemented with rTMS (five weekly sessions for 2 weeks). Significant improvements were observed in both groups over baseline in MADRS, HAMA and PSQI scores at the 2nd, 4th, 8th and 12th week assessments (p < 0.05). The group receiving rTMS in addition to conventional treatment exhibited superior improvements in all measures at the 8th and 12th weeks. The addition of rTMS to conventional treatment methods for BZD dependence significantly betters the recovery in terms of depression, anxiety and sleep quality, highlighting the role of rTMS as an effective adjunct therapy.

Clinical Efficacy of Taxol Plus Platinum (TP) Chemotherapy Combined with Delayed Administration of PD-1 Inhibitors in Patients with Locally Advanced, Recurrent or Metastatic Esophageal Squamous Cell Carcinoma: A Retrospective Study.

Purpose: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have become the first-line standard treatment for locally advanced or metastatic esophageal squamous cell carcinoma (ESCC). The evidence also demonstrates improved synergistic effects of chemotherapy when combined with delayed administration of ICIs. In this study, we conducted a retrospective investigation into the treatment efficacy of taxol plus platinum (TP) chemotherapy combined with delayed administration of PD-1 inhibitors for ESCC patients. Patients and Methods: Clinical data of ESCC patients who received PD-1 inhibitors 3-5 days after TP chemotherapy as first-line treatment was retrospectively reviewed between January 2019 and April 2023. Clinical outcomes and treatment safety were analyzed. The potential roles of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and pan-immune-inflammation value (PIV) were investigated. Results: A total of 34 locally advanced, recurrent or metastatic ESCC patients received PD-1 inhibitors 3-5 days following TP chemotherapy were included. The objective response rate (ORR) and disease control rate (DCR) were 85.3% and 97.1% respectively. The median progression-free survival (PFS) and overall survival (OS) were 13.2 and 19.1 month respectively. Seven patients received radical surgery, 1 patient achieved pathologic complete response (pCR) and 3 patients achieved major pathologic response (MPR). Among the 27 patients without surgery, the median PFS and OS were 9.7 and 19.1 month respectively. A more favorable prognosis was correlated with NLR less than 3 at the 3rd and 4th cycle of immunochemotherapy. No significant correlations between other parameters (PLR, MLR and PIV) and prognosis were observed. A total of 22 patients developed grade 3-4 toxicity events. Conclusion: The optimized sequence of PD-1 inhibitors administered 3-5 days after TP chemotherapy as the first-line treatment of ESCC demonstrated favorable treatment efficacy. Pretreatment NLR of less than 3 at the 3rd and 4th cycle of immunochemotherapy is associated with a better prognosis.

Multiple-resonance thermally activated delayed fluorescence materials based on phosphorus central chirality for efficient circularly polarized electroluminescence.

Circularly polarized organic light-emitting diodes (CP-OLEDs) hold great potential for naked-eye 3D displays, necessitating efficient chiral luminescent materials with an optimal CP luminescence (CPL) dissymmetry factor (g). Herein, we present the first chiral multiple resonance thermally activated delayed fluorescence (MR-TADF) materials containing a phosphorus chiral center by incorporating 5-phenylbenzo[b]phosphindole-5-oxide into the para-position of two MR-TADF cores. The compounds, NBOPO and NBNPO, exhibit photoluminescence peaks at 462 and 498 nm with narrow full-width at half-maximum values of 25 and 24 nm in toluene, respectively. Notably, (R/S)-NBOPO and (R/S)-NBNPO enantiomers display high quantum yields of 87% and 93% and symmetric CPL with |gPL| factors of 1.18 × 10-3 and 4.30 × 10-3, respectively, in doped films. Moreover, the corresponding CP-OLEDs show impressive external quantum efficiencies of 16.4% and 28.3%, along with symmetric CP electroluminescence spectra with |gEL| values of 7.0 × 10-4 and 1.4 × 10-3, respectively.

Do Children with Autism Spectrum Disorders Show Selective Trust in Social Robots?

PURPOSE: Previous researches suggest that social robots can facilitate the learning of children with Autism Spectrum Disorder (ASD) by enhancing their interests, engagement, and attention. However, there is limited understanding regarding whether children with ASD can learn directly from the testimony of social robots and whether they can remain vigilant based on the perceived accuracy of these robots. Therefore, the present study was conducted to examine whether children with ASD demonstrated selective trust towards social robots. METHODS: Twenty-nine children with ASD between ages of 4-7 years, and 38 typically-developing (TD) age and IQ-matched peers participated in classic selective trust tasks. During the tasks, they learned the names of novel objects from either a pair of social robots or a pair of human informants, where one informant had previously been established as accurate and the other inaccurate. RESULTS: Children with ASD trusted information from an accurate social robot over an inaccurate one, similar to their performance with human informants. However, compared to TD children, children with ASD exhibited lower levels of selective trust regardless of the type of informants they learned from. CONCLUSIONS: Our study suggests that children with ASD can selectively trust and acquire knowledge from social robots, shedding light on the potential use of social robots in supporting individuals with ASD.

Efficient hydroxyl radical generation of an activatable phthalocyanine photosensitizer: oligomer higher than monomer and nanoaggregate.

It remains a challenge to develop a single-component organic photosensitizer that efficiently produces hydroxyl radicals (˙OH) without oxygen involvement, especially while maintaining tumor-targeting capability. Herein, we propose an intelligent molecular design strategy whereby a tumor-targeted phthalocyanine is initially ˙OH-free and can be activated by overexpressed ß-nicotinamide adenine dinucleotide sodium salt hydrate (NAD(P)H) in hypoxic tumors to efficiently produce ˙OH under light irradiation. Furthermore, the oligomer models based on the phthalocyanine molecules were constructed by a supramolecular regulation strategy, which were in an intermediate state between monomer and nanoaggregate, to achieve enhanced ˙OH generation. The level of NAD(P)H in cancer cells can be exhausted through two pathways, including spontaneous redox and the photocatalytic redox of phthalocyanines. As a result, the in vivo and in vitro assays illustrated that the oligomeric phthalocyanine containing N-O units (OligPcNOB) can specifically target cancer cells and tumor tissue with overexpressing biotin receptors. OligPcNOB exhibited significant photocytotoxicity even in an extremely low oxygen environment and successfully inhibited tumor progression.

Interplay of miRNAs and molecular pathways in spaceflight-induced depression: Insights from a rat model using simulated complex space environment.

Depression is a significant concern among astronauts, yet the molecular mechanisms underlying spaceflight-induced depression remain poorly understood. MicroRNAs (miRNAs) have emerged as potential regulators of neuropsychiatric disorders, including depression, but their specific role in space-induced depression remains unexplored. This study aimed to elucidate the involvement of candidate miRNAs (miR-455-3p, miR-206-3p, miR-132-3p, miR-16-5p, miR-124-3p, and miR-145-3p) and their interaction with differentially expressed genes (DEGs) in the neurobiology of spaceflight-induced depressive behavior. Using a simulated space environmental model (SCSE) for 21 days, depressive behavior was induced in rats, and candidate miRNA expressions and DEGs in the cortex region were analyzed through qRT-PCR and HPLC, respectively. Results showed that SCSE-exposed rats exhibited depressive behaviors, including anhedonia, increased immobility, and anxiousness compared to controls. Further analysis revealed increased hydrogen peroxide levels and decreased superoxide dismutase levels in the SCSE group, indicating abnormal oxidative stress in the cerebral cortex. Moreover, miRNA analysis demonstrated significant upregulation of miR-455-3p, miR-206-3p, miR-132-3p, and miR-16-5p expression. Among the DEGs identified, the in silico analysis highlighted their involvement in crucial pathways such as glutamatergic signaling, GABA synaptic pathway, and calcium signaling, implicating their role in spaceflight-induced depression. Protein-protein interaction analysis identified hub genes, including DLG4, DLG3, GRIN1, GRIN2B, GRIN2A, SYNGAP1, DLGAP1, GRIK2, and GRIN3A, impacting neuronal dysfunction functions in the cortex region of SCSE depressive rats. DLG4 emerged as a core gene regulated by miR-455-3p and miR-206-3p. Overall, this study underscores the potential of miRNAs as biomarkers for mood disorders and neurological abnormalities associated with spaceflight, advancing health sciences, and space health care.

Ecliptasaponin A protects heart against acute ischemia-induced myocardial injury by inhibition of the HMGB1/TLR4/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Eclipta prostrata (Linn.) is a traditional medicinal Chinese herb that displays multiple biological activities, such as encompassing immunomodulatory, anti-inflammatory, anti-tumor, liver-protective, antioxidant, and lipid-lowering effects. Ecliptasaponin A (ESA), a pentacyclic triterpenoid saponin isolated from Eclipta prostrata (Linn.), has been demonstrated to exert superior anti-inflammatory activity against many inflammatory disorders. AIM OF THE STUDY: Inflammation plays a critical role in acute myocardial infarction (AMI). This study aims to explore the treatment effects of ESA in AMI, as well as the underlying mechanism. METHODS: An AMI mouse model was established in mice via left anterior descending coronary artery (LAD) ligation. After surgery, ESA was injected at doses of 0.5, 1.25, and 2.5 mg/kg, respectively. Myocardial infarction size, cardiomyocyte apoptosis and cardiac echocardiography were studied. The potential mechanism of action of ESA was investigated by RNA-seq, Western blot, surface plasmon resonance (SPR), molecular docking, and immunofluorescence staining. RESULTS: ESA treatment not only significantly reduced myocardial infarct size, decreased myocardial cell apoptosis, and inhibited inflammatory cell infiltration, but also facilitated to improve cardiac function. RNA-seq and Western blot analysis proved that ESA treatment-induced differential expression genes mainly enriched in HMGB1/TLR4/NF-κB pathway. Consistently, ESA treatment resulted into the down-regulation of IL-1ß, IL-6, and TNF-α levels after AMI. Furthermore, SPR and molecular docking results showed that ESA could bind directly to HMGB1, thereby impeding the activation of the downstream TLR4/NF-κB pathway. The immunofluorescence staining and Western blot results at the cellular level also demonstrated that ESA inhibited the activation of the HMGB1/TLR4/NF-κB pathway in H9C2 cells. CONCLUSION: Our study was the first to demonstrate a cardiac protective role of ESA in AMI. Mechanism study indicated that the treatment effects of ESA are mainly attributed to its anti-inflammatory activity that was mediated by the HMGB1/TLR4/NF-κB pathway.

Self-Regenerating Photothermal Agents for Tandem Photothermal and Thermodynamic Tumor Therapy.

Small molecule-based photothermal agents (PTAs) hold promising future for photothermal therapy; however, unexpected inactivation exerts negative impacts on their application clinically. Herein, a self-regenerating PTA strategy is proposed by integrating 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS•+) with a thermodynamic agent (TDA) 2,2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH). Under NIR laser, the photothermal effect of ABTS•+ accelerates the production of alkyl radicals by AIPH, which activates the regeneration of ABTS•+, thus creating a continuous positive feedback loop between photothermal and thermodynamic effects. The combination of ABTS•+ regeneration and alkyl radical production leads to the tandem photothermal and thermodynamic tumor therapy. In vitro and in vivo experiments confirm that the synergistic action of thermal ablation, radical damage, and oxidative stress effectively realizes tumor suppression. This work offers a promising approach to address the unwanted inactivation of PTAs and provides valuable insights for optimizing combination therapy.

A Renal Clearable Nano-Assembly with Förster Resonance Energy Transfer Amplified Superoxide Radical and Heat Generation to Overcome Hypoxia Resistance in Phototherapeutics.

Given that type I photosensitizers (PSs) possess a good hypoxic tolerance, developing an innovative tactic to construct type I PSs is crucially important, but remains a challenge. Herein, we present a smart molecular design strategy based on the Förster resonance energy transfer (FRET) mechanism to develop a type I photodynamic therapy (PDT) agent with an encouraging amplification effect for accurate hypoxic tumor therapy. Of note, benefiting from the FRET effect, the obtained nanostructured type I PDT agent (NanoPcSZ) with boosted light-harvesting ability not only amplifies superoxide radical (O2•-) production but also promotes heat generation upon near-infrared light irradiation. These features facilitate NanoPcSZ to realize excellent phototherapeutic response under both normal and hypoxic environments. As a result, both in vitro and in vivo experiments achieved a remarkable improvement in therapeutic efficacy via the combined effect of photothermal action and type I photoreaction. Notably, NanoPcSZ can be eliminated from organs (including the liver, lung, spleen, and kidney) apart from the tumor site and excreted through urine within 24 h of its systemic administration. In this way, the potential biotoxicity of drug accumulation can be avoided and the biosafety can be further enhanced.

Operando Spectroscopic Elucidation of the Bubble Sunshade Effect in Inorganic-Biological Hybrids for Photosynthetic Hydrogen Production.

Hydrogen production by photosynthetic hybrid systems (PBSs) offers a promising avenue for renewable energy. However, the light-harvesting efficiency of PBSs remains constrained due to unclear intracellular kinetic factors. Here, we present an operando elucidation of the sluggish light-harvesting behavior for existing PBSs and strategies to circumvent them. By quantifying the spectral shift in the structural color scattering of individual PBSs during the photosynthetic process, we observe the accumulation of product hydrogen bubbles on their outer membrane. These bubbles act as a sunshade and inhibit light absorption. This phenomenon elucidates the intrinsic constraints on the light-harvesting efficiency of PBSs. The introduction of a tension eliminator into the PBSs effectively improves the bubble sunshade effect and results in a 4.5-fold increase in the light-harvesting efficiency. This work provides valuable insights into the dynamics of transmembrane transport gas products and holds the potential to inspire innovative designs for improving the light-harvesting efficiency of PBSs.

Deciphering the Molecular Nexus: An In-Depth Review of Mitochondrial Pathways and Their Role in Cell Death Crosstalk.

Cellular demise is a pivotal event in both developmental processes and disease states, with mitochondrial regulation playing an essential role. Traditionally, cell death was categorized into distinct types, considered to be linear and mutually exclusive pathways. However, the current understanding has evolved to recognize the complex and interconnected mechanisms of cell death, especially within apoptosis, pyroptosis, and necroptosis. Apoptosis, pyroptosis, and necroptosis are governed by intricate molecular pathways, with mitochondria acting as central decision-makers in steering cells towards either apoptosis or pyroptosis through various mediators. The choice between apoptosis and necroptosis is often determined by mitochondrial signaling and is orchestrated by specific proteins. The molecular dialogue and the regulatory influence of mitochondria within these cell death pathways are critical research areas. Comprehending the shared elements and the interplay between these death modalities is crucial for unraveling the complexities of cellular demise.

Comparing GDF9 in mature follicles and clinical outcomes across different PCOS phenotype.

Background: Polycystic ovary syndrome (PCOS) is main cause of anovulatory infertility in women with gestational age. There are currently four distinct phenotypes associated with individualized endocrinology and metabolism. Growth differentiation factor 9 (GDF9) is a candidate as potential biomarker for the assessment of oocyte competence. The effect on oocyte capacity has not been evaluated and analyzed in PCOS phenotypes. Objective: We aimed to screen the expression levels of GDF9 in mature follicles of women with controlled ovarian hyperstimulation (COS) with different PCOS phenotypes. To determine the correlation between the expression level of GDF9 and oocyte development ability. Methods: In Part 1, we conducted a retrospective study comparing the clinical outcomes and endocrine characteristics of patients with PCOS according to different subgroups (depending on the presence or absence of the main features of polycystic ovarian morphology (PCOM), hyperandrogenism (HA), and oligo-anovulation (OA)) and non-PCOS control group. We stratified PCOS as phenotype A (n = 29), phenotype B (n = 18) and phenotype D (n = 24). In Part 2, the expression of GDF9 in follicular fluid (FF) and cumulus cells (CCs) were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. Results: In Part 1, the baseline clinical, hormonal, and ultrasonographic characteristics of the study population were matched with the presence or absence of the cardinal features of each PCOS phenotypes showed a clear difference. Phenotypes A and D had statistically significant associations with blastocyst formation and clinical pregnancy compared with phenotypes B (p < 0.001). In Part 2, the levels of GDF9 in FF and CCs for phenotype A and B were significantly were higher than those of phenotype D (P = 0.019, P = 0.0015, respectively). Multivariate logistic regression analysis showed that GDF9 was an important independent predictor of blastocyst formation (P＜0.001). The blastocyst formation rate of phenotype A was higher than that of phenotype B and D (P＜0.001). Combining the results of the two parts, GDF9 appears to play a powerful role in the development of embryos into blastocysts. Conclusions: GDF9 expression varies with different PCOS phenotypes. Phenotype A had higher GDF9 levels and blastocyst formation ability.

Lymph Node-on-Chip Technology: Cutting-Edge Advances in Immune Microenvironment Simulation.

Organ-on-a-chip technology is attracting growing interest across various domains as a crucial platform for drug screening and testing and is set to play a significant role in precision medicine research. Lymph nodes, being intricately structured organs essential for the body's adaptive immune responses to antigens and foreign particles, are pivotal in assessing the immunotoxicity of novel pharmaceuticals. Significant progress has been made in research on the structure and function of the lymphatic system. However, there is still an urgent need to develop prospective tools and techniques to delve deeper into its role in various diseases' pathological and physiological processes and to develop corresponding immunotherapeutic therapies. Organ chips can accurately reproduce the specific functional areas in lymph nodes to better simulate the complex microstructure of lymph nodes and the interactions between different immune cells, which is convenient for studying specific biological processes. This paper reviews existing lymph node chips and their design approaches. It discusses the applications of the above systems in modeling immune cell motility, cell-cell interactions, vaccine responses, drug testing, and cancer research. Finally, we summarize the challenges that current research faces in terms of structure, cell source, and extracellular matrix simulation of lymph nodes, and we provide an outlook on the future direction of integrated immune system chips.

A Portable Device for in Situ Noninvasive Monitoring of Cell Secretions and Communications with Fluorescence and Nanochannel Electrochemistry.

In situ monitoring of cell secretions and communications plays a fundamental role in screening of disease diagnostic biomarkers and drugs. Quantitative detection of cell secretions and monitoring of intercellular communication have been separately reported, which often rely on target labeling or complex pretreatment steps, inevitably causing damage to the target. Simultaneous in situ noninvasive detection of cell secretions and monitoring of intercellular communication are challenging and have never been reported. Herein, we smartly developed a portable device for in situ label-free monitoring of cell secretions and communications with fluorescence and ion-transport-based nanochannel electrochemistry. Based on the dual signal mode, a series of nonelectroactive secretions were sensitively and accurately quantified. The detection limits for VEGF, MUC1, and ATP were 3.84 pg/mL, 32.7 pg/mL, and 47.4 fM (3σ/S), which were 1/3.9, 1/1.1, and 1/41 of those of commercial ELISA kits, respectively. More interestingly, under the released secretions, the gradual opening of the nanochannel connected the two cells in the left and right chambers of the device; thus, the secretion mediated intercellular communication can be monitored. The proposed platform may provide a promising tool for understanding the mechanism of intercellular communication and discovering new therapeutic targets.

Ultrasensitive Proteomics of Trace Cardiac Tissues with Anchor-Nanoparticles.

Pathological cardiac hypertrophy is a complex process that often leads to heart failure. Label-free proteomics has emerged as an important platform to reveal protein variations and to elucidate the mechanisms of cardiac hypertrophy. Endomyocardial biopsy is a minimally invasive technique for sampling cardiac tissue, but it yields only limited amounts of an ethically permissible specimen. After regular pathological examination, the remaining trace samples pose significant challenges for effective protein extraction and mass spectrometry analysis. Herein, we developed trace cardiac tissue proteomics based on the anchor-nanoparticles (TCPA) method. We identified an average of 6666 protein groups using ∼50 µg of myocardial interventricular septum samples by TCPA. We then applied TCPA to acquire proteomics from patients' cardiac samples both diagnosed as hypertrophic hearts and myocarditis controls and identified significant alterations in pathways such as regulation of actin cytoskeleton, oxidative phosphorylation, and cGMP-PKG signaling pathway. Moreover, we found multiple lipid metabolic pathways to be dysregulated in transthyretin cardiac amyloidosis compared to other types of cardiac hypertrophy. TCPA offers a new technique for studying pathological cardiac hypertrophy and can serve as a platform toolbox for proteomic research in other cardiac diseases.

Major Facilitator Superfamily Domain Containing 12 Is Overexpressed in Lung Cancer and Exhibits an Oncogenic Role in Lung Adenocarcinoma Cells.

Major facilitator superfamily domain containing 12 (MFSD12) regulates lysosomal cysteine import and promotes the proliferation and survival of melanoma cells. However, the expression and function of MFSD12 in other cancers, particularly in lung cancer, remain unclear. The expression of MFSD12 across various types of cancers and corresponding control tissues was examined using TIMER. MFSD12 expression in lung adenocarcinoma (LUAD) and its correlation with distinct clinicopathological features of LUAD patients were analyzed with UALCAN. The correlation between MFSD12 expression and survival of LUAD patients was assessed using the R package, survival, and the relationship between MFSD12 expression and immune infiltration status in LUAD was investigated using CIBERSORT. In addition, MFSD12 expression was knocked down in PC9 LUAD cells and their proliferation, capacity for expansion, cell cycle, apoptosis, and migration/invasion were evaluated through CCK-8 assays, colony formation assays, 7-AAD staining, Annexin V/PI staining, and Transwell assays, respectively. The stemness of these PC9 cells was determined through Western blotting, flow cytometry, and tumor sphere formation assays. MFSD12 mRNA levels were significantly elevated in multiple types of cancers, including LUAD. MFSD12 expression was also positively correlated with cancer stage, nodal metastasis, and infiltration of various immune cells in LUAD, and high MFSD12 levels predicted poor survival among LUAD patients. Knockdown of MFSD12 in PC9 cells resulted in decreased proliferation, attenuated colony formation capacity, cell cycle arrest, elevated apoptosis, impaired migration/invasion, and reduced stemness in PC9 cells. MFSD12 is an oncogene in LUAD.