Parameter-free super-resolution structured illumination microscopy via a physics-enhanced neural network.

With full-field imaging and high photon efficiency advantages, structured illumination microscopy (SIM) is one of the most potent super-resolution (SR) modalities in bioscience. Regarding SR reconstruction for SIM, spatial domain reconstruction (SDR) has been proven to be faster than traditional frequency domain reconstruction (FDR), facilitating real-time imaging of live cells. Nevertheless, SDR relies on high-precision parameter estimation for reconstruction, which tends to suffer from low signal-to-noise ratio (SNR) conditions and inevitably leads to artifacts that seriously affect the accuracy of SR reconstruction. In this Letter, a physics-enhanced neural network-based parameter-free SDR (PNNP-SDR) is proposed, which can achieve SR reconstruction directly in the spatial domain. As a result, the peak-SNR (PSNR) of PNNP-SDR is improved by about 4 dB compared to the cross-correlation (COR) SR reconstruction; meanwhile, the reconstruction speed of PNNP-SDR is even about five times faster than the fast approach based on principal component analysis (PCA). Given its capability of achieving parameter-free imaging, noise robustness, and high-fidelity and high-speed SR reconstruction over conventional SIM microscope hardware, the proposed PNNP-SDR is expected to be widely adopted in biomedical SR imaging scenarios.

Three New Species and a New Record of the Lichen Genus Peltula (Peltulaceae) from Helan Mountain in China.

In this study, a systematic taxonomic analysis was carried out on the lichen genus Peltula, collected from Helan Mountain in China; three new species (Peltula helanense, P. overlappine, and P. reticulata) and a new record (P. crispatula (Nyl.) Egea) for China were identified. Four species were identified by morph-anatomical, chemical, and phylogenetic analyses by combining two gene loci (ITS and LSU). Peltula helanense is with tiny individual thalli up to 1mm, attached by creamy-white cylindrical rhizoids and apothecia filling the whole squamule. Peltula overlappine is characterized by thallus squamulose forming rosette-shaped patches and squamules with distinctive thickened margins. Peltula reticulata is characterized by brownish brown thallus and squamules with densely reticulate upper surface. P. crispatula is characterized by irregular squamules attached to a tuft of hyphae. The four species are described in detail, compared, and discussed with similar species, and images of morpho-anatomical structures of the four species are also provided. Moreover, a key to the species of Peltula from Helan Mountain is provided. The results enrich the data of the genus Peltula and also indicate that the rich diversity of lichen species in Helan Mountain is worthy of in-depth study.

Cost-effectiveness of atezolizumab plus bevacizumab as first-line therapy for metastatic renal cell carcinoma.

OBJECTIVES: Recently, the IMmotion151 trial evaluated the safety and efficacy of atezolizumab plus bevacizumab in metastatic renal cell carcinoma (mRCC) and found that this combination led to longer progression-free survival. However, no studies have evaluated the cost-effectiveness of atezolizumab plus bevacizumab. METHODS: We constructed a Markov model to evaluate the cost-effectiveness of atezolizumab plus bevacizumab, using costs and utilities from the published studies. We set the willingness-to-pay (WTP) threshold at $150,000. One-way and probabilistic sensitivity analyses were performed to ensure that our results were robust. We performed a threshold analysis to explore a more appropriate price for atezolizumab. RESULTS: Our results found that although atezolizumab plus bevacizumab provided more quality-adjusted life years (QALYs), its incremental cost-effectiveness ratio (ICER) was $1,640,532/QALY, well above the WTP threshold. One-way and probabilistic sensitivity analysis results confirmed the robust of this conclusion. Based on the threshold analysis, for atezolizumab plus bevacizumab to be cost-effective, the price of them would need to be reduced by 46.3% or more. CONCLUSIONS: From the perspective of US payers, atezolizumab plus bevacizumab is not cost-effective for mRCC patients. To make this combination cost-effective in the future, the price of atezolizumab and bevacizumab needs to be reduced.

Pro-apoptotic gene BAX is a pan-cancer predictive biomarker for prognosis and immunotherapy efficacy.

BACKGROUND: Apoptosis Regulator BCL2 Associated X (BAX) is a pro-apoptotic gene. Apoptosis is one of the important components of immune response and immune regulation. However, there is no systematic pan-cancer analysis of BAX. METHODS: Original data of this study were downloaded from TCGA databases and GTEX databases. We conducted the gene expression analysis and survival analysis of BAX in 33 types of cancer via Gene Expression Profiling Interactive Analysis (GEPIA) database. Real-time PCR and immunohistochemistry (IHC) were further performed to examine the BAX expression in cancer cells and tissues. Moreover, the relationship between BAX and immune infiltration and gene alteration was studied by the Tumor Immune Estimation Resource (TIMER) and cBioPortal tools. Protein-protein interaction analysis was performed in the STRING database. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were utilized to evaluate the enrichment analysis. RESULTS: BAX was highly expressed in most cancers and was associated with poor prognosis in nine cancer types. In addition, BAX showed significant clinical relevance, and the mRNA expression of BAX was also strongly associated with drug sensitivity of many drugs. Furthermore, BAX may participate in proliferation and metastasis of many cancers and was associated with methylation. Importantly, BAX expression was positively correlated with most immune infiltrating cells. CONCLUSION: Our findings suggested that BAX can function as an oncogene and may be used as a potential predictive biomarker for prognosis and immunotherapy efficacy of human cancer, which could provide a new approach for cancer therapy.

Effect of electroacupuncture of "Zusanli" (ST36) combined with capeOX on apoptosis and ferroptosis in nude mice with colorectal cancer. / 电针"足三里"联合capeOXæ–¹æ¡ˆå¯¹ç»“ç›´è‚ ç™Œè£¸é¼ è‚¿ç˜¤ç»†èƒžå‡‹äº¡å’Œé“æ­»äº¡çš„å½±å“.

OBJECTIVES: To investigate the impact of combined treatment of colorectal cancer (CRC) with electroacupuncture (EA) and capeOX (combined administration of fluorouracil, oxaliplatin and capecitabine) on the tumor volume, weight, spleen coefficient, apoptosis and ferroptosis of tumor tissue, and liver and kidney functions in nude mice with CRC, so as to explore its mechanisms underlying inhibiting CRC and alleviating toxic reactions of capeOX. METHODS: Female Balb/c nude mice were randomly assigned to 3 groups：model, capeOX, and EA+capeOX, with 8 nude mice in each group. The CRC model was established by subcutaneous injection of colon cancer cells at the right inguinal region. Nude mice of the capeOX group received intraperitoneal injection of oxaliplatin for 1 day and gavage of capecitabine from day 2 to day 7. EA (1 mA, 2 Hz/100 Hz) was applied to bilateral "Zusanli" (ST36) for 20 min, once daily for 7 days. During the interven-tion, the tumor volume and weight were measured every day, and at the end of intervention, the weight of the tumor tissue and spleen were measured, with tumor volume difference and spleen coefficient calculated. The proportion of apoptotic cells was measured by flow cytometry, and the contents of serum malondialdehyde (MDA), alanine aninotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (Cr) were detected using ELISA. The expression level of glutathione peroxidase 4 (GPX4, a key regulator for ferroptosis) protein of the tumor tissue was determined using Western blot. RESULTS: Compared to the model group, both the capeOX group and EA+capeOX group showed a decrease in the tumor volume (on day 3 and 4 in the capeOX group, and from day 2 to 7 in the EA+capeOX group) and body weight (P<0.05, on day 3 to 7 in the EA+capeOX group and on day 2 to 7 in the capeOX group), being evidently lower in the tumor volume on day 7 in the EA+capeOX than in the capeOX group (P<0.05), and evidently higher in the body weight on day 6 and 7 in the EA+capeOX group than in the capeOX group (P<0.05). In comparison with the model group, the tumor volume difference, tumor weight and spleen coefficient in both capeOX and EA+capeOX groups were significantly decreased (P<0.05), and MDA content in EA+capeOX group was significantly decreased (P<0.05), while the contents of ALT, BUN and Cr in the capeOX group, the proportion of apoptotic cells in both capeOX and EA+capeOX groups, and the GPX4 expression level in the EA+capeOX group were all significantly increased (P<0.05). The tumor volume difference, tumor weight, and contents of MDA, ALT, AST, BUN and Cr in the EA+capeOX group were markedly lower than in the capeOX group (P<0.05), while the spleen coefficient, proportion of apoptotic cells and GPX4 expression level in the EA+capeOX group were markedly higher than those in the capeOX group (P<0.05). CONCLUSIONS: EA of ST36 can enhance the effect of capeOX in inhibiting colorectal cancer growth in nude mice with CRC, which may be related with its functions in promoting tumor cell apoptosis, inhibiting ferroptosis, and modulating immune tolerance. In addition, EA can lower the side effects of capeOX in hematopoietic and immune, liver, and kidney functions.

Automated detection of steps in videos of strabismus surgery using deep learning.

BACKGROUND: Learning to perform strabismus surgery is an essential aspect of ophthalmologists' surgical training. Automated classification strategy for surgical steps can improve the effectiveness of training curricula and the efficient evaluation of residents' performance. To this end, we aimed to develop and validate a deep learning (DL) model for automated detecting strabismus surgery steps in the videos. METHODS: In this study, we gathered 479 strabismus surgery videos from Shanghai Children's Hospital, affiliated to Shanghai Jiao Tong University School of Medicine, spanning July 2017 to October 2021. The videos were manually cut into 3345 clips of the eight strabismus surgical steps based on the International Council of Ophthalmology's Ophthalmology Surgical Competency Assessment Rubrics (ICO-OSCAR: strabismus). The videos dataset was randomly split by eye-level into a training (60%), validation (20%) and testing dataset (20%). We evaluated two hybrid DL algorithms: a Recurrent Neural Network (RNN) based and a Transformer-based model. The evaluation metrics included: accuracy, area under the receiver operating characteristic curve, precision, recall and F1-score. RESULTS: DL models identified the steps in video clips of strabismus surgery achieved macro-average AUC of 1.00 (95% CI 1.00-1.00) with Transformer-based model and 0.98 (95% CI 0.97-1.00) with RNN-based model, respectively. The Transformer-based model yielded a higher accuracy compared with RNN-based models (0.96 vs. 0.83, p < 0.001). In detecting different steps of strabismus surgery, the predictive ability of the Transformer-based model was better than that of the RNN. Precision ranged between 0.90 and 1 for the Transformer-based model and 0.75 to 0.94 for the RNN-based model. The f1-score ranged between 0.93 and 1 for the Transformer-based model and 0.78 to 0.92 for the RNN-based model. CONCLUSION: The DL models can automate identify video steps of strabismus surgery with high accuracy and Transformer-based algorithms show excellent performance when modeling spatiotemporal features of video frames.

Long non-coding RNA HOTAIR: from pan-cancer analysis to colorectal cancer-related uridine metabolism.

Long non-coding RNAs (lncRNAs) are involved significantly in the development of human cancers. lncRNA HOTAIR has been reported to play an oncogenic role in many human cancers. Its specific regulatory role is still elusive. And it might have enormous potential to interpret the malignant progression of tumors in a broader perspective, that is, in pan-cancer. We comprehensively investigated the effect of HOTAIR expression on tumor prognosis across human malignancies by analyzing multiple cancer-related databases like The Cancer Genome Atlas (TCGA) and Tumor Immune Estimation Resource (TIMER). Bioinformatics data indicated that HOTAIR was overexpressed in most of these human malignancies and was significantly associated with the prognosis of patients with cancer, especially in colorectal cancer (CRC). Subsequently, this study further clarified the utility of HOTAIR that downregulation of its expression could result in reduced proliferation and invasion of CRC cells. Mechanistically, HOTAIR upregulated the metabolic enzymes UPP1 by recruiting histone methyltransferase EZH2, thereby increasing the tumor progression. Our results highlight the essential role of HOTAIR in pan-cancer and uridine bypass, suggesting that the HOTAIR/EZH2/UPP1 axis might be a novel target for overcoming CRC. We anticipate that the role of HOTAIR in metabolism could be important in the context of CRC and even exploited for therapeutic purposes.

Efficacy and safety of therapies related to acupuncture for acute herpes zoster: A PRISMA systematic review and network meta-analysis.

BACKGROUND: Herpes zoster (HZ) is mainly characterized by intense pain and severe skin lesions, particularly during the acute phase, which seriously affects the patient's quality of life. Acupuncture is a widely used and effective treatment for HZ. However, there are many types of acupuncture, which have different curative efficacy. This study employed a network meta-analysis (NMA) to assess and rank the clinical efficacy of different acupuncture therapies. METHODS: The database of Cochrane Library, Web of Science, PubMed, MEDLINE, Embase, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Database, VIP Database, and Wanfang Database were searched from inception to December 31, 2022 to identify eligible randomized controlled trials (RCTs) of acupuncture related therapies in the treatment of acute HZ. The outcome indicators measured were visual analogue scale (VAS), date of cessation of herpes increase (DCHI), effective rate (ER), postherpetic neuralgia (PHN), and adverse events (AEs). Bayesian network meta-analyses were performed using the GeMTC package (version 1.0-1) and R software (version 4.2.3). RESULTS: A total of 59 RCTs with 3930 patients were included. The results of this NMA were as follows: compared with pharmacotherapy, electroacupuncture (EA) + pricking and cupping (PC) shown the best efficacy to improve VAS score and reduce DCHI. In terms of ER, EA + fire needle (FN) had the highest results of probability ranking. PC was more effective in reducing the incidence of PHN. Furthermore, this study shown that the incidence of AEs associated with acupuncture-related therapies was acceptable. CONCLUSIONS: This study indicated that therapies related to acupuncture were both effective and safe in treating acute HZ, and could significantly reduce patients' symptoms such as pain and skin lesions with fewer adverse events. Clinically, the selection of the appropriate therapy should be based on practical considerations. However, due to the limitations of this study, more high-quality trials are required to evaluate the efficacy and safety of acupuncture-related therapy for the treatment of acute HZ.

Macrophage scavenger receptor-A1 promotes skeletal muscle regeneration after hindlimb ischemia.

Macrophages mediated inflammatory response is crucial for the recovery of skeletal muscle following ischemia. Thus, it's necessary to exploit macrophages based therapeutic targets for ischemic disease. Here, we found mRNA level of SR-A1 was elevated in patients with critical limb ischemia by analysis of gene expression omnibus (GEO) database. Then we investigated the role and the underlined mechanisms of macrophage SR-A1 in a mouse HLI model. Compared with the SR-A1 fl/fl mice, the Lyz Cre/+/SR-A1 flox/flox (SR-A1 ΔMΦ) mice showed significantly lower laser doppler blood flow in the ischemic limb at day 7 after HLI. Consistently, histological analysis exhibited that ischemic limb of SR-A1 ΔMΦ mice displayed more sever and sustained necrotic morphology, inflammation and fibrosis, decreased vessel density and regeneration rate, compared with which of control SR-A1 fl/fl mice. Furthermore, restoration of wild-type myeloid cells to SR-A1 knock-out mice effectively relieved the doppler perfusion in the ischemic limb and restrained skeletal muscle damage 7 days post HLI. In line with in vivo findings, when co-cultivating macrophages with the mouse myoblast line C2C12, SR-A1 -/- bone marrow macrophage significantly inhibited myoblast differentiation in vitro. Mechanically, SR-A1 enhanced skeletal muscle regeneration response to HLI by inhibiting the oncostatin M (OSM) production via suppressed NF-κB signaling activation. These results indicates that SR-A1 is a promising candidate molecule to improve tissue repair and regeneration in peripheral ischemic arterial disease.

A peripheral system disease-Pulmonary hypertension.

Pulmonary hypertension (PH) is a cardiovascular disorder characterized by substantial morbidity and mortality rates. It is a chronic condition characterized by intricate pathogenesis and uncontrollable factors. We summarized the pathological effects of estrogen, genetics, neuroinflammation, intestinal microbiota, metabolic reorganization, and histone modification on PH. PH is not only a pulmonary vascular disease, but also a systemic disease. The findings emphasize that the onset of PH is not exclusively confined to the pulmonary vasculature, consequently necessitating treatment approaches that extend beyond targeting pulmonary blood vessels. Hence, the research on the pathological mechanism of PH is not limited to target organs such as pulmonary vessels, but also focuses on exploring other fields (such as estrogen, genetics, neuroinflammation, intestinal microbiota, metabolic reorganization, and histone modification).

Magnetic field-assisted adsorption of phosphate on biochar loading amorphous Zr-Ce (carbonate) oxide composite.

For metal-based phosphate adsorbents, the dispersity and utilization of surface metal active sites are crucial factors in their adsorption performance and synthesis cost. In this study, a biochar material modified with amorphous Zr-Ce (carbonate) oxides (BZCCO-13) was synthesized for the phosphate uptake, and the adsorption process was enhanced by magnetic field. The beside-magnetic field was shown to have a better influence than under-magnetic field on adsorption, with maximum adsorption capacities (123.67 mg P/g) 1.14-fold greater than that without magnetic field. The beside-magnetic field could also accelerate the adsorption rate, and the time to reach 90% maximum adsorption capacity decreased by 83%. BZCCO-13 has a wide range of application pHs from 5.0 to 10.0, with great selectivity and reusability. The results of XPS and ELNES showed that the "magnetophoresis" of Ce3+ under the magnetic field was the main reason for the enhanced adsorption performance. In addition, increased surface roughness, pore size and oxygen vacancies, enhanced mass transfer by Lorentz force under a magnetic field, all beneficially influenced the adsorption process. The mechanism of phosphate adsorption by BZCCO-13 could be attributed to electrostatic attraction and CO32-dominated ligand exchange. This study not only provided an effective strategy for designing highly effective phosphate adsorbents, but also provides a new light on the application of rare earth metal-based adsorbent in magnetic field.

Exploring pectin-casein micelles as novel carriers for oral drug delivery of artesunate in the treatment of systemic lupus erythematosus.

The oral route of administration is considered the optimal choice for treating chronic diseases due to its convenience and non-invasiveness, which can help prevent physical and mental harm to patients undergoing long-term treatment. However, challenges such as safety, gastrointestinal stability, and bioavailability of oral drugs often limit their effectiveness. Natural biomacromolecule micelles, known for their safety, stability, biocompatibility, and diverse functions, have emerged as promising carriers for oral treatment of chronic diseases like systemic lupus erythematosus (SLE) with fat-soluble drugs. This study introduces an innovative approach by developing an oral delivery system using chemically synthesized natural biomacromolecules to load artesunate for treating SLE. By synthesizing amphiphilic polymer micelles from pectin and casein through a carbodiimide reaction, a more stable structure is achieved. The hydrophobic core of these micelles encapsulates artesunate, resulting in the formation of an oral delivery system (PC-AS) with several advantages, including high drug loading and encapsulation efficiency, small particle size, negative potential, strong stability in the gastrointestinal tract, low toxicity and side effects, strong adhesion in the small intestine, and high bioavailability. These advantages facilitate efficient absorption of artesunate in the gastrointestinal tract, leading to improved bioavailability and effective alleviation of SLE-like symptoms in MRL/lpr mice. By utilizing chemically synthesized natural macromolecular micelles for delivering artesunate in the treatment of SLE, this study overcomes the oral barriers associated with the original drug and presents a novel solution for the long-term oral treatment of chronic diseases.

High Performance As-Cast Organic Solar Cells Enabled by a Refined Double-Fibril Network Morphology and Improved Dielectric Constant of Active Layer.

High performance organic solar cells (OSCs) are usually realized by using post-treatment and/or additive, which can induce the formation of metastable morphology, leading to unfavorable device stability. In terms of the industrial production, the development of high efficiency as-cast OSCs is crucially important, but it remains a great challenge to obtain appropriate active layer morphology and high power conversion efficiency (PCE). Here, efficient as-cast OSCs are constructed via introducing a new polymer acceptor PY-TPT with a high dielectric constant into the D18:L8-BO blend to form a double-fibril network morphology. Besides, the incorporation of PY-TPT enables an enhanced dielectric constant and lower exciton binding energy of active layer. Therefore, efficient exciton dissociation and charge transport are realized in D18:L8-BO:PY-TPT-based device, affording a record-high PCE of 18.60% and excellent photostability in absence of post-treatment. Moreover, green solvent-processed devices, thick-film (300 nm) devices, and module (16.60 cm2) are fabricated, which show PCEs of 17.45%, 17.54%, and 13.84%, respectively. This work brings new insight into the construction of efficient as-cast devices, pushing forward the practical application of OSCs.

Erratum: [Corrigendum] Chloroquine potentiates the anticancer effect of sunitinib on renal cell carcinoma by inhibiting autophagy and inducing apoptosis.

[This corrects the article DOI: 10.3892/ol.2017.7635.].

Paradoxical Activation of Oncogenic Signaling as a Cancer Treatment Strategy.

Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress response programs that counteract the inherent toxicity of such aberrant signaling. Although inhibition of oncogenic signaling pathways has been explored extensively, there is increasing evidence that overactivation of the same pathways can also disrupt cancer homeostasis and cause lethality. We show here that inhibition of protein phosphatase 2A (PP2A) hyperactivates multiple oncogenic pathways and engages stress responses in colon cancer cells. Genetic and compound screens identify combined inhibition of PP2A and WEE1 as synergistic in multiple cancer models by collapsing DNA replication and triggering premature mitosis followed by cell death. This combination also suppressed the growth of patient-derived tumors in vivo. Remarkably, acquired resistance to this drug combination suppressed the ability of colon cancer cells to form tumors in vivo. Our data suggest that paradoxical activation of oncogenic signaling can result in tumor-suppressive resistance. Significance: A therapy consisting of deliberate hyperactivation of oncogenic signaling combined with perturbation of the stress responses that result from this is very effective in animal models of colon cancer. Resistance to this therapy is associated with loss of oncogenic signaling and reduced oncogenic capacity, indicative of tumor-suppressive drug resistance.

Phase separation of SHP2E76K promotes malignant transformation of mesenchymal stem cells by activating mitochondrial complexes.

Mesenchymal stem cells (MSCs), suffering from diverse gene hits, undergo malignant transformation and aberrant osteochondral differentiation. Src homology region 2-containing protein tyrosine phosphatase 2 (SHP2), a nonreceptor protein tyrosine phosphatase, regulates multicellular differentiation, proliferation, and transformation. However, the role of SHP2 in MSC fate determination remains unclear. Here, we showed that MSCs bearing the activating SHP2E76K mutation underwent malignant transformation into sarcoma stem-like cells. We revealed that the SHP2E76K mutation in mouse MSCs led to hyperactive mitochondrial metabolism by activating mitochondrial complexes I and III. Inhibition of complexes I and III prevented hyperactive mitochondrial metabolism and malignant transformation of SHP2E76K MSCs. Mechanistically, we verified that SHP2 underwent liquid-liquid phase separation (LLPS) in SHP2E76K MSCs. SHP2 LLPS led to its dissociation from complexes I and III, causing their hyperactivation. Blockade of SHP2 LLPS by LLPS-defective mutations or allosteric inhibitors suppressed complex I and III hyperactivation as well as malignant transformation of SHP2E76K MSCs. These findings reveal that complex I and III hyperactivation driven by SHP2 LLPS promotes malignant transformation of SHP2E76K MSCs and suggest that inhibition of SHP2 LLPS could be a potential therapeutic target for the treatment of activated SHP2-associated cancers.

Regulation of depressive-like behaviours by palmitoylation: Role of AKAP150 in the basolateral amygdala.

BACKGROUND AND PURPOSE: Protein palmitoylation is involved in learning and memory, and in emotional disorders. Yet, the underlying mechanisms in these processes remain unclear. Herein, we describe that A-kinase anchoring protein 150 (AKAP150) is essential and sufficient for depressive-like behaviours in mice via a palmitoylation-dependent mechanism. EXPERIMENTAL APPROACH: Depressive-like behaviours in mice were induced by chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS). Palmitoylated proteins in the basolateral amygdala (BLA) were assessed by an acyl-biotin exchange assay. Genetic and pharmacological approaches were used to investigate the role of the DHHC2-mediated AKAP150 palmitoylation signalling pathway in depressive-like behaviours. Electrophysiological recording, western blotting and co-immunoprecipitation were performed to define the mechanistic pathway. KEY RESULTS: Chronic stress successfully induced depressive-like behaviours in mice and enhanced AKAP150 palmitoylation in the BLA, and a palmitoylation inhibitor was enough to reverse these changes. Blocking the AKAP150-PKA interaction with the peptide Ht-31 abolished the CRS-induced AKAP150 palmitoylation signalling pathway. DHHC2 expression and palmitoylation levels were both increased after chronic stress. DHHC2 knockdown prevented CRS-induced depressive-like behaviours, as well as attenuating AKAP150 signalling and synaptic transmission in the BLA in CRS-treated mice. CONCLUSION AND IMPLICATIONS: These results delineate that DHHC2 modulates chronic stress-induced depressive-like behaviours and synaptic transmission in the BLA via the AKAP150 palmitoylation signalling pathway, and this pathway may be considered as a promising novel therapeutic target for major depressive disorder.

Metformin alleviates genetic and traumatic heterotopic ossification by inhibiting infiltration and mitochondrial metabolism of myeloid cells.

OBJECTIVES: Heterotopic ossification (HO), whether hereditary or traumatic, refers to the abnormal formation of bone in extraskeletal sites, often triggered by inflammation or flare-ups. Unfortunately, there are currently no effective treatments for HO. Metformin is well-known for its anti-diabetic, anti-inflammatory, anti-aging, and anti-cancer effects. However, its potential role in treating HO remains uncertain. METHODS: Metformin was dissolved into water and given to mice. All the mice in this study were examined by microCT and myeloid cell quantification using flow cytometry. Complex activity kit was used to examine the activity of mitochondrial complexes of myeloid cells. RESULTS: In this study, we discovered that metformin effectively inhibits genetic and traumatic HO formation and progression. Additionally, we observed a significant increase in myeloid cells in the genetic and traumatic HO mouse model compared to uninjured mice. Notably, metformin specifically reduced the infiltration of myeloid cells into the injured sites of the genetic and traumatic HO model mice. Further investigations revealed that metformin targets mitochondrial complex I and suppresses mitochondrial metabolism in myeloid cells. CONCLUSION: These findings suggest that metformin suppresses HO development by potentially downregulating the mitochondrial metabolism of myeloid cells, offering a promising therapeutic option for HO treatment.

Mechanism of SO2/H2O enhanced rare earth tailings catalysts in NH3-SCR at medium and high temperature.

Rare earth tailings (RET) NH3-SCR catalysts were prepared by mechanical and microwave activation of a large amount of rare earth tailings after beneficiation of Bayan Ebo rare earth ore. The effects of SO2/H2O on the denitrification performance of the RET catalysts were evaluated by conducting denitrification activity tests, SO2/H2O tolerance tests and in situ DRIFTs mechanistic analysis. The results showed that the denitrification activity was significantly increased in the presence of SO2/H2O. And in situ DRIFTs analysis showed that in the presence of SO2/H2O, SO2 could be adsorbed as SO32- groups by the hydroxyl groups on the catalyst surface and react with SO42- to form S2O72- species. And in the presence of NH3, S2O72- would decompose into unstable SO42- species and SO32- and continue to react cyclically to form S2O72- species, providing the RET catalyst provides more acid sites, facilitating the SCR reaction.

Bibliometric analysis of evolutionary trajectory and prospective directions of LAG-3 in cancer.

Objectives: Perform a bibliometric analysis on the role of LAG-3 in the domain of cancer, elucidate the prevailing areas of research, and visually depict the evolutionary trajectory and prospective directions of LAG-3 research over the past twenty-three decades. Materials and methods: Between 2000 and 2023, a comprehensive review of scholarly articles pertaining to LAG-3 research in the context of cancer was carried out using the Web of Science Core Collection (WoSCC) database. Bibliometric analysis can be conducted by taking advantage of VOSviewer (version 1.6.16) and CiteSpace (version 6.2.R4). Create a network diagram to visually represent various authors, countries, and organizations while assessing the publishing years, journals, references, and keywords. Results: In conclusion, 1841 records were identified and published in 587 publications. These records were authored by 12,849 individuals affiliated with 2491 institutes across 74 countries. There has been a substantial surge in publications subsequent to 2013. The USA, China, and Germany gave the majority of records, amounting to 69.69%. American institutions actively engage in collaboration with institutions located in other countries. Triebel, F., Vignali, Dario A. A., Workman, Creg J. Drake, Charles G., and Elkord, Eyad are highly regarded authors in their respective fields. However, it is worth noting that Triebel exhibits limited collaboration with other writers. The examination of the role of LAG-3 in cancer and its potential for use in clinical settings is a discernible trend, as seen by keyword analysis. Conclusion: The scientific interest in and attention towards LAG-3 has experienced a significant rise since 2013. The United States is leading the way, with China following closely behind. Promoting collaboration among writers, nations, and institutions with varied backgrounds is imperative. The discipline of immunotherapy is currently seeing ongoing progress. A thorough investigation of the distinctive cis ligand TCR-CD3 complex of LAG-3 and its signal transduction mechanism is necessary. Additionally, it is worthwhile to explore novel combinations of LAG-3 therapy.