Rapid and accurate detection of cinnamon oil adulteration in perilla leaf oil using atmospheric solids analysis probe-mass spectrometry.

Perilla leaf oil (PLO) is a global premium vegetable oil with abundant nutrients and substantial economic value, rendering it susceptible to potential adulteration by unscrupulous entrepreneurs. The addition of cinnamon oil (CO) is one of the main adulteration avenues for illegal PLOs. In this study, new and real-time ambient mass spectrometric methods were developed to detect CO adulteration in PLO. First, atmospheric solids analysis probe tandem mass spectrometry combined with principal component analysis and principal component analysis-linear discriminant analysis was employed to differentiate between authentic and adulterated PLO. Then, a spectral library was established for the instantaneous matching of cinnamaldehyde in the samples. Finally, the results were verified using the SRM mode of ASAP-MS/MS. Within 3 min, the three methods successfully identified CO adulteration in PLO at concentrations as low as 5% v/v with 100% accuracy. The proposed strategy was successfully applied to the fraud detection of CO in PLO.

Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery.

JOURNAL/nrgr/04.03/01300535-202501000-00030/figure1/v/2024-05-14T021156Z/r/image-tiff Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery. Our previous in vitro study demonstrated that exosomes/small extracellular vesicles (sEVs) isolated from cerebral endothelial cells (CEC-sEVs) of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a (miR-27a) is an elevated miRNA in ischemic CEC-sEVs. In the present study, we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a (27a-sEVs) further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs. 27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector. Small EVs isolated from CECs transfected with a scramble vector (Scra-sEVs) were used as a control. Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs. An array of behavior assays was used to measure neurological function. Compared with treatment of ischemic stroke with Scra-sEVs, treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side, and significantly improved neurological outcomes. In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth. Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone, while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a, and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone. Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs. Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes. Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.

Maintaining moderate levels of hypochlorous acid promotes neural stem cell proliferation and differentiation in the recovery phase of stroke.

JOURNAL/nrgr/04.03/01300535-202503000-00029/figure1/v/2024-06-17T092413Z/r/image-tiff It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke. Indeed, previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain tissue. Our previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke, but its specific role and mechanism are currently unclear. To simulate stroke in vivo, a middle cerebral artery occlusion rat model was established, with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic stroke. We found that in the early stage (within 24 hours) of ischemic stroke, neutrophils produced a large amount of hypochlorous acid, while in the recovery phase (10 days after stroke), microglia were activated and produced a small amount of hypochlorous acid. Further, in acute stroke in rats, hypochlorous acid production was prevented using a hypochlorous acid scavenger, taurine, or myeloperoxidase inhibitor, 4-aminobenzoic acid hydrazide. Our results showed that high levels of hypochlorous acid (200 µM) induced neuronal apoptosis after oxygen/glucose deprivation/reoxygenation. However, in the recovery phase of the middle cerebral artery occlusion model, a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and astrocytes. This suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion injury. Lower levels of hypochlorous acid (5 and 100 µM) promoted nuclear translocation of ß-catenin. By transfection of single-site mutation plasmids, we found that hypochlorous acid induced chlorination of the ß-catenin tyrosine 30 residue, which promoted nuclear translocation. Altogether, our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

Sacral neuromodulation for Organophosphate-induced delayed neuropathy neurogenic lower urinary tract dysfunction: a case report.

BACKGROUND: Organophosphate-Induced Delayed Neuropathy (OPIDN) is a rare neurological disorder triggered by exposure to organophosphorus compounds. These compounds exert their neurotoxic effects by impacting the nervous system, leading to systemic manifestations. Urinary system symptoms are infrequently observed in clinical settings. Currently, effective therapeutic interventions for OPIDN-related urinary symptoms are lacking. Sacral nerve modulation therapy, an FDA-approved approach for managing lower urinary tract symptoms, presents as a promising option. Herein, we present a case of OPIDN-induced lower urinary tract obstruction successfully treated with sacral nerve modulation therapy, resulting in substantial symptom relief. CASE REPORT: A 27-year-old male patient presented with severe bilateral hydronephrosis, attributed to low bladder compliance and accompanied by a fever persisting for 6 days. The patient's medical history revealed accidental ingestion of organophosphate pesticide (Dimethoate) with no concomitant underlying diseases. In consideration of the potential for OPIDN, surgical intervention in the form of sacral neuromodulation (phase I) was undertaken. Subsequent evaluation one month post-surgery revealed notable improvements in both bladder compliance and bilateral hydronephrosis, necessitating sacral neuromodulation (phase II). Presently, following a 5-month follow-up period, the patient remains asymptomatic and in favorable health. CONCLUSION: This patient achieved long-term relief using sacral neuromodulation.

Solving Zero-Shot Sparse-View CT Reconstruction With Variational Score Solver.

Computed tomography (CT) stands as a ubiquitous medical diagnostic tool. Nonetheless, the radiation-related concerns associated with CT scans have raised public apprehensions. Mitigating radiation dosage in CT imaging poses an inherent challenge as it inevitably compromises the fidelity of CT reconstructions, impacting diagnostic accuracy. While previous deep learning techniques have exhibited promise in enhancing CT reconstruction quality, they remain hindered by the reliance on paired data, which is arduous to procure. In this study, we present a novel approach named Variational Score Solver (VSS) for solving sparse-view reconstruction without paired data. Our approach entails the acquisition of a probability distribution from densely sampled CT reconstructions, employing a latent diffusion model. High-quality reconstruction outcomes are achieved through an iterative process, wherein the diffusion model serves as the prior term, subsequently integrated with the data consistency term. Notably, rather than directly employing the prior diffusion model, we distill prior knowledge by finding the fixed point of the diffusion model. This framework empowers us to exercise precise control over the process. Moreover, we depart from modeling the reconstruction outcomes as deterministic values, opting instead for a distribution-based approach. This enables us to achieve more accurate reconstructions utilizing a trainable model. Our approach introduces a fresh perspective to the realm of zero-shot CT reconstruction, circumventing the constraints of supervised learning. Our extensive qualitative and quantitative experiments unequivocally demonstrate that VSS surpasses other contemporary unsupervised and achieves comparable results compared with the most advance supervised methods in sparse-view reconstruction tasks. Codes are available in https://github.com/fpsandnoob/vss.

Genome-wide Association Study Identifies Genetic Polymorphisms for Folate-related Biomarkers in Chinese Preconception Women.

BACKGROUND: SNP allele frequencies, dietary habits, folate status and their associations vary across ethnic populations. Little is known about the SNPs accounting for variations of folate-related biomarkers for Chinese preparing-for-pregnant females. OBJECTIVE: We aimed to identify SNPs contributing to RBC and serum folate, vitamin B-12, and homocysteine levels in Chinese female preconception population. METHODS: A GWAS was conducted on 1000 randomly selected preconception Chinese women from SPCC. SNPs were genotyped using Illumina chips, and associations with biomarkers were assessed using simple linear regression models under the assumption of an additive genetic model. Genome-wide significance was considered at P < 10-7. RESULTS: The MTHFR rs1801133 was the major genetic coding variant contributing to RBC folate, serum folate and homocysteine concentrations (P=2.28×10-16; P=8.85×10-8, and P=2.46×10-13). It is associated with increased RBC folate (ß=0.154 per additional risk allele after log transform), decreased serum folate (ß=-0.951 per additional risk allele) and increased serum homocysteine concentrations (ß=1.153 per additional risk allele). The predominant SNP associated with serum folate was rs147162222 in NTRK2 (P=2.55×10-8) while the one associated with homocysteine was rs77025184 located between PDE7B and LINC00271 (P=4.91×10-17). For vitamin B-12, FUT2 rs1047781 was the dominant genetic variant (P=1.59×10-10). The numbers of signals with P value <10-7 for RBC folate, serum folate, vitamin B-12 and homocysteine were 12, 18, 8 and 614 respectively. CONCLUSIONS: This study represents the first GWAS focusing on folate-related biomarkers in a Chinese preparing-for-pregnant female population. The contributions of dominent SNPs to each biomarker were partly different from other populations. The study detected rs1801133 (C677T) in MTHFR as the predominant genetic variant contributing to RBC folate and rs1047781 (A385T) in FUT2 as the primary one explaining vitamin B-12. Notably, the intronic rs147162222 and non-coding rs77025184 were both first detected as the predominant SNPs for serum folate and homocysteine respectively.

A cephalometric study on Le Fort â ¢ osteotomy related anatomical features of anterior cranial base in syndromic craniosynostosis.

PURPOSE: This study aims to investigate the anatomical features relating to nasofrontal and septum osteotomy during Le Fort Ⅲ osteotomy among patients with syndromic craniosynostosis, and to compare them with normal controls using computed tomographic cephalometry. MATERIALS AND METHODS: A total of 63 subjects were included (syndromic craniosynostosis, n = 21; controls, n = 42). The craniosynostosis subjects were subdivided into group A (craniosynostosis patients without history of previous surgery, n = 8) and group B (craniosynostosis patients with history of previous surgery, n = 13). Cephalometric measurements based on computed tomographic images were analyzed. RESULTS: The angle between the refencing plane (HP) of the anterior cranial base and the most inferior point of the sphenoid sinus via Nasion (∠HP-N-ISS) was 23.85 ± 3.10°, 21.15 ± 4.64° and 28.32 ± 2.92° for group A, group B and the control group, respectively. The angle between HP and the posterior nasal spine (PNS) via nasion (∠HP- N- PNS) was 42.63 ± 2.02°, 38.50 ± 4.84° and 47.68 ± 2.62° for group A, group B and the control group, respectively. CONCLUSION: This study characterized the surgically relevant anatomical features in nasofrontal osteotomy during Le Fort Ⅲ osteotomy. The safe range for osteotomy angle is significantly different between normal and syndromic craniosynostosis subjects. Awareness of this difference may prevent further complications.

Decafluorinated and Perfluorinated Warped Nanographenes: Synthesis, Structural Analysis, and Properties.

Fluorination is a useful approach for tailoring the physicochemical properties of nanocarbon materials. However, owing to the violent reactivity of fluorination, achieving edge-perfluorination of nanographene while maintaining its original π-conjugated structure is challenging. Instead of using traditional fluorination, here, we employed a bottom-up strategy involving fluorine preinstallation and synthesized decafluorinated and perfluorinated warped nanographenes (DFWNG and PFWNG, respectively) through a 10-fold Suzuki-Miyaura coupling followed by a harsh Scholl reaction, whereby precisely edge-perfluorinated nanographene with an intact π-conjugated structure was achieved for the first time. X-ray crystallography confirmed the intact π-conjugated structure and more twisted saddle-shaped geometry of PFWNG compared to that of DFWNG. Dynamic study revealed that the 26-ring carbon framework of PFWNG is less flexible than that of DFWNG and the pristine WNG, enabling chirality resolution of PFWNG and facilitating the achievement of CD spectra at -10 °C. The edge-perfluorination of PFWNG resulted in improved solubility, lower lowest unoccupied molecular orbital, and a surface electrostatic potentials/dipole moment direction opposite those of the pristine WNG. Likely owing to its intact π-conjugated structure, PFWNG exhibits comparable electron mobility with well-known PC61BM. Furthermore, perfluorination improves thermal stability and hydrophobicity, making PFWNG suitable for use as a thermostable/hydrophobic n-type semiconductor material. In the future, this fluorination strategy can be used to synthesize other perfluorinated nanocarbon materials, such as perfluorinated graphene nanoribbons and porous nanocarbon.

Genome-wide identification of sweet potato U-Box E3 ubiquitin ligases and roles of IbPUB52 in negative regulation of drought stress.

The plant U-box (PUB) proteins, a family of ubiquitin ligases (E3) enzymes, are pivotal in orchestrating many biological processes and facilitating plant responses to environmental stressors. Despite their critical roles, exploring the PUB gene family's characteristics and functional diversity in sweet potato (Ipomoea batatas (L.) Lam.) has been notably limited. There were 81 IbPUB genes identified within the sweet potato genome, and they were categorized into eight distinct groups based on domain architecture, revealing a non-uniform distribution across the 15 chromosomes of I. batatas. The investigation of cis-acting elements has shed light on the potential of PUBs to participate in a wide array of biological processes, particularly emphasizing their role in mediating responses to abiotic stresses. Transcriptome profiles revealed that IbPUB genes displayed a wide range of expression levels among different tissues and were regulated by salt or drought stress. IbPUB52 has emerged as a gene of significant interest due to its induction by salt and drought stresses. Localization studies have confirmed the presence of IbPUB52 in both the nucleus and the cytoplasm, and its ubiquitination activity has been validated through rigorous in vitro and in vivo assays. Intriguingly, the heterogeneous expression of IbPUB52 in Arabidopsis resulted in decreased drought tolerance. The virus-induced gene silencing (VIGS) of IbPUB52 in sweet potatoes led to enhanced resistance to drought. This evidence suggests that IbPUB52 negatively regulates the drought tolerance of plants. The findings of this study are instrumental in advancing our comprehension of the functional dynamics of PUB E3 ubiquitin ligases in sweet potatoes.

Visible light-promoted C3-H alkoxycarbonylation of quinoxalin-2(1H)-ones or coumarins with alkyloxalyl chlorides.

Herein, we describe a green and efficient photoredox catalytic C3-H alkoxycarbonylation between quinoxalin-2(1H)-ones or coumarins and readily available alkyloxalyl chlorides under ambient conditions. A series of quinoxaline-3-carbonyl and coumarin-3-carbonyl compounds are prepared through the radical addition of in situ-generated alkoxycarbonyl radicals. Notably, this protocol features mild conditions, operational simplicity, and excellent functional group tolerance. More importantly, the carboxylated products can be readily derivatized into other important compounds that would be of great potential for the exploitation of pharmaceutically active compounds.

Allogeneic CAR-T cells for cancer immunotherapy.

Autologous chimeric antigen receptor (CAR)-modified T (CAR-T) cell therapy has displayed high efficacy in the treatment of hematological malignancies. Up to now, 11 autologous CAR-T cell products have been approved for the management of malignancies globally. However, the application of autologous CAR-T cell therapy has many individual limitations, long time-consuming, highly cost, and the risk of manufacturing failure. Indeed, some patients would not benefit from autologous CAR-T cell products because of rapid disease progression. Allogeneic CAR-T cells especially universal CAR-T (U-CAR-T) cell therapy are superior to these challenges of autologous CAR-T cells. In this review, we describe basic study and clinical trials of U-CAR-T cell therapeutic methods for malignancies. In addition, we summarize the problems encountered and potential solutions.

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Multi-site DNA methylation alterations of peripheral blood mononuclear cells serve as novel biomarkers for the diagnosis of AIS/stage I lung adenocarcinoma: A multi-center cohort study.

BACKGROUND: Early diagnosis remains an obstacle for improving the outcome of lung adenocarcinoma (LUAD). DNA methylation changes in peripheral blood mononuclear cells (PBMCs) could reflect immune response to tumorigenesis, providing the theoretical basis for early cancer diagnosis based on immune cell profiling. METHODS: This multi-center study evaluated the DNA methylation patterns based on PBMCs samples from 1115 individuals at nine medical centers. Genome-wide DNA methylation profiling of PBMCs in a discovery cohort (35 LUAD patients and 50 healthy controls) was performed using Illumina 850K microarray. Candidate differentially methylated CpG positions (DMPs) were selected and validated in a two-step DMPs screening cohort (65 LUAD patients and 80 healthy controls) by pyrosequencing and multiple target region methylation enrichment sequencing (MTRMES). Then, an early LUAD Diagnostic Panel (LDP score) based on multi-site methylation-specific chip-based digital PCR was constructed in a training set and then confirmed in a validation set from the LDP score development cohort (389 AIS/stage I LUAD patients and 293 healthy controls). Besides, we included 157 other cancer patients, including 52 gastric cancer (GC) patients, 50 breast cancer (BC) patients, and 55 colorectal cancer (CRC) patients to assess the specificity of LDP score. In addition, we also evaluated the early warning ability of LDP score for LUAD in a prospective cohort (46 people who were at high-risk of developing LC). RESULTS: A total of 1415 LUAD-specific DMPs were identified. Then, six DMPs were selected for validation and three DMPs were finally verified. The LDP score was constructed by combining the three DMPs, age, and gender, and showed an AUC of 0.916, sensitivity of 88.17%, and specificity of 80.20% in combined set, outperforming traditional methods, such as CEA and CT (detection rate: 87.79% vs. 4.69%; 87.79% vs. 35.21%). This diagnostic performance was confirmed in sub-types of LUAD with clinical challenges, such as 6-20 mm LUAD (AUC: 0.914, 95%CI: 0.889-0.934) and ground-glass nodules (AUC: 0.916, 95%CI: 0.889-0.938). Importantly, our LDP score had significant improvement in terms of selecting high-risk individuals who should receive low-dose computed tomography (87.80% vs. 9.28%). Remarkably, LDP score could predict LUAD around two years before clinical diagnosis in our prospective cohort. CONCLUSIONS: The novel developed LDP score represented a convenient and effective assay for the detection of AIS/stage I LUAD with high sensitivity and specificity, and had demonstrated unique advantages over traditional detection methods.

Biomarkers and pathways in autism spectrum disorder: An individual meta-analysis based on proteomic and metabolomic data.

The utilization of biomarkers for the diagnosis and management of autism spectrum disorders (ASD) remains a relatively unexplored frontier in clinical practice. Proteomics and metabolomics are important tools for revealing key biomarkers and evaluating biological pathways in ASD. We conducted an individual meta-analysis to compare the consistency of biomarkers of ASD from central nervous system (brain and cerebrospinal fluid), circulatory system (blood), and non-invasive samples (urine, saliva, and faeces) and performed pathway enrichment analyses to identify pathways enriched in ASD. After screening 926 proteomics and 619 metabolomics articles, we collected data from 10 studies involving 940 differential proteins and 16 studies assessing a total of 748 differential metabolites. In brain tissue, blood, and urine of ASD cases and controls, flotillin-2 (FLOT2), apolipoprotein E (ApoE), and EH domain-containing protein 3 (EHD3) exhibit differential expression, while vinculin (VCL) displays variations in saliva, blood, and urine. Similarly, in case-control studies, gelsolin (GSN) shows differential expression in brain tissue, saliva, and urine, and malate dehydrogenase 2 (MDH2) in brain tissue, blood, and saliva. Hippuric acid and salicyluric acid were simultaneously found in the brain, blood, urine, and faeces. In terms of pathways, glycolysis/gluconeogenesis, carbon metabolism, and glutathione metabolism were enriched in the brain as well as in saliva or urine. In our study, we identified six shared protein and two metabolic markers in central nervous system, circulatory system, and non-invasive samples, underscoring their potential value for ASD diagnosis and management, warranting further research.

Achromatic Full Stokes Polarimetry Metasurface for Full-Color Polarization Imaging in the Visible Range.

Metasurfaces provide an ultrathin platform for compact, real-time polarimetry. However, their applications in polychromatic scenes are restricted by narrow operating bandwidths that causes spectral information loss. Here, we demonstrate full-color polarization imaging using an achromatic polarimeter consisting of four polarization-dependent metalenses. Leveraging an intelligent design scheme, we achieve effective arbitrary phase compensation and multiobjective matching with a limited database. This system provides broadband achromaticity across wavelengths from 450 to 650 nm, resulting in a relative bandwidth of approximately 0.364 for full Stokes imaging. Experimental reconstruction errors for wavelengths of 450, 550, and 650 nm are 7.5%, 5.9%, and 3.8%, respectively. Performance is evaluated based on both achromatic bandwidth and crosstalk, with our design achieving three times the performance of the current state-of-the-art. The full-color, full-polarization imaging capability of the device is further validated with a customized object. The proposed scheme advances polarization imaging for practical applications.

PAIP1 binds to pre-mRNA and regulates alternative splicing of cancer pathway genes including VEGFA.

BACKGROUND: Poly (A) binding protein interacting protein 1 (PAIP1) has been shown to causally contribute to the development and progression of cancer. However, the mechanisms of the PAIP1 regulation in tumor cells remain poorly understood. RESULTS: Here, we used a recently developed UV cross-linking and RNA immunoprecipitation method (iRIP-seq) to map the direct and indirect interaction sites between PAIP1 and RNA on a transcriptome-wide level in HeLa cells. We found that PAIP1 not only binds to 3'UTRs, but also to pre-mRNAs/mRNAs with a strong bias towards the coding region and intron. PAIP1 binding sites are enriched in splicing enhancer consensus GA-rich motifs. RNA-seq analysis revealed that PAIP1 selectively modulates the alternative splicing of genes in some cancer hallmarks including cell migration, the mTOR signaling pathway and the HIF-1 signaling pathway. PAIP1-regulated alternative splicing events were strongly associated with PAIP1 binding, demonstrating that the binding may promote selection of the nearby splice sites. Deletion of a PAIP1 binding site containing seven repeats of GA motif reduced the PAIP1-mediated suppression of the exon 6 inclusion in a VEGFA mRNA isoform. Proteomic analysis of the PAIP1-interacted proteins revealed the enrichment of the spliceosome components and splicing factors. CONCLUSIONS: These findings suggest that PAIP1 is both a polyadenylation and alternative splicing regulator, that may play a large role in RNA processing via its role in alternative splicing regulation.

Quantitative proteomics combined independent PRM analysis reveals the mitochondrial and synaptic mechanism underlying norisoboldine's antidepressant effects.

Major depressive disorder (MDD) is a common disease affecting 300 million people worldwide. The existing drugs are ineffective for approximately 30% of patients, so it is urgent to develop new antidepressant drugs with novel mechanisms. Here, we found that norisoboldine (NOR) showed an antidepressant efficacy in the chronic social defeat stress (CSDS) depression model in the tail suspension, forced swimming, and sucrose consumption tests. We then utilized the drug-treated CSDS mice paradigm to segregate and gain differential protein groups of CSDS versus CON (CSDSCON), imipramine (IMI)-treated versus CSDS (IMICSDS), and NOR-treated versus CSDS (NORCSDS) from the prefrontal cortex. These protein expression alterations were first analyzed by ANOVA with p < 0.05. The protein cluster 1 and cluster 3, in which the pattern of protein levels similar to the mood pattern, showed enrichment in functions and localizations related to mitochondrion, ribosome and synapses. Further GO analysis of the common proteins for NORCSDS groups and NORIMI groups supported the findings from ANOVA analysis. We employed Protein-Protein interaction (PPI) analysis to examine the proteins of NORCSDS and NORIMI, revealing an enrichment of the proteins associated with the mitochondrial ribosomal and synaptic functions. Further independent analysis using parallel reaction monitoring (PRM) revealed that Cox7c, Mrp142, Naa30, Ighm, Apoa4, Ssu72, Mrps30, Apoh, Acbd5, and Cdv3, exhibited regulation in the NOR-treated group to support the homeostasis of mitochondrial functions. Additionally, Dcx, Arid1b, Rnf112, and Fam3c, were also observed to undergo modulation in the NOR-treated groups to support the synaptic formation and functions. These findings suggest that the proteins involved in depression treatment exert effects in strengthen the mitochondrial and synaptic functions in the mice PFC. Western blot analysis supported the data that the levels of Mrpl42, Cox7c, Naa30, Rnf112, Dcx Apoa4, Apoh and Fam3c were altered in the CSDS mice, and rescued by NOR treatment, supporting the PRM data. NOR treatment also rescued the NLRP3 inflammasome activation in CSDS mice. In summary, the current proteomic research conducted on the prefrontal cortex has provided valuable insights into the specific and shared molecular mechanisms underlying pathophysiology and treatment to CSDS-induced depression, shedding light on the therapeutic effects of Norisoboldine.

PD-L1+ neutrophils induced NETs in malignant ascites is a potential biomarker in HCC.

BACKGROUND: Since differentiating malignant ascites from benign ascites has always been a clinical difficult, recognition of novel biomarkers in malignant ascites of hepatocellular carcinoma (HCC) patients could be helpful for establishing a diagnosis for HCC patients with ascitic fluids. METHODS: Thirty-five HCC patients with malignant ascites and chronic liver diseases patients with benign ascites were enrolled. Serum and ascites specimens were collected to determine TAN subpopulations and NETs concentration. Then, the correlation between ascitic NETs levels and clinical features were analyzed, and ROC curves were generated to evaluate the diagnostic value of NETs. For in vitro study, fresh neutrophils were employed to explore the underlying mechanism of TAN polarization and NETs formation using RNAseq analysis. RESULTS: Significantly increased pro-tumor PD-L1+ TANs and higher lactate levels were measured in HCC ascites. RNAseq data showed that lactate regulated genes expression involving PD-L1 expression and NETs formation, suggesting that ascitic lactate might be responsible for tumor progression in TME. Then, NETs-related markers including calprotectin, dsDNA, CitH3, MPO and MPO-DNA were found dramatically elevated in malignant ascites. Next, correlation analysis revealed that ascitic NETs levels positively correlated with LDH, a classic ascitic biochemical indicator. Furthermore, we identified the diagnostic values of NETs in discriminating malignant ascites from benign ascites. CONCLUSIONS: Our findings highlighted that elevated ascitic NETs served as a biomarker in HCC patients with malignant ascites, which provided useful insights for both clinical and basic research for malignant ascites diagnosis and management.

Facile Tailor on the Surface of Mo Foil Toward High-Efficient Flexible CZTSSe Solar Cells.

Flexible Cu2ZnSn(S,Se)4 (CZTSSe) solar cells is attracting much attention because of their enormous application prospects. However, current flexible CZTSSe solar cells with Mo foil as substrate still suffer from severe back interface problems due to the complexity of substrate surfaces. Herein, a facile approach to tailor the surface of the flexible substrate and modify the back interface between CZTSSe and Mo foil is proposed. The study discloses that a simple polishing can not only improve the wettability of the precursor solution on the substrate unexpectedly and thus improve the quality of the CZTSSe film, but also increase the mechanical stability of the absorber layer grown on Mo foil. The subsequent UV-ozone treatment helps to form a favorite MoO3 layer for efficient CZTSSe devices. Surprisingly, the quasi-ohmic contact is formed between CZTSSe/Mo foil by such combined treatments and thus promoting the carrier collection. Consequently, the efficiency of the flexible CZTSSe solar cell is significantly improved from 4.94% to 10.32% without anti-reflection layer. The bending durability of the cell fabricated on the treated Mo foil is increased greatly. This work discloses that back contact interface is very important for the carrier collection and thus the highly efficient flexible thin film solar cells.