Microplastics and nanoplastics released from injection syringe, solid and liquid dimethylpolysiloxane (PDMS).

For a plastic syringe, a stopper at the end of plunger is usually made of polydimethylsiloxane (PDMS, and co-ingredients). To reduce friction and prevent leakage between the stopper and barrel, short chain polymer of liquid PDMS is also used as lubricant. Consequently, an injection process can release solid PDMS debris from the stopper and barrel, and liquid PDMS droplets from the lubricant, both of which are confirmed herein as solid and liquid micro(nano)plastics. From molecular spectrum perspective to directly visualise those micro(nano)plastics, Raman imaging was employed to analyse hundreds-to-thousands of spectra (hyper spectrum or hyperspectral matrix) and significantly enhance signal-to-noise ratio. From morphology perspective to provide high resolution of image, scanning electron microscopy (SEM) was engaged to cross-check with Raman images and increase assignment / quantification certainty. The weak Raman imaging signal of nanoplastics was extracted using image deconvolution algorithm to remove the background noise and average the signal variation. To increase the result's representativeness and avoid quantification bias, multiple syringes were tested and multiple areas were randomly scanned toward statistical results. It was estimated that thousands of microplastics and millions of nanoplastics of solid/liquid PDMS might be injected when using a plastic syringe of 1 mL. Overall, Raman imaging (along with algorithm and SEM) can be helpful for further research on micro(nano)plastics, and it should be cautious to use plastic syringe due to the increasing concern on the emerging contamination of not only solid but also liquid micro(nano)plastics.

Rocaglamide promotes infiltration and differentiation of T cells and coordinates with PD-1 inhibitor to overcome checkpoint resistance in multiple tumor models.

Tumor-infiltrating lymphocyte (TIL) deficiency is the most conspicuous obstacle to limit the cancer immunotherapy. Immune checkpoint inhibitors (ICIs), such as anti-PD-1 antibody, have achieved great success in clinical practice. However, due to the limitation of response rates of ICIs, some patients fail to benefit from monotherapy. Thus, novel combination therapy that could improve the response rates emerges as new strategies for cancer treatment. Here, we reported that the natural product rocaglamide (RocA) increased tumor-infiltrating T cells and promoted Th17 differentiation of CD4+ TILs. Despite RocA monotherapy upregulated PD-1 expression of TILs, which was considered as the consequence of T cell activation, combining RocA with anti-PD-1 antibody significantly downregulated the expression of PD-1 and promoted proliferation of TILs. Taken together, these findings demonstrated that RocA could fuel the T cell anti-tumor immunity and revealed the remarkable potential of RocA as a therapeutic candidate when combining with the ICIs.

Establishing connectivity through microdissections of midbrain stimulation-related neural circuits.

Comprehensive understanding of the neural circuits involving the ventral tegmental area is essential for elucidating the anatomo-functional mechanisms governing human behaviour as well as the therapeutic and adverse effects of deep brain stimulation for neuropsychiatric diseases. While the ventral tegmental area has been successfully targeted with deep brain stimulation for different neuropsychiatric diseases, the axonal connectivity of the region has not been fully understood. Here using fiber micro-dissections in human cadaveric hemispheres, population-based high-definition fiber tractography, and previously reported deep brain stimulation hotspots, we find that the ventral tegmental area participates in an intricate network involving the serotonergic pontine nuclei, basal ganglia, limbic system, basal forebrain, and prefrontal cortex, which is implicated in the treatment of obsessive-compulsive disorder, major depressive disorder, Alzheimer's disease, cluster headaches, and aggressive behaviors.

Traditional Chinese Medicine for Cancer Treatment.

In recent years, due to advancements in medical conditions and the development of scientific research, the fundamental research of TCM antitumor treatments has progressed from the cellular level to the molecular and genetic levels. Previous studies have demonstrated the significant role of traditional Chinese medicine (TCM) in antitumor therapy through various mechanisms and pathways. Its mechanism of action is closely associated with cancer biology across different stages. This includes inhibiting tumor cell proliferation, blocking invasion and metastasis to surrounding tissues, inducing tumor cell apoptosis, inhibiting tumor angiogenesis, regulating immune function, maintaining genome stability, preventing mutation, and regulating cell energy metabolism. The use of TCM for eliciting antitumor effects not only has a good therapeutic effect and low side effects, it also provides a solid theoretical basis for clinical treatment and medication. This paper reviews the mechanism of the antitumor effects of TCM based on tumor characteristics. Through our review, we found that TCM not only directly inhibits tumors, but also enhances the body's immunity, thereby indirectly inducing an antitumor effect. This function aligns with the TCM theory of "strengthening the body's resistance to eliminate pathogenic factors". Furthermore, TCM will play a significant role in tumor treatment in clinical settings.

How to Identify and Quantify Microplastics and Nanoplastics Using Raman Imaging?

While microplastics and nanoplastics are emerging as a big environmental concern, their characterization is still a challenge, particularly for identification and simultaneous quantification analysis where imaging via a hyper spectrum is generally needed. In the past few years, Raman imaging has been greatly advanced, but the analysis protocol is complicated and not yet standardized because imaging analysis is different from traditional analysis. Herein we provide a step-by-step demonstration of how to employ confocal Raman techniques to image microplastics and nanoplastics.

P. gingivalis in oral-prostate axis exacerbates benign prostatic hyperplasia via IL-6/IL-6R pathway.

BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. There is increasing evidence that periodontitis increases the risk of BPH, but the specific mechanism remains unclear. This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis (P. gingivalis) in the development of BPH. METHODS: The subgingival plaque (Sp) and prostatic fluid (Pf) of patients with BPH concurrent periodontitis were extracted and cultured for 16S rDNA sequencing. Ligature-induced periodontitis, testosterone-induced BPH and the composite models in rats were established. The P. gingivalis and its toxic factor P. gingivalis lipopolysaccharide (P.g-LPS) were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate. P.g-LPS was used to construct the prostate cell infection model for mechanism exploration. RESULTS: P. gingivalis, Streptococcus oralis, Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Pf and Sp of patients with BPH concurrent periodontitis, and the average relative abundance of P. gingivalis was found to be the highest. P. gingivalis was detected in both Pf and Sp in 62.5% of patients. Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes. P. gingivalis and P.g-LPS infection could induce obvious hyperplasia of the prostate epithelium and stroma (epithelial thickness was 2.97- and 3.08-fold that of control group, respectively), and increase of collagen fibrosis (3.81- and 5.02-fold that of control group, respectively). P. gingivalis infection promoted prostate cell proliferation, inhibited apoptosis, and upregulated the expression of inflammatory cytokines interleukin-6 (IL-6; 4.47-fold), interleukin-6 receptor-α (IL-6Rα; 5.74-fold) and glycoprotein 130 (gp130; 4.47-fold) in prostatic tissue. P.g-LPS could significantly inhibit cell apoptosis, promote mitosis and proliferation of cells. P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex, which destroys the imbalance between proliferation and apoptosis of prostate cells, induces BPH. CONCLUSION: P. gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis. P. gingivalis infection can promote BPH, which may affect the progression of BPH via inflammation and the Akt signaling pathway.

Bacterial community analysis of the skin microbiota of cultured Chinese giant salamander infected with Ranavirus.

Skin microorganisms are an important component of host innate immunity and serve as the first line of defense against pathogenic infections. The relative abundance of bacterial species, microbial community assembly, and secretion of specific bacterial metabolites are closely associated with host health. In this study, we investigated the association between the skin microbiome and Ranavirus, and compared the bacterial community assemblage, alpha and beta diversity, and functional predictions of the skin bacterial assemblage in cultured healthy Chinese giant salamanders (Andrias davidianus) and individuals infected with Chinese giant salamander iridovirus (GSIV or ADRV). To achieve this, we employed 16S rRNA amplicon sequencing. The results identified Proteobacteria, Firmicutes, Bacteroidota, and Actinobacteriota as the dominant phyla in the diseased and healthy groups. Alpha diversity analysis indicated that the skin bacterial community in the diseased group exhibited no significant differences in bacterial species diversity and lower species richness compared to the healthy group. Beta diversity suggested that the two group bacterial community was quite different. Kyoto encyclopedia of genes and genomes (KEGG) pathway analyze and clusters of orthologous groups of proteins (COG) function predictions revealed that changes and variations occurred in the metabolic pathways and function distribution of skin bacterial communities in two groups.

Ultrasonic degradation of per-and polyfluoroalkyl substances (PFAS), aqueous film-forming foam (AFFF) and foam fractionate (FF).

The ubiquitousness of per- and polyfluoroalkyl substances (PFAS) is a big concern and PFAS remediation is urgently needed such as via degradation. While previous studies have explored ultrasonic degradation of PFAS, work evaluating the operational parameters is rare, especially concerning real wastes such as aqueous film-forming foam (AFFF) and foam fractionate (FF). This study investigates the key operational parameters affecting the degradation efficiency of PFAS, encompassing ultrasonication frequency (580-1144 kHz), power intensity (125-187.5 W), initial concentration (0.08-40 ppm), treatment duration (0.5-3 h), sample volume (100-500 mL), and PFAS structure (perfluorooctanoic acid or PFOA; perfluorooctane sulfonate or PFOS; 6:2 fluorotelomer sulfonate or 6:2 FTS). The defluorination kinetics is different from the removal/degradation kinetics due to the generation of degradation intermediates, suggesting the complex degradation mechanism, which should be evaluated to close the mass balance effectively. Notably, the optimised ultrasonic system achieves ∼125%/∼115% defluorination in AFFF/FF example wastes (compared to ∼65%/∼97% removal) despite their complex composition and the involvement of total oxidizable precursor (TOP) assay. In the meantime, a few new PFAS are detected in the post-treatments, including perfluorohexane sulfonic acid (PFHxS) and 10:2 fluorotelomer sulfonate (10:2 FTS) in the AFFF, and perfluorooctane sulfonamide (FOSA) and 8:2 fluorotelomer sulfonate (8:2 FTS) in the FF, again suggesting the complex degradation mechanism. Overall, ultrasonication is effective to degrade PFAS real example wastes, advancing its potential for scale-up applications.

QL1604 plus paclitaxel-cisplatin/carboplatin in patients with recurrent or metastatic cervical cancer: an open-label, single-arm, phase II trial.

OBJECTIVE: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. METHODS: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. RESULTS: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46). The median duration of response was 9.6 months (95% confidence interval [CI]=5.5-not estimable). The median progression-free survival was 8.1 months (95% CI=5.7-14.0). Forty-five (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). CONCLUSION: QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can't tolerate bevacizumab, which needs to be further verified in phase III confirmatory study. Trial RegistrationClinicalTrials.gov Identifier: NCT04864782.

An Open Resource: MR and light sheet microscopy stereotaxic atlas of the mouse brain.

We have combined MR histology and light sheet microscopy (LSM) of five postmortem C57BL/6J mouse brains in a stereotaxic space based on micro-CT yielding a multimodal 3D atlas with the highest spatial and contrast resolution yet reported. Brains were imaged in situ with multi gradient echo (mGRE) and diffusion tensor imaging (DTI) at 15 µm resolution (∼ 2.4 million times that of clinical MRI). Scalar images derived from the average DTI and mGRE provide unprecedented contrast in 14 complementary 3D volumes, each highlighting distinct histologic features. The same tissues scanned with LSM and registered into the stereotaxic space provide 17 different molecular cell type stains. The common coordinate framework labels (CCFv3) complete the multimodal atlas. The atlas has been used to correct distortions in the Allen Brain Atlas and harmonize it with Franklin Paxinos. It provides a unique resource for stereotaxic labeling of mouse brain images from many sources.

Rationale for immune checkpoint inhibitors plus targeted therapy for advanced renal cell carcinoma.

Renal cell carcinoma (RCC) is a frequent urological malignancy characterized by a high rate of metastasis and lethality. The treatment strategy for advanced RCC has moved through multiple iterations over the past three decades. Initially, cytokine treatment was the only systemic treatment option for patients with RCC. With the development of medicine, antiangiogenic agents targeting vascular endothelial growth factor and mammalian target of rapamycin and immunotherapy, immune checkpoint inhibitors (ICIs) have emerged and received several achievements in the therapeutics of advanced RCC. However, ICIs have still not brought completely satisfactory results due to drug resistance and undesirable side effects. For the past years, the interests form researchers have been attracted by the combination of ICIs and targeted therapy for advanced RCC and the angiogenesis and immunogenic tumor microenvironmental variations in RCC. Therefore, we emphasize the potential principle and the clinical progress of ICIs combined with targeted treatment of advanced RCC, and summarize the future direction.

White matter microstructure organization across the transition to fatherhood.

The transition to parenthood remains an understudied window of potential neuroplasticity in the adult brain. White matter microstructural (WMM) organization, which reflects structural connectivity in the brain, has shown plasticity across the lifespan. No studies have examined how WMM organization changes from the prenatal to postpartum period in men becoming fathers. This study investigates WMM organization in men transitioning to first-time fatherhood. We performed diffusion-weighted imaging to identify differences in WMM organization, as indexed by fractional anisotropy (FA). We also investigated whether FA changes were associated with fathers' postpartum mental health. Associations between mental health and WMM organization have not been rarely examined in parents, who may be vulnerable to mental health problems. Fathers exhibited reduced FA at the whole-brain level, especially in the cingulum, a tract associated with emotional regulation. Fathers also displayed reduced FA in the corpus callosum, especially in the forceps minor, which is implicated in cognitive functioning. Postpartum depressive symptoms were linked with increases and decreases in FA, but FA was not correlated with perceived or parenting stress. Findings provide novel insight into fathers' WMM organization during the transition to parenthood and suggest postpartum depression may be linked with fathers' neuroplasticity during the transition to parenthood.

Corrigendum: Endothelial ß-catenin deficiency causes blood-brain barrier breakdown via enhancing the paracellular and transcellular permeability.

[This corrects the article DOI: 10.3389/fnmol.2022.895429.].

Efficacy and safety of first-line chemotherapies for patients with advanced pancreatic ductal adenocarcinoma: A systematic review and network meta-analysis.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, often diagnosed at an advanced stage. Systemic chemotherapy is the primary treatment, but direct comparisons of different regimens are limited. This study conducted a systematic review and network meta-analysis (NMA) to compare the efficacy and safety of various chemotherapy regimens, with the unique advantage of only including Phase III randomized controlled trials (RCTs). Methods: NMA was conducted regarding the searched phase III RCTs by comparing overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) of different chemotherapy protocols. Results: The analysis included 24 studies with 11470 patients across 25 treatment modalities. Among the chemotherapy regimens evaluated, FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin) demonstrated the highest OS and PFS, with a risk ratio (logHR) of 4.5 (95 % confidence interval 4.32-4.68) compared to gemcitabine monotherapy. The PEFG regimen (cisplatin, epirubicin, 5-fluorouracil, and gemcitabine) exhibited the highest ORR, with an odds ratio (OR) of 6.67 (2.08-20) compared to gemcitabine monotherapy. Notably, gemcitabine plus sorafenib was associated with the lowest hematological toxicity, with an odds ratio (OR) of 0.1 (0.02-0.48). Conclusion: Combination therapies may offer greater benefits but also cause more toxic effects. However, combinations with targeted agents seem to have fewer adverse reactions.

Rocaglamide regulates iron homeostasis by suppressing hepcidin expression.

The anemia of inflammation (AI) is characterized by the presence of inflammation and abnormal elevation of hepcidin. Accumulating evidence has proved that Rocaglamide (RocA) was involved in inflammation regulation. Nevertheless, the role of RocA in AI, especially in iron metabolism, has not been investigated, and its underlying mechanism remains elusive. Here, we demonstrated that RocA dramatically suppressed the elevation of hepcidin and ferritin in LPS-treated mice cell line RAW264.7 and peritoneal macrophages. In vivo study showed that RocA can restrain the depletion of serum iron (SI) and transferrin (Tf) saturation caused by LPS. Further investigation showed that RocA suppressed the upregulation of hepcidin mRNA and downregulation of Fpn1 protein expression in the spleen and liver of LPS-treated mice. Mechanistically, this effect was attributed to RocA's ability to inhibit the IL-6/STAT3 pathway, resulting in the suppression of hepcidin mRNA and subsequent increase in Fpn1 and TfR1 expression in LPS-treated macrophages. Moreover, RocA inhibited the elevation of the cellular labile iron pool (LIP) and reactive oxygen species (ROS) induced by LPS in RAW264.7 cells. These findings reveal a pivotal mechanism underlying the roles of RocA in modulating iron homeostasis and also provide a candidate natural product on alleviating AI.

Is paper bag plastic-free, without plastic in colourful logo area?

The concern over plastic contamination has led to bans on plastic shopping bags, often replaced by paper ones. However, logos painted or printed on paper bags may still contain plastics, as investigated herein. In some logos, for example, white pigment of titanium dioxide (TiO2) nanoparticles are bound with plastic binder onto the cellulose surface of the paper. This hybrid of plastic and nanoparticle is examined using scanning electron microscope (SEM) to characterise morphology physically, and Raman imaging to identify and visualise them chemically. Raman imaging scans the sample to separate images and identify not only plastic but also the co-formulated pigment. The scan generates a hyperspectral matrix containing hundreds to thousands of spectra, and subsequent analysis can enhance the signal-to-noise ratio. Decoding the hyperspectral matrix using chemometrics like principal component analysis (PCA) can effectively map plastic and pigment separately with increased certainty. The image can be further refined through 3-dimensional surface fitting for deconvolution, providing direct visualisation of the plastic-nanoparticle hybrid at a density of approximately 7.3 million particles per square millimetre. Overall, caution should be exercised when using paper bags, as they may not be entirely free of plastics. Raman imaging proves to be an effective method for identifying and visualising complex components, including plastics and nanoparticles. ENVIRONMENTAL IMPLICATION: The concern over plastic contamination has led to bans on plastic shopping bags, replaced by paper alternatives. However, some logos on paper bags may still contain plastics, which is investigated to confirm the presence of plastic-nanoparticle hybrid using SEM and Raman imaging. By employing decoding algorithms such as PCA to separately map plastic and pigment, and utilising 3D surface fitting to deconvolute the image, the hybrid plastic-nanoparticle is estimated at a density of approximately 7.3 million particles per square millimetre. It's important to exercise caution and not assume these items are plastic-free. This aspect of plastics may have been overlooked as another potential source of contamination.

Diffusion and functional MRI in surgical neuromodulation.

Surgical neuromodulation has witnessed significant progress in recent decades. Notably, deep brain stimulation (DBS), delivered precisely within therapeutic targets, has revolutionized the treatment of medication-refractory movement disorders and is now expanding for refractory psychiatric disorders, refractory epilepsy, and post-stroke motor recovery. In parallel, the advent of incisionless treatment with focused ultrasound ablation (FUSA) can offer patients life-changing symptomatic relief. Recent research has underscored the potential to further optimize DBS and FUSA outcomes by conceptualizing the therapeutic targets as critical nodes embedded within specific brain networks instead of strictly anatomical structures. This paradigm shift was facilitated by integrating two imaging modalities used regularly in brain connectomics research: diffusion MRI (dMRI) and functional MRI (fMRI). These advanced imaging techniques have helped optimize the targeting and programming techniques of surgical neuromodulation, all while holding immense promise for investigations into treating other neurological and psychiatric conditions. This review aims to provide a fundamental background of advanced imaging for clinicians and scientists, exploring the synergy between current and future approaches to neuromodulation as they relate to dMRI and fMRI capabilities. Focused research in this area is required to optimize existing, functional neurosurgical treatments while serving to build an investigative infrastructure to unlock novel targets to alleviate the burden of other neurological and psychiatric disorders.

Toy building bricks as a potential source of microplastics and nanoplastics.

Microplastics and nanoplastics have become noteworthy contaminants, affecting not only outdoor ecosystems but also making a notable impact within indoor environments. The release of microplastics and nanoplastics from commonly used plastic items remains a concern, and the characterisation of these contaminants is still challenging. This study focused on evaluating the microplastics and nanoplastics produced from plastic building bricks. Using Raman spectroscopy and correlation analysis, the plastic material used to manufacture building blocks was determined to be either acrylonitrile butadiene styrene (correlation value of 0.77) or polycarbonate (correlation value of 0.96). A principal component analysis (PCA) algorithm was optimised for improved detection of the debris particles released. Some challenges in microplastic analysis, such as the interference from the colourants in the building block materials, was explored and discussed. Combining Raman results with scanning electron microscopy - energy-dispersive X-ray spectroscopy, we found the scratches on the building blocks to be a significant source of contamination, estimated several thousand microplastics and several hundred thousand nanoplastics were generated per mm2 following simulated play activities. The potential exposure to microplastics and nanoplastics during play poses risks associated with the ingestion and inhalation of these minute plastic particles.