Fluorescent multichannel sensor array based on three carbon dots derived from Tibetan medicine waste for the quantification and discrimination of multiple heavy metal ions in water.

A fluorescent multichannel sensor array has been established based on three carbon dots derived from Tibetan medicine waste for rapid quantification and discrimination of six heavy metal ions. Due to the chelation between metal ions and carbon dots (CDs), this fluorescence "turn off" mode sensing array can quantify six metal ions as low as "µM" level. Moreover, the six heavy metal ions display varying quenching effects on these three CDs owing to diverse chelating abilities between each other, producing differential fluorescent signals for three sensing channels, which can be plotted as specific fingerprints and converted into intuitive identification profiles via principal component analysis (PCA) and hierarchical cluster analysis (HCA) technologies to accurately distinguish Cu2+, Fe3+, Mn2+, Ag+, Ce4+, and Ni2+ with the minimum differentiated concentration of 5 µM. Valuably, this sensing array unveils good sensitivity, exceptional selectivity, ideal stability, and excellent anti-interference ability for both mixed standards and actual samples. Our contribution provides a novel approach for simultaneous determination of multiple heavy metal ions in environmental samples, and it will inspire the development of other advanced optical sensing array for simultaneous quantification and discrimination of multiple targets.

pH sensor based on tilted fiber Bragg grating surface plasmon resonance with a polyaniline reaction deposition film layer.

In this paper, we propose a surface plasmon resonance (SPR) fiber-optic pH sensor combined with a tilted fiber Bragg grating (TFBG) by continuously coating gold and polyaniline (PANI) onto the surface of a TFBG. The micron-scale thickness polyaniline film provides the sensor with good sensitivity, and it achieves accurate measurement of pH values ranging from 2 to 12 by utilizing the pH-responsive mechanism of PANI and the surface plasmon resonance characteristics. Experimental results show that within the 2-12 pH range, the sensitivity of the TFBG surface plasmon resonance pH sensor based on PANI coating is 0.50335 nm/pH, and results demonstrate, a linear correlation coefficient between wavelength and pH value reaching 0.96614. This indicates significant potential for future engineering applications in real-world pH measurement using this sensor.

Efficacy and safety of bimekizumab in the treatment of psoriatic arthritis: a systematic review and meta-analysis.

BACKGROUND: Bimekizumab, a humanized monoclonal IgG1 antibody targeting both interleukin (IL)-17A and IL-17F, could be effective for treating Psoriatic arthritis (PsA). This study aimed to systematically evaluate the efficacy and safety of bimekizumab in the management of PsA. RESEARCH DESIGN AND METHODS: A comprehensive literature search by August 2023 was performed through PubMed, Embase, Cochrane Controlled Register of Trials, and ClinicalTrials.gov. investigating the efficacy or safety data of bimekizumab in the treatment of PsA. Data was pooled using the random-effects models. Egger tests were used to evaluate potential publication bias. RESULTS: A total of 4 RCTs, involving 892 PsA patients and 467 placebo controls, were included in this analysis. Bimekizumab significantly increased the rates of PASI75 and PASI100 compared with placebos [RR = 7.22, 95% CI (5.24, 9.94), p < 0.001; RR = 10.12, 95% CI (6.00, 17.09), p < 0.001]. The rate of overall adverse events was slightly higher in the bimekizumab group [RR = 1.42, 95% CI (1.05, 1.93) p = 0.023). However, there were fewer adverse severe drug reactions in the bimekizumab group compared to the placebo. CONCLUSION: Bimekizumab had a significant clinical benefit in managing PsA and an acceptable safety profile.

Inter- and trans-generational impacts of real-world PM2.5 exposure on male-specific primary hypogonadism.

Exposure to PM2.5, a harmful type of air pollution, has been associated with compromised male reproductive health; however, it remains unclear whether such exposure can elicit transgenerational effects on male fertility. Here, we aim to examine the effect of paternal exposure to real-world PM2.5 on the reproductive health of male offspring. We have observed that paternal exposure to real-world PM2.5 can lead to transgenerational primary hypogonadism in a sex-selective manner, and we have also confirmed this phenotype by using an external model. Mechanically, we have identified small RNAs (sRNAs) that play a critical role in mediating these transgenerational effects. Specifically, miR6240 and piR016061, which are present in F0 PM sperm, regulate intergenerational transmission by targeting Lhcgr and Nsd1, respectively. We have also uncovered that piR033435 and piR006695 indirectly regulate F1 PM sperm methylation by binding to the 3'-untranslated region of Tet1 mRNA. The reduced expression of Tet1 resulted in hypermethylation of several testosterone synthesis genes, including Lhcgr and Gnas, impaired Leydig cell function and ultimately led to transgenerational primary hypogonadism. Our findings provide insights into the mechanisms underlying the transgenerational effects of paternal PM2.5 exposure on reproductive health, highlighting the crucial role played by sRNAs in mediating these effects. The findings underscore the significance of paternal pre-conception interventions in alleviating the adverse effects of environmental pollutants on reproductive health.

Precise reconstruction of the entire mouse kidney at cellular resolution.

The kidney is an important organ for excreting metabolic waste and maintaining the stability of the body's internal environment. The renal function involves multiple complex and fine structures in the whole kidney, and any change in these structures may cause impaired nephric function. Consequently, achieving three-dimensional (3D) reconstruction of the entire kidney at a single-cell resolution is of significant importance for understanding the kidney's structural characteristics and exploring the pathogenesis of kidney diseases. In this paper, we propose a pipeline from sample preparation to optical microscopic imaging of the entire kidney, followed by data processing for 3D reconstruction of the whole mouse kidney. We employed transgenic fluorescent labeling and propidium iodide (PI) labeling to obtain detailed information about the vascular structure and cytoarchitecture of the kidney. Subsequently, the entire mouse kidney was imaged at submicron-resolution using high-definition fluorescent micro-optical sectioning tomography (HD-fMOST). Finally, we reconstructed the structures of interest through various data processing methods on the original images. This included detecting glomeruli throughout the entire kidney, as well as the segmentation and visualization of the renal arteries, veins, and three different types of nephrons. Our method provides a powerful tool for studying the renal microstructure and its spatial relationships throughout the entire kidney.

Integrated chromosomal instability and tumor microbiome redefined prognosis-related subtypes of pancreatic cancer.

BACKGROUND: Pancreatic cancer is a common malignancy with poor prognosis and limited treatment. Here we aimed to investigate the role of host chromosomal instability (CIN) and tumor microbiome in the prognosis of pancreatic cancer patients. METHODS: One hundred formalin-fixed paraffin-embedded (FFPE) pancreatic cancer samples were collected. DNA extracted from FFPE samples were analyzed by low-coverage whole-genome sequencing (WGS) via a customized bioinformatics workflow named ultrasensitive chromosomal aneuploidy detector. RESULTS: Samples are tested according to the procedure of ultrasensitive chromosomal aneuploidy detector (UCAD). We excluded 2 samples with failed quality control, 1 patient lost to follow-up and 6 dead in the perioperative period. The final 91 patients were admitted for the following analyses. Thirteen (14.3%) patients with higher CIN score had worse overall survival (OS) than those with lower CIN score. The top 20 microbes in pancreatic cancer samples included 15 species of bacteria and 5 species of viruses. Patients with high human herpesvirus (HHV)-7 and HHV-5 DNA reads exhibited worse OS. Furthermore, we classified 91 patients into 3 subtypes. Patients with higher CIN score (n =13) had the worst prognosis (median OS 6.9 mon); patients with lower CIN score but with HHV-7/5 DNA load (n = 24) had worse prognosis (median OS 10.6 mon); while patients with lower CIN score and HHV-7/5 DNA negative (n = 54) had the best prognosis (median OS 21.1 mon). CONCLUSIONS: High CIN and HHV-7/5 DNA load were associated with worse survival of pancreatic cancer. The novel molecular subtypes of pancreatic cancer based on CIN and microbiome had prognostic value.

Curriculum vitae of CUG binding protein 1 (CELF1) in homeostasis and diseases: a systematic review.

RNA-binding proteins (RBPs) are kinds of proteins with either singular or multiple RNA-binding domains (RBDs), and they can assembly into ribonucleic acid-protein complexes, which mediate transportation, editing, splicing, stabilization, translational efficiency, or epigenetic modifications of their binding RNA partners, and thereby modulate various physiological and pathological processes. CUG-BP, Elav-like family 1 (CELF1) is a member of the CELF family of RBPs with high affinity to the GU-rich elements in mRNA, and thus exerting control over critical processes including mRNA splicing, translation, and decay. Mounting studies support that CELF1 is correlated with occurrence, genesis and development and represents a potential therapeutical target for these malignant diseases. Herein, we present the structure and function of CELF1, outline its role and regulatory mechanisms in varieties of homeostasis and diseases, summarize the identified CELF1 regulators and their structure-activity relationships, and prospect the current challenges and their solutions during studies on CELF1 functions and corresponding drug discovery, which will facilitate the establishment of a targeted regulatory network for CELF1 in diseases and advance CELF1 as a potential drug target for disease therapy.

Helicobacter pylori upregulates circPGD and promotes development of gastric cancer.

PURPOSE: Helicobacter pylori (H. pylori) has unique biochemical traits and pathogenic mechanisms, which make it a substantial cause of gastrointestinal cancers. Circular RNAs (circRNAs) have concurrently been identified as an important participating factor in the pathophysiology of several different cancers. However, the underlying processes and putative interactions between H. pylori and circRNAs have received very little attention. To address this issue, we explored the interaction between H. pylori and circRNAs to investigate how they might jointly contribute to the occurrence and development of gastric cancer. METHODS: Changes in circPGD expression in H. pylori were detected using qRT-PCR. Cell proliferation and migration changes were assayed by colony formation, the CCK-8 assay and the transwell assay. Apoptosis was measured by flow cytometry. Western blot was conducted to detect changes in cell migration, apoptosis, proliferation and inflammation-associated proteins. QRT-PCR was used to measure changes in circPGD and inflammation-associated factors. RESULTS: We found that H. pylori induced increased circPGD expression in infected human cells and facilitated gastric cancer progression in three ways by promoting cell proliferation and migration, enhancing the inflammatory response, and inhibiting apoptosis. CONCLUSIONS: CircPGD appears to play a role in H. pylori-related gastric cancer and may thus be a viable, novel target for therapeutic intervention.

Contrast-enhanced ultrasound (CEUS) and shear wave elastography (SWE) features for characterizing serous microcystic adenomas (SMAs): In comparison to pancreatic neuroendocrine tumors (pNETs).

Objectives: Serous microcystic adenoma (SMA), a primary benign pancreatic tumor which can be clinically followed-up instead of undergoing surgery, are sometimes mis-distinguished as pancreatic neuroendocrine tumor (pNET) in regular preoperative imaging examinations. This study aimed to analyze preoperative contrast-enhanced ultrasound (CEUS) and shear wave elastography (SWE) features of SMAs in comparison to pNETs. Material and methods: In this retrospective study, patients with imaging-diagnosed pancreatic lesions were screened between October 2020 to October 2022 (ethical approval No. B2020-309R). Performing by a Siemens Sequoia (Siemens Medical Solutions, Mountain View, CA, USA) equipped with a 5C-1 curved array transducer (3.0-4.5 MHz), CEUS examination was conducted to observe the microvascular perfusion patterns of pancreatic lesions in arterial phase, venous/late phases (VLP) using SonoVue® (Bracco Imaging Spa, Milan, Italy) as the contrast agent. Virtual touch tissue imaging and quantification (VTIQ) - SWE was used to measure the shear wave velocity (SWV, m/s) value to represent the quantitative stiffness of pancreatic lesions. Multivariate logistic regression was performed to analyze potential ultrasound and clinical features in discriminating SMAs and pNETs. Results: Finally, 30 SMA and 40 pNET patients were included. All pancreatic lesions were pathologically proven via biopsy or surgery. During the arterial phase of CEUS, most SMAs and pNETs showed iso- or hyperenhancement (29/30, 97 % and 31/40, 78 %), with a specific early honeycomb enhancement pattern appeared in 14/30 (47 %) SMA lesions. During the VLP, while most of the SMA lesions remained iso- or hyperenhancement (25/30, 83 %), nearly half of the pNET lesions revealed an attenuated hypoenhancement (17/40, 43 %). The proportion of hypoenhancement pattern during the VLP of CEUS differed significantly between SMAs and pNETs (P = 0.021). The measured SWV value of SMAs was significantly higher than pNETs (2.04 ± 0.70 m/s versus 1.42 ± 0.44 m/s, P = 0.002). Taking a SWV value > 1.83 m/s as a cutoff in differentiating SMAs and pNETs, the area under the receiver operating characteristic curve (AUROC) was 0.825, with sensitivity, specificity and likelihood ratio (+) of 85.71 %, 72.73 % and 3.143, respectively. Multivariate logistic regression revealed that SWV value (m/s) of the pancreatic lesion was an independent variable in discriminating SMA and pNET. Conclusion: By comprehensively evaluating CEUS patterns and SWE features, SMA and pNET may be well differentiated before the operation. While SMA typically presents as harder lesion in VTIQ-SWE, exhibiting a specific honeycomb hyperenhancement pattern during the arterial phase of CEUS, pNET is characterized by relative softness, occasionally displaying a wash-out pattern during the VLP of CEUS.

Normal value of virtual touch imaging quantification elastography in measurements of pancreas.

OBJECTIVE: To evaluate pancreatic tissue stiffness and provide a normal reference shear wave velocity (SWV) value of pancreas from healthy adults by Virtual Touch Imaging Quantification (VTIQ) measurements. METHODS: Healthy adult volunteers without known history of hepatobiliary or pancreatic diseases were included. VTIQ elastography (Siemens ACUSON Sequoia, 5C-1 transducer) was used. SWV values were measured at the cephalic, corpus and tail of pancreas and replicated different operators' obtained data. Subgroups were classified according to the volunteers' gender, age, body mass index (BMI), depth of measurements and the echogenicity of the pancreas. RESULTS: From February 2023 to July 2023, 33 healthy adult volunteers were included. The success rate of VTIQ measurements in cephalic, corpus and tail regions was 90.90 % (30/33), 96.97 % (32/33) and 90.90 % (30/33) respectively. The color elastograms of healthy adult pancreas showed uniform blue or simultaneously blue and green. The average SWV values were 0.97±0.26 m/s for cephalic, 0.91±0.24 m/s for corpus and 0.97±0.25 m/s for pancreatic tail respectively (P = 0.198). The mean SWV values of pancreas did not show significant difference with age, gender or depth (P >  0.05). BMI was an influence factor in the measurements of SWV values of cephalic and tail of pancreas (P <  0.05). Pancreas with hyperechoic parenchyma showed higher mean SWV values (P <  0.05). The intra-observer (ICC = 0.938 [95% CI: 0.869-0.971]) and the inter-observer (ICC = 0.887 [95% CI: 0.760-0.947]) agreements of VTIQ measurements were excellent. CONCLUSIONS: The mean SWV value of the pancreas in healthy adults was 0.96±0.20 m/s (range: 0.52-1.74 m/s). VTIQ technique can be used in pancreatic stiffness measurements with good reliability.

Phylogenomic analyses sheds new light on the phylogeny and diversification of Corydalis DC. in Himalaya-Hengduan Mountains and adjacent regions.

The Himalaya-Hengduan Mountains (HHM), a renowned biodiversity hotspot of the world, harbors the most extensive habitats for alpine plants with extraordinary high levels of endemism. Although the general evolution pattern has been elucidated, the underlying processes driving spectacular radiations in many species-rich groups remain elusive. Corydalis DC. is widely distributed throughout the Northern Hemisphere containing more than 500 species, with high diversity in HHM and adjacent regions. Using 95 plastid genes, 3,258,640 nuclear single nucleotide polymorphisms (SNPs) and eight single-copy nuclear genes (SCNs) generated from genome skimming data, we reconstructed a robust time-calibrated phylogeny of Corydalis comprising more than 100 species that represented all subgenera and most sections. Molecular dating indicated that all main clades of Corydalis began to diverge in the Eocene, with the majority of extant species in HHM emerged from a diversification burst after the middle Miocene. Global pattern of mean divergence times indicated that species distributed in HHM were considerably younger than those in other regions, particularly for the two most species-rich clades (V and VI) of Corydalis. The early divergence and the recent diversification of Corydalis were most likely promoted by the continuous orogenesis and climate change associated with the uplift of the Qinghai-Tibetan Plateau (QTP). Our study demonstrates the effectivity of phylogenomic analyses with genome skimming data on the phylogeny of species-rich taxa, and sheds lights on how the uplift of QTP has triggered the evolutionary radiations of large plant genera in HHM and adjacent regions.

High salt diet exacerbates cognitive deficits and neurovascular abnormalities in APP/PS1 mice and induces AD-like changes in wild-type mice.

High salt diet (HSD) is a risk factor of hypertension and cardiovascular disease. Although clinical data do not clearly indicate the relationship between HSD and the prevalence of Alzheimer's disease (AD), animal experiments have shown that HSD can cause hyperphosphorylation of tau protein and cognition impairment. However, whether HSD can accelerate the progression of AD by damaging the function of neurovascular unit (NVU) in the brain is unclear. Here, we fed APP/PS1 mice (an AD model) or wild-type mice with HSD and found that the chronic HSD feeding increased the activity of enzymes related to tau phosphorylation, which led to tau hyperphosphorylation in the brain. HSD also aggravated the deposition of Aß42 in hippocampus and cortex in the APP/PS1 mice but not in the wild-type mice. Simultaneously, HSD caused the microglia proliferation, low expression of Aqp-4, and high expression of CD31 in the wild-type mice, which were accompanied with the loss of pericytes (PCs) and increase in blood brain barrier (BBB) permeability. As a result, wild-type mice fed with HSD performed poorly in Morris Water Maze and object recognition test. In the APP/PS1 mice, HSD feeding for 8 months worsen the cognition and accompanied the loss of PCs, the activation of glia, the increase in BBB permeability, and the acceleration of calcification in the brain. Our data suggested that HSD feeding induced the AD-like pathology in wild-type mice and aggravated the development of AD-like pathology in APP/PS1 mice, which implicated the tau hyperphosphorylation and NVU dysfunction.

Chinese patent medicine as a complementary and alternative therapy for type 2 diabetes mellitus: A scoping review.

OBJECTIVE: This scoping review aims to document Chinese Patent Medicines (CPMs) for Type 2 Diabetes Mellitus, explore whether CPMs can improve patients' health outcomes, and set priorities in addressing research gaps in this area. METHODS: Following the framework of PRISMA-SCr, we proposed the research questions based on PICOS principle, and searched the CPMs for T2DM from three drug lists, followed by a systematic search of the literature in eight databases from their inception to June 22, 2023. Then, we developed the eligibility criteria and systematically reviewed the relevant studies, retained the studies about CPMs for T2DM, extracted the related data, and identified the differences across studies in structured charts. RESULTS: A total of 25 types of CPMs were extracted from the three drug lists. Radix astragali appeared most frequently (19 times) among the herbal medicinal ingredients of CPMs. A total of 449 articles were included in the full-paper analysis ultimately, all of which were about 20 types of CPMs, and there were no related reports on the remaining five CPMs. Except about a quarter (25.39 %, 114/449) using CPMs alone, the remaining studies all involved the combination with oral hypoglycemics for T2DM. Biguanides are the most common drugs used in combination with CPMs (50.14 %, 168/335). Fasting plasma glucose (FPG) is the most frequently reported outcomes in efficacy evaluation (82.41 %, 370/449). CONCLUSION: There are a total of 25 types of CPMs currently available for T2DM patients. However, the volume of related evidence on these CPMs varies. It is necessary to standardize the combined use of CPMs and conventional medicine and select appropriate outcomes in future studies.

Curcumin alleviates traumatic brain injury induced by gas explosion through modulating gut microbiota and suppressing the LPS/TLR4/MyD88/NF-κB pathway.

Gas explosions (GE) are a prevalent and widespread cause of traumatic brain injury (TBI) in coal miners. However, the impact and mechanism of curcumin on GE-induced TBI in rats remain unclear. In this study, we simulated GE-induced TBI in rats and administered curcumin orally at a dose of 100 mg/kg every other day for 7 days to modulate the gut microbiota in TBI rats. We employed 16S rRNA sequencing and LC-MS/MS metabolomic analysis to investigate changes in the intestinal flora and its metabolic profile. Additionally, we utilized ELISA, protein assays, and immunohistochemistry to assess neuroinflammatory signaling molecules for validation. In a rat TBI model, GE resulted in weight loss, pathological abnormalities, and cortical hemorrhage. Treatment with curcumin significantly mitigated histological abnormalities and microscopic mitochondrial structural changes in brain tissue. Furthermore, curcumin treatment markedly ameliorated GE-induced brain dysfunction by reducing the levels of several neuroinflammatory signaling molecules, including neuron-specific enolase, interleukin (IL)-1ß, IL-6, and cryptothermic protein 3. Notably, curcumin reshaped the gut microbiome by enhancing evenness, richness, and composition. Prevotella_9, Alloprevotella, Bacilli, Lactobacillales, Proteobacteria, and Gammaproteobacteria were identified as prominent members of the gut microbiota, increasing the linear discriminant analysis scores and specifically enhancing the abundance of bacteria involved in the nuclear factor (NF)-κB signaling pathway, such as Lachnospiraceae and Roseburia. Additionally, there were substantial alterations in serum metabolites associated with metabolic NF-κB signaling pathways in the model group. Curcumin administration reduced serum lipopolysaccharide levels and downregulated downstream Toll-like receptor (TLR)4/myeloid differentiation primary response 88 (MyD88)/NF-κB signaling. Furthermore, curcumin alleviated GE-induced TBI in rats by modulating the gut microbiota and its metabolites. Based on these protective effects, curcumin may exert its influence on the gut microbiota and the TLR4/MyD88/NF-κB signaling pathways to ameliorate GE-induced TBI.

Risk factors for venous ulceration in patients with varicose veins of lower extremities.

The aim of this case-control study was to explore the potential risk factors for venous ulceration in patients with varicose veins of lower extremities and to establish a simplified diagnostic score model. Seventy subjects with varicose veins of lower extremities and venous ulceration were compared with 1164 controls with varicose veins of lower extremities and no history of venous ulceration. Stepwise multivariate logistic regression analysis was used to identify the risk factors for venous ulceration. The steps in developing the diagnostic score model were based on the Framingham Heart study. The area under the receiver operating characteristic curve (AUC) was calculated to assess the diagnostic ability of the diagnostic score model. Multivariate analysis showed that men, overweight, obesity, longer duration varicose veins, deep venous valve insufficiency, low lymphocyte counts, and high fibrinogen content were independently associated with an increased risk of venous ulceration. The AUC for the diagnostic score model was 0.75, which indicated good discriminatory ability. Special attention should be paid to the high-risk group of patients with lower extremity varicose veins. The diagnostic score model might be a useful screening tool for clinicians, policy makers, and patients.

Evaluation of therapeutic benefits of botulinum toxin for foot dystonia associated with Parkinson's disease.

BACKGROUND: Foot dystonia occurs in patients with Parkinson's disease (PD) and leads to pain, malformation, and difficulty with walking. Botulinum toxin injections may be effective for foot dystonia, but the extent of improvement and effects on motor function are unclear. METHODS: In this study, we performed botulinum toxin injections for foot dystonia in 25 patients with PD. At 3 weeks and 3 months post-infection, we assessed changes in plantar pressure distribution utilizing the Pressure Plate system; dystonia using the Modified Ashworth Spasm score; pain using the visual analog scale (VAS) score; and lower extremity function using the Calf-raise Senior (CRS) test, Timed Up and Go (TUG) test, and gait parameters (eg, stride length, step length). RESULTS: We found improved Modified Ashworth Spasm score (p < 0.01) and VAS score (p < 0.01) post-injection. CRS test score (3 weeks, p = 0.006; 3 months, p = 0.068), stride length (3 weeks, p = 0.012; 3 months, p = 0.715), and step length (3 weeks, p = 0.011; 3 months, p = 0.803) also improved. Plantar pressure distribution improved after botulinum toxin injection (metatarsal 1, 3 weeks, p = 0.031; 3 months, p = 0.144; metatarsal 2, 3 weeks, p = 0.049; 3 months, p = 0.065; metatarsal 3, 3 weeks, p = 0.002; 3 months, p = 0.017; metatarsal 4, 3 weeks, p = 0.017; 3 months, p = 0.144; medial heel, 3 weeks, p = 0.01; 3 months, p = 0.395; lateral heel, 3 weeks, p = 0.035; 3 months, p = 0.109). CONCLUSION: Botulinum toxin injection for foot dystonia in patients with PD can reduce spasms and pain and normalize plantar pressure distribution, which improves balance and lower extremity function.

Synthesis of ß-acids loaded chitosan-sodium tripolyphosphate nanoparticle towards controlled release, antibacterial and anticancer activity.

The development of nanoparticles loaded with natural active ingredients is one of the hot trends in the pharmaceutical industry. Herein, chitosan was selected as the base material, and sodium tripolyphosphate was chosen as the cross-linking agent. Chitosan nanoparticles loaded with ß-acids from hops were prepared by the ionic cross-linking method. The results of Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) indicated that chitosan nanoparticles successfully encapsulated ß-acids. The loading capacity of chitosan nanoparticles with ß-acids was 2.00 %-18.26 %, and the encapsulation efficiency was 0.58 %-55.94 %. Scanning electron microscopy (SEM), transmission electron microscope (TEM), particle size, and zeta potential results displayed that the nanoparticles revealed a sphere-like distribution with a particle size range of 241-261 nm, and the potential exhibited positive potential (+14.47-+16.27 mV). The chitosan nanoparticles could slowly release ß-acids from different simulated release media. Notably, the ß-acids-loaded nanoparticles significantly inhibited Staphylococcus aureus ATCC25923 (S. aureus) and Escherichia coli ATCC25922 (E. coli). Besides, ß-acids-loaded chitosan nanoparticles were cytotoxic to colorectal cancer cells (HT-29 and HCT-116). Therefore, applying chitosan nanoparticles can further expand the application of ß-acids in biomedical fields.

Perturbation of IP3R-dependent endoplasmic reticulum calcium homeostasis by PPARδ-activated metabolic stress leads to mouse spermatocyte apoptosis: A direct mechanism for perfluorooctane sulfonic acid-induced spermatogenic disorders.

Perfluorooctane sulfonic acid (PFOS) as an archetypal representative of per- and polyfluoroalkyl substances (PFAS) is ubiquitously distributed in the environment and extensively detected in human bodies. Although accumulating evidence is suggestive of the deleterious effects of PFOS on male reproduction, the direct toxicity of PFOS towards spermatogenic cells and the relevant mechanisms remain poorly understood. The aims of the present study were to explore the direct effects and underlying molecular mechanisms of PFOS on spermatogenesis. Through integrating animal study, transcriptome profiling, in silico toxicological approaches, and in vitro validation study, we identified the molecular initiating event and key events contributing to PFOS-induced spermatogenic impairments. The mouse experiments revealed that spermatocytes were involved in PFOS-induced spermatogenic disorders and the activation of peroxisome proliferator-activated receptor delta (PPARδ) was linked to spermatocyte loss in PFOS-administrated mice. GC-2spd(ts) cells were treated with an increased gradient of PFOS, which was relevant to environmental and occupational exposure levels of PFOS in populations. Following 72-h treatment, cells was harvested for RNA sequencing. The transcriptome profiling and benchmark dose (BMD) modeling identified endoplasmic reticulum (ER) stress as the key event for PFOS-mediated spermatocyte apoptosis and determined the point-of-departure (PoD) for perturbations of ER stress signaling. Based on the calculated PoD value, further bioinformatics analyses combined with in vitro and in vivo validations showed that PFOS caused metabolic stress by activating PPARδ in mouse spermatocytes, which was responsible for Beclin 1-involved inositol 1,4,5-trisphosphate receptor (IP3R) sensitization. The disruption of IP3R-mediated ER calcium homeostasis triggered ER calcium depletion, leading to ER stress and apoptosis in mouse spermatocytes exposed to PFOS. This study systematically investigated the direct impacts of PFOS on spermatogenesis and unveiled the relevant molecular mechanism of PFOS-induced spermatogenic disorders, providing novel insights and potential preventive/therapeutic targets for PFAS-associated male reproductive toxicity.

Review on Pediatric Malignant Focal Liver Lesions with Imaging Evaluation: Part I.

Malignant focal liver lesions (FLLs) are commonly reported in adults but rarely seen in the pediatric population. Due to the rarity, the understanding of these diseases is still very limited. In children, most malignant FLLs are congenital. It is very important to choose appropriate imaging examination concerning various factors. This paper will outline common pediatric malignant FLLs, including hepatoblastoma, hepatocellular carcinoma, and cholangiocarcinoma and discuss them against the background of the latest knowledge on comparable/similar tumors in adults. Medical imaging features are of vital importance for the non-invasive diagnosis and follow-up of treatment of FLLs in pediatric patients. The use of CEUS in pediatric patients for characterizing those FLLs that remain indeterminate on conventional B mode ultrasounds may be an effective option in the future and has great potential to be integrated into imaging algorithms without the risk of exposure to ionizing radiation.