Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

PLC-CN-NFAT1 signaling-mediated Aß and IL-1ß crosstalk synergistically promotes hippocampal neuronal damage.

Alzheimer's disease (AD) is a progressive neurodegenerative disease. Neuronal calcium overload plays an important role in Aß deposition and neuroinflammation, which are strongly associated with AD. However, the specific mechanisms by which calcium overload contributes to neuroinflammation and AD and the relationship between them have not been elucidated. Phospholipase C (PLC) is involved in regulation of calcium homeostasis, and CN-NFAT1 signaling is dependent on intracellular Ca2+ ([Ca2+]i) to regulate transcription of genes. Therefore, we hypothesized that the PLC-CN-NFAT1 signaling might mediate the interaction between Aß and inflammation to promote neuronal injury in AD. In this experiment, the results showed that the levels of Aß, IL-1ß and [Ca2+]i in the hippocampal primary neurons of APP/PS1 mice (APP neurons) were significantly increased. IL-1ß exposure also significantly increased Aß and [Ca2+]i in HT22 cells, suggesting a close association between Aß and IL-1ß in the development of AD. Furthermore, PLC activation induced significant calcium homeostasis imbalance, cell apoptosis, Aß and ROS production, and significantly increased expressions of CN and NFAT1, while PLC inhibitor significantly reversed these changes in APP neurons and IL-1ß-induced HT22 cells. Further results indicated that PLC activation significantly increased the expressions of NOX2, APP, BACE1, and NCSTN, which were inhibited by PLC inhibitor in APP neurons and IL-1ß-induced HT22 cells. All indications point to a synergistic interaction between Aß and IL-1ß by activating the PLC-CN-NFAT1 signal, ultimately causing a vicious cycle, resulting in neuronal damage in AD. The study may provide a new idea and target for treatment of AD.

Platinum-based adjuvant chemoradiotherapy versus adjuvant radiotherapy in patients with head and neck adenoid cystic carcinoma.

PURPOSE: The objective of the study was to assess the effectiveness and toxicity of platinum-based adjuvant chemoradiotherapy (POCRT) in comparison to postoperative radiotherapy (PORT) in patients with head and neck adenoid cystic carcinoma (HNACC). MATERIALS AND METHODS: This retrospective study analyzed patients diagnosed with HNACC at our center between January 2010 and April 2020. A 1:1 propensity score matching method was used to create a matched cohort. RESULTS: In this study, 206 patients were analyzed, with 147 patients (71.4%) receiving postoperative radiotherapy (PORT) and 59 patients (28.6%) receiving POCRT. Twenty-one patients experienced local-regional failure. The 3-, 5-, and 10-yr local-regional control (LRC) rate for the cohort were 92.0%, 90.6%, and 86.9%, respectively. In both the entire cohort and the matched cohort, the POCRT group exhibited superior LRC compared to the PORT group (Gray's test, all P < 0.05*). Multivariate analysis identified adjuvant concurrent chemotherapy as an independent prognostic factor for LRC (Competing risks regression, HR = 0.144, 95% CI 0.026-0.802, P = 0.027*). In addition, the POCRT group had higher incidences of upper gastrointestinal toxicity and hematologic toxicities, including leukopenia, neutropenia, and anemia (all P < 0.05*). CONCLUSION: In terms of reducing locoregional failures in HNACC patients, POCRT may potentially offer a more effective therapeutic approach than using PORT alone, although it also entails an augmented burden of treatment-related toxicity.

Efficacy and safety of fibrin sealant application in patients undergoing thyroidectomy: a systematic review and meta-analysis.

Various studies have focused on the application of fibrin sealants (FS) in thyroid surgery. Utilizing a meta-analysis, this systematic review analyzed the findings of recent randomized controlled trials on the safety and efficacy of FS in patients who underwent thyroidectomy. The Cochrane Library, Web of Science, Embase, PubMed, and Medline databases were searched for relevant studies, without any language restrictions. Seven randomized controlled trials were included in the originally identified 69 studies. Overall, 652 patients received FS during thyroid surgery; their outcomes were compared with those of conventionally treated patients. The primary outcomes were total volume of wound drainage, length of hospitalization, and operative time. Significant differences were observed in the total volume of wound drainage (mean deviation (MD): -29.75, 95% confidence interval (CI): -55.39 to -4.11, P = 0.02), length of hospitalization (MD: -0.84, 95% CI: -1.02 to -0.66, P < 0.00001), and surgery duration (MD: -7.60, 95% CI: -14.75 to -0.45, P = 0.04). Secondary outcomes were seroma and hypoparathyroidism development. The risk of hypoparathyroidism did not differ between the FS and conventional groups (I = 0%, relative risk = 1.31, P = 0.38). Analysis of "seroma formation that required invasive treatment" indicated that FS showed some benefit (I2 = 8%, relative risk 0.44, P = 0.15). Heterogeneity among the different trials limited their conclusions. The meta-analysis showed that although FS use did not significantly reduce seroma or hypoparathyroidism incidence in patients after thyroidectomy, it significantly reduced the total drainage volume, length of hospitalization, and duration of surgery.

Cordyceps militaris Extract and Cordycepin Alleviate Oxidative Stress, Modulate Gut Microbiota and Ameliorate Intestinal Damage in LPS-Induced Piglets.

Cordycepin is considered a major bioactive component in Cordyceps militaris extract. This study was performed to evaluate the ameliorative effect of Cordyceps militaris extract (CME) and cordycepin (CPN) supplementation on intestinal damage in LPS-challenged piglets. The results showed that CPN or CME supplementation significantly increased the villus height (p < 0.01) and villus height/crypt depth ratio (p < 0.05) in the jejunum and ileum of piglets with LPS-induced intestinal inflammation. Meanwhile, CPN or CME supplementation alleviated oxidative stress and inflammatory responses by reducing the levels of MDA (p < 0.05) and pro-inflammatory cytokines in the serum. Additionally, supplementation with CPN or CME modulated the structure of the intestinal microbiota by enriching short-chain fatty acid-producing bacteria, and increased the level of butyrate (p < 0.05). The RNA-seq results demonstrated that CME or CPN altered the complement and coagulation-cascade-related genes (p < 0.05), including upregulating gene KLKB1 while downregulating the genes CFD, F2RL2, CFB, C4BPA, F7, C4BPB, CFH, C3 and PROS1, which regulate the complement activation involved in inflammatory and immune responses. Correlation analysis further demonstrated the potential relation between the gut microbiota and intestinal inflammation, oxidative stress, and butyrate in piglets. In conclusion, CPN or CME supplementation might inhibit LPS-induced inflammation and oxidative stress by modulating the intestinal microbiota and its metabolite butyrate in piglets.

Physical Properties of Paste Synthesized from Wet- and Dry-Processed Silver Powders.

This study compares the characteristics and low-temperature curing properties of pastes prepared from silver (Ag) powders synthesized by either wet powder (WP) or dry powder (DP) processing. The WP synthesis of electrode particles has the advantage of controlling the average particle size and particle size distribution but the disadvantage of producing low-purity, crystalline particles because they are synthesized through chemical reduction at less than 100 °C. Conversely, the DP synthesis of electrode particles has the advantage of producing pure, highly crystalline particles (due to synthesis at high temperatures) but the disadvantage of a high processing cost. WP and DP were used to manufacture pastes for low-temperature curing, and the physical properties of the pastes and the electrode characteristics after low-temperature curing were compared between powder types. Shear stress as a function of the shear rate shows that the WP paste is a plastic fluid, whereas the DP paste is a pseudoplastic fluid, closer to a Newtonian fluid. Screen printing the Ag pastes and curing for 30 min at 130 °C produces a nonconductive WP paste, whereas it produces a DP paste with a conductivity of 61 mΩ/sq, indicating that the highly crystalline DP paste is advantageous for low-temperature curing.

Genomics-based analysis of four porcine-derived lactic acid bacteria strains and their evaluation as potential probiotics.

The search for probiotics and exploration of their functions are crucial for livestock farming. Recently, porcine-derived lactic acid bacteria (LAB) have shown great potential as probiotics. However, research on the evaluation of porcine-derived LAB as potential probiotics through genomics-based analysis is relatively limited. The present study analyzed four porcine-derived LAB strains (Lactobacillus johnsonii L16, Latilactobacillus curvatus ZHA1, Ligilactobacillus salivarius ZSA5 and Ligilactobacillus animalis ZSB1) using genomic techniques and combined with in vitro tests to evaluate their potential as probiotics. The genome sizes of the four strains ranged from 1,897,301 bp to 2,318,470 bp with the GC contents from 33.03 to 41.97%. Pan-genomic analysis and collinearity analysis indicated differences among the genomes of four strains. Carbohydrate active enzymes analysis revealed that L. johnsonii L16 encoded more carbohydrate active enzymes than other strains. KEGG pathway analysis and in vitro tests confirmed that L. johnsonii L16 could utilize a wide range of carbohydrates and had good utilization capacity for each carbohydrate. The four strains had genes related to acid tolerance and were tolerant to low pH, with L. johnsonii L16 showing the greatest tolerance. The four strains contained genes related to bile salt tolerance and were able to tolerate 0.1% bile salt. Four strains had antioxidant related genes and exhibited antioxidant activity in in vitro tests. They contained the genes linked with organic acid biosynthesis and exhibited antibacterial activity against enterotoxigenic Escherichia coli K88 (ETEC K88) and Salmonella 6,7:c:1,5, wherein, L. johnsonii L16 and L. salivarius ZSA5 had gene clusters encoding bacteriocin. Results suggest that genome analysis combined with in vitro tests is an effective approach for evaluating different strains as probiotics. The findings of this study indicate that L. johnsonii L16 has the potential as a probiotic strain among the four strains and provide theoretical basis for the development of probiotics in swine production.

Alteration in gut microbiota is associated with immune imbalance in Graves' disease.

Background: Graves' disease (GD), characterized by immune aberration, is associated with gut dysbiosis. Despite the growing interest, substantial evidence detailing the precise impact of gut microbiota on GD's autoimmune processes remains exceedingly rare. Objective: This study was designed to investigate the influence of gut microbiota on immune dysregulation in GD. Methods: It encompassed 52 GD patients and 45 healthy controls (HCs), employing flow cytometry and enzyme-linked immunosorbent assay to examine lymphocyte and cytokine profiles, alongside lipopolysaccharide (LPS) levels. Gut microbiota profiles and metabolic features were assessed using 16S rRNA gene sequencing and targeted metabolomics. Results: Our observations revealed a disturbed B-cell distribution and elevated LPS and pro-inflammatory cytokines in GD patients compared to HCs. Significant differences in gut microbiota composition and a marked deficit in short-chain fatty acid (SCFA)-producing bacteria, including ASV263(Bacteroides), ASV1451(Dialister), and ASV503(Coprococcus), were observed in GD patients. These specific bacteria and SCFAs showed correlations with thyroid autoantibodies, B-cell subsets, and cytokine levels. In vitro studies further showed that LPS notably caused B-cell subsets imbalance, reducing conventional memory B cells while increasing naïve B cells. Additionally, acetate combined with propionate and butyrate showcased immunoregulatory functions, diminishing cytokine production in LPS-stimulated cells. Conclusion: Overall, our results highlight the role of gut dysbiosis in contributing to immune dysregulation in GD by affecting lymphocyte status and cytokine production.

Biportal endoscopic transforaminal thoracic interbody fusion for the treatment of thoracic myelopathy.

BACKGROUND: Biportal endoscopic spine surgery independently controls two hands, similar to microscopic surgery, and utilizes a broader working space that is not disturbed by retractors under clear-magnified endoscopic vision. These advantages facilitate successful neural decompression and safe transforaminal interbody fusion, even in patients with thoracic spondylotic myelopathy. METHODS: A wide laminectomy and precise total facetectomy, in conjunction with partial pediculotomy, establish a secure transforaminal space for cage insertion. Endplate preparation and cage insertion were performed without retracting the spinal cord under direct endoscopic vision. CONCLUSION: Biportal endoscopic transforaminal thoracic interbody fusion can be a feasible technique for treating thoracic spondylotic myelopathy at the thoracolumbar junction levels.

Effectiveness of a healthy lifestyle program based on a mobile serious game for childhood cancer survivors: A quasi-randomized trial.

PURPOSE: This study aimed to develop and evaluate the effectiveness of a healthy lifestyle program based on a mobile serious game (HLP-MSG) to enhance the lifestyles of childhood cancer survivors (CCSs). METHODS: This program proceeded in two stages: development and evaluation, using a non-synchronized design with a quasi-randomized trial. The participants were CCSs aged 6-13 years whose treatment was terminated at least 12 months prior. Data were collected at baseline, and post-intervention, with a follow-up after four weeks using the Child Healthy Lifestyle Profile (CHLP). The experimental (n = 26) and control groups (n = 25) were compared. Data were analyzed using descriptive statistics, chi-squared tests, t-tests, and repeated-measures ANOVA. RESULTS: The HLP-MSG promoted a healthy lifestyle by solving 26 quests, including seven sub-elements (nutrition, exercise, hygiene, interpersonal relationships, stress management, meaning of life, and health responsibility). This study revealed significant differences in the interaction between measurement time and group assignment in the CHLP (p = .006) and physical activity (p = .013), one of the seven sub-dimensions. CONCLUSIONS: A healthy lifestyle program based on a mobile serious game is a feasible health education modality to enhance the physical, psychological, social, and spiritual health of CCSs. IMPLICATIONS TO PRACTICE: The findings add to scientific evidence on a mobile serious game for health education among CCSs. The HLP-MSG provides an evolutionary educational modality that can be delivered non-face-to-face to promote CCSs' continuous healthy behavior maintenance. Moreover, the HLP-MSG is adolescent-friendly and can be utilized as a healthcare tool for parents and children to cooperate.

High species diversity of Phintella and Phintella-like spiders (Araneae: Salticidae) in Vietnam revealed by DNA-based species delimitation analyses.

Salticidae (jumping spiders) usually exhibit pronounced sexual dimorphism in adult morphology, particularly body coloration and size and shape of the first legs. Consequently, the male and female from the same species might be erroneously assigned to different species or even different genera, which could generate synonymies in classification if only morphological data were used. Phintella is a species-rich genus of Salticidae, which currently exhibits 76 named species. However, the male-female counterpart is unknown for nearly half of the species. In this study, we used a molecular approach to delineate the species boundaries for Phintella and Phintella-like specimens collected in Vietnam, using morphological information as supporting data. We used three gene fragments (mitochondrial COI, 16S-ND1, and nuclear 28S) and biogeographical considerations for species delimitation. A total of 22 putative species were recognized: 18 species of the genus Phintella, one species of the genus Lechia (L. squamata), and three species of the genus Phinteloides. Eleven undescribed species were discovered, of which seven have a male-female combination, two species have only males, and two species have only females. The crown age of Phintella was estimated at the Serravallian stage of the Miocene after the increase of species number around 16 MYA. The crown ages of most putative species recognized in this study were estimated in the Pleistocene, and the divergence among sister species likely occurred from the mid-Miocene to the Pliocene. Our ancestral range reconstruction results showed that the diversification of our ingroup was governed by progressive dispersal events, i.e., Phintella and their related species in Vietnam diversified while expanding their range on the continent. Our results provide fundamental biodiversity data for a high-diversity genus in Vietnamese Phintella spiders.

Neoadjuvant chemo-immunotherapy with camrelizumab plus nab-paclitaxel and cisplatin in resectable locally advanced squamous cell carcinoma of the head and neck: a pilot phase II trial.

Neoadjuvant chemoimmunotherapy has emerged as a potential treatment option for resectable head and neck squamous cell carcinoma (HNSCC). In this single-arm phase II trial (NCT04826679), patients with resectable locally advanced HNSCC (T2‒T4, N0‒N3b, M0) received neoadjuvant chemoimmunotherapy with camrelizumab (200 mg), nab-paclitaxel (260 mg/m2), and cisplatin (60 mg/m2) intravenously on day one of each three-week cycle for three cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included pathologic complete response (pCR), major pathologic response (MPR), two-year progression-free survival rate, two-year overall survival rate, and toxicities. Here, we report the perioperative outcomes; survival outcomes were not mature at the time of data analysis. Between April 19, 2021 and March 17, 2022, 48 patients were enrolled and received neoadjuvant therapy, 27 of whom proceeded to surgical resection and remaining 21 received non-surgical therapy. The ORR was 89.6% (95% CI: 80.9, 98.2) among 48 patients who completed neoadjuvant therapy. Of the 27 patients who underwent surgery, 17 (63.0%, 95% CI: 44.7, 81.2) achieved a MPR or pCR, with a pCR rate of 55.6% (95% CI: 36.8, 74.3). Treatment-related adverse events of grade 3 or 4 occurred in two patients. This study meets the primary endpoint showing potential efficacy of neoadjuvant camrelizumab plus nab-paclitaxel and cisplatin, with an acceptable safety profile, in patients with resectable locally advanced HNSCC.

Post-COVID-19 Pandemic Rebound of Macrolide-Resistant Mycoplasma pneumoniae Infection: A Descriptive Study.

The rebound characteristics of respiratory infections after lifting pandemic control measures were uncertain. From January to November 2023, patients presenting at a teaching hospital were tested for common respiratory viruses and Mycoplasma pneumoniae using a combination of antigen, nucleic acid amplification, and targeted next-generation sequencing (tNGS) tests. The number and rate of positive tests per month, clinical and microbiological characteristics were analyzed. A rapid rebound of SARS-CoV-2 was followed by a slower rebound of M. pneumoniae, with an interval of 5 months between their peaks. The hospitalization rate was higher, with infections caused by respiratory viruses compared to M. pneumoniae. Though the pediatric hospitalization rate of respiratory viruses (66.1%) was higher than that of M. pneumoniae (34.0%), the 4094 cases of M. pneumoniae within 6 months posed a huge burden on healthcare services. Multivariate analysis revealed that M. pneumoniae-infected adults had more fatigue, comorbidities, and higher serum C-reactive protein, whereas children had a higher incidence of other respiratory pathogens detected by tNGS or pathogen-specific PCR, fever, and were more likely to be female. A total of 85% of M. pneumoniae-positive specimens had mutations detected at the 23rRNA gene, with 99.7% showing A2063G mutation. Days to defervescence were longer in those not treated by effective antibiotics and those requiring a change in antibiotic treatment. A delayed but significant rebound of M. pneumoniae was observed after the complete relaxation of pandemic control measures. No unusual, unexplained, or unresponsive cases of respiratory infections which warrant further investigation were identified.

Omission of radiotherapy to lymph node level III in patients with cN0 adenoid cystic carcinoma of the major salivary gland: a single center experience.

PURPOSE: Due to the rarity of adenoid cystic carcinoma (ACC) of the major salivary gland, there is no consensus on the extent of prophylactic neck irradiation (PNI) for patients with clinically negative lymph nodes (cN0) disease. MATERIALS AND METHODS: We conducted a retrospective analysis of all patients with ACC of the major salivary gland who received treatment at our center between January 2010 and April 2020. The primary endpoint was regional failure-free survival (RRFS). Secondary endpoints included overall survival (OS), distant metastasis-free survival (DMFS), local recurrence-free survival (LRFS), and acute toxicity. RESULTS: A total of 139 patients were included in the analysis. For cN0 patients, the 5-year RRFS, OS, DMFS, and LRFS were 93.2%, 90.2%, 75.7%, and 91.4%, respectively. Multivariate analysis revealed that PORT was an independent prognostic factor for RRFS and LRFS. No statistically significant differences were observed between the Level III sparing PNI group and the Standard PNI group in terms of RRFS, OS, DMFS, and LRFS. The doses delivered to the larynx and thyroid in the Level III sparing PNI group were significantly lower than those in the Standard PNI group. CONCLUSION: In patients with cN0 ACC of the major salivary gland, PNI improves regional control, and the level III nodal region sparing radiotherapy does not increase the risk of level III recurrence, while potentially reducing toxicity.

Daily fluctuation of Lactobacillus species and their antibiotic resistome in the colon of growing pigs.

There are various types of bacteria inhabiting the intestine that help maintain the balance of the intestinal microbiota. Lactobacillus is one of the important beneficial bacteria and is widely used as a food starter and probiotic. In this study, we investigated the daily fluctuation of the colonic Lactobacillus species and their distribution of antibiotic resistance genes (ARGs) as well as antibiotic susceptibility in pigs. Metagenomic analysis revealed that genus Lactobacillus was one of the most dominant genera in the colon of growing pigs. Rhythmicity analysis revealed that 84 out of 285 Lactobacillus species exhibited rhythmic patterns. Lactobacillus johnsonii and Lactobacillus reuteri were the two most abundant lactobacilli with circadian oscillation, which increased during the day and decreased at night. The profile of the antibiotic resistome was modified over time within 24-h period. Elfamycin resistance genes were the most enriched class found in Lactobacillus. Furthermore, the seven strains of Lactobacillus isolated from the pig intestine mainly exhibited resistance to gentamicin, erythromycin, and lincomycin. The whole genome annotation of four Lactobacillus strains indicated the presence of multiple ARGs, including elfamycin resistance genes, however, the most abundant ARG was optrA in genome of four strains. These results indicate the presence of various Lactobacillus species harboring a large number of ARGs in the swine intestine. This implies that when using animal-derived lactobacilli, it is essential to assess antibiotic resistance to prevent further transmission between animals and the environment.

Neutrophil Nanodecoys Inhibit Tumor Metastasis by Blocking the Interaction between Tumor Cells and Neutrophils.

Cancer metastasis is the main cause of cancer-related deaths and involves the interaction between tumor cells and neutrophils. In this study, we developed activated neutrophil membrane-coated nanoparticles (aNEM NPs) as nanodecoys to block neutrophil-mediated cancer metastasis. The aNEM NPs were fabricated by cloaking poly(lactic acid) nanoparticles with membranes derived from activated neutrophils and inherited the functional proteins of activated neutrophils. We demonstrated that aNEM NPs could interfere with the recruitment of neutrophils to the primary tumor and premetastatic niches, inhibit the adhesion of neutrophils to tumor vascular endothelium and circulating tumor cells (CTCs), and disrupt the formation of CTC-neutrophil clusters in vitro and in vivo. In 4T1-bearing mice, aNEM NPs could effectively reduce breast cancer metastasis to various organs in mice. Our results suggest that aNEM NPs are a promising nanomedicine for preventing or treating cancer metastasis by acting as neutrophil nanodecoys.

Atomic-Scale Cryo-TEM Studies of the Electrochemistry of Redox Mediator in Li-O2 Batteries.

Rechargeable aprotic lithium (Li)-oxygen battery (LOB) is a potential next-generation energy storage technology because of its high theoretical specific energy. However, the role of redox mediator on the oxide electrochemistry remains unclear. This is partly due to the intrinsic complexity of the battery chemistry and the lack of in-depth studies of oxygen electrodes at the atomic level by reliable techniques. Herein, cryo-transmission electron microscopy (cryo-TEM) is used to study how the redox mediator LiI affects the oxygen electrochemistry in LOBs. It is revealed that with or without LiI in the electrolyte, the discharge products are plate-like LiOH or toroidal Li2 O2 , respectively. The I2 assists the decomposition of LiOH via the formation of LiIO3 in the charge process. In addition, a LiI protective layer is formed on the Li anode surface by the shuttle of I3 - , which inhibits the parasitic Li/electrolyte reaction and improves the cycle performance of the LOBs. The LOBs returned to 2e- oxygen reduction reaction (ORR) to produce Li2 O2 after the LiI in the electrolyte is consumed. This work provides new insight on the role of redox mediator on the complex electrochemistry in LOBs which may aid the design LOBs for practical applications.

Deciphering molecular basis of pesticide-induced recurrent pregnancy loss: insights from transcriptomics analysis.

Recent studies have revealed a notable connection between pesticide exposure and Recurrent Pregnancy Loss (RPL), yet the precise molecular underpinning of this toxicity remains elusive. Through the alignment of Differentially Expressed Genes (DEGs) of healthy and RPL patients with the target genes of 9 pesticide components, we identified a set of 12 genes responsible for RPL etiology. Interestingly, biological process showed that besides RPL, those 12 genes also associated with preeclampsia and cardiovascular disease. Enrichment analysis showed the engagement of these genes associated with essential roles in the molecular transport of small molecules, as well as the aldosterone-regulated sodium reabsorption, endocrine and other factor-regulated calcium reabsorption, mineral absorption, ion homeostasis, and ion transport by P-type ATPases. Notably, the crosstalk targets between pesticide components played crucial roles in influencing RPL results, suggesting a role in attenuating pesticide agents that contribute to RPL. It is important to note that non-significant concentration of the pesticide components observed in both control and RPL samples should not prematurely undermine the potential for pesticides to induce RPL in humans. This study emphasizes the complexity of pesticide induced RPL and highlights avenues for further research and precautionary measures.

Optimizing BP neural network algorithm for Pericarpium Citri Reticulatae (Chenpi) origin traceability based on computer vision and ultra-fast gas-phase electronic nose data fusion.

This study utilized computer vision to extract color and texture features of Pericarpium Citri Reticulatae (PCR). The ultra-fast gas-phase electronic nose (UF-GC-E-nose) technique successfully identified 98 volatile components, including olefins, alcohols, and esters, which significantly contribute to the flavor profile of PCR. Multivariate statistical Analysis was applied to the appearance traits of PCR, identifying 57 potential marker-trait factors (VIP > 1 and P < 0.05) from the 118 trait factors that can distinguish PCR from different origins. These factors include color, texture, and odor traits. By integrating multivariate statistical Analysis with the BP neural network algorithm, a novel artificial intelligence algorithm was developed and optimized for traceability of PCR origin. This algorithm achieved a 100% discrimination rate in differentiating PCR samples from various origins. This study offers a valuable reference and data support for developing intelligent algorithms that utilize data fusion from multiple intelligent sensory technologies to achieve rapid traceability of food origins.

Ginsenoside Rg1 attenuates lipopolysaccharide-induced chronic liver damage by activating Nrf2 signaling and inhibiting inflammasomes in hepatic cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng (Panax ginseng C. A. Meyer) is a precious traditional Chinese medicine with multiple pharmacological effects. Ginsenoside Rg1 is a main active ingredient extracted from ginseng, which is known for its age-delaying and antioxidant effects. Increasing evidence indicates that Rg1 exhibits anti-inflammatory properties in numerous diseases and may ameliorate oxidative damage and inflammation in many chronic liver diseases. AIM OF THE STUDY: Chronic inflammatory injury in liver cells is an important pathological basis of many liver diseases. However, its mechanism remains unclear and therapeutic strategies to prevent its development need to be further explored. Thus, our study is to delve the protective effect and mechanism of Rg1 against chronic hepatic inflammatory injuries induced by lipopolysaccharide (LPS). MATERIALS AND METHODS: The chronic liver damage model in mice was build up by injecting intraperitoneally with LPS (200 µg/kg) for 21 days. Serum liver function indicators and levels of IL-1ß, IL-6 and TNF-α were examined by using corresponding Kits. Hematoxylin and Eosin (H&E), Periodic acid-Schiff (PAS), and Masson stains were utilized to visualize hepatic histopathological damage, glycogen deposition, and liver fibrosis. The nuclear import of p-Nrf2 and the generation of Col4 in the liver were detected by IF, while IHC was employed to detect the expressions of NLRP3 and AIM2 in the hepatic. The Western blot and q-PCR were used to survey the expressions of proteins and mRNAs of fibrosis and apoptosis, and the expressions of Keap1, p-Nrf2 and NLRP3, NLRP1, AIM2 inflammasome-related proteins in mouse liver. The cell viability of human hepatocellular carcinoma cells (HepG2) was detected by Cell Counting Kit-8 to select the action concentration of LPS, and intracellular ROS generation was detected using a kit. The expressions of Nuclear Nrf2, HO-1, NQO1 and NLRP3, NLRP1, and AIM2 inflammasome-related proteins in HepG2 cells were detected by Western blot. Finally, the feasibility of the molecular interlinking between Rg1 and Nrf2 was demonstrated by molecular docking. RESULTS: Rg1 treatment for 21 days decreased the levels of ALT, AST, and inflammatory factors of serum IL-1ß, IL-6 and TNF-α in mice induced by LPS. Pathological results indicated that Rg1 treatment obviously alleviated hepatocellular injury and apoptosis, inflammatory cell infiltration and liver fibrosis in LPS stimulated mice. Rg1 promoted Keap1 degradation and enhanced the expressions of p-Nrf2, HO-1 and decreased the levels of NLRP1, NLRP3, AIM2, cleaved caspase-1, IL-1ß and IL-6 in livers caused by LPS. Furthermore, Rg1 effectively suppressed the rise of ROS in HepG2 cells induced by LPS, whereas inhibition of Nrf2 reversed the role of Rg1 in reducing the production of ROS and NLRP3, NLRP1, and AIM2 expressions in LPS-stimulated HepG2 cells. Finally, the molecular docking illustrated that Rg1 exhibits a strong affinity towards Nrf2. CONCLUSION: The findings indicate that Rg1 significantly ameliorates chronic liver damage and fibrosis induced by LPS. The mechanism may be mediated through promoting the dissociation of Nrf2 from Keap1 and then activating Nrf2 signaling and further inhibiting NLRP3, NLRP1, and AIM2 inflammasomes in liver cells.