Phthalate exposure and subfecundity in preconception couples: A nested case-control study.

BACKGROUND: Phthalates (PAEs) are endocrine-disrupting chemicals ubiquitously found in the environment. This study aimed to examine the association between exposure of PAEs and subfecundity in preconception couples. METHODS: This is a nested case-control study based on preconception cohort. Preconception couples with intention to conceive were enrolled and followed up until a clinically confirmed pregnancy or 12 menstrual cycles of preparation for conception. A total of 107 couples with subfecundity- time to pregnancy (TTP) more than 12 menstrual cycles, and 144 couples ≤12 cycles were included in the analysis. The levels of PAE metabolites in one spot urine samples were detected and compared between the groups. The weighted quantile sum (WQS) regression model and Bayesian kernel machine regression (BKMR) model were used to examine the joint effects of couples' exposure to PAEs on subfecundity. RESULTS: Using the multivariate binary logistic regression model, compared to the lowest quartile of urinary ∑PAEs concentration group, both preconception females (aOR=2.42, 95% CI: 1.10-5.30, p=0.027) and males (aOR=2.99, 95% CI: 1.36-6.58, p=0.006) in the highest quartile group had an increased risk of subfecundity, and a dose-response relationship was observed between PAEs and the risk of subfecundity. The WQS analyses found that co-exposure to PAE mixture was a risk factor for subfecundity in preconception female (aOR=1.76, 95% CI: 1.38-2.26, p<0.001), male (aOR=1.58, 95% CI: 1.20-2.08, p=0.001), and couple (aOR=2.39, 95% CI: 1.61-3.52, p<0.001). The BKMR model found a positive combined effect of mixed exposure to PAEs on the risk of subfecundity. CONCLUSIONS: PAEs increase the risk of subfecundity in preconception couples. Our research reinforced the need of monitoring PAE exposure for the purpose of improving human reproductive health.

Collapse of carbon nanotubes due to local high-pressure from van der Waals encapsulation.

Van der Waals (vdW) assembly of low-dimensional materials has proven the capability of creating structures with on-demand properties. It is predicted that the vdW encapsulation can induce a local high-pressure of a few GPa, which will strongly modify the structure and property of trapped materials. Here, we report on the structural collapse of carbon nanotubes (CNTs) induced by the vdW encapsulation. By simply covering CNTs with a hexagonal boron nitride flake, most of the CNTs (≈77%) convert from a tubular structure to a collapsed flat structure. Regardless of their original diameters, all the collapsed CNTs exhibit a uniform height of ≈0.7 nm, which is roughly the thickness of bilayer graphene. Such structural collapse is further confirmed by Raman spectroscopy, which shows a prominent broadening and blue shift in the Raman G-peak. The vdW encapsulation-induced collapse of CNTs is fully captured by molecular dynamics simulations of the local vdW pressure. Further near-field optical characterization reveals a metal-semiconductor transition in accompany with the CNT structural collapse. Our study provides not only a convenient approach to generate local high-pressure for fundamental research, but also a collapsed-CNT semiconductor for nanoelectronic applications.

Acanthopanax senticosus improves cognitive impairment in Alzheimer's disease by promoting the phosphorylation of the MAPK signaling pathway.

Background: Acanthopanax senticosus (AS) can improve sleep, enhance memory, and reduce fatigue and is considered as an effective drug for Alzheimer's disease (AD). The therapeutic effect and mechanism need to be further investigated. Methods: To confirm the AS play efficacy in alleviating memory impairment in mice, 5×FAD transgenic mice were subjected to an open-field experiment and a novelty recognition experiment. Network pharmacology technique was used to analyze the information of key compounds and potential key targets of AS for the treatment of AD, molecular docking technique was applied to predict the binding ability of targets and compounds, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were also performed on the targets to derive the possible metabolic processes and pathway mechanisms of AS in treating AD. Quantitative real-time PCR (qRT-PCR) and western blot technique were carried out to validate the candidate genes and pathways. Results: In the open-field experiment, compared with the wild-type (WT) group, the number of times the mice in the AD group crossed the central zone was significantly reduced (P< 0.01). Compared with the AD group, the number of times the mice in the AS group crossed the central zone was significantly increased (P< 0.001). In the new object recognition experiment, compared with the WT group, the percentage of times the AD group explored new objects was significantly reduced (P< 0.05). Compared with the AD group, the AS group had an increase in the percentage of time spent exploring new things and the number of times it was explored (P< 0.05). At the same time, the donepezil group had a significantly higher percentage of times exploring new things (P< 0.01). By using network pharmacology technology, 395 common targets of AS and AD were retrieved. The Cytoscape software was used to construct the protein-protein interaction (PPI) network of common targets. Using the algorithm, nine key targets were retrieved: APP, NTRK1, ESR1, CFTR, CSNK2A1, EGFR, ESR2, GSK3B, and PAK1. The results of molecular docking indicate that 11 pairs of compounds and their corresponding targets have a significant binding ability, as the molecular binding energies were less than -7.0. In comparison to the AD group, the mRNA expression of the key target genes was significantly decreased in the AS treatment group (P< 0.001). The KEGG analysis showed that the MAPK signaling pathway was significantly enriched, and Western blot confirmed that the TRAF6 protein decreased significantly (P< 0.0001). Meanwhile, the levels of MAP3K7 and P38 phosphorylation increased, and there was also an increase in the expression of HSP27 proteins. Conclusion: Our study indicates that the multi-component and multi-target properties of AS play an important role in the alleviation of anxiety and memory impairment caused by AD, and the mechanism is involved in the phosphorylation and activation of the MAPK signaling pathway. The results of this study could provide a novel perspective for the clinical treatment of AD.

Development of a multi-spectroscopy method coupling µ-FTIR and µ-Raman analysis for one-stop detection of microplastics in environmental and biological samples.

Current techniques for microplastics (MPs) analysis are diverse. However, most techniques have individual limitations like the detection limit of spatial resolution, susceptibility, high cost, and time-consuming detection. In this study, we proposed a multi-spectroscopy method coupling µ-FTIR and µ-Raman analysis for one-stop MPs detection, in which barium fluoride was used as the substrate alternative to the filter membrane. Compared with commonly used filter membranes (alumina, silver, PTFE and nylon membranes), the barium fluoride substrate showed better spectroscopic detection performance on microscopic observation, broader transmittable wavenumber range for µ-FTIR (750-4000 cm-1) and µ-Raman (250-4000 cm-1) detection, thus suitable for the multi-spectroscopy analysis of spiked samples. Further, the real environmental and biological samples (indoor air, bottled water and human exhaled breath) were collected and detected to verify the applicability of the developed multi-spectroscopy method. The results indicated that the average content of detected MPs could be increased by 30.4 ± 29.9 % for indoor air, 17.1 ± 13.2 % for bottled water and 38.4 ± 16.0 % for human exhaled breath, respectively in comparison with widely used µ-Raman detection, which suggested that MPs exposure might be underestimated using single spectroscopy detection. Moreover, the majority of underestimated MPs were colored and smaller sized (<50 µm) MPs, which could pose higher risks to human body. In addition, the proposed method consumed lower sample pre-treatment costs and was environmental-friendly since the barium fluoride substrate could be used repeatedly after being cleaned by organic solvent with reliable results (n = 10, CV = 10 %, ICC = 0.961), which reduced the cost of MPs detection by at least 2.49 times compared with traditional methods using silver membrane.

A radiomics model based on T2WI and clinical indexes for prediction of lateral lymph node metastasis in rectal cancer.

OBJECTIVE: The aim of this study was to explore the clinical value of a radiomics prediction model based on T2-weighted imaging (T2WI) and clinical indexes in predicting lateral lymph node (LLN) metastasis in rectal cancer patients. METHODS: This was a retrospective analysis of 106 rectal cancer patients who had undergone LLN dissection. The clinical risk factors for LLN metastasis were selected by multivariable logistic regression analysis of the clinical indicators of the patients. The LLN radiomics features were extracted from the pelvic T2WI of the patients. The least absolute shrinkage and selection operator algorithm and backward stepwise regression method were adopted for feature selection. Three LLN metastasis prediction models were established through logistic regression analysis based on the clinical risk factors and radiomics features. Model performance was assessed in terms of discriminability and decision curve analysis in the training, verification and test sets. RESULTS: The model based on the combined T2WI radiomics features and clinical risk factors demonstrated the highest accuracy, surpassing the models based solely on either T2WI radiomics features or clinical risk factors. Specifically, the model achieved an AUC value of 0.836 in the test set. Decision curve analysis revealed that this model had the greatest clinical utility for the vast majority of the threshold probability range from 0.4 to 1.0. CONCLUSION: Combining T2WI radiomics features with clinical risk factors holds promise for the noninvasive assessment of the biological characteristics of the LLNs in rectal cancer, potentially aiding in therapeutic decision-making and optimizing patient outcomes.

Tip Growth of Quasi-Metallic Bilayer Graphene Nanoribbons with Armchair Chirality.

Graphene nanoribbons (GNRs), quasi one-dimensional (1D) narrow strips of graphene, have shown promise for high-performance nanoelectronics due to their exceptionally high carrier mobility and structurally tunable bandgaps. However, producing chirality-uniform GNRs on insulating substrates remains a big challenge. Here, we report the successful growth of bilayer GNRs with predominantly armchair chirality and ultranarrow widths (<5 nm) on insulating hexagonal boron nitride (h-BN) substrates using chemical vapor deposition (CVD). The growth of GNRs is catalyzed by transition metal nanoparticles, including Fe, Co, and Ni, through a unique tip-growth mechanism. Notably, GNRs catalyzed by Ni exhibit a high purity (97.3%) of armchair chirality. Electron transport measurements indicate that the ultrathin bilayer armchair GNRs exhibit quasi-metallic behavior. This quasi-metallicity is further supported by density functional theory (DFT) calculations, which reveal a significantly reduced bandgap in bilayer armchair GNRs. The chirality-specific GNRs reported here offer promising advancements for the application of graphene in nanoelectronics.

Continuous oral exposure to micro- and nanoplastics induced gut microbiota dysbiosis, intestinal barrier and immune dysfunction in adult mice.

Micro/nanoplastics in the environment can be ingested by organisms and spread throughout the food chain, ultimately posing a threat to human health. However, the risk of continuous oral exposure in mammals remains unresolved. In this study, we utilized a continuous gavage mouse model to investigate the potential intestinal risks associated with oral exposure to polystyrene micro/nanoplastics (PS-MNPs) with environmentally relevant concentrations. The effects of PS-MNPs with different particle sizes on the gut microbiota, intestinal barrier, and intestinal immune function were evaluated. PS-MNPs can accumulate in the intestine after oral exposure and alter the composition of the gut microbiota. Exposure to PS-MNPs significantly reduced the ratio of Firmicutes to Bacteroidetes as well as the number of potentially beneficial bacteria in the gut, while the number of potentially harmful bacteria significantly increased. The short-chain fatty acids metabolized by gut microbiota were significantly changed by PS-MNPs. Exposure to PS-MNPs disrupts the function of the intestinal barrier and leads to inflammation in the intestines. The levels of secretory immunoglobulin A in the intestine and the differentiation of CD4+ and CD8+ T cells in mesenteric lymph nodes were significantly decreased by PS-MNPs. Moreover, the impact of PS-MNPs on mammalian intestinal health is influenced by the exposure duration and particle size, rather than the concentration. It also suggests that nanoplastics may pose more severe environmental risks.

A Comparison of Adjustable Positioning and Free Positioning After Pars Plana Vitrectomy for Rhegmatogenous Retinal Detachment: A Prospective Randomized Controlled Study.

Purpose: To compare the effectiveness and safety of adjustable and free postoperative positioning after pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD). Design: Prospective, randomized controlled study. Methods: A total of 94 eyes with RRD were enrolled from April 2020 to April 2023 and monitored postoperatively for at least 3 months. All patients underwent PPV combined with silicone oil injection or gas tamponade and were randomly divided postoperatively into two groups: an adjustable positioning group and a free positioning group. The success of the outcome was based on the retinal reattachment rate, best corrected visual acuity (BCVA), postoperative complications, and ocular biometric parameters such as anterior chamber depth (ACD) and lens thickness (LT). Results: The initial retinal reattachment rate was 97.9% in the adjustable positioning group and 95.7% in the free positioning group, manifesting no statistical difference between the two groups. Similarly, no statistical difference was observed between the two groups in the final BCVA, which was significantly improved compared to the preoperative BCVA. The comparison of the 1-month postoperative ACD and LT with the preoperative values showed no statistically significant differences in the two groups. The rates of complications were not statistically different in the two groups. Conclusion: After treating RRD using PPV, neither the adjustable nor the free postoperative positioning affected the retinal reattachment rate or the incidence of complications. Therefore, our study showed that it is safe and effective to adopt free positioning postoperatively, which may provide more options for patients with RRD undergoing PPV.

A novel SLC25A1 inhibitor, parthenolide, suppresses the growth and stemness of liver cancer stem cells with metabolic vulnerability.

Liver cancer stem cells (LCSCs) are recognized as key contributors to hepatocarcinogenesis, progression, and recurrence. Consequently, eradicating LCSCs has a great chance of increasing long-term survival in patients with liver cancer. Parthenolide (PTL), a natural sesquiterpene lactone product, possesses robust antitumor activity. However, the effects of PTL on LCSCs and underlying mechanisms remain unknown. Here we show that administration of PTL stimulated cell cycle arrest at the G1 phase, induced apoptosis, and decreased the stemness of LCSCs. Further research indicates that PTL caused the production of ROS and the reduction of oxidative phosphorylation (OXPHOS) and mitochondrial membrane potential (MMP) levels of LCSCs. RNA sequencing (RNA-Seq) further shows that PTL decreased SLC25A1 expression at the mRNA level and that inhibition of SLC25A1 synergistically decreased the expression of IDH2 and several pivotal genes involved in mitochondrial respiratory chain complex, resulting in the production of ROS and mitochondrial dysfunction. In addition, the inhibitory effect of PTL on mitochondrial function and self-renewal capacity of LCSCs was abolished by the knockdown of SLC25A1 or treatment with SLC25A1 inhibitor CTPI-2. Importantly, PTL prevented liver cancer growth in vivo without clearly causing toxicity. Our research shows that PTL inhibits the growth and stemness of LCSCs through SLC25A1-mediated mitochondrial function. PTL may be a potential candidate natural agent for liver cancer treatment.

An Analysis of the Gene Expression Associated with Lymph Node Metastasis in Colorectal Cancer.

Objective: This study aimed to explore the genes regulating lymph node metastasis in colorectal cancer (CRC) and to clarify their relationship with tumor immune cell infiltration and patient prognoses. Methods: The data sets of CRC patients were collected through the Cancer Gene Atlas database; the differentially expressed genes (DEGs) associated with CRC lymph node metastasis were screened; a protein-protein interaction (PPI) network was constructed; the top 20 hub genes were selected; the Gene Ontology functions and the Kyoto Encyclopedia of Genes and Genomes pathways were enriched and analyzed. The Least Absolute Shrinkage and Selection Operator (LASSO) regression method was employed to further screen the characteristic genes associated with CRC lymph node metastasis in 20 hub genes, exploring the correlation between the characteristic genes and immune cell infiltration, conducting a univariate COX analysis on the characteristic genes, obtaining survival-related genes, constructing a risk score formula, conducting a Kaplan-Meier analysis based on the risk score formula, and performing a multivariate COX regression analysis on the clinical factors and risk scores. Results: A total of 62 DEGs associated with CRC lymph node metastasis were obtained. Among the 20 hub genes identified via PPI, only calcium-activated chloride channel regulator 1 (CLCA1) expression was down-regulated in lymph node metastasis, and the rest were up-regulated. A total of nine characteristic genes associated with CRC lymph node metastasis (KIF1A, TMEM59L, CLCA1, COL9A3, GDF5, TUBB2B, STMN2, FOXN1, and SCN5A) were screened using the LASSO regression method. The nine characteristic genes were significantly related to different kinds of immune cell infiltration, from which three survival-related genes (TMEM59L, CLCA1, and TUBB2B) were screened. A multi-factor COX regression showed that the risk scores obtained from TMEM59L, CLCA1, and TUBB2B were independent prognostic factors. Immunohistochemical validation was performed in tissue samples from patients with rectal and colon cancer. Conclusion: TMEM59L, CLCA1, and TUBB2B were independent prognostic factors associated with lymphatic metastasis of CRC.

Pathogens are an important driving force for the rapid spread of symbionts in an insect host.

One of the biggest challenges for pathogens invading hosts is microbial symbionts but the role of pathogens in symbionts in nature is unknown. By tracking the dynamics of the entomopathogenic fungal Cordyceps javanica and symbionts in natural populations of the whitefly Bemisia tabaci from 2016 to 2021 across China, we reveal that Rickettsia, a newly invaded symbiont, is positively correlated with the pathogen in both frequency and density. We confirm that applying pathogen pressure can selectively drive Rickettsia to sudden fixation in whiteflies both in the laboratory and in the field. Furthermore, the driving force is elucidated by the Rickettsia-conferred suppression of pathogen infection quantity, proliferation and sporulation, acting as a potential barrier of onward transmission of the pathogen. These results show that pathogens are an important driving force for rapid shifts in host symbionts in the natural niche.

A novel role for astrocytic fragmented mitochondria in regulating morphine addiction.

Chronic morphine exposure causes the development of addictive behaviors, accompanied by an increase in neuroinflammation in the central nervous system. While previous researches have shown that astrocytes contribute to brain diseases, the role of astrocyte in morphine addiction through induced neuroinflammation remain unexplored. Here we show that morphine-induced inflammation requires the crosstalk among neuron, astrocyte, and microglia. Specifically, astrocytes respond to morphine-induced neuronal activation by increasing glycolytic metabolism. The dysregulation of glycolysis leads to an increased in the generation of mitochondrial reactive oxygen species and causes excessive mitochondrial fragmentation in astrocytes. These fragmented, dysfunctional mitochondria are consequently released into extracellular environment, leading to activation of microglia and release of inflammatory cytokines. We also found that blocking the nicotinamide adenine dinucleotide salvage pathway with FK866 could inhibit astrocytic glycolysis and restore the mitochondrial homeostasis and effectively attenuate neuroinflammatory responses. Importantly, FK866 reversed morphine-induced addictive behaviors in mice. In summary, our findings illustrate an essential role of astrocytic immunometabolism in morphine induced neural and behavioral plasticity, providing a novel insight into the interactions between neurons, astrocytes, and microglia in the brain affected by chronic morphine exposure.

Staphylococcal Enterotoxin C2 Mutant-Induced Antitumor Immune Response Is Controlled by CDC42/MLC2-Mediated Tumor Cell Stiffness.

As a biological macromolecule, the superantigen staphylococcal enterotoxin C2 (SEC2) is one of the most potent known T-cell activators, and it induces massive cytotoxic granule production. With this property, SEC2 and its mutants are widely regarded as immunomodulating agents for cancer therapy. In a previous study, we constructed an MHC-II-independent mutant of SEC2, named ST-4, which exhibits enhanced immunocyte stimulation and antitumor activity. However, tumor cells have different degrees of sensitivity to SEC2/ST-4. The mechanisms of immune resistance to SEs in cancer cells have not been investigated. Herein, we show that ST-4 could activate more powerful human lymphocyte granule-based cytotoxicity than SEC2. The results of RNA-seq and atomic force microscopy (AFM) analysis showed that, compared with SKOV3 cells, the softer ES-2 cells could escape from SEC2/ST-4-induced cytotoxic T-cell-mediated apoptosis by regulating cell softness through the CDC42/MLC2 pathway. Conversely, after enhancing the stiffness of cancer cells by a nonmuscle myosin-II-specific inhibitor, SEC2/ST-4 exhibited a significant antitumor effect against ES-2 cells by promoting perforin-dependent apoptosis and the S-phase arrest. Taken together, these data suggest that cell stiffness could be a key factor of resistance to SEs in ovarian cancer, and our findings may provide new insight for SE-based tumor immunotherapy.

EFFECT OF ANESTHESIA DURATION ON INTRAVITREAL INJECTION PAIN: A double-blinded, randomized, comparative study.

PURPOSE: To determine the effect of different durations of topical anesthesia on intravitreal injection (IVI) pain. METHODS: This was a double-blinded, randomized, comparative study . Three hundred and twelve sequential eyes undergoing IVI were randomized to one of six groups according to the duration of topical anesthesia (from 1 to 30 minutes, one group for every 5-minute range, Groups 1-6). Topical anesthesia before IVI was standardized. Patients graded their pain using the visual analog scale and the Wong-Baker FACES scale at 15 minutes after the procedure. RESULTS: The pain scores among the six groups were significantly different for the visual analog scale ( P = 0.013) and Wong-Baker FACES scale ( P = 0.024). The mean pain scores for Group 4 were 1.97 ± 1.04 (visual analog scale) and 2.02 ± 1.08 (Wong-Baker FACES scale) and were significantly lower than those of Group 1, 2, 5, or 6. CONCLUSION: The duration of topical anesthesia significantly correlated with IVI pain. Preoperative 0.5% proparacaine hydrochloride drops were most effective in relieving IVI pain 11 to 20 minutes after topical administration.

Tunable growth of one-dimensional graphitic materials: graphene nanoribbons, carbon nanotubes, and nanoribbon/nanotube junctions.

Graphene nanoribbons (GNRs) and carbon nanotubes (CNTs), two representative one-dimensional (1D) graphitic materials, have attracted tremendous research interests due to their promising applications for future high-performance nanoelectronics. Although various methods have been developed for fabrication of GNRs or CNTs, a unified method allowing controllable synthesis of both of them, as well as their heterojunctions, which could largely benefit their nano-electronic applications, is still lacking. Here, we report on a generic growth of 1D carbon using nanoparticles catalyzed chemical vapor deposition (CVD) on atomically flat hexagonal boron nitride (h-BN) substrates. Relative ratio of the yielded GNRs and CNTs is able to be arbitrarily tuned by varying the growth temperature or feeding gas pressures. The tunability of the generic growth is quantitatively explained by a competing nucleation theory: nucleation into either GNRs or CNTs by the catalysts is determined by the free energy of their formation, which is controlled by the growth conditions. Under the guidance of the theory, we further realized growth of GNR/CNT intramolecular junctions through changing H2 partial pressure during a single growth process. Our study provides not only a universal and controllable method for growing 1D carbon nanostructures, but also a deep understanding of their growth mechanism, which would largely benefit future carbon-based electronics and optoelectronics.

Development of human dermal PBPK models for the bisphenols BPA, BPS, BPF, and BPAF with parallel-layered skin compartment: Basing on dermal administration studies in humans.

Risk assessment of human exposure to bisphenols (BPs) including bisphenol A, S, F and AF (BPA, BPS, BPF and BPAF) have suggested that except for ingestion, health risk resulting from dermal contact is not negligible. However, the absorption kinetics of BPA substitutes in humans following dermal exposure have been poorly studied. This study aimed to address the knowledge gap in physiologically based pharmacokinetic (PBPK) modeling of BPA and its high-concerned substitutes (BPS, BPF and BPAF) following dermal administration. Parallel-layered skin compartmental model for dermal absorption of BPs was for the first time proposed and human dermal administration studies were conducted to determine dermal bio-accessibility of BPS from thermal paper (TP) (n = 4), BPF (n = 4) and BPAF (n = 5) from personal care products (PCPs). Further, pharmacokinetics of BPS and its metabolites following human handling TP were investigated and the dermal PBPK models for BPA and BPS were validated using the available human biomonitoring data. Overall, 28.03 % ± 13.76 % of BPS in TP was transferred to fingers followed by absorption of 96.17 % ± 2.78 % of that. The dermal bio-accessibilities of BPs in PCPs were 31.65 % ± 2.90 % for BPF and 12.49 % ± 1.66 % for BPAF. Monte Carlo analysis indicated that 90 % of the predicted variability fell within one order of magnitude, which suggested that the developed PBPK models had medium uncertainty. Global sensitivity analysis revealed that the model uncertainty is mainly attributed to the variabilities of dermal absorption parameters. Compared with the previous models for BPs, the developed dermal PBPK models were capable of more accurate predictions of the internal dose metric in target organs following human dermal exposure to BPs via TP and PCPs routes. These results suggested that the developed human dermal PBPK models would provide an alternative tool for assessing the risk of human exposure to BPs through dermal absorption.

The consequences of laparoscopic fascial space priority approach to lateral lymph node dissection on urinary and sexual functionality.

Introduction: In this prospective observational study, we aimed to evaluate the consequences of laparoscopic fascia space priority lymph node dissection on urination and sexual function. Aim: To assess the consequences of laparoscopic lateral lymph node dissection (LLND) using the fascial space priority approach on urinary and sexual function in patients with advanced middle and low rectal cancer. Material and methods: Consecutive patients undergoing laparoscopic LLND using the fascial space priority approach from December 2020 to November 2022 were identified from Tianjin Union Medical Center. Clinical data including patient characteristics, surgical details, and pathology were analysed. The urinary function was assessed by international prostate symptom score (IPSS) questionnaire and residual urine volume. The sexual function was investigated using the international index of erectile function (IIEF) questionnaire. Results: A total of 51 patients, mean age 60.5 ±10.9 years, were identified. The lymph nodes were positive in 70.6% (36/51) of the patients. There was no significant difference between the preoperative IPSS score and that at 6 months (5.2 ±2.1 vs. 5.6 ±1.5; p = 0.16). And there was no significant difference between the residual urine volume and that at 6 months (9.5 ±10.6 vs. 8.6 ±6.3; p = 0.61). The IIEF score before the surgery showed no significant difference from that at 6 months after the surgery (21.1 ±2.2 vs. 20.6 ±2.3; p = 0.26). Conclusions: Laparoscopic LLND using a fascial space priority approach can effectively protect the autonomic nerves. The procedure reduces short-term urination and sexual function, but it has little effect on long-term function.

Network Pharmacology-Based Analysis of the Potential Biological Mechanisms of Coix Seed against Colorectal Cancer.

Objective: The aim of this study was to explore the potential biological mechanisms of coix seed in the treatment of colorectal cancer (CRC) based on network pharmacology analysis. Methods: The active components of coix seed and their potential action targets were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The disease targets related to CRC were obtained from the DisGeNET database. The intersection targets of the drug targets and disease targets were selected, and a component-target-disease network was built using Cytoscape 3.8.0 tool. A global network of the core target protein interactions was constructed using String database. Biological function analysis and pathway enrichment analysis of core targets were conducted to explore the potential. Results: A total of nine active components were obtained from the TCMSP database corresponding to 37 targets. Further analysis showed that 18 overlapping targets were associated with CRC. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was conducted based on the 18 targets and 11 significantly enriched signaling pathways implicated in CRC were identified. Conclusion: The multicomponent and multitarget characteristics of coix seed are preliminarily verified, and the potential biological mechanisms of coix seed in the treatment of CRC are predicted, which provides a theoretical basis for the experimental research.

The DPY30-H3K4me3 Axis-Mediated PD-L1 Expression in Melanoma.

Background: DPY30 is a common subunit of the human SET1/MLL complex and is an essential protein required for the activity of SET1/MLL methyltransferase. DPY30 regulates the histone H3K4 modification, and dysfunction of DPY30 might contribute to the regulation of cancer immune evasion. However, the functions and regulation of DPY30 in the expression of programmed cell death ligand 1 (PD-L1) is still not completely explored. Methods: Various online databases were used for data processing and visualization, including UALCAN, Oncomine, cBioPortal, SangerBox, TISIDB, TIMER, and GEPIA databases. The expression of DPY30 and PD-L1 in melanoma tissues were evaluated by IHC. Chromatin Immunoprecipitation (ChIP), RT-PCR and flow cytometry were used to elucidate the underlying molecular mechanism of PD-L1 expression regulation and its function. Results: The mRNA level of DPY30 in melanoma was higher than in normal tissues. The expression of DPY30 was positively associated with TMB, neoantigens and PD-L1 expression. Furthermore, DPY30 expression showed significant positive correlations with immune suppressor cells and ICP genes involved in T-cell exhaustion. IHC showed that the positive rates of DPY30 and PD-L1 in melanoma tissues were 62% and 58%, respectively. Correlation analysis revealed that DPY30 over-expression was positively associated with PD-L1 expression. Silencing of DPY30 by specific siRNA significantly inhibited PD-L1 expression. ChIP analysis revealed that H3K4me3 levels were enriched in the proximal PD-L1 promoter region in tumor cells. Inhibition of DPY30 still suppressed the PD-L1 level in IFN-γ treated MMAC-SF cells. Furthermore, the apoptosis of PD1+ T-cells in co-culture with MMAC-SF cells by knockdown of DPY30 were markedly reduced. Conclusion: This study shows the roles of DPY30 in regulating the cancer immune evasion in melanoma. Targeting the DPY30-H3K4me3 axis might be an alternative approach to enhance the efficacy of checkpoint immunotherapy.