Postnatal eye size in mice is controlled by SREBP2-mediated transcriptional repression of Lrp2 and Bmp2.

Eye size is a key parameter of visual function, but the precise mechanisms of eye size control remain poorly understood. Here, we discovered that the lipogenic transcription factor sterol regulatory element-binding protein 2 (SREBP2) has an unanticipated function in the retinal pigment epithelium (RPE) to promote eye size in postnatal mice. SREBP2 transcriptionally represses low density lipoprotein receptor-related protein 2 (Lrp2), which has been shown to restrict eye overgrowth. Bone morphogenetic protein 2 (BMP2) is the downstream effector of Srebp2 and Lrp2, and Bmp2 is suppressed by SREBP2 transcriptionally but activated by Lrp2. During postnatal development, SREBP2 protein expression in the RPE decreases whereas that of Lrp2 and Bmp2 increases as the eye growth rate reduces. Bmp2 is the key determinant of eye size such that its level in mouse RPE inversely correlates with eye size. Notably, RPE-specific Bmp2 overexpression by adeno-associated virus effectively prevents the phenotypes caused by Lrp2 knock out. Together, our study shows that rapid postnatal eye size increase is governed by an RPE-derived signaling pathway, which consists of both positive and negative regulators of eye growth.

Upregulation of Siglec-6 induces mitochondrial dysfunction by promoting GPR20 expression in early-onset preeclampsia.

BACKGROUND: Preeclampsia, especially early-onset preeclampsia (EO-PE), is a pregnancy complication that has serious consequences for the health of both the mother and the fetus. Although abnormal placentation due to mitochondrial dysfunction is speculated to contribute to the development of EO-PE, the underlying mechanisms have yet to be fully elucidated. METHODS: The expression and localization of Siglec-6 in the placenta from normal pregnancies, preterm birth and EO-PE patients were examined by RT-qPCR, Western blot and IHC. Transwell assays were performed to evaluate the effect of Siglec-6 on trophoblast cell migration and invasion. Seahorse experiments were conducted to assess the impact of disrupting Siglec-6 expression on mitochondrial function. Co-IP assay was used to examine the interaction of Siglec-6 with SHP1/SHP2. RNA-seq was employed to investigate the mechanism by which Siglec-6 inhibits mitochondrial function in trophoblast cells. RESULTS: The expression of Siglec-6 in extravillous trophoblasts is increased in placental tissues from EO-PE patients. Siglec-6 inhibits trophoblast cell migration and invasion and impairs mitochondrial function. Mechanismly, Siglec-6 inhibits the activation of NF-κB by recruiting SHP1/SHP2, leading to increased expression of GPR20. Notably, the importance of GPR20 function downstream of Siglec-6 in trophoblasts is supported by the observation that GPR20 downregulation rescues defects caused by Siglec-6 overexpression. Finally, overexpression of Siglec-6 in the placenta induces a preeclampsia-like phenotype in a pregnant mouse model. CONCLUSIONS: This study indicates that the regulatory pathway Siglec-6/GPR20 has a crucial role in regulating trophoblast mitochondrial function, and we suggest that Siglec-6 and GPR20 could serve as potential markers and targets for the clinical diagnosis and therapy of EO-PE.

Effect of the residual levofloxacin on hydroponic vegetables with sewage treatment plant tailwater: Microbial community, discharge risk and control strategy.

Tailwater-based hydroponic vegetable is a promising strategy for domestic wastewater recycling. However, the effect of residual antibiotics on the hydroponic vegetable system and the relation between hydroponic culture parameters and the residual water quality are still unclear. Here, the typical antibiotic Levofloxacin (LVFX) was employed, and the effect of LVFX (5 mg/L) on the residual water quality, plant growth and microbial community of water spinach hydroponic culture system were investigated under different hydraulic residence times (HRT). Obvious toxic effects on water spinach were observed, and the highest removal rate of LVFX (about 6 %) and TN (25.67±1.43 %) was observed when HRT was 7 days. Hydroponic culture increased the microbial abundance, diversity, and microbial community stability. To optimize the hydroponic culture, actual sewage plant tailwater spiked with 20 µg/L LVFX, along with three common planting substrates (sponge, ceramsite, and activated carbon) were used for the hydroponic culture of lettuce (seasonal reasons). The inhibition effect of LVFX on the removal of NO3--N and TN was observed even as the LVFX concentration decreased significantly (from 14.62 ± 0.44 µg/L to 0.65 ± 0.07 µg/L). The best growth situation of lettuce and removal rates of NH4+-N, NO3--N, TN, especially LVFX (up to 95.65 ± 0.54 %) were observed in the activated carbon treated group. The overall results indicate the negative effect of residual antibiotics on the hydroponic vegetable systems, and adding activated carbon as substrate is an effective strategy for supporting plant growth and controlling discharged risk.

Regulation of the co-transport of toluene and dichloromethane by adsorbed phase humic acid under different hydro-chemical conditions.

The transport behavior of combined organic pollutants in soil and groundwater has attracted significant attention in recent years. Research on the influence of humic acid (HA) on organic pollutant transport behavior mainly focuses on the study of the mobile phase HA, with less research on the adsorbed phase HA, especially regarding its interaction with combined pollutants. To enhance understanding of the regulation of co-transport and retention of combined pollutants by adsorbed phase HA, in this study, tests were conducted to investigate how toluene (TOL) and dichloromethane (DCM) are transported in the presence of adsorbed phase HA at different pH levels and ionic strengths. As the proportions of HA-coated sand increased, so did its adsorption capacity for TOL and DCM, which can be attributed to adsorbed phase HA providing more adsorption sites compared to plain sand, thereby reducing the transport potential of the pollutants. The presence of both TOL and DCM facilitated their mutual transportation due to competitive adsorption controlled by the adsorbed phase HA content in the porous medium. Furthermore, it was observed that pH levels influenced the transport behavior of TOL and DCM when adsorbed phase HA was present since adsorbed phase HA transformation into mobile phase was regulated by pH levels. The transport patterns can be effectively simulated using the chemical nonequilibrium two-site sorption model in HYDRUS-1D, accurately reflecting the retardation coefficients and transport distances based on model parameters. This work sheds new light on the regulatory role of adsorbed phase HA in TOL and DCM transport under diverse hydrochemical conditions, with implications for accurately depicting the behavior of combined pollutants, optimizing the remediation strategies and improving remediation efficiency in contaminated sites.

Scutellarein protects against cardiac hypertrophy via suppressing TRAF2/NF-κB signaling pathway.

BACKGROUND: Scutellarein, a widely studied ingredient of scutellaria herbs, has higher bioavailability and solubility than that of scutellarin. Although the scutellarein had been reported to modulate numerous biological functions, its ability in suppressing cardiac hypertrophy remains unclear. Hence, the present study attempted to investigate whether scutellarein played critical roles in preventing phenylephrine (PE)-induced cardiac hypertrophy. METHODS AND RESULTS: Immunocytochemistry (ICC) was employed for evaluating the morphology of the treated cardiomyocytes. Real-time PCR and western blot were respectively applied to assess the mRNA levels and protein expression of the relevant molecules. Bioinformatics analyses were carried out to investigate the potential mechanisms by which scutellarein modulated the PE-induced cardiac hypertrophy. The results showed that Scutellarein treatment significantly inhibited PE-induced increase in H9c2 and AC16 cardiomyocyte size. Besides, scutellarein treatment also dramatically suppressed the expression of the cardiac hypertrophic markers: ANP, BNP and ß-MHC. Furthermore, the effects of scutellarein on attenuating the cardiac hypertrophy might be mediated by suppressing the activity of TRAF2/NF-κB signaling pathway. CONCLUSIONS: Collectively, our data indicated that scutellarein could protect against PE-induced cardiac hypertrophy via regulating TRAF2/NF-κB signaling pathway using in vitro experiments.

Aberrant methylation modifications reflect specific drug responses in small cell lung cancer.

In the study, Methylated DNA immunoprecipitation sequencing, RNA sequencing, and whole-exome sequencing were employed to clinical small cell lung cancer (SCLC) patients. Then, we verified the therapeutic predictive effects of differentially methylated genes (DMGs) in 62 SCLC cell lines. Of 4552 DMGs between chemo-sensitive and chemo-insensitive group, coding genes constituted the largest percentage (85.08%), followed by lncRNAs (10.52%) and miRNAs (3.56%). Both two groups demonstrated two methylation peaks near transcription start site and transcription end site. Two lncRNA-miRNA-mRNA networks suggested the extensive genome connection between chemotherapy efficacy-related non-coding RNAs (ncRNAs) and mRNAs. Combing miRNAs and lncRNAs could effectively predict chemotherapy response in SCLC. In addition, we also verified the predictive values of mutated genes in SCLC cell lines. This study was the first to evaluate multiple drugs efficacy-related ncRNAs and mRNAs which were modified by methylation in SCLC. DMGs identified in our research might serve as promising therapeutic targets to reverse drugs-insensitivity by complex lncRNA-miRNA-mRNA mechanisms in SCLC.

Collagen Type III Alpha 1 chain regulated by GATA-Binding Protein 6 affects Type II IFN response and propanoate metabolism in the recurrence of lower grade glioma.

Some studies suggested the prognosis value of immune gene in lower grade glioma (LGG). Recurrence in LGG is a tough clinical problem for many LGG patients. Therefore, prognosis biomarker is required. Multivariate prognosis Cox model was constructed and then calculated the risk score. And differential expressed transcription factors (TFs) and differential expressed immune genes (DEIGs) were co-analysed. Besides, significant immune cells/pathways were identified by single sample gene set enrichment analysis (ssGSEA). Moreover, gene set variation analysis (GSVA) and univariate Cox regression were applied to filter prognostic signalling pathways. Additionally, significant DEIG and immune cells/pathways, and significant DEIG and pathways were co-analysed. Further, differential enriched pathways were identified by GSEA. In sum, a scientific hypothesis for recurrence LGG including TF, immune gene and immune cell/pathway was established. In our study, a total of 536 primary LGG samples, 2,498 immune genes and 318 TFs were acquired. Based on edgeR method, 2,164 DEGs, 2,498 DEIGs and 31 differentials expressed TFs were identified. A total of 106 DEIGs were integrated into multivariate prognostic model. Additionally, the AUC of the ROC curve was 0.860, and P value of Kaplan-Meier curve < 0.001. GATA6 (TF) and COL3A1 (DEIG) were selected (R = 0.900, P < 0.001, positive) as significant TF-immune gene links. Type II IFN response (P < 0.001) was the significant immune pathway. Propanoate metabolism (P < 0.001) was the significant KEGG pathway. We proposed that COL3A1 was positively regulated by GATA6, and by effecting type II IFN response and propanoate metabolism, COL3A1 involved in LGG recurrence.

An innovative smartphone-based otorhinoendoscope and its application in mobile health and teleotolaryngology.

BACKGROUND: The traditional otorhinoendoscope is widely used in the diagnosis of a variety of ear and nose diseases, but only one doctor can use it at a time. It is also very difficult to share observations from one doctor with another doctor. With advances in electronic health technology, the extended potential application of smartphones to support medical practice or mobile health has grown steadily. OBJECTIVE: The first phase of the study discussed how smartphones may be used for otorhinoscopic imaging and image management via an innovative adaptor. The second phase of the study was to evaluate the diagnostic capability of the smartphone-based otorhinoendoscope, as compared to the traditional otorhinoendoscope, and its application in mobile health and teleotolaryngology. METHODS: We designed a unique adaptor to connect the otorhinoendoscope and smartphone in order to perform smartphone-based otorhinoendoscopy. The main aim was to transform the smartphone into an otorhinoendoscope. We devised a method that would allow us to use the smartphone's camera to capture otorhinoscopic images. Using a freely available Web-based real-time communication application platform and the 3G (or WIFI) network, the smartphone-based otorhinoendoscope could synchronize the smartphone-based otorhinoscopic image with smartphones, tablet PCs, computer notebooks, or personal computers. RESULTS: We investigated the feasibility of telemedicine using a smartphone, tablet PC, and computer notebook. Six types of clinical otorhinoscopic images were acquired via the smartphone-based otorhinoendoscope from six patients, which were examined in this study. Three teleconsultants (doctors A, B, and C) reviewed the six types of clinical otorhinoscopic images and made a telediagnosis. When compared to the face-to-face diagnosis, which was made in-person via a traditional otorhinoendoscope, the three teleconsultants obtained scores of a correct primary telediagnosis 83% (5/6), 100% (6/6), and 100% (6/6) of the time, respectively. When the clinical data were provided, the three teleconsultants obtained a correct secondary telediagnosis score of 100% (6/6), 100% (6/6), and 100% (6/6) of the time, respectively. CONCLUSIONS: The use of previously available technologies in the absence of any additional expensive devices could significantly increase the quality of diagnostics while lowering extraneous costs. Furthermore, this could also increase the connectivity between most isolated family doctors and remote referral centers.

Effect of Zinc and Severe Plastic Deformation on Mechanical Properties of AZ61 Magnesium Alloy.

This study investigates the effects of zinc (4 wt.%) and severe plastic deformation on the mechanical properties of AZ61 magnesium alloy through the stir-casting process. Severe plastic deformation (Equal Channel Angular Pressing (ECAP)) has been performed followed by T4 heat treatment. The microstructural examinations revealed that the addition of 4 wt.% Zn enhances the uniform distribution of ß-phase, contributing to a more uniformly corroded surface in corrosive environments. Additionally, dynamic recrystallization (DRX) significantly reduces the grain size of as-cast alloys after undergoing ECAP. The attained mechanical properties demonstrate that after a single ECAP pass, AZ61 + 4 wt.% Zn alloy exhibits the highest yield strength (YS), ultimate compression strength (UCS), and hardness. This research highlights the promising potential of AZ61 + 4 wt.% Zn alloy for enhanced mechanical and corrosion-resistant properties, offering valuable insights for applications in diverse engineering fields.

Identification of key metabolism-related genes and pathways in spontaneous preterm birth: combining bioinformatic analysis and machine learning.

Background: Spontaneous preterm birth (sPTB) is a global disease that is a leading cause of death in neonates and children younger than 5 years of age. However, the etiology of sPTB remains poorly understood. Recent evidence has shown a strong association between metabolic disorders and sPTB. To determine the metabolic alterations in sPTB patients, we used various bioinformatics methods to analyze the abnormal changes in metabolic pathways in the preterm placenta via existing datasets. Methods: In this study, we integrated two datasets (GSE203507 and GSE174415) from the NCBI GEO database for the following analysis. We utilized the "Deseq2" R package and WGCNA for differentially expressed genes (DEGs) analysis; the identified DEGs were subsequently compared with metabolism-related genes. To identify the altered metabolism-related pathways and hub genes in sPTB patients, we performed multiple functional enrichment analysis and applied three machine learning algorithms, LASSO, SVM-RFE, and RF, with the hub genes that were verified by immunohistochemistry. Additionally, we conducted single-sample gene set enrichment analysis to assess immune infiltration in the placenta. Results: We identified 228 sPTB-related DEGs that were enriched in pathways such as arachidonic acid and glutathione metabolism. A total of 3 metabolism-related hub genes, namely, ANPEP, CKMT1B, and PLA2G4A, were identified and validated in external datasets and experiments. A nomogram model was developed and evaluated with 3 hub genes; the model could reliably distinguish sPTB patients and term labor patients with an area under the curve (AUC) > 0.75 for both the training and validation sets. Immune infiltration analysis revealed immune dysregulation in sPTB patients. Conclusion: Three potential hub genes that influence the occurrence of sPTB through shadow participation in placental metabolism were identified; these results provide a new perspective for the development and targeting of treatments for sPTB.

Facilitated transport of toluene and naphthalene with humic acid in high- and low-permeability systems: Role of ionic strength and cationic type.

The occurrence of colloids on pollutants transport in groundwater has attracted more attention. However, the research on the regulation mechanism of colloids on combined pollutants transport in heterogeneous aquifers is limited. In this study, a series of tank experiments were conducted to systematically investigate the effects of ionic strength, and cation type on humic acid (HA) facilitated transport of toluene (TOL), and naphthalene (NAP) in high- and low-permeability systems. The results showed that HA facilitated pollutants transport in low Na+ solution. In Ca2+ solution, the presence of HA hindered pollutants transport, and the inhibition increased with the increase of ionic strength. Both in Na+ solution and low Ca2+ solution, the influence of heterogeneous structure on pollutant transport played a dominant role, and TOL and NAP had a greater transport potential in the high permeability zone (HPZ) due to the preferential flow. Whereas, deposition of HA aggregates, and electrostatic attractive interaction had negative effects on transport than groundwater flow in high Ca2+ solution. Pollutants were prone to accumulate at the bottom of the HPZ, and the top of the low permeability zone (LPZ). These new findings provide insights into the mechanism of colloids influence on the pollutants transport in heterogenous aquifer.

E. coli cotransport with composite colloid in unsaturated porous media: Multi-risk on migration and biomolecular response.

The diversity of colloidal types and the differences in the composite ratios in porous media are important factors governing the migration and biological risk of pathogenic microorganisms in the subsurface environment. In this study, E. coli O157:H7 was subjected to co-migration experiments with different compositions of the composite colloid montmorillonite (MMT)-Fe2O3, and the biomolecular response of E. coli under the action of colloids was analyzed by Raman spectroscopy to quantify the risk of E. coli under the action of composite colloids based on both. The results showed that Fe2O3 colloids inhibited E. coli migration mainly by electrostatic adsorption and reduced E. coli metabolism. MMT colloid inhibited E. coli migration mainly by blockage, and E. coli metabolism increased, and surface macromolecules decreased to reduce E. coli adhesion. MMT-Fe2O3 complex colloids inhibited migration through electrostatic attraction between the two and formation of cohesive colloids, with reduced E. coli metabolism and insignificant biomolecular response. It was briefly assessed that the composite colloids reduced E. coli risk less strongly than single colloids, stemming from the difference in the mechanism of influence and the actual need to consider colloid interactions. This conclusion can inform the management and control of pathogen risk in porous media environments.

The landscape of implantation and placentation: deciphering the function of dynamic RNA methylation at the maternal-fetal interface.

The maternal-fetal interface is defined as the interface between maternal tissue and sections of the fetus in close contact. RNA methylation modifications are the most frequent kind of RNA alterations. It is effective throughout both normal and pathological implantation and placentation during pregnancy. By influencing early embryo development, embryo implantation, endometrium receptivity, immune microenvironment, as well as some implantation and placentation-related disorders like miscarriage and preeclampsia, it is essential for the establishment of the maternal-fetal interface. Our review focuses on the role of dynamic RNA methylation at the maternal-fetal interface, which has received little attention thus far. It has given the mechanistic underpinnings for both normal and abnormal implantation and placentation and could eventually provide an entirely novel approach to treating related complications.

The dose- and time-dependent effectiveness and safety associated with COVID-19 vaccination during pregnancy: a systematic review and meta-analysis.

OBJECTIVES: This study aimed to provide guidance for clinical treatment and increase public confidence in COVID-19 vaccines. METHODS: The Cochrane Library, Embase, PubMed, Web of Science, ClinicalKey, and other COVID-19 datasets were searched from December 2019 to May 2022. Case-control studies and prospective cohort studies of COVID-19 vaccine effectiveness and safety in pregnant women were included. RESULTS: From day 11 to day 13, after the first dose of the COVID-19 messenger RNA vaccine, the effectiveness was 54% (95% confidence interval: 0.33-0.69). On days 14 to 27, the effectiveness was 59%. There was a 14% increase in vaccine effectiveness 28 days after the first dose was given. The inactivated vaccines showed similar effectiveness. The proportions of placental abruptions, postpartum hemorrhages, miscarriages, stillbirths, premature births, and small for gestational age infants were not significantly different between vaccinated and nonvaccinated pregnant women. Fatigue and fever were also not associated with pregnancy. CONCLUSION: Our findings affirm that the effectiveness varies for different types of vaccines and is significantly and positively correlated with time in the pregnant population. COVID-19 vaccines have also been deemed safe for pregnant women. Thus, we developed a comprehensive understanding of the role of vaccines in pregnant women.

Migration risk of Escherichia coli O157:H7 in unsaturated porous media in response to different colloid types and compositions.

The vadose zone is a critical zone for microbial entry into the subsurface environment, and various types of inorganic and organic colloids can affect the migration of pathogenic bacteria. In the study, we explored the migration behavior of Escherichia coli O157:H7 with humic acids (HA), iron oxides (Fe2O3) or their mixture, uncovering their migration mechanisms in the vadose zone. The effect of complex colloids on the physiological properties of E. coli O157:H7 was analyzed based on the measured particle size, zeta potential and contact angle. HA colloids significantly promoted the migration of E. coli O157:H7, where Fe2O3 was opposite. The migration mechanism of E. coli O157:H7 with HA and Fe2O3 is obviously different. Multiple colloids dominated by organic colloid will further highlight its promoting effect on E. coli O157:H7 under the guidance of electrostatic repulsion due to the influence of colloidal stability. Multiple colloids dominated by metallic colloid will inhibit the migration of E. coli O157:H7 under the control of capillary force due to the restriction of contact angle. The risk of secondary release of E. coli O157:H7 can be effectively reduced when the ratio of HA/Fe2O3 is ≥ 1. Combining this conclusion with the distribution characteristics of soil in China, an attempt was made to analyse the migration risk of E. coli O157:H7 on a national scale. In China, from north to south, the migration capacity of E. coli O157:H7 gradually decreased, and the risk of secondary release gradually increased. These results provide ideas for the subsequent study of the effect of other factors on the migration of pathogenic bacteria on a national scale and provide risk information about soil colloids for the construction of pathogen risk assessment model under comprehensive conditions in the future.

Construction of Metastasis-Specific Regulation Network in Ovarian Cancer Based on Prognostic Stemness-Related Signatures.

WE aimed to reveal the correlation between ovarian cancer (OV) metastasis and cancer stemness in OV. RNA-seq data and clinical information of 591 OV samples (551 without metastasis and 40 with metastasis) were obtained from TCGA. The edgeR method was used to determine differentially expressed genes (DEGs) and transcription factors (DETFs). Then, mRNA expression-based stemness index was calculated using one-class logistic regression (OCLR). Weighted gene co-expression network analysis (WGCNA) was used to define stemness-related genes (SRGs). Univariate and multivariate Cox proportional hazard regression were conducted to identify the prognostic SRGs (PSRGs). PSRGs, DETFs, and 50 hallmark pathways quantified by gene set variation analysis (GSVA) were integrated into Pearson co-expression analysis. Significant co-expression interactions were utilized to construct an OV metastasis-specific regulation network. Cell communication analysis was carried out based on single cell RNA sequencing data to explore the molecular regulation mechanism of OV. Eventually, assay for targeting accessible-chromatin with high throughout sequencing (ATAC), chromatin immunoprecipitation sequencing (ChIP-seq) validation, and multiple data sets were used to validate the expression levels and prognostic values of key stemness-related signatures. Moreover, connectivity map (CMap) was used to identify potential inhibitors of stemness-related signatures. Based on edgeR, WGCNA, and Cox proportional hazard regression, 22 PSRGs were defined to construct a prognostic prediction model for metastatic OV. In the metastasis-specific regulation network, key TF-PSRS interaction pair was NR4A1-EGR3 (correlation coefficient = 0.81, p < 0.05, positive), and key PSRG-hallmark pathway interaction pair was EGR3-TNFα signaling via NFκB (correlation coefficient = 0.44, p < 0.05, positive), which were validated in multi-omics databases. Thioridazine was postulated to be the most significant compound in treatment of OV metastasis. PSRGs played critical roles in OV metastasis. Specifically, EGR3 was the most significant PSRG, which was positively regulated by DETF NR4A1, inducing metastasis via TNFα signaling.

Physiological characteristics, geochemical properties and hydrological variables influencing pathogen migration in subsurface system: What we know or not?

The global outbreak of coronavirus infectious disease-2019 (COVID-19) draws attentions in the transport and spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in aerosols, wastewater, surface water and solid wastes. As pathogens eventually enter the subsurface system, e.g., soils in the vadose zone and groundwater in the aquifers, they might survive for a prolonged period of time owing to the uniqueness of subsurface environment. In addition, pathogens can transport in groundwater and contaminate surrounding drinking water sources, possessing long-term and concealed risks to human society. This work critically reviews the influential factors of pathogen migration, unravelling the impacts of pathogenic characteristics, vadose zone physiochemical properties and hydrological variables on the migration of typical pathogens in subsurface system. An assessment algorithm and two rating/weighting schemes are proposed to evaluate the migration abilities and risks of pathogens in subsurface environment. As there is still no evidence about the presence and distribution of SARS-CoV-2 in the vadose zones and aquifers, this study also discusses the migration potential and behavior of SARS-CoV-2 viruses in subsurface environment, offering prospective clues and suggestions for its potential risks in drinking water and effective prevention and control from hydrogeological points of view.

Current progress and mechanisms of bone metastasis in lung cancer: a narrative review.

Lung cancer is a kind of malignant tumor with rapid progression and poor prognosis. Distant metastasis has been the main cause of mortality among lung cancer patients. Bone is one of the most common sites. Among all lung cancer patients with bone metastasis, most of them are osteolytic metastasis. Some serious clinical consequences like bone pain, pathological fractures, spinal instability, spinal cord compression and hypercalcemia occur as well. Since the severity of bone metastasis in lung cancer, it is undoubtedly necessary to know how lung cancer spread to bone, how can we diagnose it and how can we treat it. Here, we reviewed the process, possible mechanisms, diagnosis methods and current treatment of bone metastasis in lung cancer. We divided the process of bone metastasis in lung cancer into three steps: tumor invasion, tumor cell migration and invasion in bone tissue. It may be influenced by genetic factors, microenvironment and other adhesion-related factors. Imaging examination, laboratory examination, and pathological examination are used to diagnose lung cancer metastasis to bone. Surgery, radiotherapy, targeted therapy, bisphosphonate, radiation therapy and chemotherapy are the common clinical treatment methods currently. We also found some problems remained to be solved. For example, drugs for skeletal related events mainly target on osteoclasts at present, which increase the ratio of patients in osteoporosis and fractures in the long term. In all, this review provides the direction for future research on bone metastasis in lung cancer.

Deposition and mobilization of viruses in unsaturated porous media: Roles of different interfaces and straining.

The vadose zone is the first natural layer preventing groundwater pollution. Understanding virus transport and retention in the vadose zone is necessary. The effects of different interfaces and mechanisms on virus transport and retention were investigated by studying Escherichia coli phage migration in laboratory-scale columns under unsaturated conditions. The E. coli phage was used as a model virus. Colloid filtration theory, extended Derjagin-Landau-Verwey-Overbeek theory and two-site kinetic deposition model were used to calculate fitted parameters and interaction energies to assess virus retention at different interfaces. The collector diameters and the size of E. coli phages in the influent and effluent were compared to assess the effect of straining. The results indicated that the roles of solid-water interfaces (SWIs) and air-water interfaces (AWIs) in retaining E. coli phages are strongly controlled by the moisture content and hydrochemical conditions. Decreasing the moisture content and increasing the ionic strength (IS) of the suspension increased E. coli phage retention. At suspension ISs of 0.01 or 0.03 M and various moisture contents, E. coli phages were mainly retained at the SWIs rather than AWIs. When the IS was increased to 0.06 M, the viruses were strongly retained by becoming attached to both SWIs and AWIs. The role of straining in virus retention could not be ignored. Viruses were retained more at the SWIs and less straining occurred under acidic conditions than under neutral or alkaline conditions. This was mainly because of the effects of the pH and IS on surface charges and the model virus particle size. This study has important implications for modeling and predicting virus transport in soil affected by rainfall, snowmelt, and human activities (e.g., irrigation and artificial groundwater recharging).

The landscape of immune checkpoints expression in non-small cell lung cancer: a narrative review.

With the increasing clinical potential of tumor immunotherapy, more and more clinical trials are undergoing with immune checkpoint inhibitors (ICIs). Immune checkpoints (ICs) have been identified as crucial regulators of the immune response and have improved ICIs-inhibitor therapeutic strategies. The most important ICs in lung cancer include programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), lymphocyte activation gene-3 (LAG-3), major histocompatibility complex class II (MHC II), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), and Galectin-9 (GAL-9), OX-40, OX40L. However, the expression and prognostic value of these ICs are still controversial. Among them, high expression of PD-L1 on tumor cells (>50%) predicts a better therapeutic effect of anti-PD-1 monoclonal antibody compared to patients with low PD-L1 expression. However, only 20-30% of non-small cell lung cancer (NSCLC) patients seem to get benefit from immunotherapy. In order to improve the immunotherapy outcomes, more and more attention is paid to combination immunotherapy. Analyzing the co-expression of ICs can give us a more comprehensive basis for combination immunotherapy. This review article summarized our comprehensive expression of ICs based on our previous research, and analyzed their correlation with prognosis in NSCLC patients. We also provided suggestions for potentially personalized combination immunotherapy in NSCLC.