Long-term dynamic changes and influencing factors of corneal morphology after multiple intravitreal injections of anti-VEGF drugs.

To observe alterations in corneal morphology caused by repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF). Prospective cohort study. Seventy-seven eyes were treated with intravitreal injection of anti-VEGF from June 2021 to March 2023. There were 25 eyes of neovascular age-related macular degeneration (nAMD), 24 eyes of diabetic macular edema (DME), and 28 eyes of retinal vein occlusion (RVO). Aflibercept was used in 37 eyes and Ranibizumab was used in 40 eyes. 3 + PRN was used. Corneal endothelium and corneal thickness were measured using a corneal endothelial microscope. The data related to central corneal thickness, corneal endothelial cell density (ECD), average cell size, coefficient of variation (CV), proportion of hexagonal cells (Hex%) was collected. A comparison was also made between baseline and the dynamic changes of all indexes 1 year following the last injection. It was observed that in comparison to baseline, ECD and Hex% decreased significantly after the 3rd injection of Aflibercept and Ranibizumab. However, ECD did not decrease further and remained at the same level as after the last injection. Hex% and average cell size increased to a certain extent in comparison to the last injection. All the changes were found to be statistically significant (P < .01). After 3 injections, ECD in DME group was markedly lower than that in nAMD and RVO group, but the CV in DME group was higher than that in nAMD as well as RVO groups, and all the differences were statistically significant (P < .05). Following intravitreal anti-VEGF therapy, DME is more likely than other disorders to result in a decrease in ECD. Repeated intravitreal injections of anti-VEGF drugs can reduce the Hex% and ECD to a certain extent. After the last injection, Hex% can progressively recover, and ECD can remain stable without further declining. After injections, ECD in DME group was found to be significantly lower than that in nAMD and RVO groups, but CV in DME group was significantly higher in comparison to the other 2 groups. In patients with macular edema, repeated intravitreal injections of anti-VEGF may have certain effects on corneal morphology. Patients with diabetes mellitus in particular should pay special attention to corneal safety following repeated intravitreal injections if they have significantly reduced ECD at baseline.

Shared genetic factors and causal association between chronic hepatitis C infection and diffuse large B cell lymphoma.

BACKGROUND: Epidemiological research and systematic meta-analyses indicate a higher risk of B-cell lymphomas in patients with chronic hepatitis C virus (HCV) compared to non-infected individuals. However, the genetic links between HCV and these lymphomas remain under-researched. METHODS: Mendelian randomization analysis was employed to explore the association between chronic hepatitis C (CHC) and B-cell lymphomas as well as chronic lymphocytic leukemia (CLL). Approximate Bayes Factor (ABF) localization analysis was conducted to find shared genetic variants that might connect CHC with B-cell lymphomas and chronic lymphocytic leukemia (CLL). Furthermore, The Variant Effect Predictor (VEP) was utilized to annotate the functional effects of the identified genetic variants. RESULTS: Mendelian randomization revealed a significant association between CHC and increased diffuse large B cell lymphoma (DLBCL) risk (OR: 1.34; 95% CI: 1.01-1.78; P = 0.0397). Subsequent colocalization analysis pinpointed two noteworthy variants, rs17208853 (chr6:32408583) and rs482759 (chr6:32227240) between these two traits. The annotation of these variants through the VEP revealed their respective associations with the butyrophilin-like protein 2 (BTNL2) and notch receptor 4 (NOTCH4) genes, along with the long non-coding RNA (lncRNA) TSBP1-AS1. CONCLUSION: This research provides a refined genetic understanding of the CHC-DLBCL connection, opening avenues for targeted therapeutic research and intervention.

Black soldier fly larvae mitigate greenhouse gas emissions from domestic biodegradable waste by recycling carbon and nitrogen and reconstructing microbial communities.

Black soldier fly larvae have been proven to reduce greenhouse gas emissions in the treatment of organic waste. However, the microbial mechanisms involved have not been fully understood. The current study mainly examined the dynamic changes of carbon and nitrogen, greenhouse gas emissions, the succession of microbial community structure, and changes in functional gene abundance in organic waste under larvae treatment and non-aeration composting. Thirty percent carbon and 55% nitrogen in the organic waste supplied were stored in larvae biomass. Compared to the non-aeration composting, the larvae bioreactor reduced the proportion of carbon and nitrogen converted into greenhouse gases (CO2, CH4, and N2O decreased by 62%, 87%, and 95%, respectively). 16S rRNA sequencing analysis indicated that the larvae bioreactor increased the relative abundance of Methanophaga, Marinobacter, and Campylobacter during the bioprocess, enhancing the consumption of CH4 and N2O. The metagenomic data showed that the intervention of larvae reduced the ratio of (nirK + nirS + nor)/nosZ in the residues, thereby reducing the emission of N2O. Larvae also increased the functional gene abundance of nirA, nirB, nirD, and nrfA in the residues, making nitrite more inclined to be reduced to ammonia instead of N2O. The larvae bioreactor mitigated greenhouse gas emissions by redistributing carbon and nitrogen and remodeling microbiomes during waste bioconversion, giving related enterprises a relative advantage in carbon trading.

FLAMES overlaying anti-N-methyl-D-aspartate receptor encephalitis: a case report and literature review.

BACKGROUND: In recent years, simultaneous or sequential occurrence of MOG antibody disease and anti-NMDAR encephalitis in the same patient has been reported with increasing frequency. Scholars refer to the overlapping occurrence of these two disorders as MOG antibody disease and anti-NMDAR encephalitis overlap syndrome (MNOS). Cortical T2-weighted fluid-attenuated inversion recovery (FLAIR) -hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES) is a rare clinical phenotype of MOGAD in which cortical FLAIR high-signal lesions are unilateral, with little spread to the cortex and meninges bilaterally. Although cases of FLAMES have been consistently reported. However, to our knowledge, such cases of FLAMES combined with NMDARE are rare. CASE PRESENTATION: Here, we describe a case of FLAMES combined with anti-NMDARE. The patient was a young male, 29 years old, admitted to our hospital with isolated seizures, whose MRI showed unilateral thalamic and bilateral frontal and parietal leptomeningeal involvement. Since we were unaware of the possibility of bilateral meningo-cortical MOGAD manifestations, the case was initially diagnosed as viral encephalitis and was given antiviral therapy. The diagnosis was not clarified until anti-NMDAR-IgG and MOG-IgG positivity was detected in the cerebrospinal fluid and serum. The patient was then treated with high-dose corticosteroids and his symptoms responded well to the steroids. Therefore, this case expands the clinical spectrum of MNOS overlap syndrome. In addition, we describe the clinical features of MNOS by summarizing the existing literature and exploring the possible mechanisms of its immune response. CONCLUSIONS: Our case serves as a reminder to clinicians that when patients present with atypical clinical manifestations such as seizures, consideration should be given to MNOS and conduct testing for various relevant autoantibodies (including MOG abs) and viruses in both serum and cerebrospinal fluid, as it is easy to misdiagnose the disease as other CNS diseases, such as viral meningoencephalitis. This syndrome exhibits a high responsiveness to steroids, highlighting the critical importance of recognizing the clinical and neuroimaging features of this overlap syndrome for prompt diagnosis and treatment. Furthermore, it enriches the disease spectrum of MNOS.

Brain-wide neuronal circuit connectome of human glioblastoma.

Glioblastoma (GBM), a universally fatal brain cancer, infiltrates the brain and can be synaptically innervated by neurons, which drives tumor progression 1-6 . Synaptic inputs onto GBM cells identified so far are largely short-range and glutamatergic 7-9 . The extent of integration of GBM cells into brain-wide neuronal circuitry is not well understood. Here we applied a rabies virus-mediated retrograde monosynaptic tracing approach 10-12 to systematically investigate circuit integration of human GBM organoids transplanted into adult mice. We found that GBM cells from multiple patients rapidly integrated into brain-wide neuronal circuits and exhibited diverse local and long-range connectivity. Beyond glutamatergic inputs, we identified a variety of neuromodulatory inputs across the brain, including cholinergic inputs from the basal forebrain. Acute acetylcholine stimulation induced sustained calcium oscillations and long-lasting transcriptional reprogramming of GBM cells into a more invasive state via the metabotropic CHRM3 receptor. CHRM3 downregulation suppressed GBM cell invasion, proliferation, and survival in vitro and in vivo. Together, these results reveal the capacity of human GBM cells to rapidly and robustly integrate into anatomically and molecularly diverse neuronal circuitry in the adult brain and support a model wherein rapid synapse formation onto GBM cells and transient activation of upstream neurons may lead to a long-lasting increase in fitness to promote tumor infiltration and progression.

Molecular mechanisms of ferroptosis and its roles in leukemia.

Cell death is a complex process required to maintain homeostasis and occurs when cells are damage or reach end of life. As research progresses, it is apparent that necrosis and apoptosis do not fully explain the whole phenomenon of cell death. Therefore, new death modalities such as autophagic cell death, and ferroptosis have been proposed. In recent years, ferroptosis, a new type of non-apoptotic cell death characterized by iron-dependent lipid peroxidation and reactive oxygen species (ROS) accumulation, has been receiving increasing attention. Ferroptosis can be involved in the pathological processes of many disorders, such as ischemia-reperfusion injury, nervous system diseases, and blood diseases. However, the specific mechanisms by which ferroptosis participates in the occurrence and development of leukemia still need to be more fully and deeply studied. In this review, we present the research progress on the mechanism of ferroptosis and its role in leukemia, to provide new theoretical basis and strategies for the diagnosis and treatment of clinical hematological diseases.

Causal relationships between circulating inflammatory cytokines and diffuse large B cell lymphoma: a bidirectional Mendelian randomization study.

Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Studies indicated that inflammatory cytokines involved in the occurrence and progression of DLBCL and it is challenging to discern causality from the effects due to the presence of feedback loops. We conducted a bidirectional Mendelian randomization (MR) study to investigate the potential causal relationship between DLBCL and inflammatory cytokines. The genetic variants associated with inflammatory cytokines were obtained from a genome-wide association study (GWAS) involving 8293 European participants, and the data on 1010 individuals with DLBCL were sourced from the FinnGen consortium. The primary method employed in this study was the inverse-variance weighted (IVW) method, with supplementary analyses conducted using the MR-Egger, weighted median, and MR-PRESSO approaches. Based on the IVW method, genetically predicted that increasing level of Monokine induced by interferon gamma (MIG/CXC chemokine ligand 9, CXCL9) [OR: 1.31; 95% CI: 1.05-1.62; P = 0.01] and interferon gamma-induced protein 10(IP-10/CXC chemokine ligand 10, CXCL10) [OR: 1.30; 95% CI: 1.02-1.66; P = 0.03] showed suggestive associations with DLBCL risk. DLBCL may increase the level of macrophage colony-stimulating factor (M-CSF) [OR: 1.12; 95% CI: 1.01-1.2; P = 0.03], tumor necrosis factor beta (TNF-ß) [OR: 1.16; 95% CI: 1.02-1.31; P = 0.02] and TNF-related apoptosis-inducing ligand (TRAIL) [OR: 1.07; 95% CI: 1.01-1.13; P = 0.02]. This study presents evidence supporting a causal relationship between inflammation cytokines and DLBCL. Specifically, MIG/CXCL9 and IP-10/CXCL10 were identified as indicators of upstream causes of DLBCL; while, DLBCL itself was found to elevate the levels of M-CSF, TNF-ß, and TRAIL. These findings suggest that targeting specific inflammatory factors through regulation and intervention could serve as a potential approach for the treatment and prevention of DLBCL.

Integration analysis of tumor metagenome and peripheral immunity data of diffuse large-B cell lymphoma.

Background/purpose: It has been demonstrated that gut microbes are closely associated with the pathogenesis of lymphoma, but the gut microbe landscape and its association with immune cells in diffuse large B-cell lymphoma (DLBCL) remain largely unknown. In this study, we explored the associations between gut microbiota, clinical features and peripheral blood immune cell subtypes in DLBCL. Method: A total of 87 newly diagnosed DLBCL adults were enrolled in this study. The peripheral blood samples were collected from all patients and then submitted to immune cell subtyping using full-spectral flow cytometry. Metagenomic sequencing was applied to assess the microbiota landscape of 69 of 87 newly diagnosed DLBCL patients. The microbiotas and peripheral blood immune cell subsets with significant differences between different National Comprehensive Center Network-International Prognostic Indexes (NCCN-IPIs) (low-risk, low-intermediate-risk, intermediate-high-risk, high-risk) groups were screened. Results: A total of 10 bacterial phyla, 31 orders and 455 bacteria species were identified in 69 patients with newly diagnosed DLBCL. The abundances of 6 bacteria, including Blautia sp.CAG 257, Actinomyces sp.S6 Spd3, Streptococcus parasanguinis, Bacteroides salyersiae, Enterococcus faecalls and Streptococcus salivarius were significantly different between the low-risk, low-intermediate-risk, intermediate-high-risk and high-risk groups, among which Streptococcus parasanguinis and Streptococcus salivarius were markedly accumulated in the high-risk group. The different bacteria species were mostly enriched in the Pyridoxal 5'-phosphate biosynthesis I pathway. In addition, we found that 2 of the 6 bacteria showed close associations with the different immune cell subtypes which were also identified from different NCCN-IPIs. In detail, the abundance of Bacteroides salyersiae was negatively correlated with Treg cells, CD38+ nonrescue exhausted T cells, nature killer 3 cells and CD38+CD8+ effector memory T cells, while the abundance of Streptococcus parasanguinis was negatively correlated with HLA-DR+ NK cells, CD4+ Treg cells, HLA-DR+ NKT cells and HLA-DR+CD94+CD159c+ NKT cells. Conclusion: This study first reveals the gut microbiota landscape of patients with newly diagnosed DLBCL and highlights the association between the gut microbiota and immunity, which may provide a new idea for the prognosis assessment and treatment of DLBCL.

Drug-induced lactate confers ferroptosis resistance via p38-SGK1-NEDD4L-dependent upregulation of GPX4 in NSCLC cells.

Ferroptosis is a newly defined non-apoptotic programmed cell death resulting from the accumulation of lipid peroxides. Whether ferroptosis plays any role in chemotherapy remains to be established. Here, we reported that ferroptosis represents a part of the chemotherapeutic drug etoposide-induced cell death response in Small Cell Lung Cancer (SCLC) cells and adaptive signaling molecule lactate protects Non-Small Cell Lung Cancer (NSCLC) from etoposide-induced ferroptosis. Lactate derived from metabolic reprogramming increases the expression of glutathione peroxidase 4 (GPX4) to promote ferroptosis resistance in NSCLC. Furthermore, we identified E3-ubiquitin ligase NEDD4L as a major regulator of GPX4 stability. Mechanistically, Lactate increases mitochondrial ROS generation and drives activation of the p38-SGK1 pathway, which attenuates the interaction of NEDD4L with GPX4 and subsequent ubiquitination and degradation of GPX4. Our data implicated the role of ferroptosis in chemotherapeutic resistance and identified a novel post-translational regulatory mechanism for the key Ferroptosis mediator GPX4.

Gene Mutations and Targeted Therapies of Myeloid Sarcoma.

OPINION STATEMENT: Myeloid sarcoma, a rare malignant tumor characterized by the invasion of extramedullary tissue by immature myeloid cells, commonly occurs concomitantly with acute myeloid leukemia, myelodysplastic syndromes, or myeloproliferative neoplasms. The rarity of myeloid sarcoma poses challenges for diagnosis and treatment. Currently, treatments for myeloid sarcoma remain controversial and primarily follow protocols for acute myeloid leukemia, such as chemotherapy utilizing multi-agent regimens, in addition to radiation therapy and/or surgery. The advancements in next-generation sequencing technology have led to significant progress in the field of molecular genetics, resulting in the identification of both diagnostic and therapeutic targets. The application of targeted therapeutics, such as FMS-like tyrosine kinase 3(FLT3) inhibitors, isocitrate dehydrogenases(IDH) inhibitors, and the B cell lymphoma 2(BCL2) inhibitors, has facilitated the gradual transformation of traditional chemotherapy into targeted precision therapy for acute myeloid leukemia. However, the field of targeted therapy for myeloid sarcoma is relatively under-investigated and not well-described. In this review, we comprehensively summarize the molecular genetic characteristics of myeloid sarcoma and the current application of targeted therapeutics.

Glucagon-like peptide-1 receptor agonists decrease hyperinsulinemia and hyperandrogenemia in dehydroepiandrosterone-induced polycystic ovary syndrome mice and are associated with mitigating inflammation and inducing browning of white adipose tissue†.

Polycystic ovary syndrome is a complicated hormonal and metabolic disorder. The exact pathogenesis of polycystic ovary syndrome is not clear thus far. Inflammation is involved in the progression of polycystic ovary syndrome. In addition, brown adipose tissue activity is impaired in polycystic ovary syndrome. Interestingly, glucagon-like peptide-1 receptor agonists have been reported to alleviate inflammation and promote browning of white adipose tissue. In this study, the effects of glucagon-like peptide-1 receptor agonists on polycystic ovary syndrome mice were explored. Mice were randomly assigned into four groups: control, dehydroepiandrosterone, dehydroepiandrosterone + liraglutide, and dehydroepiandrosterone + semaglutide. Relative indexes were measured after glucagon-like peptide-1 receptor agonist intervention. Glucose metabolism in polycystic ovary syndrome mice was ameliorated by glucagon-like peptide-1 receptor agonists, while the reproductive endocrine disorder of polycystic ovary syndrome mice was partially reversed. The messenger ribonucleic acid levels of steroidogenic enzymes and the expression of inflammatory mediators in serum and ovaries of polycystic ovary syndrome mice were improved. Furthermore, toll-like receptor 4 and phosphorylation of nuclear factor-kappa B protein levels were decreased by glucagon-like peptide-1 receptor agonists in ovary. Notably, after glucagon-like peptide-1 receptor agonist intervention, the expression of brown adipose tissue marker levels was considerably raised in the white adipose tissue of polycystic ovary syndrome mice. In conclusion, the hyperinsulinemia and hyperandrogenemia of polycystic ovary syndrome mice were alleviated by glucagon-like peptide-1 receptor agonist intervention, which was associated with mitigating inflammation and stimulating adipose tissue browning.

Sequential Therapy of Linezolid and Contezolid to Treat Vancomycin-Resistant Enterococcus faecium Pneumonia in a Centenarian Patient: Case Report.

Enterococcus faecium (E. faecium) is one of the core components of enterococci and causes serious illnesses in the elderly and immunocompromised patients. Due to its adaptive traits and antibiotic resistance, E. faecium has evolved as a worldwide hospital-associated pathogen, especially vancomsycin-resistant Enterococcus faecium (VREfm). Pneumonia caused by VREfm is quite rare in clinical settings, and optimal treatment has not yet been determined. Here, we present a case of nosocomial VREfm pneumonia with lung cavitation following adenovirus infection, which was successfully treated with linezolid and contezolid.

Structural and functional integration of human forebrain organoids with the injured adult rat visual system.

Brain organoids created from human pluripotent stem cells represent a promising approach for brain repair. They acquire many structural features of the brain and raise the possibility of patient-matched repair. Whether these entities can integrate with host brain networks in the context of the injured adult mammalian brain is not well established. Here, we provide structural and functional evidence that human brain organoids successfully integrate with the adult rat visual system after transplantation into large injury cavities in the visual cortex. Virus-based trans-synaptic tracing reveals a polysynaptic pathway between organoid neurons and the host retina and reciprocal connectivity between the graft and other regions of the visual system. Visual stimulation of host animals elicits responses in organoid neurons, including orientation selectivity. These results demonstrate the ability of human brain organoids to adopt sophisticated function after insertion into large injury cavities, suggesting a translational strategy to restore function after cortical damage.

Case report: Recurrent lung infections following treatment with pralsetinib for an elderly patient with RET-fusion positive NSCLC.

Patients with RET fusions represent 1-2% of all cases of non-small cell lung cancer (NSCLC), the majority of whom are younger, and are extremely rare in the elderly. As a selective RET inhibitor, pralsetinib has been shown to be efficacious and well-tolerated in patients with RET-fusion NSCLC. Nevertheless, there are currently insufficient data available for assessing the activity and safety of pralsetinib in elderly patients with NSCLC. Herein, we report an 81-year-old NSCLC patient with KIF5B-RET fusion, who achieved stable disease for more than 9 months at a low-dose of pralsetinib as second-line therapy. Of particular note, during pralsetinb therapy, his clinical course was complicated by cryptococcal pneumonia and staphylococcus aureus lung abscess. Our study demonstrates that pralsetinib is an effective therapeutic option that provides survival benefits for elderly NSCLC patients harboring RET fusion. However, during pralsetinb therapy, treating physicians should maintain particular vigilance for the increased risk of infection, especially in elderly patients.

Circ_0002111 modulates the growth process of papillary thyroid carcinoma cells by targeting the miR-363-3p/HMGB1 axis.

Previous studies have suggested that circular RNAs (circRNAs) are engaged in the progression of papillary thyroid carcinoma (PTC). However, the mechanism of circ_0002111 in PTC is still unclear. In this study, quantitative real-time PCR was carried out to measure the expressions of circ_0002111, microRNAs (miRNAs) and high-mobility group box 1 (HMGB1). Immunohistochemistry assay and western blot were applied for the determination of protein levels. The assays of 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide and thymidine analog 5-ethynyl-2'-deoxyuridine were deployed to assess PTC cell viability and proliferation, respectively. Besides, the capacities of cell apoptosis, invasion and angiogenesis were determined by flow cytometry, transwell and tube formation assays, respectively. Moreover, the interaction between miR-363-3p and circ_0002111 or HMGB1 was confirmed using a dual-luciferase reporter assay. Lastly, we established a xenograft model for the examination of the function of circ_0002111 in vivo. It was found that the expression of circ_0002111 was enhanced in PTC tissues and cells. Silencing circ_0002111 apparently retarded the viability, proliferation, invasion and tube formation, as well as expedited the apoptosis of PTC cells. Besides, circ_0002111 knockdown impeded the growth of the tumor in vivo. For mechanism analysis, circ_0002111 adjusted the expression of HMGB1 by sponge adsorption of miR-363-3p. Moreover, miR-363-3p inhibitor regained the influence of cellular malignant phenotype caused by circ_0002111 knockdown. Additionally, miR-363-3p overexpression impacted the cell functions by targeting HMGB1 in PTC. Thus, silencing circ_0002111 constrained the progression of PTC by the miR-363-3p/HMGB1 axis, which perhaps provided a novel idea of the therapeutic in PTC.

Macrophage­derived exosomal miRNA­155 promotes tubular injury in ischemia­induced acute kidney injury.

Tubule injury is a characteristic pathological feature of acute kidney injury (AKI) and determines the prognosis of kidney disease. However, the exact mechanism of tubule injury remains largely unclear. In the present study, the exact mechanism of tubule injury was investigated. Bilateral renal ischemia/reperfusion (I/R) injury (I/RI) was induced in mice and exosome secretion inhibitor GW4869 and miRNA­155 inhibitor were used. In addition, the exosomal microRNA (miR)­155­mediated cross­talk between macrophage and tubular cells was also investigated. It was determined that tubular injury was observed in an I/R­induced AKI model, which was closely associated with macrophage infiltration. Interestingly, blocking exosome production using GW4869 ameliorated tubular injury in I/R­induced AKI. Mechanistically, once released, activated macrophage­derived exosomal miR­155 was internalized by tubular cells, resulting in increased tubule injury through targeting of suppressor of cytokine signaling­1 (SOCS­1), a negative regulator of NF­κB signaling. In addition, a dual­luciferase reporter assay confirmed that SOCS­1 was the direct target of miR­155 in tubular cells. Notably, injection of these miR­155­enriched exosomes into renal parenchyma resulted in increased tubule injury in vivo. Thus, the present study demonstrated that exosomal miR­155 mediated the communication between activated macrophages and injured tubules, leading to progression of AKI, which not only provide novel insights into the pathophysiology of AKI but also offer a new therapeutic strategy for kidney diseases.

MSLN Correlates With Immune Infiltration and Chemoresistance as a Prognostic Biomarker in Ovarian Cancer.

Mesothelin (MSLN) is a glycoprotein with various expression degrees in different tumors including mesothelioma, ovarian cancer, pancreatic cancer, etc. MSLN is considered to play an important role in cell survival, proliferation, and tumor progression. Although the expression of MSLN in tumors makes it a potential therapeutic target, its mechanism of action is still unclear, especially its correlation with immune cells infiltration in the tumor microenvironment has not been investigated. In this study, we detected the overexpression of MSLN in ovarian cancer using database analysis and tissue-array staining. We further evaluated the diagnostic value of MSLN and found it was associated with poor overall survival in ovarian cancer. In addition, the high expression of MSLN was significantly related to the immune-related genes and chemoresistant genes. We confirmed the overexpression of MSLN in the chemoresistant ovarian cancer cell lines. Our research suggests that MSLN participates in a variety of pathways related to the suppression of immune activation and promotion of chemoresistance, leading to a poor prognosis in ovarian cancer.

Self-assembly synthesis of diorganotin complexes based on arylformylhydrazone possessing ONO donor set: anticancer activity and mechanism.

Fourteen new organotin(IV) complexes were successfully synthesized and characterized by elemental analyses, Fourier transform infrared spectroscopy (FT-IR), multinuclear (1H, 13C, and 119Sn) NMR spectroscopy, high-resolution mass spectrometry (HRMS), and X-ray single-crystal techniques. Crystallographic data showed that the complexes 1b, 2b, 3b, and 5b were macrocyclic compounds, 4b exhibited a one-dimensional spiral chain structure with distorted trigonal bipyramidal geometry, other complexes were centrosymmetric dimers, and there was an Sn2O2 four-membered ring in the middle of the molecule. In-vitro anticancer activity against the three human tumor cell lines NCI-H460, MCF-7, and HepG2 was studied, and the dibutyltin complex 5a is a more potent antitumor agent than other complexes and cisplatin. Cell apoptosis study of 5a with the highest activity on HepG2 cancer cell lines was done by flow cytometry; it was shown that the antitumor activity of 5a was related to apoptosis, and it inhibited proliferation by blocking cells in the G2/M phase. The single-cell gel electrophoresis assay results show that 5a induces DNA damage. 5a interacts with ct-DNA by intercalating the mode of interaction. UV-visible absorption spectrometry, fluorescence competitive, viscosity measurements, and gel electrophoresis results also support the intercalative mode of interaction for 5a with DNA.

Adoption of Two-Dimensional Ultrasound Gastrointestinal Filling Contrast on Artificial Intelligence Algorithm in Clinical Diagnosis of Gastric Cancer.

This research was aimed to explore the value of gastrointestinal filling contrast-enhanced ultrasound (CEUS) and computed tomography (CT-)-enhanced scanning based on artificial intelligence (AI) algorithm in the evaluation of gastric cancer staging. 102 patients with gastric cancer were selected as the research objects. All of them underwent CEUS of gastrointestinal filling and 64-slice spiral CT before surgery. In addition, an improved mean shift algorithm was proposed based on differential optical flow and deep convolutional neural network (D-CNN), which was applied in image processing. The predicted positive rate (PPR), sensitivity, specificity, and accuracy of gastric cancer in different stages by CEUS and CT were calculated using pathological diagnosis results as the gold standard. 17 patients with T1 stage, 41 patients with T2-T3 stage, and 35 patients with T4 stage were detected by CEUS. 13 patients with T1 stage, 34 patients with T2-T3 stage, and 30 patients with T4 stage were detected by CT enhanced examination. The PPRs of CEUS for T1, T2-T3, and T4 stages of gastric cancer were higher than those of CT enhanced (P < 0.05). The PPR of CEUS for N0 staging of gastric cancer was higher than that of CT enhanced (P < 0.05), and it for N3 staging of gastric cancer was lower than that of CT enhanced (P < 0.05). From the analysis of M staging of gastric cancer, the PPRs of CEUS for M0 and M1 staging of gastric cancer were not statistically different from the PPRs of CT enhanced (P > 0.05). The sensitivity (95.6%), specificity (81.82%), and accuracy (94.12%) of CEUS in assessing resectability were significantly higher than those of CT enhancement (89.01%, 63.67%, and 86.27%, respectively), and the differences were statistically significant (P < 0.05). In summary, CEUS gastrointestinal filling based on the D-CNN algorithm could better improve the display rate of the tissue lesions around the stomach. It also helped to judge the lesion progress, the depth of infiltration, and lymph node metastasis of the lesion. In addition, it had excellent performance in evaluating the resectability of gastric cancer before surgery and had clinical promotion value.

A bioinspired solar evaporator with a horizontal channel-like framework for efficient and stable high-salinity brine desalination.

In recent years, solar steam generation has been one of the most promising and sustainable techniques for water desalination. However, the heat loss to bulk water dramatically decreases the evaporation rate. Besides, salt deposition on the evaporation surface during brine treatment limits the long-term operation of evaporators. Herein, solar evaporators with a horizontal channel-like framework are reported and high efficiency and outstanding salt resistance are achieved. Firstly, eggplants with a hollow fiber alignment structure were carbonized as CEP evaporators. The CEP-H evaporator with a horizontal fiber growth direction shows a high evaporation efficiency of 90.6% and excellent salt resistance when treating high-salinity brine (20 wt%). The low thermal conductivity perpendicular to the fiber growth direction impedes the conductive heat transfer into bulk water, and fast water transport along the fiber growth direction is beneficial for salt resistance. In addition, a proof-of-concept evaporator polypyrrole-coated polypropylene hollow fiber membrane with a horizontal channel-like framework (PPy/PP-H) has also been developed. This hollow fiber membrane shows a high evaporation rate of 1.64 kg m-2 h-1 due to multiangle evaporation and also demonstrates excellent salt-resisting performance for high-salinity brine treatment (20 wt%). The study demonstrates the effect of the horizontal channel-like framework for high evaporation performance and salt resistance, providing new insights into the solar evaporator design for seawater desalination and wastewater treatment.