The Growth and Shape Evolution of Indium Nanoplates Studied by In Situ Liquid Cell TEM.

Understanding the growth mechanisms of nanomaterials is crucial for effectively controlling their morphology which may affect their properties. Here, the growth process of indium nanoplates is studied using in situ liquid cell transmission electron microscopy. Quantitative analysis shows that the growth of indium nanoplate is limited by surface reaction. Besides, the growth process has two stages, which is different from that of other metal nanoplates reported previously. At the first stage, indium particles transform gradually from face-centered cubic to body-centered tetragonal (bct) structure as the seeds grow. At the second stage, the seeds grow faster than at the first stage and form indium triangular nanoplates. Indium triangular nanoplates have a bct structure with {011}-twin, which is found to form through kinetic reactions. In addition, the shape evolution of truncated triangle nanoplate with multiple twin planes is studied. The growth rate of truncated edge changes with the varied number of re-entrant grooves. The present work provides valuable insights into the growth mechanism of metal nanoplates with low-symmetric structure and the role of twin planes in the shape evolution of plate-like metal nanomaterials.

Sirt1 inhibits macrophage polarization and inflammation in gouty arthritis by inhibiting the MAPK/NF-κB/AP-1 pathway and activating the Nrf2/HO-1 pathway.

OBJECTIVE AND DESIGN: To elucidate Sirt1's role in gouty arthritis inflammation and its potential mechanisms. MATERIAL: Constructed murine models of gouty arthritis and conducted THP-1 cell experiments. TREATMENT: 1 mg of MSU crystals injected into mice ankle joints for a 72-h intervention. After a 3-h pre-treatment with Sirt1-specific inhibitor (EX527) and agonist (SRT2104), inflammation was induced for 21 h using lipopolysaccharide (LPS) plus MSU crystals. METHODS: We assessed gouty arthritis severity through joint inflammation index, swelling, and hematoxylin and eosin (H&E) staining, and measured CD68 mononuclear macrophages and Sirt1 expression in synovial tissue via immunohistochemistry. ELISA, NO assay, RT-qPCR, Flow cytometry, and Western blot were utilized to examine macrophage inflammatory factors, polarization, reactive oxygen species(ROS), MAPK/NF-κB/AP-1 and Nrf2/HO-1 pathways proteins. RESULTS: Significant joint swelling, synovial tissue edema, and inflammatory cell infiltration were observed. CD68 mononuclear macrophages and Sirt1 expression were elevated in synovium. Sirt1 activation decreased inflammatory factors, M1 polarization, and ROS generation. Sirt1 activation reduced p38/JNK phosphorylation, thereby inhibiting downstream NF-κB p65/AP-1 and enhancing Nrf2/HO-1, thus suppressing inflammation. CONCLUSIONS: Sirt1 alleviates M1 macrophage polarization and inflammation in gouty arthritis by inhibiting the MAPK/NF-κB/AP-1 pathway and activating the Nrf2/HO-1 pathway. Thus, activating Sirt1 may provide a new therapeutic target for gouty arthritis.

A Chemo-Enzymatic Approach for Preparing Efinaconazole with High Optical Yield.

Herein, we present a novel and ecofriendly biocatalytic approach for synthesizing efinaconazole (7), a clinically used antifungal agent. This method involves utilizing benzaldehyde lyase (BAL) to catalyze the crucial benzoin condensation step in the ketone precursor. Treating 2,4-difluorobenzaldehyde with BAL in the presence of thiamin-diphosphate (ThDP) and Mg2+ resulted in the formation of α-hydroxy ketone which then underwent the preparation of 7. This innovative approach not only provides a greener alternative but also offers significant advantages over the traditional chemical process. Through our efforts and development work, we have established efficient and scalable procedures that enable the production of 7 in a moderate 38% yield.

Cardiovascular events in adult polymyositis and dermatomyositis: a meta-analysis of observational studies.

OBJECTIVES: We aimed to review whether PM and DM patients have an increased cardiovascular (CV) risk, including ischaemic heart disease (IHD), cerebrovascular accidents (CVA) and venous thromboembolism. METHODS: We searched PubMed, Embase and the Cochrane database for relevant studies from inception to February 2021. RESULTS: Twenty-two studies comprising 25 433 patients were included. With PM/DM vs general populations, the risk was significantly increased for CV events [relative risk (RR) = 2.37, 95% CI: 1.86, 3.02]. The RR of CV events for males with PM/DM was higher than for females (RR = 1.43; 95% CI: 1.17, 1.74). PM/DM patients followed for one to five years had a significantly higher CV risk than those followed for five to ten years (RR = 3.51, 95% CI: 1.95, 6.32). The risk was increased for North Americans (RR = 4.28, 95% CI: 2.57, 7.11), Europeans (RR = 2.29, 95% CI: 1.58, 3.31) and Asians (RR = 2.03, 95% CI: 1.41, 2.90). Our meta-analysis found that the elevated CV event risk was related to PM (RR = 2.35, 95% CI: 1.51, 3.66) and DM (RR = 2.55, 95% CI: 1.66, 3.93). Subgroup analyses showed that the risk was significantly increased for IHD (RR = 1.76, 95% CI: 1.40, 2.21), CVA morbidity (RR = 1.31, 95% CI: 1.03, 1.67) and ischaemic stroke (IS) (RR = 1.47, 95% CI: 1.26, 1.73), with no statistically significant increased risk of haemorrhagic stroke mortality (RR = 1.43, 95% CI: 0.92, 2.21). The CV event risk was increased for venous thromboembolism (RR = 4.60, 95% CI: 3.17, 6.66), deep venous thrombosis (RR = 5.53, 95% CI: 3.25, 9.39) and pulmonary embolism (RR = 5.26, 95% CI: 2.62, 10.55). CONCLUSION: This meta-analysis found that PM/DM patients had a ∼2.37 times increased CV risk, particularly males diagnosed in the previous five years. PM/DM may be an independent risk factor for developing IHD, IS, deep venous thrombosis and pulmonary embolism.

ATP1A3 mutation as a candidate cause of autosomal dominant cone-rod dystrophy.

Cone-rod dystrophy (CORD) is an inherited retinal degenerative disease characterized by progressive loss of cone and rod photoreceptors. Although several genes have been reported to cause autosomal dominant CORD (adCORD), the genetic causes of adCORD have not been fully elucidated. Here, we identified the ATP1A3 gene, encoding the α3 subunit of Na+, K+-ATPase, as a novel gene associated with adCORD. Using whole-exome sequencing (WES), we found a candidate mutation of ATP1A3 that co-segregated with the disease in an analysis of two affected patients and one healthy relative in an adCORD family. According to our RNA-seq data, we demonstrated that the Atp1a3 mRNA level was extremely high in the murine retina. Overexpression of mutant ATP1A3 in vitro led to a reduced oxygen consumption rate (OCR), reflecting the limited mitochondrial reserve capacity. Furthermore, we generated transgenic mice expressing the ATP1A3 cDNA with patient variant and found decreased electroretinogram (ERG) responses. Moreover, the mutant ATP1A3 is highly expressed in photoreceptor inner segment, where mitochondria are enriched. These results suggest that the ATP1A3 mutation is a new genetic cause responsible for adCORD and indicate that ATP1A3 plays an important role in retinal function.

PODXL might be a new prognostic biomarker in various cancers: a meta-analysis and sequential verification with TCGA datasets.

ABSRACT: BACKGROUND: Several studies have investigated the associations between the podocalyxin-like protein (PODXL) expression quantity or locations and cancers survival, but the results were far from conclusive. Therefore, we proceeded a meta-analysis on PODXL in various human cancers to find its prognostic value and followed confirmation using the TCGA datasets. METHODS: We performed a systematic search, and 18 citations, including 5705 patients were pooled in meta-analysis. The results were verified with TCGA datasets. RESULTS: Total eligible studies comprised 5705 patients with 10 types of cancer. And the result indicated that PODXL high-expression or membrane-expression were significantly related to poor overall survival (OS). However, subgroup analysis showed a significant association between high expressed PODXL and poor OS in the colorectal cancer, pancreatic cancer, urothelial bladder cancer, renal cell carcinoma and glioblastoma multiforme. Then, we validated the inference using TCGA datasets, and the consistent results were demonstrated in patients with pancreatic cancer, glioblastoma multiforme, gastric cancer, esophageal cancer and lung adenocarcinoma. CONCLUSION: The result of meta-analysis showed that high expressed PODXL was significantly linked with poor OS in pancreatic cancer and glioblastoma multiforme, but not in gastric cancer, esophageal cancer or lung adenocarcinoma. And the membrane expression of PODXL might also associate with poor OS. PODXL may act as tumor promotor and may serve as a potential target for antitumor therapy.

pH-Responsive aggregates transition from spherical micelles to WLMs induced by hydrotropes based on the dynamic imine bond.

In recent years, the use of dynamic chemical bonds to construct stimulus-responsive micelle systems has received increasing attention. However, current reports focus on the construction of dynamic covalent bond surfactants using dynamic chemical bonds, and the method of applying dynamic covalent bonds to hydrotropes has not been reported yet. In this study, a novel pH-responsive worm-like micelle system was constructed by mixing cetyltrimethylammonium bromide (CTAB), 4-hydroxybenzaldehyde (HB) and p-toluidine (MB) at the molar ratio of 60 mM : 40 mM : 40 mM. The formation mechanism of the dynamic covalent bond hydrotropes and the rheological behavior of the micelles were investigated via rheology, 1H-NMR spectroscopy and Cryo-TEM. The results show that as the pH increases, the viscosity of the solution first decreases and then increases rapidly. The microscopic aggregates in the solution transition from spherical micelles to worm-like micelles (WLMs), and the solution changes from a water-like fluid without viscosity to a gel system that can withstand its own weight. The transformation of the aggregates and their rheology can be attributed to the formation of MB-HB-, which is a type of hydrotrope with dynamic covalent bonds. Moreover, the transition from spherical micelles to worm-like micelles in this system is reversible.

Plasma fractalkine levels are associated with renal inflammation and outcomes in immunoglobulin A nephropathy.

BACKGROUND: A recognized noninvasive biomarker to improve risk stratification of immunoglobulin A nephropathy (IgAN) patients is scarce. Fractalkine has been shown to play a key role in glomerular disease as chemoattractant, adhesion and even fibrosis factor. The current study assessed the possibility of plasma fractalkine as a novel biomarker in IgAN patients. METHODS: Plasma fractalkine was measured in 229 patients with renal biopsy consistent IgAN from 2012 to 2014, and clinical, pathological and prognostic relationships were analyzed. RESULTS: The plasma fractalkine levels in IgAN patients were significantly correlated with the creatinine level and 24-h urine protein by both univariate and multivariate analysis. Mesangial hypercellularity was still significantly correlated with the plasma fractalkine levels even after adjustment for other potential predictor variables by multivariate analysis. In addition, the counts of CD20+ B cells or CD68+ macrophage in renal biopsies of IgAN patients were significantly correlated with the plasma fractalkine levels, but not CD4+ and CD8+ T cells. Finally, we concluded that patients with higher plasma fractalkine levels had higher risk of poor renal outcome compared with those with lower plasma fractalkine levels. No association was observed between the CX3CR1 polymorphisms and clinical parameters including plasma fractalkine levels and prognosis. Recombinant fractalkine induced mesangial cells extracellular matrix synthesis and promoted the migration of microphage cells RAW264.7. CONCLUSIONS: Plasma fractalkine levels were associated with creatinine level, 24-h urine protein, mesangial hypercellularity pathological damage, the CD68+ macrophage and CD20+ B cell infiltration in renal tissue and renal outcome in IgAN patients. Plasma fractalkine might be a potential prognosis novel predictor in Chinese patients with IgAN.

[Identification of a novel FBN1 variant in a pedigree affected with Marfan syndrome].

OBJECTIVE: To explore the genetic basis for a pedigree affected with Marfan syndrome (MFS). METHODS: Clinical data of the patients was collected. With genomic DNA extracted from peripheral blood samples, potential mutation was detected by targeted exome sequencing. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. RESULTS: Targeted exome sequencing and Sanger sequencing revealed a missense c.649T to C(p.Trp217Arg) variant in the exon 7 of FBN1 gene, which was unreported previously. Bioinformatics analysis suggested that the variant can cause amino acid replacement and affect the structure and function of fibrillin-1. CONCLUSION: A novel missense variant of the FBN1 gene was identified, which probably underlies the autosomal dominant MFS in this pedigree.

Analysis of 4931 renal biopsy data in central China from 1994 to 2014.

The purpose of this study is to investigate the changing spectrum and clinicopathologic correlation of biopsy-proven renal diseases in central China. We retrospectively analyzed data of 4931 patients who underwent renal biopsy in ten hospitals between September 1994 and December 2014. Among them, 81.55% were primary glomerular diseases (GD), and 13.02% were secondary GD. IgA nephropathy (IgAN) was the most common primary GD (43.45%), followed by focal glomerulonephritis (16.79%), mesangial proliferative glomerulonephritis (MsPGN, 14.35%), and membranous nephropathy (MN, 13.28%). IgAN was leading primary GD in patients under 60 years old, while MN was the leading one over 60 years old. The most frequent secondary GD was lupus nephritis (LN) (47.35%). The prevalence of IgAN, MN and minimal change disease was found to increase significantly (p < 0.001, p < 0.001, and p < 0.01, respectively), while that of MsPGN, membranoproliferative glomerulonephritis and LN decreased significantly (p < 0.001, p < 0.001, and p < 0.05, respectively). The main indication for renal biopsy was proteinuria and hematuria (49.03%), followed by nephrotic syndrome (NS, 20.36%). IgAN was the most common cause in patients with proteinuria and hematuria, chronic-progressive kidney injury, hematuria and acute kidney injury; and MN was the leading cause of NS. Primary GD remained the predominant renal disease in central China. IgAN and LN were the most prevalent histopathologic lesions of primary and secondary GD, respectively. The spectrum of biopsy-proven renal disease had a great change in the past two decades. Proteinuria and hematuria was the main indication for renal biopsy.

Optimizing wheat prosperity: innovative drip irrigation and nitrogen management strategies for enhanced yield and quality of winter wheat in the Huang-Huai-Hai region.

Introduction: To examine the impacts of varied water and nitroge combinations on wheat yield and quality under drip irrigation in the Huang-Huai-Hai area, a field experiment was conducted over two growing seasons of winter wheat from 2019 to 2021. Methods: Traditional irrigation and fertilization methods served as the control (CK), with two nitrogen application rates set: N1 (180 kg/ha) and N2 (210 kg/ha). The irrigation schedules were differentiated by growth stages: jointing, anthesis (S2); jointing, anthesis, and filling (S3); and jointing, booting, anthesis, and filling (S4), at soil depths of 0-10 cm (M1) and 0-20 cm (M2). Results: Results indicated that compared to CK, the 3 and 4 times irrigation treatments comprehensively improved grain yield (GY) by 8.0% and 13.6% respectively, increased the average plant partial factor productivity of nitrogen fertilizer (PFPN) and irrigation use efficiency (IUE) by 57.5% and 38.2%, and 62.2% and 35.8%, respectively. The gluten content (GC) of 3 irrigations was 1.6% higher than CK, and other metrics such as dough tenacity (DT), softness (ST), water absorption (WAS), and gluten hardness (GH) also showed improvements. Furthermore, the contents of amylose, amylopectin, and total starch under 3 irrigations significantly increased by 9.4%, 11.4%, and 9.8%, respectively, with higher than 4 irrigations. The crude protein content and soluble sugar content in 3 irrigations rose by 6.5% and 9.8% respectively over two years. These irrigation treatments also optimized gelatinization characteristics of grains, such as breakdown viscosity (BDV), consistency peak viscosity (CPV), consistency setback viscosity (CSV), pasting temperature (PeT), and pasting time (PaT). Discussion: The study demonstrated that appropriate drip irrigation can effectively synchronize water and nitrogen supply during critical growth stages in winter wheat, ensuring robust late-stage development and efficient transfer of photosynthetic products into the grains, thus enhancing grain mass and yield. This also led to improved utilization of water and fertilizer and enhanced the nutritional and processing quality of the grain. However, excessive irrigation did not further improve grain quality. In conclusion, given the goals of saving water and fertilizer, achieving excellent yield, and ensuring high quality, the N1S3M1 treatment is recommended as an effective production management strategy in the Huang-Huai Hai area; N1S3M2 could be considered in years of water scarcity.

Mechanical force regulates ligand binding and function of PD-1.

Despite the success of PD-1 blockade in cancer therapy, how PD-1 initiates signaling remains unclear. Soluble PD-L1 is found in patient sera and can bind PD-1 but fails to suppress T cell function. Here, we show that PD-1 function is reduced when mechanical support on ligand is removed. Mechanistically, cells exert forces to PD-1 and prolong bond lifetime at forces <7 pN (catch bond) while accelerate dissociation at forces >8pN (slip bond). Molecular dynamics of PD-1-PD-L2 complex suggests force may cause relative rotation and translation between the two molecules yielding distinct atomic contacts not observed in the crystal structure. Compared to wild-type, PD-1 mutants targeting the force-induced distinct interactions maintain the same binding affinity but suppressed/eliminated catch bond, lowered rupture force, and reduced inhibitory function. Our results uncover a mechanism for cells to probe the mechanical support of PD-1-PD-Ligand bonds using endogenous forces to regulate PD-1 signaling.

Role of bombesin receptor activated protein in the antigen presentation by human bronchial epithelial cells.

Bombesin receptor activated protein (BRAP) was identified in a bacterial two-hybrid screen for proteins interacting with bombesin receptor subtype-3 (BRS-3). We found that BRAP is widely expressed in the airway epithelium of human lungs and may play a role during the stress response of lung epithelium. In this work, we explored the potential roles of BRAP in the antigen presenting function of human bronchial epithelial cells (HBECs). Overexpression of a BRAP recombinant protein in a human bronchial epithelial cell line resulted in a reduction of FITC-OVA uptake by HBECs, which indicated that the antigen uptake ability is inhibited. The analysis of the protein expression of surface molecules including B7 homologs and the major histocompactability complex (MHC) class II molecules showed that the expression levels of HLA-DR and B7DC increased while the levels of B7-H1 and B7.2 decreased. Since those surface molecules are all related to antigen presenting process, the altered expression pattern of those molecules provides further evidence showing that BRAP overexpression leads to a change in antigen presenting function of HBECs. Moreover, overexpression of BRAP in HBECs caused a decrease of co-cultured lymphocytes proliferation and a changed pattern of cytokines produced by lymphocytes in the presence of FITC-OVA, which indicated that changes in the maturation pattern and functions of co-cultured lymphocytes were induced by BRAP overexpression. Overall, our results suggested that overexpression of BRAP may play a role during the antigen presenting process of bronchial epithelium by inhibiting the antigen uptake ability of bronchial epithelial cells.

Hsa_Circ_0134426 Attenuates the Malignant Biological Behaviors of Multiple Myeloma by Suppressing miR-146b-3p to Upregulate NDNF.

We focused on hsa_circ_0134426 (circ_0134426) to determine its functional effects and targets in multiple myeloma (MM) development. The relative expression of circ_0134426, miR-146b-3p, and neuron-derived neurotrophic factor (NDNF) in the MM samples was confirmed by quantitative real-time PCR (qPCR) or western blotting. The protein levels of epithelial-to-mesenchymal transition (EMT)-linked markers were identified using western blotting. Xenograft models in nude mice were used for in vivo functional analysis of circ_0134426. The binding of miR-146b-3p to circ_0134426 or NDNF was confirmed by dual-luciferase and RIP assays. Poor levels of circ_0134426 and NDNF and high levels of miR-146b-3p were observed in MM bone marrow samples and cell lines. Circ_0134426 overexpression blocked MM cell growth, colony formation, and migration and impeded tumor development in xenograft models. circRNA_0134426 decoys miR-146b-3p to repress its expression. Overexpression of miR-146b-3p restored MM cell activities that were blocked by circ_0134426 overexpression. NDNF is a functional molecule targeted by miR-146b-3p, and miR-146b-3p sequesters NDNF expression. The inhibitory effects of NDNF upregulation on MM cell growth, colony formation, and migration were partially abolished by miR-146b-3p overexpression. Circ_0134426 regulates the miR-146b-3p/NDNF network to restrain the development of MM, to some extent, suggesting that the development of MM therapeutic strategies might focus on circ_0134426 regulatory networks.

Generation of 3D Tumor Spheroids for Drug Evaluation Studies.

In recent decades, in addition to monolayer-cultured cells, three-dimensional tumor spheroids have been developed as a potentially powerful tool for the evaluation of anticancer drugs. However, the conventional culture methods lack the ability to manipulate the tumor spheroids in a homogeneous manner at the three-dimensional level. To address this limitation, in this paper, we present a convenient and effective method of constructing average-sized tumor spheroids. Additionally, we describe a method of image-based analysis using artificial intelligence-based analysis software that can scan the whole plate and obtain data on three-dimensional spheroids. Several parameters were studied. By using a standard method of tumor spheroid construction and a high-throughput imaging and analysis system, the effectiveness and accuracy of drug tests performed on three-dimensional spheroids can be dramatically increased.

Identification of potential antigenic peptides of Brucella through proteome and peptidome.

BACKGROUND: Brucellosis, caused by Brucella spp., is a major zoonotic public health threat. Although several Brucella vaccines have been demonstrated for use in animals, Brucella spp. can cause human infection and to date, there are no human-use vaccines licensed by any agency. Recently, methods in vaccine informatics have made major breakthroughs in peptide-based epitopes, opening up a new avenue of vaccine development. OBJECTIVES: The purpose of this article was to identify potential antigenic peptides in Brucella by proteome and peptidome analyses. METHODS: Mouse infection models were first established by injection with Brucella and spleen protein profiles were then analysed. Subsequently, the major histocompatibility complex class I or II (major histocompatibility complex [MHC]-I/II)-binding peptides in blood samples were collected by immunoprecipitation and peptides derived from Brucella proteins were identified through liquid chromatography-mass spectrometry (LC-MS/MS). These peptides were then evaluated in a variety of ways, such as in terms of conservation in Brucella and synchronicity in predicted peptides (similarity and coverage), which allowed us to more effectively measure their antigenic potential. RESULTS: The expression of the inflammatory cytokines IL1B and IFN-γ was significantly altered in the spleen of infected mice and some Brucella proteins, such as Muri, AcpP and GroES, were also detected. Meanwhile, in blood, 35 peptides were identified and most showed high conservation, highlighting their potential as antigen epitopes for vaccine development. In particular, we identified four proteins containing both MHC-I- and MHC-II-binding peptides including AtpA, AtpD, DnaK and BAbS19_II02030. They were also compared with the predicted peptides to estimate their reliability. CONCLUSIONS: The peptides we screened could bind to MHC molecules. After being stimulated with antigen T epitopes, Memory T cells can stimulate T cell activation and promote immune responses. Our results indicated that the peptides we identified may be good candidate targets for the design of subunit vaccines and these results pave the way for the study of safer vaccines against Brucella.

Diagnostic Value of the Combined Measurement of Serum HCY and NRG4 in Type 2 Diabetes Mellitus with Early Complicating Diabetic Nephropathy.

PURPOSE: This study aimed to investigate the value of combined detection of HCY and NRG4 in the diagnosis of early diabetic kidney disease (DKD) and to explore the association between the ratio of HCY/NRG4 and DKD. METHODS: A total of 140 diabetic patients and 43 healthy people were prospectively enrolled. The plasma HCY level, NRG4 level and HCY/NRG4 of them were measured to compare their differences and analyze the correlation with DKD. The independent influencing factors of patients with DKD were screened, and the nomograph of DKD occurrence was constructed. RESULTS: The levels of HCY and HCY/NRG4 in diabetic patients were significantly increased, while the level of NRG4 was significantly decreased (p < 0.01). The AUCs of HCY/NRG4 predicted for DKD were 0.961. HCY/NRG4 and the course of DM were independent risk factors for DKD. A predictive nomograph of DKD was constructed, and decision curve analysis (DCA) showed good clinical application value. HCY/NRG4 was positively correlated with Scr, UACR, TG, UA, BUN, TCHOL and LDL and negatively correlated with eGFR and HDL (p < 0.05). CONCLUSIONS: The level of HCY and NRG4 is closely related to the severity of DM, and combined detection of HCY/NRG4 can identify patients with DKD at an early stage.

In situ study of wet chemical etching of ZnO nanowires with different diameters and polar surfaces by LCTEM.

Understanding how nanomaterials evolve during the etching process is critical in many fields. Herein, the wet chemical etching process of zinc oxide (ZnO) nanowires is studied in situ in radiolytic water via liquid cell transmission electron microscopy (LCTEM). The dissolution rate of thin nanowires is constant with reducing diameter, while thick nanowires (with the original diameter being larger than 95 nm) show complicated etching behaviors. The dissolution rate of thick nanowires is constant at the first stage and then increases. Anisotropic etching occurs at both ends of thick nanowires and distinct tips are formed. Different polarities at the two ends of the nanowire lead to differently shaped tips and different tip formation processes. The arrangement of the sidewall cones determines the macroscopic angle of the final tips. The present results are important for understanding liquid phase etching behavior in different dimensions and with different polar ends.

LTBP2 inhibits prostate cancer progression and metastasis via the PI3K/AKT signaling pathway.

Biochemical recurrence (BCR) is a cause of concern in advanced prostate cancer (PCa). Thus, novel diagnostic biomarkers are required to improve clinical care. However, research on PCa immunotherapy is also scarce. Hence, the present study aimed to explore promising BCR-related diagnostic biomarkers, and their expression pattern, prognostic value, immune response effects, biological functions, and possible molecular mechanisms were evaluated. GEO datasets (GSE46602, GSE70768, and GSE116918) were downloaded and merged as the training cohort, and differential expression analysis was performed. Lasso regression and SVM-RFE algorithm, as well as PPI analysis and MCODE algorithm, were then applied to filter BCR-related biomarker genes. The CIBERSORT and estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE) methods were used to calculate the fractions of tumor-infiltrating immune cells. GO/DO enrichment analyses were used to identify the biological functions. The expression of latent transforming growth factor ß-binding protein 2 (LTBP2) was determined by RT-qPCR and western blotting. The role of LTBP2 in PCa was determined by CCK-8, Transwell, and the potential mechanism was investigated by KEGG and GSEA and confirmed by western blotting. In total, 44 BCR-related differentially expressed genes (DEGs) in the training cohort were screened. LTBP2 was found to be a diagnostic biomarker of BCR in PCa and was associated with CD4+ T-cell infiltration and response to anti-PD-1/PD-L1 immunotherapy. Subsequently, using the ESTIMATE algorithm, it was identified that LTBP2 was associated with the tumor microenvironment and could be a predictor of the clinical benefit of immune checkpoint blockade. Finally, the expression and biological function of LTBP2 were evaluated via cellular experiments. The results showed that LTBP2 was downregulated in PCa cells and inhibited PCa proliferation and metastasis via the PI3K/AKT signaling pathway in vitro. In conclusion, LTBP2 was a promising diagnostic biomarker of BCR of PCa and had an important role in CD4+ T-cell recruitment. Moreover, it was associated with immunotherapy in patients with PCa who developed BCR, and it inhibited PCa proliferation and metastasis via the PI3K/AKT signaling pathway in vitro.

Recent development on COX-2 inhibitors as promising anti-inflammatory agents: The past 10 years.

Cyclooxygenases play a vital role in inflammation and are responsible for the production of prostaglandins. Two cyclooxygenases are described, the constitutive cyclooxygenase-1 and the inducible cyclooxygenase-2, for which the target inhibitors are the non-steroidal anti-inflammatory drugs (NSAIDs). Prostaglandins are a class of lipid compounds that mediate acute and chronic inflammation. NSAIDs are the most frequent choices for treatment of inflammation. Nevertheless, currently used anti-inflammatory drugs have become associated with a variety of adverse effects which lead to diminished output even market withdrawal. Recently, more studies have been carried out on searching novel selective COX-2 inhibitors with safety profiles. In this review, we highlight the various structural classes of organic and natural scaffolds with efficient COX-2 inhibitory activity reported during 2011-2021. It will be valuable for pharmaceutical scientists to read up on the current chemicals to pave the way for subsequent research.