CCDC66 mutations are associated with high myopia through affected cell mitosis.

BACKGROUND: High myopia (HM) refers to an eye refractive error exceeding -5.00 D, significantly elevating blindness risk. The underlying mechanism of HM remains elusive. Given the extensive genetic heterogeneity and vast genetic base opacity, it is imperative to identify more causative genes and explore their pathogenic roles in HM. METHODS: We employed exome sequencing to pinpoint the causal gene in an HM family. Sanger sequencing was used to confirm and analyse the gene mutations in this family and 200 sporadic HM cases. Single-cell RNA sequencing was conducted to evaluate the gene's expression patterns in developing human and mouse retinas. The CRISPR/Cas9 system facilitated the gene knockout cells, aiding in the exploration of the gene's function and its mutations. Immunofluorescent staining and immunoblot techniques were applied to monitor the functional shifts of the gene mutations at the cellular level. RESULTS: A suspected nonsense mutation (c.C172T, p.Q58X) in CCDC66 was found to be co-segregated with the HM phenotype in the family. Additionally, six other rare variants were identified among the 200 sporadic patients. CCDC66 was consistently expressed in the embryonic retinas of both humans and mice. Notably, in CCDC66-deficient HEK293 cells, there was a decline in cell proliferation, microtube polymerisation rate and ace-tubulin level. Furthermore, the mutated CCDC66 failed to synchronise with the tubulin system during Hela cell mitosis, unlike its wild type counterpart. CONCLUSIONS: Our research indicates that the CCDC66 variant c.C172T is associated with HM. A deficiency in CCDC66 might disrupt cell proliferation by influencing the mitotic process during retinal growth, leading to HM.

Synergistic Catalytic Performance of Pt-Au Bimetallic Catalysts on High-Crystallinity ZSM-23 Zeolite for Hexadecane Hydroisomerization: Metal-Acid Balance and Enhanced Isomerization Selectivity.

Highly crystalline ZSM-23 zeolite, exhibiting a distinctive dumbbell morphology, was synthesized via a hydrothermal method. Bifunctional catalysts, comprising single metals (Pt or Au) and bimetals (Pt-Au), were successfully prepared by using a positional precipitation method. The hydroisomerization of hexadecane served as a model reaction to assess the catalytic performance arising from the synergistic effects of bimetallic active sites. In comparison to single-metal catalysts, 0.3Au0.7Pt/ZSM-23 demonstrated increased n-C16 conversion, while 0.5Au0.5Pt/ZSM-23 exhibited enhanced i-C16 selectivity, achieving the highest i-C16 yield. The bimetallic catalyst not only finely tuned the metal site activity through bimetallic synergy but also achieved a superior balance between metal and acid catalysis, resulting in improved catalytic performance in the n-C16 hydroisomerization. The Pt-Au bimetallic catalyst approached the ideal requirements for a hydroisomerization catalyst, achieving a harmonious balance of metal and acid catalysis.

Two-year impact of COVID-19 pandemic on hospitalized patients with skin diseases in China.

To investigate the clinical characteristics of skin disorders among hospitalized patients before and during the coronavirus disease 2019 (COVID-19) pandemic, a retrospective study was conducted based on hospitalized patients with skin diseases from Xiangya Hospital of Central South University, the largest hospital in the south-central region of China, between January 1, 2018, and December 31, 2021. A total of 3039 hospitalized patients were enrolled in the study, including 1681 patients in the prepandemic group and 1358 patients in the pandemic group. The total number of hospitalized patients in the pandemic group decreased by 19.2%, with an increased proportion of patients over 60 years of age (39.8% vs. 35.8%). Moreover, compared with the prepandemic group, there were decreases in the occurrence of most skin diseases in the pandemic group, but the proportions of keratinolytic carcinoma (6.6% vs. 5.2%), dermatitis (24.0% vs. 18.9%), and psoriasis (18.0% vs. 14.8%) were higher in the pandemic group. In addition, longer hospital stays (ß = 0.07, SE = 0.02, P = 1.35 × 10-3 ) and higher hospital costs (ß = 0.06, SE = 0.03, p = 0.031) were found in the pandemic group through general linear models, even after the corresponding adjustment. In summary, the COVID-19 pandemic has had a lasting impact on patients with skin diseases, with fewer hospitalized patients, increased proportions of older patients, longer hospital stays, and increased hospital costs. These findings will facilitate better preparation for the most effective response to future pandemics.

RNA demethylase ALKBH5 regulates hypopharyngeal squamous cell carcinoma ferroptosis by posttranscriptionally activating NFE2L2/NRF2 in an m6 A-IGF2BP2-dependent manner.

BACKGROUND: Having emerged as the most abundant posttranscriptional internal mRNA modification in eukaryotes, N6-methyladenosine (m6 A) has attracted tremendous scientific interest in recent years. However, the functional importance of the m6 A methylation machinery in ferroptosis regulation in hypopharyngeal squamous cell carcinoma (HPSCC) remains unclear. METHODS: We herein performed bioinformatic analysis, cell biological analyses, transcriptome-wide m6 A sequencing (m6 A-seq, MeRIP-seq), RNA sequencing (RNA-seq), and RNA immunoprecipitation sequencing (RIP-seq), followed by m6 A dot blot, MeRIP-qPCR, RIP-qPCR, and dual-luciferase reporter assays. RESULTS: The results revealed that ALKBH5-mediated m6 A demethylation led to the posttranscriptional inhibition of NFE2L2/NRF2, which is crucial for the regulation of antioxidant molecules in cells, at two m6 A residues in the 3'-UTR. Knocking down ALKBH5 subsequently increased the expression of NFE2L2/NRF2 and increased the resistance of HPSCC cells to ferroptosis. In addition, m6 A-mediated NFE2L2/NRF2 stabilization was dependent on the m6 A reader IGF2BP2. We suggest that ALKBH5 dysregulates NFE2L2/NRF2 expression in HPSCC through an m6 A-IGF2BP2-dependent mechanism. CONCLUSION: Together, these results have revealed an association between the ALKBH5-NFE2L2/NRF2 axis and ferroptosis, providing insight into the functional importance of reversible mRNA m6 A methylation and its modulators in HPSCC.

Clinical characteristics and patient outcomes of molecular subtypes of small cell lung cancer (SCLC).

BACKGROUND: Recent studies have shown that according to the expression levels of achaete-scute homolog 1 (ASCL1), neurogenic differentiation factor 1 (NEUROD1), and POU class 2 homeobox 3 (POU2F3), small cell lung cancer (SCLC) can be divided into four subtypes: SCLC-A (ASCL1-dominant), SCLC-N (NEUROD1-dominant), SCLC-P (POU2F3-dominant), and SCLC-I (triple negative or SCLC-inflamed). However, there are limited data on the clinical characteristics and prognosis of molecular subtypes of SCLC. METHODS: Immunohistochemistry (IHC) was used to detect the expression levels of ASCL1, NEUROD1, and POU2F3 in 53 patient samples of resectable SCLC. The subtype was defined by the differential expression of the transcription factors for ASCL1, NEUROD1, and POU2F3 or the low expression of all three factors with an inflamed gene signature (SCLC-A, SCLC-N, SCLC-P, and SCLC-I, respectively). The clinicopathological characteristics, immunological features (programmed death ligand 1 [PD-L1] expression and CD8+ tumor infiltrating lymphocyte [TIL] density), and patient outcomes of the four subtypes of SCLC were analyzed. RESULTS: Positive ASCL1, NEUROD1, and POU2F3 staining was detected in 43 (79.2%), 27 (51.0%), and 17 (32.1%) SCLC specimens by IHC. According to the results of IHC analysis, SCLC was divided into four subtypes: SCLC-A (39.6%), SCLC-N (28.3%), SCLC-P (17.0%), and SCLC-I (15.1%). The 5-year overall survival (OS) rates of these four subtypes were 61.9%, 69.3%, 41.7%, and 85.7%, respectively (P=0.251). There were significant differences in smoking status among different subtypes of SCLC (P= 0.031). However, we did not confirm the correlation between subtypes of SCLC and other clinicopathological factors or immune profiles. Cox multivariate analysis showed that N stage (P=0.025), CD8+ TILs (P=0.024), Ki-67 level (P=0.040), and SCLC-P (P=0.023) were independent prognostic factors for resectable SCLC. CONCLUSIONS: Our IHC-based study validated the proposed classification of SCLC using the expression patterns of key transcriptional regulatory factors. We found that SCLC-P was associated with smokers and was one of the poor prognostic factors of limited-stage SCLC. In addition, no correlation was found between PD-L1 expression or CD8+ TIL density and SCLC subtypes.

Sonidegib Suppresses Production of Inflammatory Mediators and Cell Migration in BV2 Microglial Cells and Mice Treated with Lipopolysaccharide via JNK and NF-κB Inhibition.

Our structure-based virtual screening of the FDA-approved drug library has revealed that sonidegib, a smoothened antagonist clinically used to treat basal cell carcinoma, is a potential c-Jun N-terminal kinase 3 (JNK3) inhibitor. This study investigated the binding of sonidegib to JNK3 via 19F NMR and its inhibitory effect on JNK phosphorylation in BV2 cells. Pharmacological properties of sonidegib to exert anti-inflammatory and anti-migratory effects were also characterized. We found that sonidegib bound to the ATP binding site of JNK3 and inhibited JNK phosphorylation in BV2 cells, confirming our virtual screening results. Sonidegib also inhibited the phosphorylation of MKK4 and c-Jun, the upstream and downstream signals of JNK, respectively. It reduced the lipopolysaccharide (LPS)-induced production of pro-inflammatory factors, including interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), and nitric oxide (NO), and the expression of inducible NO synthase and cyclooxygenase-2. The LPS-induced cell migration was suppressed by sonidegib. Sonidegib inhibited the LPS-induced IκBα phosphorylation, thereby blocking NF-κB nuclear translocation. Consistent with these findings, orally administered sonidegib attenuated IL-6 and TNF-α levels in the brains of LPS-treated mice. Collectively, our results indicate that sonidegib suppresses inflammation and cell migration in LPS-treated BV2 cells and mice by inhibiting JNK and NF-κB signaling. Therefore, sonidegib may be implicated for drug repurposing to alleviate neuroinflammation associated with microglial activation.

LncRNA TTTY15 knockdown alleviates H2O2-stimulated myocardial cell injury by regulating the miR-98-5p/CRP pathway.

Acute myocardial infarction (AMI) can lead to myocardial injury, and long non-coding RNA (lncRNA) has been found to play an important regulatory role in the process of myocardial injury. However, the role and potential mechanisms of lncRNA testis-specific transcript Y-linked 15 (TTTY15) in AMI-induced myocardial injury has not been fully elucidated. Hydrogen peroxide (H2O2)-induced AMI cell model was built and AMI mice model were constructed. Relative expression levels of TTTY15, miR-98-5p and C-reactive protein (CRP) were determined by quantitative real-time PCR (qRT-PCR). Cell counting kit 8 (CCK8) assay, flow cytometry and enzyme-linked immunosorbent assay (ELISA) were employed to assess cell viability, apoptosis, inflammatory response and oxidative stress. Western blot (WB) analysis was used to assess the protein expression levels. The mechanism of TTTY15 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Our results revealed that TTTY15 was upregulated and miR-98-5p was downregulated in AMI patients and H2O2-stimulated myocardial cells. Knockdown of TTTY15 could alleviate H2O2-stimulated myocardial cell injury in vitro and AMI progression in vivo. Bioinformatics analysis and the rescue experiments confirmed that TTTY15 positively regulated H2O2-induced myocardial cell injury via regulating CRP by sponging miR-98-5p. Our research proposed that lncRNA TTTY15 promoted myocardial cell injury by regulating the miR-98-5p/CRP axis, suggesting that TTTY15 might be a potential target for alleviating AMI-caused myocardial cell injury.

Synthesis of Tribenzo[b,d,f]azepines via Palladium-Catalyzed Annulation Reaction of 2-Iodobiphenyls with 2-Halogenoanilines.

A palladium-catalyzed annulation reaction of 2-iodobiphenyls with 2-halogenoanilines has been developed. A variety of 2-iodobiphenyls and 2-halogenoanilines can undergo this transformation. Diversified tribenzo[b,d,f]azepine derivatives can be synthesized in moderate to excellent yields according to this method.

Mesenchymal stem cells as a double-edged sword in tumor growth: focusing on MSC-derived cytokines.

Mesenchymal stem cells (MSCs) show homing capacity towards tumor sites. Numerous reports indicate that they are involved in multiple tumor-promoting processes through several mechanisms, including immunosuppression; stimulation of angiogenesis; transition to cancer-associated fibroblasts; inhibition of cancer cell apoptosis; induction of epithelial-mesenchymal transition (EMT); and increase metastasis and chemoresistance. However, other studies have shown that MSCs suppress tumor growth by suppressing angiogenesis, incrementing inflammatory infiltration, apoptosis and cell cycle arrest, and inhibiting the AKT and Wnt signaling pathways. In this review, we discuss the supportive and suppressive impacts of MSCs on tumor progression and metastasis. We also discuss MSC-based therapeutic strategies for cancer based on their potential for homing to tumor sites.

Paeonol suppresses the effect of ox-LDL on mice vascular endothelial cells by regulating miR-338-3p/TET2 axis in atherosclerosis.

Atherosclerosis is the common vascular disease. Vascular smooth muscle cell proliferation and vascular endothelial cell (VEC) dysfunction are involved in the causes of atherosclerosis. And oxidized low-density lipoprotein (ox-LDL)-induced vascular endothelial cells (VECs) are suitable models for studying atherosclerosis development. Paeonol was reported to repress ox-LDL-induced VEC progression. However, its detailed mechanism was not fully reported. MicroRNAs (miRNAs) acted as regulators in multiple diseases. Previous findings found that microRNA-338-3p (miR-338-3p) was overexpressed in Atherosclerosis process. However, the function and underlying mechanism of miR-338-3p in ox-LDL-treated VECs needed to be elucidated. The purpose of this research was to reveal the role of miR-338-3p in paeonol-regulated ox-LDL-induced VEC progression. Cell counting kit-8 (CCK-8) and flow cytometry were employed to determine cell viability and apoptosis, respectively. Moreover, the levels of IL-6 and IL-1ß were analyzed using enzyme-linked immunosorbent assay, as well as the contents of reactive oxygen species, lactate dehydrogenase, and malonic dialdehyde were investigated using related kits. Furthermore, quantitative real-time polymerase chain reaction was carried out to determine the expression of miR-338-3p. Western blot assay was conducted to detect the level of tet methylcytosine dioxygenase 2 (TET2). Besides, the interaction between miR-338-3p and TET2 was predicted by DIANA, and then confirmed by the dual-luciferase reporter assay and RNA immunoprecipitation assay. Ox-LDL repressed mice VEC viability, and promoted apoptosis, inflammatory response, and oxidative injury. Paeonol inhibited the effect of ox-LDL on the growth of the VECs. Furthermore, paeonol regulated VEC development via downregulating miR-338-3p expression. Interestingly, miR-338-3p targeted TET2 and inhibited TET2 expression. MiR-338-3p modulated ox-LDL-treated VEC growth through suppressing TET2 expression. We demonstrated that paeonol attenuated the effect of ox-LDL on the development of mice VECs via modulating miR-338-3p/TET2 axis, providing a theoretical basis for the treatment of AS.

Xanthoangelol Prevents Ox-LDL-Induced Endothelial Cell Injury by Activating Nrf2/ARE Signaling.

OBJECTIVE: Atherosclerosis (AS) contributes to the development of several cardiovascular diseases such as myocardial infarction and stroke. Oxidized low-density lipoprotein (Ox-LDL)-induced endothelial cell injury plays a key role in the pathogenesis of AS. Thus, this study was conducted to examine the effects of a naturally occurring flavonoid compound, xanthoangelol (XAG), on Ox-LDL-induced cell injury. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were used as the in vitro cell model. The number of viable cells was determined using CCK-8 assay. Cell apoptosis was detected using Hoechst staining. Percentage of apoptotic cells was quantified by flow cytometry. The cellular levels of malondialdehyde (MDA), superoxide dismutase, catalase (CAT), and glutathione peroxidase were determined using enzyme-linked immunosorbent assays. The cellular reactive oxygen species level was detected by flow cytometry after fluorescence staining. The mRNA expression levels of nuclear factor-E2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1), and NQO-1 were determined using quantitative real-time polymerase chain reaction assay. The protein levels of cleaved caspase-3, cleaved poly ADP-ribose polymerase, Bax, Bcl-2, Nrf2, Keap1, HO-1, and NQO-1 were measured by using Western blot assay. The HUVECs were transfected with Nrf2 siRNA to reduce the expression of Nrf2. RESULTS: XAG could effectively protect against Ox-LDL-stimulated cell death in HUVECs. These cytoprotective effects were due to its anti-apoptotic and anti-oxidant activities, as supported by the increase of SOD, CAT, and glutathione peroxidase activities, and the decrease of MDA and reactive oxygen species levels in injured HUVECs induced by Ox-LDL. Moreover, the results showed that XAG activated Nrf2/ARE signaling in a dose-dependent manner. Importantly, blockade of Nrf2 signaling using siRNA or specific inhibitor notably abolished the cytoprotective activities of XAG. CONCLUSIONS: These data suggest that XAG cytoprotects against Ox-LDL-induced cell injury through activating Nrf2/ARE-mediated antioxidative stress. Cumulatively, these findings show that EX has the potential to prevent and treat AS.

Heme Oxygenase-1 Reduces Sepsis-Induced Endoplasmic Reticulum Stress and Acute Lung Injury.

BACKGROUND: Sepsis leads to severe acute lung injury/acute respiratory distress syndrome (ALI/ARDS) that is associated with enhanced endoplasmic reticulum (ER) stress. Heme oxygenase-1 (HO-1), an ER-anchored protein, exerts antioxidant and protective functions under ALI. However, the role of HO-1 activation in the development of endoplasmic reticulum (ER) stress during sepsis remains unknown. METHODS: Cecal ligation and puncture (CLP) model was created to induce septic ALI. Lung tissue ER stress was measured 18 hours after CLP. The effects of HO-1 on ER stress during septic ALI were investigated in vivo using HO-1 agonist hemin and antagonist ZnPP. RESULTS: Compared with the sham group, ER stress in septic lung increased significantly 18 hours after CLP, which was significantly reduced by pretreatment with the ER inhibitor 4-phenylbutyrate (4-PBA). The lung injury score and the lung wet to dry (W/D) ratio in lungs were significantly reduced in septic rats after ER stress inhibition. Similarly, lung ER stress-related genes' (PERK, eIF2-α, ATF4, and CHOP) levels were attenuated after ER stress inhibition. Furthermore, HO-1 activation by hemin reduced p-PERK, p-eIF2-α, ATF4, and CHOP protein expression and oxidative stress and lung cell apoptosis. Additionally, HO-1 antagonist could aggregate the ER stress-related ALI. CONCLUSIONS: ER stress was activated during CLP-induced ALI, which may represent a mechanism by which CLP induces ALI. HO-1 activation could inhibit CLP-induced lung ER stress and attenuate CLP-induced ALI.

Rapid start-up and performance of denitrifying granular sludge in an upflow sludge blanket (USB) reactor treating high concentration nitrite wastewater.

Denitrifying granular sludge reactor holds better nitrogen removal efficiency than other kinds of denitrifying reactors, while this reactor commonly needs seeding anaerobic granular sludge and longer period for start-up in practice, which restricted the application of denitrifying granular sludge reactor. This study presented a rapid and stable start-up method for denitrifying granular sludge. An upflow sludge blanket (USB) reactor with packings was established with flocculent activated sludge for treatment of high concentration nitrite wastewater. Results showed mature denitrifying granular sludge appeared only after 15 days with highest nitrogen removal rate of 5.844 kg N/(m3 day), which was much higher than that of compared anoxic sequencing batch reactor (ASBR). No significant nitrite inhibition occurred in USB and denitrification performance was mainly influenced by hydraulic retention time, influent C/N ratio and internal reflux ratio. Hydraulic shear force created by upflow fluid, shearing of gaseous products and stable microorganisms adhesion on the packings might be the reasons for rapid achievement of granular sludge. Compared to inoculated sludge and ASBR, remarkable microbial communitiy variations were detected in USB. The dominance of Proteobacteria and Bacteroidetes and enrichment of species Pseudomonas_stutzeri should be responsible for the excellent denitrification performance, which further verified the feasibility of start-up method.

Detailed mechanism study of volatile organic compound decomposition and oxidation removal based on a ReaxFF MD method.

Volatile organic compounds (VOCs) are typical air pollutants as well as gaseous wastes that contain energy. Utilization and disposition of VOCs is currently an important research hotspot in the field of atmospheric environment. In this paper, the thermal cracking and oxidation reaction processes of typical VOCs components were modelled and analyzed by combining molecular dynamics and detailed reaction mechanisms, focusing on the effects of temperature, oxygen and other conditions on the conversion of VOCs. The results of molecular dynamics studies show that improving temperature and reaction time benefit the decomposition of VOCs. High temperatures under an inert atmosphere can sufficiently crack the VOCs themselves, but other by-products are generated, which in turn cause secondary pollution. The activation energies derived by ReaxFF-MD calculation are 328 kJ mol-1, 147 kJ mol-1 and 121 kJ mol-1 for toluene, styrene and benzaldehyde respectively, which is consistent with experimental results. Under the oxygen atmosphere, the conversion rate of VOCs is greatly increased and the reaction temperature is significantly reduced. Meanwhile, the oxidation reaction fully converts VOCs into non-polluting products such as CO2 and H2O. Detailed kinetic studies show that initial oxidation of toluene molecules raised by hydrogen abstraction reaction is the dominant step during toluene oxidation, which significantly improved the decomposition efficiency of toluene.

Uncovering hidden dangers: The combined toxicity of abamectin and lambda-cyhalothrin on honey bees.

Studying the toxic effects of pesticides on bees has consistently been a prominent area of interest for researchers. Nonetheless, existing research has predominantly concentrated on individual toxicity assessments, leaving a gap in our understanding of mixed toxicity. This study delves into the individual and combined toxic effects of abamectin (ABA) and lambda-cyhalothrin (LCY) on honey bees (Apis mellifera) in laboratory settings. We discovered that ABA (96 h-LC50 value of 0.079 mg/L) exhibited greater acute toxicity to honey bees compared to LCY (96 h-LC50 value of 9.177 mg/L). Moreover, the mixture of ABA and LCY presented an acute antagonistic effect on honey bees. Additionally, our results indicated that exposure to LCY, at medium concentration, led to a reduction in the abundance of gut core bacterium Snodgrassella. However, an increase in the abundance of Bifidobacterium was noted when exposed to a medium concentration of LCY and its mixture with ABA. Transcriptomic analysis revealed significant regulation of certain genes in the medium concentration of all three treatments compared to the control group, primarily enriching in metabolism and immune-related pathways. Following chronic exposure to field-relevant concentrations of ABA, LCY, and their mixture, there were significant alterations in the activities of immunity-related enzyme polyphenol oxidase (PPO) and detoxification enzymes glutathione S-transferase (GST) and carboxylesterase (CarE). Additionally, the expression of four genes (abaecin, cyp9e2, cyp302a1, and GstD1) associated with immune and detoxification metabolism was significantly altered. These findings suggest a potential health risk posed by the insecticides ABA and LCY to honey bees. Despite exhibiting acute antagonistic effect, mixed exposure still induced damage to bees at all levels. This study advances our knowledge of the potential adverse effects of individual or combined exposure to these two pesticides on non-target pollinators and offers crucial guidance for the use of insecticides in agricultural production.

Serine/Threonine Kinase (STK) 33 promotes the proliferation and metastasis of human esophageal squamous cell carcinoma via inflammation-related pathway.

The serine/threonine kinase (STK) 33 plays a key role in cancer cell proliferation and metastasis. Abnormal STK33 expression is closely related to malignancy of numerous cancers. This study suggests the important role of STK33 in the pathogenesis and metastatic progression of esophageal squamous cell carcinoma (ESCC). STK33 expression in human ESCC tissues was detected by immunohistochemical technique. Further, we analyzed the relationship between STK33 and clinical and pathological factors as well as the prognosis of patients. ECa109 cell line was cultured and transfected with STK33-RNAi lentiviral vector to perform Hochest33342 & PI and metastasis experiments. The TCGA database was used to analyze the STK33 expression level in ESCC. All statistical analyses were performed in SPSS 23.0 software. Differences with P < 0.05 were considered statistically significant. In human ESCC specimens, STK33 was overexpressed and associated with poor prognosis. Silencing STK33 expression suppressed ESCC proliferation, migration, invasion, and tumor growth. STK33 also mediated angiogenesis, TGFß, and inflammatory response in ESCC. Mechanistic investigations revealed that STK33 regulates ESCC through multiple complex pathways. Dysregulated STK33 signaling promotes ESCC growth and progression. Thus, our findings identified STK33 as a candidate treatment target that improves ESCC therapy.

Evaluation of relative isotopic abundance measurements in a quadrupole time-of-flight mass spectrometer for elemental composition determination of natural products in traditional Chinese medicine.

The relative isotopic abundance (RIA) measurement errors of a quadrupole time-of-flight (Q-ToF) instrument incorporating analog-to-digital converter detectors were systemically evaluated by stochastically collecting about 200 data in positive ion mass spectrometry (MS) mode. Errors varied with peak intensities at definite spectral acquisition rates but were very close, even if peak intensities changed sharply at different spectral acquisition rates with the same concentration. Intensity thresholds were systematically defined at 1 Hz of spectral acquisition rates. RIA measurement errors were also evaluated using peak area. It seemed that peak area was better adapted for the high-intensity ions while peak intensity was suited for very low-intensity ions. Several known compounds were selected for RIA measurements for product ions in tandem mass spectropmetry (MS/MS) mode. An extract of a representative traditional Chinese medicinal, Paederia scandens was analyzed with high-performance liquid chromatography-electrospray ionization-QToF-MS/MS. The unique elemental compositions of some compounds could not be identified even with exact masses and MS/MS spectra of measured and reference compounds. RIA errors, especially of (M+2)M(-1), provided vital information for determining the elemental composition.

DPred_3S: identifying dihydrouridine (D) modification on three species epitranscriptome based on multiple sequence-derived features.

Introduction: Dihydrouridine (D) is a conserved modification of tRNA among all three life domains. D modification enhances the flexibility of a single nucleotide base in the spatial structure and is disease- and evolution-associated. Recent studies have also suggested the presence of dihydrouridine on mRNA. Methods: To identify D in epitranscriptome, we provided a prediction framework named "DPred_3S" based on the machine learning approach for three species D epitranscriptome, which used epitranscriptome sequencing data as training data for the first time. Results: The optimal features were evaluated by the F-score and integration of different features; our model achieved area under the receiver operating characteristic curve (AUROC) scores 0.955, 0.946, and 0.905 for Saccharomyces cerevisiae, Escherichia coli, and Schizosaccharomyces pombe, respectively. The performances of different machine learning algorithms were also compared in this study. Discussion: The high performances of our model suggest the D sites can be distinguished based on their surrounding sequence, but the lower performance of cross-species prediction may be limited by technique preferences.