Determinant of m6A regional preference by transcriptional dynamics.

N6-Methyladenosine (m6A) is the most abundant chemical modification occurring on eukaryotic mRNAs, and has been reported to be involved in almost all stages of mRNA metabolism. The distribution of m6A sites is notably asymmetric along mRNAs, with a strong preference toward the 3' terminus of the transcript. How m6A regional preference is shaped remains incompletely understood. In this study, by performing m6A-seq on chromatin-associated RNAs, we found that m6A regional preference arises during transcription. Nucleosome occupancy is remarkedly increased in the region downstream of m6A sites, suggesting an intricate interplay between m6A methylation and nucleosome-mediated transcriptional dynamics. Notably, we found a remarkable slowdown of Pol-II movement around m6A sites. In addition, inhibiting Pol-II movement increases nearby m6A methylation levels. By analyzing massively parallel assays for m6A, we found that RNA secondary structures inhibit m6A methylation. Remarkably, the m6A sites associated with Pol-II pausing tend to be embedded within RNA secondary structures. These results suggest that Pol-II pausing could affect the accessibility of m6A motifs to the methyltransferase complex and subsequent m6A methylation by mediating RNA secondary structure. Overall, our study reveals a crucial role of transcriptional dynamics in the formation of m6A regional preference.

ART1 knockdown decreases the IL-6-induced proliferation of colorectal cancer cells.

Colorectal cancer (CRC) is a worldwide health concern. Chronic inflammation is a risk factor for CRC, and interleukin-6 (IL-6) plays a pivotal role in this process. Arginine-specific mono-ADP-ribosyltransferase-1 (ART1) positively regulates inflammatory cytokines. ART1 knockdown reduces the level of glycoprotein 130 (gp130), a key transducer in the IL-6 signalling pathway. However, the relationship between ART1 and IL-6 and the resulting effects on IL-6-induced proliferation in CRC cells remain unclear. The aims of this study were to investigate the effects of ART1 knockdown on IL-6-induced cell proliferation in vitro and use an in vivo murine model to observe the growth of transplanted tumours. The results showed that compared with the control, ART1-sh cancer cells induced by IL-6 exhibited reduced viability, a lower rate of colony formation, less DNA synthesis, decreased protein levels of gp130, c-Myc, cyclin D1, Bcl-xL, and a reduced p-STAT3/STAT3 ratio (P < 0.05). Moreover, mice transplanted with ART1-sh CT26 cells that had high levels of IL-6 displayed tumours with smaller volumes (P < 0.05). ART1 and gp130 were colocalized in CT26, LoVo and HCT116 cells, and their expression was positively correlated in human CRC tissues. Overall, ART1 may serve as a promising regulatory factor for IL-6 signalling and a potential therapeutic target for human CRC.

Down-conversion and frequency spectrum convolution of the broadband signal based on active mode-locking technology.

A multifunction processor for a broadband signal based on the active mode-locking optoelectronic oscillator (OEO) is proposed and experimentally demonstrated. The central frequency down-conversion and frequency spectrum convolution of the target broadband signal (TBS) are realized by just tuning the wavelength of the optical carrier or by the time domain product, respectively. To achieve the central frequency down-conversion of the TBS, an optical tunable delay line (OTDL) is adopted to match the delay time of the OEO loop with the repetition period of the TBS. Then the spectrum convolution of the TBS is produced by just injecting a lower frequency signal consistent with the free spectral range (FSR) of the OEO loop. Moreover, the frequency convolution repetition is also greatly increased by harmonic mode-locking injection. The equivalent bandwidth of the TBS is enlarged by ∼50 times, benefiting from the frequency convolution. The central frequency conversion flexibility and the bandwidth compatibility are also discussed in detail. This work provides a multifunction processor system and may have potential usage in multifunctional integrated radar systems.

PARG Promotes Esophagus Cancer Cell Metastasis by Activation of the Wnt/ß-Catenin Pathway.

Esophagus cancer (EC) is a highly malignant and metastatic cancer. Poly(ADP-ribose) glycohydrolase (PARG), a DNA replication and repair regulator, inhibits cancer cell replication defects. This study aimed to explore the role of PARG in EC. The biological behaviors were analyzed using MTT assay, Transwell assay, scratch test, cell adhesion assay, and western blot. PARG expression was detected using quantitative PCR and immunohistochemical assay. The regulation of the Wnt/ß-catenin pathway was assessed using western blot. The results showed that PARG was highly expressed in EC tissues and cells. Knockdown of PARG suppressed cell viability, invasion, migration, adhesion, and epithelial-mesenchymal transition. Conversely, overexpression of PARG promoted the biological behaviors mentioned above. Moreover, overexpression of PARG promoted the activation of the Wnt/ß-catenin pathway rather than the STAT and Notch pathways. XAV939, the Wnt/ß-catenin pathway inhibitor, partly abolished the biological behaviors mediated by PARG overexpression. In conclusion, PARG promoted the malignant advancement of EC via activating the Wnt/ß-catenin pathway. These findings suggested that PARG might be a new therapeutic target for EC.

Effect of respiratory training on swallowing function in swallowing disorders: a systematic review and meta-analysis.

PURPOSE: To determine the clinical efficacy of different respiratory training interventions on swallowing function in patients with swallowing disorders through the systematic review. METHODS: We reviewed the literature regarding the application of respiratory training therapy in patients with swallowing disorders, followed by a PRISMA search of published literature in five databases (PubMed, Web of Science, The Cochrane Library, CINAHL and EMBASE) in December 2022. Two reviewers performed study selection, quality evaluation, and risk of bias, followed by data extraction and detailed analysis. RESULTS: A total of six randomized controlled studies with a total sample size of 193 cases were included. Respiratory training improved swallowing safety (PAS (n = 151, SMD = 0.69, 95% CI - 1.11 to - 0.26, I2 = 36, p < 0.001)) and swallowing efficiency [residual (n = 63, SMD = 1.67, 95% CI - 2.26 to - 1.09, I2 = 23%, p < 0.001)] compared to control groups. The results of the qualitative analysis conducted in this study revealed that respiratory training enhanced hyoid bone movement but had no effect on swallowing quality of life. CONCLUSIONS: Respiratory training interventions may improve swallowing safety and efficiency in patients with dysphagia. However, the level of evidence is low, and there is a limited amount of research on the effectiveness and physiology of this intervention to improve swallowing function. In the future, there is a need to expand clinical studies, standardize measurement tools, and improve study protocols.

Mechanism of Phosphate Desorption from Activated Red Mud Particle Adsorbents.

Herein, activated red mud particles are used as adsorbents for phosphorus adsorption. HCl solutions with different concentrations and deionized water are employed for desorption tests, and the desorption mechanism under the following optimal conditions is investigated: HCl concentration = 0.2 mol/L, desorbent dosage = 0.15 L/g, desorption temperature = 35 °C, and desorption time = 12 h. Under these conditions, the phosphate desorption rate and amount reach 99.11% and 11.29 mg/g, respectively. Notably, the Langmuir isothermal and pseudo-second-order kinetic linear models exhibit consistent results: monomolecular-layer surface desorption is dominant, and chemical desorption limits the rate of surface desorption. Thermodynamic analysis indicates that phosphorus desorption by the desorbents is spontaneous and that high temperatures promote such desorption. Moreover, an intraparticle diffusion model demonstrates that the removal of phosphorus in the form of precipitation from the surface of an activated hematite particle adsorbent primarily occurs via a chemical reaction, and surface micromorphological analysis indicates that desorption is primarily accompanied by Ca dissolution, followed by Al and Fe dissolutions. The desorbents react with the active elements in red mud, and the vibrations of the [SiO4]4- functional groups of calcium-iron garnet and calcite or aragonite disappear. Further, in Fourier-transform infrared spectra, the intensities of the peaks corresponding to the PO43- group considerably decrease. Thus, desorption primarily involves monomolecular-layer chemical desorption.

Formulation Optimization and Performance Prediction of Red Mud Particle Adsorbents Based on Neural Networks.

Red mud (RM), a bauxite residue, contains hazardous radioactive wastes and alkaline material and poses severe surface water and groundwater contamination risks, necessitating recycling. Pretreated RM can be used to make adsorbents for water treatment. However, its performance is affected by many factors, resulting in a nonlinear correlation and coupling relationship. This study aimed to identify the best formula for an RM adsorbent using a mathematical model that examines the relationship between 11 formulation types (e.g., pore-assisting agent, component modifier, and external binder) and 9 properties (e.g., specific surface area, wetting angle, and Zeta potential). This model was built using a back-propagation neural network (BP) based on single-factor experimental data and orthogonal experimental data. The model trained and predicted the established network structure to obtain the optimal adsorbent formula. The RM particle adsorbents had a pH of 10.16, specific surface area (BET) of 48.92 m2·g-1, pore volume of 2.10 cm3·g-1, compressive strength (ST) of 1.12 KPa, and 24 h immersion pulverization rate (ηm) of 3.72%. In the removal of total phosphorus in flotation tailings backwater, it exhibited a good adsorption capacity (Q) and total phosphorous removal rate (η) of 48.63 mg·g-1 and 95.13%, respectively.

An integrated analysis of Dynamin 1 Like: A new potential prognostic indicator in hepatocellular carcinoma.

Dynamin 1 Like (DNM1L), a member of dynamin superfamily capable of mediating mitochondrial outer membrane division, plays a key role in the progression of different types of tumors. However, the prognostic value, clinical significance of DNM1L and its specific mechanism involved in tumorigenesis of hepatocellular carcinoma (HCC) have not been investigated clearly. In this study, we found that the expression of DNM1L were significantly higher in HCC tissues than adjacent/normal liver tissues based on multiple data sets obtained from TCGA, GEO and ONCOMINE database, also its protein expression form Drp1 is significantly higher in HCC tissues than adjacent tissues, and is related to the degree of differentiation. Kaplan-Meier curves suggested that high DNM1L expression prominently correlated with poorer overall survival, progression-free survival, relapse-free survival and disease-specific survival. Multivariate analysis showed that higher DNM1L expression was independent prognostic factors of shorter overall survival and disease-free survival. Kyoto Encyclopedia of Genes and Genomes and Gene set enrichment analysis analysis combined with validation experiments revealed the regulatory role of DNM1L on key molecules in the metabolism of xenobiotics by cytochrome p450 pathway, and DNM1L may also affects invasion and metastasis capability of HCC by mediating extracellular matrix -receptor interaction pathway. Moreover, analysis showed that higher DNM1L, CYP2C9, CYP3A4, CYP1A2 expression were associated with the resistance to sorafenib therapy. TIMER and CIBERSORT analysis indicated that the increase of DNM1L expression may affect the infiltration of immune cells in the tumor microenvironment. Taken together, the above results indicated that DNM1L could be able to serve as a promising independent predictor and therapeutic target for HCC patients.

Association Between Estradiol and Human Aggression: A Systematic Review and Meta-Analysis.

OBJECTIVE: Although several studies have examined the association between estradiol and human aggression, a consistent understanding of their correlation has yet to be established. This study aimed to investigate this relationship comprehensively. METHODS: We systematically searched five English databases (PubMed, Web of Science, EMBASE, Cochrane Library, and CINAHL) from their inception to June 5, 2023. Two authors independently screened publications and extracted data based on predefined inclusion and exclusion criteria. Statistical analyses were performed using Review Manager 5.4, and a random-effects model was used to pool the data. RESULTS: We identified 14 eligible studies comprising data from 1820 participants that met the inclusion criteria. This meta-analysis indicated a positive correlation between estradiol and human aggression, albeit a weak one. The pooled Fisher z value was 0.16 (95% confidence interval = 0.05-0.26; I2 = 73%, p <.00001). Furthermore, we found that participants' sex and age, the measures of aggression, and the literature quality might be sources of heterogeneity. CONCLUSIONS: Human aggression exhibited a weak positive correlation with estradiol concentration, whereas this relationship was influenced by participants' sex and age, the measure of aggression used, and the quality assessment of the literature. Gaining a better understanding of the association between estradiol and aggression could aid in the identification of populations prone to aggression.

A recurrent SHANK1 mutation implicated in autism spectrum disorder causes autistic-like core behaviors in mice via downregulation of mGluR1-IP3R1-calcium signaling.

The genetic etiology and underlying mechanism of autism spectrum disorder (ASD) remain elusive. SHANK family genes (SHANK1/2/3) are well known ASD-related genes. However, little is known about how SHANK missense mutations contribute to ASD. Here, we aimed to clarify the molecular mechanism of and the multilevel neuropathological features induced by Shank1 mutations in knock-in (KI) mice. In this study, by sequencing the SHANK1 gene in a cohort of 615 ASD patients and 503 controls, we identified an ASD-specific recurrent missense mutation, c.2621 G > A (p.R874H). This mutation demonstrated strong pathogenic potential in in vitro experiments, and we generated the corresponding Shank1 R882H-KI mice. Shank1 R882H-KI mice displayed core symptoms of ASD, namely, social disability and repetitive behaviors, without confounding comorbidities of abnormal motor function and heightened anxiety. Brain structural changes in the frontal cortex, hippocampus and cerebellar cortex were observed in Shank1 R882H-KI mice via structural magnetic resonance imaging. These key brain regions also showed severe and consistent downregulation of mGluR1-IP3R1-calcium signaling, which subsequently affected the release of intracellular calcium. Corresponding cellular structural and functional changes were present in Shank1 R882H-KI mice, including decreased spine size, reduced spine density, abnormal morphology of postsynaptic densities, and impaired hippocampal long-term potentiation and basal excitatory transmission. These findings demonstrate the causative role of SHANK1 in ASD and elucidate the underlying biological mechanism of core symptoms of ASD. We also provide a reliable model of ASD with core symptoms for future studies, such as biomarker identification and therapeutic intervention studies.

Full-field electroretinogram recorded with skin electrodes in 6- to 12-year-old children.

PURPOSE: To determine the full-field electroretinogram (ffERG) parameters, including the light-adapted (LA) 3 ERG and the photopic negative response (PhNR), in 6- to 12-year-old children. METHODS: ffERG data were obtained from 214 eyes of 214 healthy subjects. The amplitudes and peak time of the ffERG responses were obtained from children divided into 6- to 8-year-old and 9- to 12-year-old groups. Using a skin electrode, electrical signals were measured in response to white stimulating light and white background light (LA 3 ERG). A blue background light and red flashes were then used to elicit the PhNR. RESULTS: The a-wave amplitude ranged from 0.40 to 9.20 µV, the b-wave ranged from 4.70 to 30.80 µV, and the PhNR ranged from 1.30 to 39.90 µV. The b-wave peak time (33.20 ms) of 6- to 8-year-old groups was slightly shorter than that of the 9- to 12-year-old groups (33.60 ms, P = 0.01), but no differences in amplitudes or in peak time of other components. There were significant correlations between the amplitudes (a-wave and b-wave: r = 0.43, p < 0.001; a-wave and PhNR: r = 0.25, p < 0.001; b-wave and PhNR: r = 0.45, p < 0.001). There was a moderate correlation between the a-wave and b-wave peak time (r = 0.31, P < 0.001). CONCLUSIONS: We determined the largest dataset of the LA 3 ERG and PhNR parameters in a population of healthy children, aged 6-12 years, which may provide a useful reference value when evaluating children with potential retinal defects.

Accuracy of new-generation intraocular lens calculation formulas in eyes with variations in predicted refraction.

PURPOSE: To investigate the characteristics of eyes with large variations in predicted refraction using four traditional intraocular lens (IOL) formulas and evaluate the accuracy of new-generation intraocular lens power calculation formulas. METHODS: Eyes that had variation in predicted refraction (≥ 0.75 D) using four traditional formulas (SRK/T, Holladay 1, Hoffer Q, and Haigis formulas) were included. Axial length (AL), anterior chamber depth (ACD), average keratometry (AK), and the ratio of axial length to corneal radius (AL/CR) were measured. New-generation formulas (Barrett Universal II, Emmetropia Verifying Optical 2.0, Kane, and Pearl-DGS formulas) and traditional formulas were compared. The median absolute error (MedAE) was the main parameter to evaluate the accuracy of formulas. RESULTS: A total of 79 participants (79 eyes) who had variation in predicted refraction of (≥ 0.75 D) using four traditional formulas out of 510 eyes (510 patients) underwent uncomplicated cataract surgeries. The Barrett Universal II (0.29 D), EVO 2.0 (0.31 D), Kane (0.30 D), and Pearl-DGS (0.33 D) formulas produced significantly lower median absolute errors (MedAEs) than the Hoffer Q (0.61 D) and Holladay 1 (0.59 D) formulas (P < 0.01). The Wang-Koch (WK) adjustment significantly improved the accuracy of the Holladay 1 formula in long eyes (P < 0.001). CONCLUSIONS: Abnormal AL, ACD, and AK are more likely to lead to prediction errors using traditional formulas. New-generation formulas and traditional formulas with WK adjustment showed satisfactory prediction accuracy.

The effect of voice training interventions on patients with oropharyngeal dysphagia: a systematic review.

BACKGROUND: Voice training has been proposed as an intervention to improve swallowing function in patients with dysphagia. However, little is known about the effects of voice training on swallowing physiology. OBJECTIVES: This systematic review investigates the effect of voice training on the swallowing function of patients with oropharyngeal dysphagia and provides the theoretical basis for improving the swallowing function and life quality of patients with oropharyngeal dysphagia. DATA SOURCES: A systematic review using a narrative synthesis approach of all published studies was sought with no date restrictions. Five electronic databases (EMBASE, PubMed, CINAHL, Web of Science, and The Cochrane Library) were searched from inception to April 2022. STUDY SELECTION: Eight studies were included. Two researchers screened the literature according to inclusion and exclusion criteria, extracted data, and carried out quality control according to the Cochrane handbook5.1.0. Data were analyzed narratively and descriptively. CONCLUSIONS: In general, statistically significant positive therapy effects were found. Voice training improves the oral and pharyngeal stages of swallowing in patients with neurological causes of dysphagia, such as stroke, and in patients with non-neurological causes of dysphagia, such as head and neck cancer. However, the current literature is limited and further primary research is required to provide more evidence to support voice training intervention in dysphagia.  Future studies could  further refine the content of voice training interventions, increase the number of patients enrolled, assess the long-term effects of voice training interventions and add associated assessments of the quality of life after treatment.

The relationships among symptom experience, family support, health literacy, and fear of progression in advanced lung cancer patients.

AIMS: Fear of progression of cancer patients can affect their psychological well-being, while research on fear of progression of advanced lung cancer patients is limited. This study aimed to describe fear of progression among advanced lung cancer patients and explore the relationships among symptom experience, family support, health literacy, and fear of progression. DESIGN: This study was a cross-sectional study. METHODS: Convenience sampling was used to select advanced lung cancer patients from September 2021 to January 2022. The Chinese version of the Fear of Progression Questionnaire-Short Form, Lung Cancer Module of the MD Anderson Symptom Inventory, Family Support Questionnaire, and Health Literacy Scale for Patients with Chronic Disease were used to collect data. The structural equation modelling was used to analyse the relationships among symptom experience, family support, health literacy, and fear of progression. RESULTS: Of 220 patients, 31.8% had dysfunctional fear of progression. Better symptom experience, higher family support, and higher health literacy were correlated directly with lower fear of progression. Higher health literacy was associated indirectly with lower fear of progression through the mediation of better symptom experience. CONCLUSION: Fear of progression among advanced lung cancer patients needs attention. Strengthening symptom management, building a strong system of family support, and improving patients' health literacy may be effective strategies to reduce fear of progression. IMPACT: The research aimed to increase our understanding of the relationships among symptom experience, family support, health literacy, and fear of progression. Fear of progression screening should be integrated into the healthcare trajectory of advanced lung cancer patients. The results emphasize that improving symptom management, family support, and health literacy is important to alleviate fear of progression. Further interventions are warranted to relieve fear of progression for advanced lung cancer patients. PATIENT OR PUBLIC CONTRIBUTION: No public or patient involvement.

Selective removal of heavy metals by Zr-based MOFs in wastewater: New acid and amino functionalization strategy.

Zr-based metal-organic frameworks (MOFs) have been developed in recent years to treat heavy metals, e.g. hexavalent chromium Cr6+ pollution, which damages the surrounding ecosystem and threaten human health. This kind of MOF is stable and convenient to prepare, but has the disadvantage of low adsorption capacity, limiting its wide application. To this end, a novel formic acid and amino modified MOFs were prepared, referred to as Form-UiO-66-NH2. Due to the modification of formic acid, its specific surface area, pore size, and crystal size were effectively expanded, and the adsorption capacity of Cr6+ was significantly enhanced. Under optimal conditions, Form-UiO-66-NH2 exhibited an excellent adsorption capacity (338.98 mg/g), ∼10 times higher than that reported for unmodified Zr-based MOFs and most other adsorbents. An in-depth study on the photoelectronic properties and pH confirmed that the adsorption mechanism of Form-UiO-66-NH2 to Cr6+ was electrostatic adsorption. After modification, the improvement of Cr6+ adsorption capacity by Form-UiO-66-NH2 was attributed to the expansion of its specific surface area and the increase in its surface charge. The present study revealed an important finding that Form-UiO-66-NH2 elucidated selective adsorption to Cr6+ in mixed wastewater containing toxic heavy metal ions and common nonmetallic water quality factors. This research provided a new acid and amino functionalization perspective for improving the adsorption capacity of Zr-based MOF adsorbents while simultaneously demonstrating their pertinence to target contaminant adsorption.

Lipid nanoparticle delivery of siRNA targeting Cyp2e1 gene attenuates subacute alcoholic liver injury in mice. / 脂质纳米粒递送靶向Cyp2e1åŸºå› çš„å°å¹²æ‰°RNAå¯å‡è½»å°é¼ äºšæ€¥æ€§é ’ç²¾æ€§è‚æŸä¼¤.

OBJECTIVES: To investigate the effect and mechanism of lipid nanoparticle (LNP) delivery of small interfering RNA (siRNA) targeting Cyp2e1 gene on subacute alcoholic liver injury in mice. METHODS: siRNA targeting Cyp2e1 gene was encapsulated in LNP (si-Cyp2e1 LNP) by microfluidic technique and the resulting LNPs were characterized. The optimal dose of si-Cyp2e1 LNP administration was screened. Forty female C57BL/6N mice were randomly divided into blank control group, model control group, si-Cyp2e1 LNP group, LNP control group and metadoxine group. The subacute alcoholic liver injury mouse model was induced by ethanol feeding for 10 d plus ethanol gavage for the last 3 d. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and the superoxide dismutase (SOD) activity as well as malondialdehyde, reactive oxygen species, glutathione, triacylglycerol, total cholesterol contents in liver tissue were measured in each group, and liver index was calculated. The expression of genes related to oxidative stress, lipid synthesis and inflammation in each group of mice were measured by realtime RT-PCR. RESULTS: Compared with the model control group, the levels of liver index, serum ALT, AST activities, malondialdehyde, reactive oxygen species, triacylglycerol, total cholesterol contents in liver tissue decreased, but the SOD activity as well as glutathione increased in the si-Cyp2e1 LNP group (all P<0.01). Hematoxylin-eosin staining result showed disorganized hepatocytes with sparse cytoplasm and a large number of fat vacuoles and necrosis in the model control group, while the si-Cyp2e1 LNP group had uniformly sized and arranged hepatocytes with normal liver tissue morphology and structure. Oil red O staining result showed si-Cyp2e1 LNP group had lower fat content of the liver compared to the model control group (P<0.01), and no fat droplets accumulated. Anti-F4/80 monoclonal antibody fluorescence immunohistochemistry showed that the si-Cyp2e1 LNP group had lower cumulative optical density values compared to the model control group (P<0.01) and no significant inflammatory reaction. Compared with the model control group, the expression of catalytic genes P47phox, P67phox and Gp91phox were reduced (all P<0.01), while the expression of the antioxidant enzyme genes Sod1, Gsh-rd and Gsh-px were increased (all P<0.01). The mRNA expression of the lipid metabolism genes Pgc-1α and Cpt1 were increased (all P<0.01) and the lipid synthesis-related genes Srebp1c, Acc and Fasn were decreased (all P<0.01); the expression of liver inflammation-related genes Tgf-ß, Tnf-α and Il-6 were decreased (all P<0.01). CONCLUSIONS: The si-Cyp2e1 LNP may attenuate subacute alcoholic liver injury in mice mainly by reducing reactive oxygen levels, increasing antioxidant activity, blocking oxidative stress pathways and reducing ethanol-induced steatosis and inflammation.

Interleukin 35: protective role and mechanism in type 1 diabetes.

Interleukin 35 (IL-35), a cytokine secreted by regulatory T (Treg) cells from the differentiation of conventional CD4+ T cells, is a member of the IL-12 family. The IL-12 family of cytokines exhibits an anti-inflammatory property. IL-35 has recently been shown to influence the immune modulation in various diseases, including inflammatory bowel disease, Graves' disease, rheumatoid arthritis, colitis, psoriasis, and type 1 diabetes (T1D). T1D is an immune-related disease caused by destruction of pancreatic ß cells, characterized by an absolute lack of insulin. Recently, studies have suggested that protective effects of IL-35 work by improving blood glucose levels and preventing an attack of inflammatory factors on the islets. The protective mechanism may be closely related to the anti-inflammatory properties of IL-35, which include regulating macrophage phenotype, suppressing T cell proliferation, decreasing the differentiation of Th17 cells, increasing the Treg cell population, and inducing IL-35-producing regulatory T cells (iTr35). Here, we review the protective effects and mechanisms of action of IL-35 in T1D.

Atomistic Observation of the Local Phase Transition in MoTe2 for Application in Homojunction Photodetectors.

Direct atomic-scale observation of the local phase transition in transition metal dichalcogenides (TMDCs) is critically required to carry out in-depth studies of their atomic structures and electronic features. However, the structural aspects including crystal symmetries tend to be unclear and unintuitive in real-time monitoring of the phase transition process. Herein, by using in situ transmission electron microscopy, information about the phase transition mechanism of MoTe2 from hexagonal structure (2H phase) to monoclinic structure (1T' phase) driven by sublimation of Te atoms after a spike annealing is obtained directly. Furthermore, with the control of Te atom sublimation by modulating the hexagonal boron nitride (h-BN) coverage in the desired area, the lateral 1T'-enriched MoTe2 /2H MoTe2 homojunction can be one-step constructed via an annealing treatment. Owing to the gradient bandgap provided by 1T'-enriched MoTe2 and 2H MoTe2 , the photodetector composed of the 1T'-enriched MoTe2 /2H MoTe2 homojunction shows fast photoresponse and ten times larger photocurrents than that consisting of a pure 2H MoTe2 channel. The study reveals a route to improve the performance of optoelectronic and electronic devices based on TMDCs with both semiconducting and semimetallic phases.

The role of histone chaperone spty2d1 in human colorectal cancer.

Colorectal cancer (CRC) remains a major public health concern, associated with a high rate of morbidity and mortality. Several factors have been implicated in its occurrence and development, which includes histone chaperones. The role of spty2d1 (spt2)-a novel histone chaperone protein-has rarely been investigated in CRC. Therefore, we demonstrated in this study that spt2 undergoes different genetic alterations in colorectal adenocarcinoma datasets and that it was associated with the proliferation of colon carcinoma. Spt2 silencing can reduce the ability of proliferation and increase the rate of apoptosis of LoVo cells. Regarding the overall survival associated with spt2, only the quartile disease-free survival of colon adenocarcinoma (COAD) was found to be statistically significant, while that of rectum adenocarcinoma (READ) was not. The positive (+++) expression of spt2 was correlated with a deeper invasion depth in colorectal adenocarcinoma, and this effect was more pronounced in COAD. These data collectively suggest that spt2 can influence the progression and prognosis in some subtypes of colorectal adenocarcinoma. Therefore, we propose spt2 as a potential target for application in enhancing the overall therapeutic efficacy in some specific subtypes of colorectal adenocarcinoma.

Active mode lock optoelectronic oscillator based on the simulated Brillouin scattering effect.

An active mode-locked optoelectronic oscillator (AML-OEO) based on the simulated Brillouin scattering (SBS) effect without an electrical filter is demonstrated here. By using phase modulation and SBS-based selective sideband amplification, the central frequency of the proposed SBS-AML-OEO is easily adjusted by simply changing the pump laser frequency instead of the filters. A microwave frequency comb signal with an adjustable central frequency and fixed bandwidth are generated by injecting a mode-locking external RF synchronizing with the free spectral ranging FSR. In addition, the harmonic SBS-AML-OEO is also achieved by harmonic signal injection. The proposed method reveals a simple solution to tune the central frequency and has the potential to be integrated on a chip since there is no structure changing in the scheme.