KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements.

Tumours use various strategies to evade immune surveillance1,2. Immunotherapies targeting tumour immune evasion such as immune checkpoint blockade have shown considerable efficacy on multiple cancers3,4 but are ineffective for most patients due to primary or acquired resistance5-7. Recent studies showed that some epigenetic regulators suppress anti-tumour immunity2,8-12, suggesting that epigenetic therapies could boost anti-tumour immune responses and overcome resistance to current immunotherapies. Here we show that, in mouse melanoma models, depletion of KDM5B-an H3K4 demethylase that is critical for melanoma maintenance and drug resistance13-15-induces robust adaptive immune responses and enhances responses to immune checkpoint blockade. Mechanistically, KDM5B recruits the H3K9 methyltransferase SETDB1 to repress endogenous retroelements such as MMVL30 in a demethylase-independent manner. Derepression of these retroelements activates cytosolic RNA-sensing and DNA-sensing pathways and the subsequent type-I interferon response, leading to tumour rejection and induction of immune memory. Our results demonstrate that KDM5B suppresses anti-tumour immunity by epigenetic silencing of retroelements. We therefore reveal roles of KDM5B in heterochromatin regulation and immune evasion in melanoma, opening new paths for the development of KDM5B-targeting and SETDB1-targeting therapies to enhance tumour immunogenicity and overcome immunotherapy resistance.

SDBA: Score Domain-Based Attention for DNA N4-Methylcytosine Site Prediction from Multiperspectives.

In tasks related to DNA sequence classification, choosing the appropriate encoding methods is challenging. Some of the methods encode sequences based on prior knowledge that limits the ability of the model to obtain multiperspective information from the sequences. We introduced a new trainable ensemble method based on the attention mechanism SDBA, which stands for Score Domain-Based Attention. Unlike other methods, we fed the task-independent encoding results into the models and dynamically ensembled features from different perspectives using the SDBA mechanism. This approach allows the model to acquire and weight sequence features voluntarily. SDBA is conceptually general and empirically powerful. It has achieved new state-of-the-art results on the benchmark data sets associated with DNA N4-methylcytosine site prediction.

Temperature Dependent Hydrogen Bond Toward High Emission in an Emerging Indium-Based Perovskite.

Low-dimensional organic-inorganic hybrid perovskites (OIHPs) with broadband emission attract immense scientific interest due to their potential application for the next generation of solid-state lighting. However, due to low exciton utilization, organic cations generally adjust structure rather than contribute the band edge to affect optical properties. Based on this, OIHPs are usually allowed to obtain a low photoluminescence quantum yield (PLQY). Herein, a good charge transfer carrier (p-phenylenediamine, PPDA) as organic cation is rationally employed and a novel indium-based perovskite is synthesized. By coupling with H2 O molecules, a strong interaction between organic and inorganic components is realized by hydrogen bonding, which has good transportability and greatly improves the exciton utilization. The regions of hydrogen bonding show high electron mobility, combined with the induced recombination center, improving the progress of charge relaxation. As a result, the regulation of hydrogen bond strength based on the microstructure optimization directly determines the optical emission intensity, realizing nearly 100% PLQY. Further, the polyhydrogen bond structure makes each component a stronger interaction, showing high stability in polar, organic, and acidic solvent, as well as long-term storing, which represents one of the highest overall performances for lighting in OIHPs.

Highly efficient electroluminescence from SnO2 nanocrystals and Er3+ co-doped silica thin film via introducing Ca2.

Efficient and stable near-infrared silicon-based light source is a challenge for future optoelectronic integration and interconnection. In this paper, alkaline earth metal Ca2+ doped SiO2-SnO2: Er3+ films were prepared by sol-gel method. The oxygen vacancies introduced by the doped Ca2+ significantly increase the near-infrared luminescence intensity of Er3+ ions. It was found that the doping concentration of Sn precursors not only modulate the crystallinity of SnO2 nanocrystals but also enhance the luminescence performance of Er3+ ions. The stable electroluminescent devices based on SiO2-SnO2: Er3+/Ca2+ films exhibit the power efficiency as high as 1.04×10-2 with the external quantum efficiency exceeding 10%.

Silver(I)-Catalyzed Tandem Reaction of Enynones and 4-Alkenyl Isoxazoles: Synthesis of 2-(Furan-2-yl)-1,2-dihydropyridines.

Silver(I)-catalyzed tandem reaction of enynones with 4-alkenyl isoxazoles provides access to 2-(furan-2-yl)-1,2-dihydropyridines. No competitive cyclopropanation of alkenes and O-H insertion via (2-furyl)carbene complexes were observed. The cascade reaction proceeds via the formation of (2-furyl)metal carbene intermediate, the N-O bond cleavage of 4-alkenyl isoxazoles/rearrangement, subsequent 6π electrocyclic reaction, and [1,5] H-shift. The successive construction of both 1,2-dihydropyridine skeleton and furan frame has been achieved in the one-pot reaction. A broad range of readily available enynones and 4-alkenyl isoxazoles are suitable to this protocol; however, when R3 is the alkyl group such as n-Bu and Me, a complicated mixture was generated without the desired products. In addition, in the case of R4 = bulky group such as R3'SiOCH2, the reaction gave an in situ oxo-product of (2-furyl)silver carbene. An atom-economic strategy for the synthesis of 2-(furan-2-yl)-1,2-dihydropyridines has been established.

Experimental observations on metal-like carrier transport and Mott hopping conduction behaviours in boron-doped Si nanocrystal multilayers.

Studies on the carrier transport characteristics of semiconductor nanomaterials are the important and interesting issues which are helpful for developing the next generation of optoelectronic devices. In this work, we fabricate B-doped Si nanocrystals/SiO2multilayers by plasma enhanced chemical vapor deposition with subsequent high temperature annealing. The electronic transport behaviors are studied via Hall measurements within a wide temperature range (30-660 K). It is found that when the temperature is above 300 K, all the B-doped Si nanocrystals with the size near 4.0 nm exhibit the semiconductor-like conduction characteristics, while the conduction of Si nanocrystals with large size near 7.0 nm transforms from semiconductor-like to metal-like at high B-doping ratios. The critical carrier concentration of conduction transition can reach as high as 2.2 × 1020cm-3, which is significantly higher than that of bulk counterpart and may be even higher for the smaller Si nanocrystals. Meanwhile, the Mott variable-range hopping dominates the carrier transport when the temperature is below 100 K. The localization radius of carriers can be regulated by the B-doping ratios and Si NCs size, which is contributed to the metallic insulator transition.

Alkaline earth metal ion doping to enhance the light emission from Er3+:SnO2 nanocrystal Co-doped silica films.

Alkaline earth metal ions (Mg2+, Ca2+, Sr2+) have been introduced into Er3+:SnO2 nanocrystal co-doped silica thin films fabricated by a sol-gel method combined with a spin-coating technique. It is found that the incorporation of alkaline earth metal ions can enhance the light emission from Er3+ at the wavelength around 1540 nm and the strongest enhancement is observed in samples doped with 5 mol% Sr2+ ions. Based on X-ray diffraction, X-ray photoelectron spectroscopy and other spectroscopic measurements, the improved light emission can be attributed to more oxygen vacancies, better crystallinity and a stronger cross-relaxation process with the introduction of alkaline earth metal ions.

Predicting COVID-19 vaccination intentions: the roles of threat appraisal, coping appraisal, subjective norms, and negative affect.

BACKGROUND: As a new disease, communities possess little natural immunity to COVID-19 and vaccines are considered critical to preventing and reducing the incidence of severe illness. This study, inspired by Protection Motivation Theory (PMT), examines the relationship between citizens' threat appraisal, coping appraisal, subjective norms, negative affect, and their COVID-19 vaccination intentions. METHODS: A sample of 340 citizens from two main cities in Mainland China, Xi'an and Wuxi, was used for data analysis. Structural Equation Modeling (SEM) was employed with latent and observed variables to test hypotheses. Data were analyzed using AMOS 24.0. RESULTS: Several findings extend current understanding. Firstly, our proposed model explains 73% of the variance in vaccination intentions. Secondly, perceived severity only indirectly shapes COVID-19 vaccination intentions through negative affect. Thirdly, negative affect and response costs are negatively related to COVID-19 vaccination intentions. Finally, Perceived probability, subjective norms, response efficacy and self-efficacy are positively related to COVID-19 vaccination intentions; among them, self-efficacy contributes the most, followed by response efficacy and subjective norms, and lastly perceived probability. CONCLUSION: Theoretically, this study increases current understanding about subjective norms and affective responses. We provoke a certain amount of thought about the role of affect response in relation to threat appraisal and vaccination intentions. Specifically, governments must be vigilant that citizens' negative affect, such as fear, may cause vaccine hesitation.

Enhanced subband light emission from Si quantum dots/SiO2 multilayers via phosphorus and boron co-doping.

Seeking light sources from Si-based materials with an emission wavelength meeting the requirements of optical telecommunication is a challenge nowadays. It was found that the subband emission centered near 1200 nm can be achieved in phosphorus-doped Si quantum dots/SiO2 multilayers. In this work, we propose the phosphorus/boron co-doping in Si quantum dots/SiO2 multilayers to enhance the subband light emission. By increasing the B co-doping ratio, the emission intensity is first increased and then decreased, while the strongest integrated emission intensity is almost two orders of magnitude stronger than that of P solely-doped sample. The enhanced subband light emission in co-doped samples can be attributed to the passivation of surface dangling bonds by B dopants. At high B co-doping ratios, the samples transfer to p-type and the subband light emission from phosphorus-related deep level is suppressed but the emission centered around 1400 nm is appeared.

Prediction of drug resistance profile of multidrug-resistant Mycobacterium tuberculosis (MDR-MTB) isolates from newly diagnosed case by whole genome sequencing (WGS): a study from a high tuberculosis burden country.

OBJECTIVES: Our aim was to assess the ability of the Whole-genome sequencing (WGS) in predicting drug resistance profile of multidrug-resistant mycobacterium tuberculosis (MDR-MTB) from newly diagnosed cases in China. METHODS: We validated the Phenotypic drug Sensitivity Test (pDST) for 12 anti-tuberculosis drugs using the Bactec MGIT 960 system. We described the characteristics of the isolates enrolled and compared the pDST results with resistance profiles predicted by WGS. RESULTS: The pDST showed that of the 43 isolates enrolled, 25.6% were sensitive to rifabutin (RFB); 97.7%、97.7%、93.0% and 93.0% were sensitive to cycloserine (Cs), amikacin/kanamycin (Ak/Km), para-aminosalicylic acid (Pas) and ethionamide Eto), respectively; 18.6% were resistant to fluoroquinolones (FQs) or second-line injections. Genotype DST determined by WGS of Ak/Km、Eto and RFP reached high consistency to 97.7% compared with pDST, followed by moxifloxacin (Mfx) 95.3%, levofloxaci (Lfx) and Pas 93%, streptomycin (Sm) 90.3%. The genotype DST of RFB and EMB showed low consistency with the pDST of 67.2 and 79.1%. WGS also detected 27.9% isolates of pyrazinamide(PZA)-related drug-resistant mutation. No mutations associated with linezolid (Lzd), bedaquiline (Bdq) and clofazimine (Cfz) were detectd. CONCLUSIONS: WGS has the potential to infer resistance profiles without time-consuming phenotypic methods, which could be provide a basis to formulate reasonable treatment in high TB burden areas.

Enhanced upconversion red light emission of TiO2:Yb,Er thin film via Mn doping.

TiO2:Yb,Er films with different concentrations of Mn2+ are grown on SiO2 glass substrates by pulsed laser deposition. It is found that the introduction of Mn2+ enhanced the intensity of upconversion emission. In particular, TiO2:Yb,Er thin film with 5% Mn2+ ions exhibits the brightest upconversion emission. The upconversion red emission intensity is increased by 2.5-fold than that of a TiO2:Yb,Er thin film without Mn2+ ions, which is ascribed to the multi-photon absorption and efficient exchange-energy transfer process between Er3+ and Mn2+. The high transmittance and good conductivity of the films made them possible to act as electron transport layer in solar cells.

AgOTf/I2-Mediated Cyclization/Cross-Coupling/Isomerization of Enynones with Phosphorus Ylides: An Expedient Route to Stereoselective Synthesis of (E)-2-Alkenylfurans.

Ag(I)-catalyzed cascade reactions involving enynone cyclization and cross-coupling with phosphorus ylides have been achieved for the first time. Subsequent treatment of the reaction mixture with I2 afforded the corresponding (E)-α-alkenylfurans in 73-95% yields with excellent stereoselectively. A reasonable mechanism has been proposed.

Transmission of multidrug-resistant tuberculosis in Shimen community in Shanghai, China: a molecular epidemiology study.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) has become a major public health problem in China, with mounting evidence suggesting that recent transmission accounts for the majority of MDR-TB. Here we aimed to reveal the transmission pattern of an MDR-TB outbreak in the Jing'an District of Shanghai between 2010 and 2015. METHODS: We used whole-genome sequencing (WGS) to conduct genomic clustering analysis along with field epidemiological investigation to determine the transmission pattern and drug resistance profile of a cluster with ten MDR-TB patients in combining field epidemiological investigation. RESULTS: The ten MDR-TB patients with genotypically clustered Beijing lineage strains lived in a densely populated, old alley with direct or indirect contact history. The analysis of genomic data showed that the genetic distances of the ten strains (excluding drug-resistant mutations) were 0-20 single nucleotide polymorphisms (SNPs), with an average distance of 9 SNPs, suggesting that the ten MDR-TB patients were infected and developed the onset of illness by the recent transmission of M. tuberculosis. The genetic analysis confirmed definite epidemiological links between the clustered cases. CONCLUSIONS: The integration of the genotyping tool in routine tuberculosis surveillance can play a substantial role in the detection of MDR-TB transmission events. The leverage of genomic analysis in combination with the epidemiological investigation could further elucidate transmission patterns. Whole-genome sequencing could be integrated into intensive case-finding strategies to identify missed cases of MDR-TB and strengthen efforts to interrupt transmission.

Multiple channels to enhance near-infrared emission from SiO2-SnO2:Er3+ films by Ba2+ ion doping.

Ba2+ ions co-doped SiO2-SnO2:Er3+ thin films are prepared using a sol-gel method combined with a spin-coating technique and post-annealing treatment. The influence of Ba2+ ion doping on the photoluminescence properties of thin films is carefully investigated. The enhancement of near-infrared (NIR) emission of Er3+ ions by as much as 12 times is obtained via co-doping with Ba2+ ions. To illustrate the relevant mechanisms, X-ray diffraction, X-ray photoelectron spectroscopy and comprehensive spectroscopic measurements are carried out. The enhanced NIR emission induced by Ba2+ co-doping can be explained by more oxygen vacancies, improved crystallinity and strong cross-relaxation processes between Er3+ ions. The incorporation of Ba2+ ions into SiO2-SnO2:Er3+ thin films results in a considerable enhancement in the NIR emission, making the thin films more suitable for Si-based optical lasers and amplifiers.

LncRNA OIP5-AS1 inhibits ferroptosis in prostate cancer with long-term cadmium exposure through miR-128-3p/SLC7A11 signaling.

Previous studies suggest that cadmium (Cd) is one of the causative factors of prostate cancer (PCa), but the effect of chronic Cd exposure on PCa progression remains unclear. Besides, whether long noncoding RNAs (lncRNAs) are involved in the regulation of prolonged exposure to Cd in PCa needs to be elucidated. In the present study, we found that the serum concentration of Cd in PCa patients was positively correlated with the Gleason score and tumor-node-metastasis (TNM) classification. To simulate chronic Cd exposure in PCa, we subjected PC3 and DU145 cells to long-term, low-dose Cd exposure and further examined tumor behavior. Functional studies identified that chronic Cd exposure promoted cell growth and ferroptosis resistance in vitro and in vivo. Furthermore, we found that lncRNA OIP5-AS1 expression was greatly elevated in PC3 and DU145 cells upon chronic Cd exposure. Dysregulation of OIP5-AS1 expression mediated cell growth and Cd-induced ferroptosis. Mechanistically, we demonstrated that OIP5-AS1 served as an endogenous sponge of miR-128-3p to regulate the expression of SLC7A11, a surrogate marker of ferroptosis. Moreover, miR-128-3p decreased cell viability by enhancing ferroptosis. Taken together, our data indicate that lncRNA OIP5-AS1 promotes PCa progression and ferroptosis resistance through miR-128-3p/SLC7A11 signaling.

Low power consumption light emitting device containing TiO2:Er3+ thin film prepared by sol-gel method.

Er3+ ions doped titanium dioxide (TiO2) thin films have been prepared by sol-gel method. The photoluminescence both in visible light range (510-580 nm and 640-690 nm) and near infrared light range (1400-1700nm) have been observed. The photoluminescence excitation spectra demonstrate that energy transfer from wide band-gap TiO2 to Er3+ ions causes the infrared light emission. It is also found that the post annealing temperature can influence the luminescence intensity significantly. Based on sol-gel prepared TiO2:Er3+ thin films, we fabricate light emitting device containing ITO/TiO2:Er3+/SiO2/n+-Si/Al structure. Both the visible and near infrared electroluminescence (EL) can be detected under the operation voltage as low as 5.6 V and the working current of 0.66 mA, which shows the lower power consumption compared with the conventional EL devices.

Plasmon-enhanced upconversion luminescence in pyrochlore phase Yb x Er2-x Ti2O7 thin film.

Pyrochlore phase Yb x Er2-x Ti2O7 (YETO) thin films have been prepared by employing a facile sol-gel method combining with spin-coating technique and post-annealing treatment at 700 °C. High concentration of Yb3+ ions can promote the transformation from Yb3+/Er3+ co-doped anatase phase TiO2 to pyrochlore phase YETO at 700 °C temperature. We find that the YETO thin film with 30 mol% Yb3+ ions exhibits the brightest upconversion (UC) emission. Moreover, the introduction of Au nanorods (Au NRs) in the YETO thin film can further enhance the UC fluorescence. By adjusting the density of Au NRs, the UC emission intensity is increased by about 2.8-fold due to the excitation field enhancement caused by the localized surface plasmon resonance effect.

Isolation of Mycobacterium arupense from pleural effusion: culprit or not?

BACKGROUND: Mycobacterium arupense, first identified in 2006, is a slow-growing nontuberculous mycobacterium (NTM) and an emerging cause of tenosynovitis, potentially associated with immunosuppression. However, unlike the diagnostic value of its isolation from osteoarticular specimens, the significance of detecting M. arupense in respiratory specimens is not yet clear. CASE PRESENTATION: To our knowledge, we, for the first time, described the identification of M. arupense from the pleural effusion of an immunocompetent patient, who presented with fever and chylothorax. The symptoms resolved with doxycycline treatment for 45 days and a low-fat, high-protein diet. Follow-up at 14 months showed no relapse. CONCLUSIONS: Because the patient fully recovered without combined anti-NTM treatment, we did not consider M. arupense the etiological cause in this case. This indicates that M. arupense detected in pleural effusion is not necessarily a causative agent and careful interpretation is needed in terms of its clinical relevance.

[Assessing the dietary nutritional status of Uygur adult residents of Kashi region in Xinjiang using diet balance index].

OBJECTIVE: To evaluate the overall diet quality and diet structure condition of Uygur adult residents of Kashi region in Xinjiang using diet balance index( DBI-07). METHODS: Using stratified random cluster sampling method, choose 1604 Uygur residents with a dietary survey of the 24-hour dietary recall method for 3 consecutive days and analyzed by the method of diet balance index. RESULTS: 75. 0% of Uygur residents of Kashi region in Xinjiang had moderate degree of unbalanced dietary quality( DQD = 33. 77), 74. 4% of them had a moderate deficiencies of intake( LBS = 26. 43) and 48. 2% of them had a low intake of excessive( HBS = 7. 34). The degree of unbalanced dietary quality and deficiencies of intake and diet excessive in the countryside were higher than in the city. Whether in the cities or the countryside, male had a higher level of dietary excessive and imbalance than female( P < 0. 05), there was no statistical significance in different ages in the city, but there was a statistically significant difference in the countryside( P < 0. 05). The degree of diet excessive in 18-44 age groups was higher than other age groups, the degree of diet deficiencies in 18-44 age groups was lower than other age groups. The higher the degree of education was in the cities, the higher the degree of diet excessive was, and the lower the degree of diet deficiencies was. Dietary pattern of Uygur residents of Kashi region in Xinjiang were the Pattern A, B, D and E, the major dietary pattern was the pattern B, which occupied 77. 0% of the total population. The intakes of vegetables and fruits, milk, beans and eggs were insufficient, especially milk and beans, and intakes of cereal, edible oil and salt were excessive. CONCLUSION: The DBI-07 method is well evaluated the dietary condition and existing problems of Uygur residents. So it is essential to improve the consciousness of Uygur residents about balanced diet with effective interventions for different populations.

Multi-scenario investment forecast of new energy projects based on multiple linear regression and comprehensive evaluation model of differentiated project priorities.

As China's resource shortage and environmental pollution intensify, the demand for new energy and electric energy substitution is becoming higher and higher. Accurately predicting the investment scale of China's new energy projects is of great practical significance for improving the efficiency of resource allocation and economically meeting energy demand. This paper builds a scientific and precise investment model for new energy projects from both macro and micro perspectives. First, from a macro perspective, considering macro indicators such as the external environment and internal economy, an annual total investment forecast model based on multiple linear regression is constructed, in order to predict the annual total investment scale of new energy investment entities and achieve preliminary accurate investment; second, designed the evaluation index system of different project priorities from three perspectives of external environment, internal development of enterprises and social development, and constructed the comprehensive weight design method based on AN-EWM and the comprehensive evaluation method of TOPSIS, in order to realize the priority of differentiated projects. Sorting; finally, a new energy project located in a city in northern China is selected as the research subject, and a multi-scenario example analysis is carried out. The results show that the new energy project investment scale index system constructed in this paper can effectively evaluate the investment capacity of the main body of the new energy project, and can better predict the total investment of the new energy investment project, so that the deviation rate can be controlled within 5 %, and the priority evaluation model constructed in this paper can provide a complete calculation method and a reference method for the judgement of the investment priority, which can promote accurate investment.