tRNA-m1A modification promotes T cell expansion via efficient MYC protein synthesis.

Naive T cells undergo radical changes during the transition from dormant to hyperactive states upon activation, which necessitates de novo protein production via transcription and translation. However, the mechanism whereby T cells globally promote translation remains largely unknown. Here, we show that on exit from quiescence, T cells upregulate transfer RNA (tRNA) m1A58 'writer' proteins TRMT61A and TRMT6, which confer m1A58 RNA modification on a specific subset of early expressed tRNAs. These m1A-modified early tRNAs enhance translation efficiency, enabling rapid and necessary synthesis of MYC and of a specific group of key functional proteins. The MYC protein then guides the exit of naive T cells from a quiescent state into a proliferative state and promotes rapid T cell expansion after activation. Conditional deletion of the Trmt61a gene in mouse CD4+ T cells causes MYC protein deficiency and cell cycle arrest, disrupts T cell expansion upon cognate antigen stimulation and alleviates colitis in a mouse adoptive transfer colitis model. Our study elucidates for the first time, to our knowledge, the in vivo physiological roles of tRNA-m1A58 modification in T cell-mediated pathogenesis and reveals a new mechanism of tRNA-m1A58-controlled T cell homeostasis and signal-dependent translational control of specific key proteins.

Metformin mitigates adipogenesis of fibro-adipogenic progenitors after rotator cuff tears via activating mTOR/ULK1-mediated autophagy.

Muscular fatty infiltration is a common issue after rotator cuff tears (RCTs), which impair shoulder function. Females suffer a higher prevalence and a more severe degree of muscular fatty infiltration after RCT when compared with males, with the underlying mechanisms remaining unclear. Fibro-adipogenic progenitors (FAPs) are the primary source of muscular fatty infiltration following RCT. Our findings disclose that gender-specific disparities in muscular fatty infiltration are linked to mTOR/ULK1-mediated autophagy of FAPs. Decreased autophagic activity contributes to adipogenic differentiation in female FAPs after RCT. Furthermore, metformin could enhance mTOR/ULK1-mediated autophagic processes of FAPs, thereby alleviating fatty infiltration and improving shoulder functionality after RCT. Together, our study reveals that gender differences in muscular fatty infiltration arise from distinct autophagic activities. Metformin could be a promising noninvasive intervention to ameliorate muscular fatty infiltration of RCT.NEW & NOTEWORTHY The current study demonstrated that gender-specific disparities in muscular fatty infiltration are attributed to mTOR/ULK1-mediated autophagy of FAPs. Decreased autophagic activity contributes to adipogenic differentiation in female FAPs after RCT. Moreover, metformin could enhance mTOR/ULK1-mediated autophagic processes of FAPs, thereby alleviating fatty infiltration and improving shoulder functionality after RCT. Therefore, metformin could be a promising noninvasive intervention to ameliorate muscular fatty infiltration of RCT.

Coregulation of Li/Li+ Spatial Distribution by Electric Field Gradient with Homogenized Li-Ion Flux for Dendrite-Free Li Metal Anodes.

Lithium (Li) metal batteries are highly sought after for their exceptional energy density. However, their practical implementation is impeded by the formation of dendrites and significant volume fluctuations in Li, which stem from the uneven distribution of Li-ions and uncontrolled deposition of Li on the current collector. Here, an amino-functionalized reduced graphene oxide covered with polyacrylonitrile (PrGN) film with an electric field gradient structure is prepared to deal with such difficulties. This novel current collector serves to stabilize Li-metal anodes by regulating Li-ion flux through vertically aligned channels formed by porous polyacrylonitrile (PAN). Moreover, the amino-functionalized reduced graphene oxide (rGN) acts as a three-dimensional (3D) host, reducing nucleation overpotential and accommodating volume expansion during cycling. The combination of the insulating PAN and conducting rGN creates an electric field gradient that promotes a bottom-up mode of Li electrodeposition and safeguards the anode from interfacial parasitic reactions. Consequently, the electrodes exhibit exceptional cycle life with stable voltage profiles and minimal hysteresis under high current densities and large areal capacities.

All-solid highly sensitive fiber-tip magnetic field sensor based on a Fabry-Perot interferometer with a breakpoint structure.

An all-solid fiber-tip Fabry-Perot interferometer (FPI) coated with a nickel film is proposed and experimentally verified for magnetic field sensing with high sensitivity. It is fabricated by splicing a segment of a thin-wall capillary tube to a standard single-mode fiber (SMF), then inserting a tiny segment of fiber with a smaller diameter into the capillary tube, and creating an ultra-narrow air-gap at the SMF end to form an FPI. When the device is exposed to magnetic field, the capillary tube is strained due to the magnetostrictive effect of the nickel film coated on its outer surface. In addition, owing to the unique breakpoint sensitivity-enhancement structure of the air-gap FPI, the elongation of the capillary tube whose length is over 100 times longer than the air-gap width is entirely transferred to the cavity length change of the FPI, and the sensor is extremely sensitive to the magnetic field as proved by our experiments, achieving a high sensitivity of up to 2.236 nm/mT for a linear magnetic field range from 40 to 60 mT, as well as a low-temperature cross-sensitivity of 56 µT/°C. The all-solid stable structure, compact size (total length of ∼3.0 mm), and reflective working mode with high magnetic field sensitivity indicate that this sensor has good application prospects.

Lithium Exposure and Risk of Major Neurocognitive Disorders: A Systematic Review and Meta-analysis.

BACKGROUND: Published studies on the association between lithium use and the decreased risk of major neurocognitive disorders (MNCDs) have shown disparities in their conclusions. We aimed to provide updated evidence of this association. METHODS: A comprehensive literature search was performed in PubMed, EMBASE, and Cochrane Library from inception until August 31, 2023. All the observational studies evaluating the association between lithium use and MNCD risk were eligible for inclusion. Pooled odds ratios (ORs) and 95% prediction intervals were computed using random-effects models. RESULTS: Eight studies with 377,060 subjects were included in the analysis. In the general population on the association between lithium use versus nonuse and dementia, the OR was 0.94 (95% confidence interval [CI] = 0.77-1.24). Further analysis also demonstrated that lithium use was not associated with an increased risk of Alzheimer's disease (OR = 0.69, 95% CI: 0.31-1.65). When the analysis was restricted to individuals with bipolar disorder to reduce the confounding by clinical indication, lithium exposure was also not associated with a decreased risk of MNCD (OR = 0.9, 95% CI = 0.71-1.15). CONCLUSION: The results of this systematic review and meta-analysis do not support a significant association between lithium use and the risk of MNCD.

Efficacy and safety of intratonsillar immunotherapy for allergic rhinitis: A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: A lower adherence rate existed in patients receiving allergen-specific immunotherapy due to its lengthy period and adverse effects even though it is the only curative treatment for IgE-mediated allergies. Therefore, exploring innovative allergen-specific immunotherapy routes is necessary. OBJECTIVE: To explore the efficacy and safety of the intratonsillar injection of house dust mite (HDM) extract in patients with HDM-induced allergic rhinitis (AR). METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 80 patients with HDM-induced AR were randomized to receive 6 intratonsillar injections with HDM extract or placebo in 3 months. The total nasal symptom score (TNSS), visual analogue scale of nasal symptoms, combined symptom and medication score, mini rhinoconjunctivitis quality of life questionnaire, and serum allergen-specific IgG4 to Dermatophagoides pteronyssinus were all monitored at baseline and 3 months, 6 months, and 12 months after the treatment was finished. The intent-to-treat and per-protocol set (PPS) are both analyzed. RESULTS: The primary end points TNSS and ΔTNSS were improved significantly at 3 months after the patients with AR finished a 3-month 6-injection intratonsillar immunotherapy compared with those in the placebo treatment in both intent-to-treat and PPS. Results of visual analogue scale, combined symptom and medication score, and mini rhinoconjunctivitis quality of life questionnaire were also improved significantly at 3 months after the treatment in PPS. However, the improvement effect of intratonsillar immunotherapy at 6 and 12 months was limited and uncertain based on the data. The increase of serum Der p IgG4 in the active group was significantly higher than that in the placebo group at 3, 6, and 12 months after the treatment was finished. Adverse events were monitored, and no systemic adverse reactions were observed. CONCLUSION: The clinical trial revealed that intratonsillar injection with HDM extract was safe and effective in patients with AR. Optimizing the protocol and allergen formulations is expected to increase and maintain the efficacy of this novel approach. TRIAL REGISTRATION: https://www.chictr.org.cn/index.html, identifier: ChiCTR-TRC-13003600.

Pseudopyrolysis of Metal-Organic Frameworks: A Synchronous Nucleation Mechanism to Synthesize Ultrafine Metal Compound Nanoparticles.

Metal-Organic frameworks (MOFs) are increasingly being investigated for the synthesis of carbon-supported metal-based ultrafine nanoparticles (UNPs). However, the collapse of the carbon framework and aggregation of metal particles in the pyrolysis process have severely hindered their stability and applications. Here, we report the synchronous nucleation pseudopyrolysis of MOFs to confine Fe/FeOx UNPs in intact porous carbon nanorods (IPCNs), revealed by in situ transmission electron microscopy experiments and ex situ structure analysis. The pseudopyrolysis mechanism enables strong physical and chemical confinement effects between UNPs and carbon by moderate thermal kinetics and abundant oxygen defects. Further, this strong confinement is greatly beneficial for subsequent chemical transformations to obtain different Fe-based UNPs and excellent electrochemical performance. As a proof of concept, the as-prepared FeSe UNPs in IPCNs show superior lithium storage performance with an ultrahigh and stable capacity of 815.1 mAh g-1 at 0.1 A g -1 and 379.7 mAh g-1 at 5 A g-1 for 1000 cycles.

[Analysis of genetic etiology in a patient with 1p36 deletion syndrome in conjunct with Snijders Blok-Campeau syndrome].

OBJECTIVE: To explore the genetic basis for a patient with unexplained developmental delay and special facial features. METHODS: A male patient admitted to the Maternal and Child Health Care Hospital of Gansu Province on May 27, 2021 due to infertility was selected as the study subject. Clinical data of the patient was collected, and genomic DNA was extracted from peripheral blood samples from the patient and his parents. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing. RESULTS: The patient was found to harbor a 2.54 Mb deletion in 1p36.33p36.32 and a heterozygous c.1123G>C (p.E375Q) variant of the CHD3 gene, neither of which was detected in his parents. CONCLUSION: The patient was diagnosed with Snijders Blok-Campeau syndrome in conjunct with 1p36 deletion syndrome, which has enabled genetic counseling for his family.

Mitochondrial transplantation attenuates traumatic neuropathic pain, neuroinflammation, and apoptosis in rats with nerve root ligation.

Traumatic neuropathic pain (TNP) is caused by traumatic damage to the somatosensory system and induces the presentation of allodynia and hyperalgesia. Mitochondrial dysfunction, neuroinflammation, and apoptosis are hallmarks in the pathogenesis of TNP. Recently, mitochondria-based therapy has emerged as a potential therapeutic intervention for diseases related to mitochondrial dysfunction. However, the therapeutic effectiveness of mitochondrial transplantation (MT) on TNP has rarely been investigated. Here, we validated the efficacy of MT in treating TNP. Both in vivo and in vitro TNP models by conducting an L5 spinal nerve ligation in rats and exposing the primary dorsal root ganglion (DRG) neurons to capsaicin, respectively, were applied in this study. The MT was operated by administrating 100 µg of soleus-derived allogeneic mitochondria into the ipsilateral L5 DRG in vivo and the culture medium in vitro. Results showed that the viable transplanted mitochondria migrated into the rats' spinal cord and sciatic nerve. MT alleviated the nerve ligation-induced mechanical and thermal pain hypersensitivity. The nerve ligation-induced glial activation and the expression of pro-inflammatory cytokines and apoptotic markers in the spinal cord were also repressed by MT. Consistently, exogenous mitochondria reversed the capsaicin-induced reduction of mitochondrial membrane potential and expression of pro-inflammatory cytokines and apoptotic markers in the primary DRG neurons in vitro. Our findings suggest that MT mitigates the spinal nerve ligation-induced apoptosis and neuroinflammation, potentially playing a role in providing neuroprotection against TNP.

HDAC Downregulation of Xiaoqinglong Decoction in the Treatment of Allergic Rhinitis.

INTRODUCTION: As one of the most common allergic diseases, allergic rhinitis (AR) has attracted wide attention all over the world. More appropriate treatment of AR should be explored thoroughly. In recent years, traditional Chinese medicine has attracted more attention in AR treatment. As a classical Chinese medicine prescription, Xiaoqinglong decoction (XQLD) has been commonly used in treating AR. Even though its therapeutic effect on AR has been clinically confirmed, more molecular mechanism remains to be further investigated. Our research aimed to investigate the therapeutic mechanism of XQLD for AR management. METHODS: The study was evaluated in an ovalbumin sensitized mouse model and liquid chromatography-mass spectrometry was adopted to test the stability of XQLD's effective components. RESULTS: The results confirmed the stability and safety of the effective components of XQLD. XQLD significantly downregulated the expression of HDACs (HDAC1, HDAC3, and HDAC4) and Th2 inflammatory factors (IL4, IL5, and IL13) in AR mice. XQLD and the HDAC inhibitor JNJ-26481585 promoted the expression of epithelial tight junction proteins (claudin-1 and ZO-1) and decreased the expression of mucins (Muc5ac and Muc5b) in the nasal mucosa of AR mice. CONCLUSIONS: In conclusion, our findings present the beneficial effects of XQLD on AR and recovery of the nasal epithelium. We also identify the decreased HDAC as a potential target of XQLD for AR treatment. This study provides an important experimental proof for elucidating the therapeutic mechanism of XQLD.

Early Identification of Pathologic Complete Response to Neoadjuvant Chemotherapy Using Multiphase DCE-MRI by Siamese Network in Breast Cancer: A Longitudinal Multicenter Study.

BACKGROUND: Siamese network (SN) using longitudinal DCE-MRI for pathologic complete response (pCR) identification lack a unified approach to phases selection. PURPOSE: To identify pCR in early-stage NAC, using SN with longitudinal DCE-MRI and introducing IPS for phases selection. STUDY TYPE: Multicenter, longitudinal. POPULATION: Center A: 162 female patients (50.63 ± 8.41 years) divided 7:3 into training and internal validation cohorts. Center B: 61 female patients (50.08 ± 7.82 years) were used as an external validation cohort. FIELD STRENGTH/SEQUENCE: Center A: single vendor 3.0 T with a compressed-sensing volume interpolated breath-hold examination sequence. Center B: single vendor 1.5 T with volume interpolated breath-hold examination sequence. ASSESSMENT: Patients underwent DCE-MRI before and after two NAC cycles, with tumor regions of interest (ROI) manually delineated. Histopathology was the reference for pCR identification. Models developed included a clinical one, four SN models based on IPS-selected phases, and integrated models combining clinical and SN features. STATISTICAL TESTS: Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). The DeLong test was used to compare AUCs. Net reclassification improvement and integrated discrimination improvement (IDI) tests were employed for performance comparison. P < 0.05 was considered significant. RESULTS: In internal and external validation cohorts, the clinical model showed AUCs of 0.760 and 0.718. SN and integrated models, with increasing phases via IPS, achieved AUCs ranging from 0.813 to 0.951 and 0.818 to 0.922. Notably, SN-3 and integrated-3 and integrated-4 outperformed the clinical model. However, input phases beyond 20% did not significantly enhance performance (IDI test: SN-4 vs. SN-3, P = 0.314 and 0.630; integrated-4 vs. integrated-3, P = 0.785 and 0.709). DATA CONCLUSION: The longitudinal multiphase DCE-MRI based on the SN demonstrates promise for identifying pCR in breast cancer. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 4.

Development of composite optical waveguide based on azobenzene-modified titanium metal-organic framework film for study of gas adsorption kinetics.

This study investigates the fabrication and gas adsorption kinetics of an azobenzene (AZB)-modified titanium metal-organic framework (AZB@Ti-MOF) film composite optical waveguide (COWG) that recognizes ethylenediamine (EDA) gas. After modification with AZB, the surface of the Ti-MOF film became rough and evolved from a hemispherical structure to a petal-like structure; a large pore size and small specific surface area accompanied the evolution of the surface morphology. The AZB@Ti-MOF film COWG exhibited a positive response to EDA gas co-existing with the same concentration (1000 ppm) of benzenes, amines, and acidic gases. It is postulated that charge transfer occurs when the AZB@Ti-MOF film COWG adsorbs EDA gas, leading to significant strengthening of the intramolecular hydrogen bonds as EDA works as an electron donor. Incomplete or prolonged EDA desorption from the film surface at room temperature resulted in a decrease in the surface sensitivity of the COWG AZB@Ti-MOF film. The kinetics of EDA adsorption were examined using pseudo-first-order and pseudo-second-order (PSO) kinetic models. The EDA adsorption kinetics fit well with the PSO model. As measured at room temperature, the adsorption capacity (qe) per unit surface of the AZB@Ti-MOF films was 46.50 × 10-2 µg·cm-2.

Diet therapy in patients with rare diseases: a scoping review.

BACKGROUND: This scoping review presents existing research evidence regarding diet therapy in patients with rare diseases (RDs). METHODS: Using the five-stage scoping review framework proposed by Arksey, O'Malley and Levac, we searched the published literature in PubMed, Web of Science, Royal Society of Chemistry, China National Knowledge Infrastructure, VIP Database and Wan Fang Database from January 2010 to November 2022. We selected diet therapy studies on 121 RDs, as categorised by the National Health Commission of China in 2018. Charts for research analysis were developed and used to categorise the data. RESULTS: We ultimately included 34 diet therapy studies from 19 countries and territories for 10 RDs and 3 RD groups. RD diet therapy studies have mainly focused on inborn errors of metabolism (92.3%) and are common in Western countries. Most studies focused on diet therapy methods for RDs (44%). In addition, 29% of studies included diet therapy management, 15% included guidelines for diet therapy and 12% included the impact of diet therapy on patients. CONCLUSIONS: Current diet therapies for RDs lack specificity and present with limited characteristics. Therefore, it is necessary to expand the scope and depth of future research and explore evidence-based recommendations and new diet therapies focused on patient needs and family support to provide a reference for improving the efficacy and safety of diet therapies for RDs.

Orbital Reconstruction in Le Fort III Fractures.

BACKGROUND: Few quantitative results are reported about the surgical effect of orbital reconstruction in Le Fort III fractures. The authors' team proposed an ordered surgery method which was effective for Le Fort III fractures. The aim of this study was to evaluate the effectiveness of this method with quantitative outcomes. METHODS: A retrospective study was conducted of all patients who were diagnosed with Le Fort III fractures and underwent orbital and facial fractures repair from January 2015 to June 2019. Surgical reconstruction was performed with an ordered surgery method. Orbital volumes were used to evaluate the effectiveness of orbital reconstruction. RESULTS: Fifteen patients (21 eyes) with Le Fort III fractures were included in this study. Preoperative and postoperative orbital volume changes were statistically significant ( P <0.01). For unilateral fractures, orbital volumes were different in 2 eyes ( P <0.01). For bilateral fractures, orbital volumes were almost the same in 2 eyes ( P =0.34). For the affected eye in unilateral fractures group and eyes in bilateral fractures group, after surgery, orbital volume were almost the same ( P =0.35). CONCLUSIONS: This study showed effectiveness and safety of the ordered surgery in the treatment of Le Fort III fractures, which would result in significant decrease in orbital volumes.

The Impact of Item Feature and Response Preference in a Mixed-Format Design.

A combination of positively and negatively worded items (termed a mixed-format design) has been widely adopted in personality and attitude assessments. While advocates claim that the inclusion of positively and negatively worded items will encourage respondents to process the items more carefully and avoid response preference, others have reported that negatively worded (NW) items may induce a nuisance factor and contaminate scale scores. The present study examined the extent of the impact of the NW-item feature and further investigated whether a mixed-format design could effectively control acquiescence and the preference for extreme response options using two datasets (Attitude toward Peace Walls, and International Personality Item Pool). A proposed multidimensional item response model was implemented to simultaneously estimate the impact of item feature and response preference. The results suggested that NW items induced an impact on item responses and that affirmative preference was negligible, regardless of the proportion of NW items in a scale. However, participants' extremity preference was large in both balanced and imbalanced mixed-format designs. It concludes that the impact of the NW-item feature is not negligible in a mixed-format scale, which exhibits good control of acquiescence but not extremity preference.

A Vehicle Trajectory Privacy Preservation Method Based on Caching and Dummy Locations in the Internet of Vehicles.

In the internet of vehicles (IoVs), vehicle users should provide location information continuously when they want to acquire continuous location-based services (LBS), which may disclose the vehicle trajectory privacy. To solve the vehicle trajectory privacy leakage problem in the continuous LBS, we propose a vehicle trajectory privacy preservation method based on caching and dummy locations, abbreviated as TPPCD, in IoVs. In the proposed method, when a vehicle user wants to acquire a continuous LBS, the dummy locations-based location privacy preservation method under road constraint is used. Moreover, the cache is deployed at the roadside unit (RSU) to reduce the information interaction between vehicle users covered by the RSU and the LBS server. Two cache update mechanisms, the active cache update mechanism based on data popularity and the passive cache update mechanism based on dummy locations, are designed to protect location privacy and improve the cache hit rate. The performance analysis and simulation results show that the proposed vehicle trajectory privacy preservation method can resist the long-term statistical attack (LSA) and location correlation attack (LCA) from inferring the vehicle trajectory at the LBS server and protect vehicle trajectory privacy effectively. In addition, the proposed cache update mechanisms achieve a high cache hit rate.

Bionic Covert Underwater Acoustic Communication Based on Time-Frequency Contour of Bottlenose Dolphin Whistle.

In order to meet the requirements of communication security and concealment, as well as to protect marine life, bionic covert communication has become a hot research topic for underwater acoustic communication (UAC). In this paper, we propose a bionic covert UAC (BC-UAC) method based on the time-frequency contour (TFC) of the bottlenose dolphin whistle, which can overcome the safety problem of traditional low signal-noise ratio (SNR) covert communication and make the detected communication signal be excluded as marine biological noise. In the proposed BC-UAC method, the TFC of the bottlenose dolphin whistle is segmented to improve the transmission rate. Two BC-UAC schemes based on the segmented TFC of the whistle, the BC-UAC scheme using the whistle signal with time-delay (BC-UAC-TD) and the BC-UAC scheme using the whistle signal with frequency-shift (BC-UAC-FS), are addressed. The original whistle signal is used as a synchronization signal. Moreover, the virtual time reversal mirror (VTRM) technique is adopted to equalize the channel for mitigating the multipath effect. The performance of the proposed BC-UAC method, in terms of the Pearson correlation coefficient (PCC) and bit error rate (BER), is evaluated under simulated and measured underwater channels. Numerical results show that the proposed BC-UAC method performs well on covertness and reliability. Furthermore, the covertness of the bionic modulated signal in BC-UAC-TD is better than that of BC-UAC-FS, although the reliability of BC-UAC-FS is better than that of BC-UAC-TD.

Cross-talk of four types of RNA modification writers defines tumor microenvironment and pharmacogenomic landscape in colorectal cancer.

BACKGROUND: The four major RNA adenosine modifications, i.e., m6A, m1A, alternative polyadenylation, and adenosine-to-inosine RNA editing, are mediated mostly by the "writer" enzymes and constitute critical mechanisms of epigenetic regulation in immune response and tumorigenesis. However, the cross-talk and potential roles of these "writers" in the tumor microenvironment (TME), drug sensitivity, and immunotherapy remain unknown. METHODS: We systematically characterized mRNA expression and genetic alterations of 26 RNA modification "writers" in colorectal cancer (CRC), and evaluated their expression pattern in 1697 CRC samples from 8 datasets. We used an unsupervised clustering method to assign the samples into two patterns of expression of RNA modification "writers". Subsequently, we constructed the RNA modification "writer" Score (WM_Score) model based on differentially expressed genes (DEGs) responsible for the RNA modification patterns to quantify the RNA modification-related subtypes of individual tumors. Furthermore, we performed association analysis for WM_Score and characteristics of TME, consensus molecular subtypes (CMSs), clinical features, transcriptional and post-transcriptional regulation, drug response, and the efficacy of immunotherapy. RESULTS: We demonstrated that multi-layer alterations of RNA modification "writer" are associated with patient survival and TME cell-infiltrating characteristics. We identified two distinct RNA modification patterns, characterized by a high and a low WM_Score. The WM_Score-high group was associated with worse patient overall survival and with the infiltration of inhibitory immune cells, such as M2 macrophages, EMT activation, and metastasis, while the WM_Score-low group was associated with a survival advantage, apoptosis, and cell cycle signaling pathways. WM_Score correlated highly with the regulation of transcription and post-transcriptional events contributing to the development of CRC. In response to anti-cancer drugs, WM_Score highly negatively correlated (drug sensitive) with drugs which targeted oncogenic related pathways, such as MAPK, EGFR, and mTOR signaling pathways, positively correlated (drug resistance) with drugs which targeted in apoptosis and cell cycle. Importantly, the WM_Score was associated with the therapeutic efficacy of PD-L1 blockade, suggesting that the development of potential drugs targeting these "writers" to aid the clinical benefits of immunotherapy. CONCLUSIONS: Our study is the first to provide a comprehensive analysis of four RNA modifications in CRC. We revealed the potential function of these writers in TME, transcriptional and post-transcriptional events, and identified their therapeutic liability in targeted therapy and immunotherapy. This work highlights the cross-talk and potential clinical utility of RNA modification "writers" in cancer therapy.

Resveratrol improves the iron deficiency adaptation of Malus baccata seedlings by regulating iron absorption.

BACKGROUND: Resveratrol (Res), a phytoalexin, has been widely reported to participate in plant resistance to fungal infections. However, little information is available on its role in abiotic stress, especially in iron deficiency stress. Malus baccata is widely used as apple rootstock in China, but it is sensitive to iron deficiency. RESULTS: In this study, we investigated the role of exogenous Res in M. baccata seedings under iron deficiency stress. Results showed that applying 100 µM exogenous Res could alleviate iron deficiency stress. The seedlings treated with Res had a lower etiolation rate and higher chlorophyll content and photosynthetic rate compared with the apple seedlings without Res treatment. Exogenous Res increased the iron content in the roots and leaves by inducing the expression of MbAHA genes and improving the H+-ATPase activity. As a result, the rhizosphere pH decreased, iron solubility increased, the expression of MbFRO2 and MbIRT1 was induced, and the ferric-chelated reductase activity was enhanced to absorb large amounts of Fe2+ into the root cells under iron deficiency conditions. Moreover, exogenous Res application increased the contents of IAA, ABA, and GA3 and decreased the contents of DHZR and BL for responding to iron deficiency stress indirectly. In addition, Res functioned as an antioxidant that strengthened the activities of antioxidant enzymes and thus eliminated reactive oxygen species production induced by iron deficiency stress. CONCLUSION: Resveratrol improves the iron deficiency adaptation of M. baccata seedlings mainly by regulating iron absorption.

Rapid and label free detection of aflatoxin B1 in alcoholic beverages with a microfluid fiber device.

A rapid and label free aflatoxin B1 (AFB1) microfluid sensor was proposed and tested. The device was fabricated with hollow-core photonics crystal fiber infiltrated with the AFB1 solution. The autofluorescence emitting from the AFB1 molecules was detected. The sensor length was optimized. The AFB1 concentration was tested with a 4 cm long sensor. The best limit of detection was achieved as low as 1.34 ng/ml, which meets the test requirement of the national standards for AFB1 in food. The effectiveness of this sensor being applied in beer solution was also verified to be a little more sensitive than in aqueous solution. Compared with traditional AFB1 detection methods, the proposed single-ended device perfectly satisfies the demand of process control in alcoholic beverages manufacture.