Histone H3 trimethylation at lysine 36 guides m6A RNA modification co-transcriptionally.

DNA and histone modifications have notable effects on gene expression1. Being the most prevalent internal modification in mRNA, the N6-methyladenosine (m6A) mRNA modification is as an important post-transcriptional mechanism of gene regulation2-4 and has crucial roles in various normal and pathological processes5-12. However, it is unclear how m6A is specifically and dynamically deposited in the transcriptome. Here we report that histone H3 trimethylation at Lys36 (H3K36me3), a marker for transcription elongation, guides m6A deposition globally. We show that m6A modifications are enriched in the vicinity of H3K36me3 peaks, and are reduced globally when cellular H3K36me3 is depleted. Mechanistically, H3K36me3 is recognized and bound directly by METTL14, a crucial component of the m6A methyltransferase complex (MTC), which in turn facilitates the binding of the m6A MTC to adjacent RNA polymerase II, thereby delivering the m6A MTC to actively transcribed nascent RNAs to deposit m6A co-transcriptionally. In mouse embryonic stem cells, phenocopying METTL14 knockdown, H3K36me3 depletion also markedly reduces m6A abundance transcriptome-wide and in pluripotency transcripts, resulting in increased cell stemness. Collectively, our studies reveal the important roles of H3K36me3 and METTL14 in determining specific and dynamic deposition of m6A in mRNA, and uncover another layer of gene expression regulation that involves crosstalk between histone modification and RNA methylation.

Manipulation of optical orbit-induced localized spin angular momentum using the periodic edge dislocation.

Orbit-induced localized spin angular momentum (OILS) has recently garnered significant attention. This paper introduces periodic edge dislocation (PED) into the tight focusing system. The study delves into the tight focusing characteristics of the radially polarized vortex plane beam with PED, demonstrating that PED serves as a straightforward and effective means of manipulating OILS, especially when both the orbital angular momentum and the polarization of the incident beam are fixed. Our findings indicate that the longitudinal OILS reaches its maximum when the difference between the period of PED and the vortex topological charge is equal to 1. Conversely, when the difference is 0, the transverse OILS reaches its maximum, while the longitudinal OILS reaches its minimum. Similar patterns are also observed in linearly polarized vortex beams. This research proposes a simple and practical way to control OILS, contributing to our understanding of optical orbit-spin coupling.

RNF7 Induces Skeletal Muscle Cell Apoptosis and Arrests Cell Autophagy via Upregulation of THBS1 and Inactivation of the PI3K/Akt Signaling Pathway in a Rat Sepsis Model.

Recently, long noncoding RNAs (lncRNAs) have been highlighted for extensive functionality in sepsis. In this study, we aimed to explore the role of RNF7 in the progression of sepsis. We initially established a rat model of sepsis through cecal ligation and puncture induction, whereupon RNF7 expression was determined by RT-qPCR. Following adenovirus infection, the role of RNF7 in muscle injury, skeletal muscle protein metabolism, oxidative stress, and inflammation in sepsis rats was analyzed. Then, downstream mechanisms of RNF7 were identified and validated. Further, lipopolysaccharide was applied to treat myoblast to further demonstrate the in vitro role of RNF7. Our results showed that RNF7 expression was upregulated during sepsis. Overexpression of RNF7 worsened the sepsis-induced skeletal muscle injury, induced skeletal muscle protein metabolism, oxidative stress, and inflammation in sepsis rats. Meanwhile, overexpression of RNF7 elevated thrombospondin-1 (THBS1) expression. Silencing of RNF7 inhibited THBS1 and activated the PI3K/Akt signaling pathway, arresting the release of inflammatory factors and oxidative stress levels in skeletal muscle cells. Altogether, RNF7 may promote skeletal muscle cell apoptosis while simultaneously inhibiting cell autophagy through the promotion of THBS1 and inactivation of the PI3K/Akt signaling pathway.

Multi-focused electric and magnetic field sourcing from an azimuthally polarized vortex circular hyperbolic umbilic beam.

In this paper, one kind of multi-focusing electric and magnetic field which is sourced from an azimuthally polarized vortex circular hyperbolic umbilic beam (APVCHUB) is presented. After passing through a high NA objective, both the electric and magnetic fields of the APVCHUBs will focus multiple times, and a high-purity longitudinal magnetic field (p q =80%) will be generated. Besides, the mutual induction of the vortex phase and azimuthal polarization changes the electric and magnetic fields' vibration state and intensity distribution, making the longitudinal magnetic field carry an m-order concentric vortex. Our findings suggest that the APVCHUB could have potential applications in magnetic particle manipulation, extremely weak magnetic detection, data storage, semiconductor quantum dot excitation, etc.

Regulation and therapy, the role of JAK2/STAT3 signaling pathway in OA: a systematic review.

Osteoarthritis (OA) is a multifactorial chronic disease primarily characterized by the degeneration of articular cartilage. Currently, there is a lack of effective treatments for OA other than surgery. The exploration of the mechanisms of occurrence is important in exploring other new and effective treatments for OA. The current evidence shows that the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway plays a vital role in cytogenesis and is involved in OA progression. The terms "JAK2", "STAT3", and "Osteoarthritis"were used in a comprehensive literature search in PubMed to further investigate the relationship between the JAK2/STAT3 signaling pathway and OA. This review focuses on the role and mechanism of JAK2/STAT3 signaling in cartilage degradation, subchondral bone dysfunction, and synovial inflammation. In addition, this review summarizes recent evidence of therapeutic approaches to treat OA by targeting the JAK2/STAT3 pathway to accelerate the translation of evidence into the progression of strategies for OA treatment. Video abstract.

Percutaneous transluminal pulmonary angioplasty for Takayasu arteritis-associated pulmonary hypertension: A single-arm meta-analysis.

BACKGROUND: The efficacy and safety of percutaneous transluminal pulmonary angioplasty (PTPA) for Takayasu arteritis-associated pulmonary hypertension (TA-PH) remain unclear. OBJECTIVES: To examine the efficacy and safety of PTPA in TA-PH. METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials Library were searched from inception to August 18, 2022, for articles investigating the efficacy and safety of PTPA for TA-PH. The primary efficacy outcomes were pulmonary vascular resistance (PVR) changes from baseline to re-evaluation and 6-minute walking distance (6MWD). The safety outcome was procedure-related complications. RESULTS: Five articles comprising 104 patients with TA-PH who underwent PTPA were included. The scores of article quality, as assessed using the methodological index for nonrandomized studies tool, were high, ranging from 13 to 15 points. The pooled treatment effects of PVR (weighted mean difference [WMD]: -4.8 WU; 95% confidence interval [CI]: -6.0 to -3.5 WU; I2 = 0.0%), 6MWD (WMD: 101.9 m; 95% CI: 60.3-143.6 m; I2 = 70.4%) significantly improved. Procedure-related complications, which predominantly present as pulmonary artery injury and pulmonary injury, occurred in 32.0% of the included patients. Periprocedural death occurred in one patient (1.0%, 1/100). CONCLUSIONS: Patients with TA-PH could benefit from PTPA in terms of hemodynamics and exercise tolerance, at the expense of procedure-related complications. PTPA should be encouraged to enhance the treatment response in TA-PH. These findings need to be confirmed by further studies, ideally, randomized controlled trials. REGISTRATION: PROSPERO CRD42022354087.

Autofocusing field constructed by ring-arrayed Pearcey Gaussian chirp beams.

In this work, we propose and demonstrate the ring-arrayed Pearcey Gaussian chirp beams (RAPGCBs) synthesized by multiple two-dimensional Pearcey beams. The general analytical formula for the propagation of RAPGCBs is presented. We find that, depending on synthesized number n, the profiles of the beams present different polygonal shapes, and the autofocusing properties can be controlled by chirp factor ß. Furthermore, we study the properties of the RAPGCBs carrying optical vortices (OVs). It shows that a single OV or two positive OVs form an autofocusing hollow field, and opposite OVs will annihilate, which results in greatly increased autofocusing ability. Our experimental results agree with the simulations. Such beams have potential applications in particle trapping and biology medical fields.

Multi-focus autofocusing circular hyperbolic umbilic beams.

We propose and demonstrate a type of multi-focus autofocusing beams, circular hyperbolic umbilic beams (CHUBs), based on the double-active variable caustics in catastrophe theory. The mathematical form is more general compared to circular Airy, Pearcey and swallowtail beams. The CHUBs can generate multi-focus at its optical axis, while the on-axis intensity fluctuates up to two orders of magnitude that of the maximum intensity in the initial plane. Using the concept of topographic prominence, we quantify the autofocusing ability. We construct the criteria for selecting the effective foci, and then explore the influence of related parameters. Our findings suggest that the CHUBs could be a suitable tool for multi-particle manipulation, optical tweezers, optical lattices and related applications.

Radiogenomics: A Valuable Tool for the Clinical Assessment and Research of Ovarian Cancer.

ABSTRACT: A new interdisciplinary approach based on medical imaging phenotypes, gene expression patterns, and clinical parameters, referred to as radiogenomics, has recently been developed for biomarker identification and clinical risk stratification in oncology, including for the assessment of ovarian cancer. Some radiological phenotypes (implant distribution, lymphadenopathy, and texture-derived features) are related to specific genetic landscapes (BRCA, BRAF, SULF1, the Classification of Ovarian Cancer), and integrated models can improve the efficiency for predicting clinical outcomes. The establishment of databases in medical images and gene expression profile with large sample size and the improvement of artificial intelligence algorithm will further promote the application of radiogenomics in ovarian cancer.

Effects of low-intensity pulsed ultrasound on knee osteoarthritis: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To systemically review the effects of low-intensity pulsed ultrasound (LIPUS) on pain relief and functional recovery in patients with knee osteoarthritis (KOA). DATA SOURCES: PubMed, Web of Science, Cochrane Library, Physiotherapy Evidence Database (PEDro), and China National Knowledge Infrastructure (CNKI) were used from inception to 18 March 2022. REVIEW METHODS: Meta-analysis was performed to evaluate pain and function recovery between control and LIPUS groups. Standardized mean difference (SMD) or mean difference (MD) and 95% confidence interval (CI) were calculated, and data were combined using the fixed or random-effect model. RESULTS: Thirteen studies involving 807 patients with KOA were included. Patients' outcomes treated by LIPUS were improved significantly, including Visual analog scale (VAS) score (MD = -0.95, 95% CI: -1.43 to -0.48，P < 0.001), Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) score (MD = -4.35, 95% CI: -8.30 to -0.40, P = 0.0309), Lysholm score (SMD = 1.59, 95% CI: 1.29 to 1.90, P < 0.001), Lequesne index (MD = -1.33, 95% CI: -1.69 to -0.96, P < 0.001), Range of motion (ROM) (MD = 2.43, 95% CI: 0.39 to 4.46, P = 0.0197) and 50 meter walking time (SMD = 1.48, 95% CI: 0.46 to 2.49, P = 0.0044). Subgroup analyses showed monotherapy of LIPUS produced a better effect on reducing VAS score (P = 0.0213), and the shorter therapeutic period (≤4 weeks) produced a more significant effect on raising the WOMAC score (P = 0.0083). CONCLUSION: LIPUS was beneficial for pain relief and functional knee recovery and maybe as an alternative therapy in KOA rehabilitation.

A high environmental composite quality factor score was associated with the risk of sick building syndrome among adults in northeast China.

OBJECTIVES: Epidemiological evidence regarding the association between the combination of indoor and outdoor neighborhood pollution and sick building syndrome (SBS) among adults is limited and inconsistent. A cross-sectional study was conducted to investigate the association between the environmental composite quality factor score and SBS among adults. METHODS: This study included 2594 females and 666 males aged 18-77 years enrolled from the Northeast China. The environmental composite quality factor score was computed based on factors potentially associated with SBS risk, including the outdoor neighborhood pollution sources (the housing on the street, the presence of pollutants within 100 m of the house (gutters, garbage stations, noise, chemical pollution, and dust pollution), and the presence of arterial roads, factories, and chimneys) and indoor pollution sources (redecoration, clean fuel used for heating/cooking, cooking oil fume (COF) outside kitchen, using of mosquito coil or repellent, and using of incense). We performed multivariate logistic regression analysis to calculate the odds ratios (ORs) and 95% confidence intervals (95%CIs) between environmental composite quality factor score, indoor pollution composite factor score, outdoor neighborhood pollution composite factor score, and SBS adjustment for covariates. Further, we also did the stratified analysis and constructed a weighted score to verify the results. RESULTS: Compared with the lowest environmental composite quality factor score, the ORs of the highest scores were: 1.58 (95% CI, 1.20-2.27, Ptrend = 0.001) for general symptoms; 1.73 (95% CI, 1.35-2.23, Ptrend < 0.001) for mucosal symptoms and 1.75 (95% CI, 1.34-2.29, Ptrend < 0.001) for dermal symptoms and 1.81 (95% CI, 1.36-2.42, Ptrend < 0.001) for all of the three symptoms. We also observed similar patterns with the using of weighted scores and stratified analysis. CONCLUSION: Higher exposure to indoor pollution sources and outdoor pollution sources near the residence may be associated with a higher risk of SBS in adults in northeast China.

Phytochemicals with protective effects against acute pancreatitis: a review of recent literature.

CONTEXT: Acute pancreatitis (AP) is an acute abdominal inflammatory disease with episodes ranging from mild to fulminant symptoms which could include necrosis, systemic inflammation and multiple organ dysfunction. Increasing experimental evidence demonstrates that specific bioactive ingredients from natural plants have a favourable therapeutic effect on AP. OBJECTIVE: The objective of this review is to summarize the protective effects and potential mechanisms of action of phytochemicals on the attenuation of AP. METHODS: Experimental studies in vivo or in vitro between January 2016 and June 2021 were sought in PubMed and Web of Science using the following search terms: ('phytochemicals' OR 'medicinal plant' OR 'traditional medicine') AND ('pancreatitis' OR 'pancreatic damage' OR 'pancreatic injury'). Data concerning the basic characteristics of phytochemicals, therapeutic dose and potential molecular mechanisms related to AP were extracted in this study. RESULTS: A total of 30 phytochemicals with potential therapeutic effects were reviewed and summarized systematically. According to their molecular pathways in AP, the underlying mechanisms of the phytochemicals were illustrated in detail. DISCUSSION AND CONCLUSIONS: The phytochemicals with anti-inflammatory and antioxidant abilities may be efficient candidate drugs for AP treatment. Importantly, more preclinical investigations are needed to illustrate the efficacy of future phytochemicals.

Safety, Tolerability, Pharmacokinetics, and Immunogenicity of a Monoclonal Antibody (SCTA01) Targeting SARS-CoV-2 in Healthy Adults: a Randomized, Double-Blind, Placebo-Controlled, Phase I Study.

SCTA01 is a novel monoclonal antibody with promising prophylactic and therapeutic potential for COVID-19. This study aimed to evaluate the safety, tolerability, pharmacokinetics (PK) and immunogenicity of SCTA01 in healthy adults. This was a randomized, double-blind, placebo-controlled, dose escalation phase I clinical trial. Healthy adults were randomly assigned to cohort 1 (n = 5; 3:2), cohort 2 (n = 8; 6:2), cohort 3, or cohort 4 (both n = 10; 8:2) to receive SCTA01 (5, 15, 30, and 50 mg/kg, respectively) versus placebo. All participants were followed up for clinical, laboratory, PK, and immunogenicity assessments for 84 days. The primary outcomes were the dose-limiting toxicity (DLT) and maximal tolerable dose (MTD), and the secondary outcomes included PK parameters, immunogenicity, and adverse events (AE). Of the 33 participants, 18 experienced treatment-related AEs; the frequency was 52.0% (13/25) in participants receiving SCTA01 and 62.5% (5/8) in those receiving placebo. All AEs were mild. There was no serious AE or death. No DLT was reported, and the MTD of SCTA01 was not reached. SCTA01 with a dose range of 5 to 50 mg/kg had nearly linear dose-proportional increases in Cmax and AUC parameters. An antidrug antibody response was detected in four (16.0%) participants receiving SCTA01, with low titers, between the baseline and day 28, but all became negative later. In conclusion, SCTA01 up to 50 mg/kg was safe and well-tolerated in healthy participants. Its PK parameters were nearly linear dose-proportional. (This study has been registered at ClinicalTrials.gov under identifier NCT04483375.).

Merging cobalt and photoredox catalysis for the C8-H alkoxylation of 1-naphthylamine derivatives with alcohols.

A combined cobalt and photoredox catalysis system to realize the C8-H alkoxylation of 1-naphthylamine derivatives with alcohols was developed. Using commercially available alkyl alcohols as raw materials and Co(OAc)2 and rose bengal as catalysts, 1-naphthylamine derivatives reacted with alcohols to generate the corresponding C8-H alkoxylation products in good yields.

Pharmacokinetic bioequivalence and safety assessment of two metformin hydrochloride tablet formulations using a phase I, randomized, open, two-period, two cross-over, single-dose, fed study in healthy Chinese adult subjects.

OBJECTIVES: To assess the bioequivalence and safety of generic metformin hydrochloride (test preparation) and glucophage (reference preparation) in healthy Chinese subjects. MATERIALS AND METHODS: A bioequivalence and safety assessment of two formulations of metformin (850 mg) using a randomized, open, two-period, two cross-over, single-dose, fed trial in 36 healthy Chinese adult subjects was performed at our center from March 22, 2018, to April 9, 2018. Bioequivalence was determined as two-sided 90% confidence intervals (CI) of the test-to-reference ratio of area under the curve (AUC) and peak concentration (Cmax) for each constituent within 80.00 - 125.00%. SAS 9.4 software was employed for the statistical analysis. RESULTS: One subject was excluded from the trial. The 90% CIs (95.36 - 101.43% for AUC0→t, 95.65 - 101.66% for AUC0→∞; 94.43 - 101.74% for Cmax) of test/reference preparation for these pharmacokinetic parameters were within the range of 80.00 - 125.00%. No severe adverse events were observed during this trial. The two preparations were safe and well-tolerated. CONCLUSION: It was concluded that generic metformin was bioequivalent and as safe as glucophage under fed conditions in healthy Chinese subjects.

Prognostic relevance of miR-137 and its liver microenvironment regulatory target gene AFM in hepatocellular carcinoma.

MiR-137 has been identified as potential hepatocellular carcinoma (HCC) prognostic biomarkers. Highly relevant HCC prognostic biomarkers may be derived from combinations of miR-137 with its target genes involved in the regulation of liver microenvironment. This study aimed at the discovery of such a combination with improved HCC prognosis performance than miR-137 or its target gene alone in a significantly higher number of HCC patients than previous studies. Analysis of the differentially expressed micro RNAs (miRNAs) between cancer and noncancer tissues reconfirmed miR-137 to be among the most relevant prognostic miRNAs and the data of 375 HCC patients and 50 normal cases were from the Cancer Genome Atlas (TCGA) data sets. Target genes were identified by the established search methods and Kaplan-Meier survival analysis of HCC patients was used to evaluate the overall survival (OS) and recurrence-free survival (RFS). Cox proportional hazards regression indicated that the miR-137 and its target gene AFM combination is an independent prognostic factor for the OS and RFS in HCC. In vitro experiments validated that miR-137 could bind to 3'-untranslated region of the AFM and promote the invasion and metastasis of HCC cell lines. The expressions of miR-137 and its liver microenvironment regulatory target gene AFM in combination significantly correlated with HCC progression in a higher number of patients than in previous studies, which suggested their potential as prognostic biomarkers for HCC.

Radiation forces on a Rayleigh particle produced by partially coherent circular Airy beams.

In this work, the radiation force on a Rayleigh dielectric particle induced by the partially coherent circular Airy beam (PCCAB) is investigated. Our numerical results show that the PCCAB can be used to trap and manipulate particles. The radiation force distribution and trapping stability have been analyzed under different coherent lengths. It is found that, with the increase of the spatial coherent length, the radiation force is increased and the particle can be stably trapped at more points. Therefore, the radiation force as well as the depth of potential well can be effectively modulated by controlling the spatial coherent length in optical micromanipulation. The trapping properties of PCCAB have also been studied under other different parameters, including the scale factor and initial radius.

ZFAS1: a novel tumor-related long non-coding RNA.

Long non-coding RNAs (lncRNA) are classified as a kind of RNA, which are longer than 200 nucleotides in length and cannot be translated into proteins. Multiple studies have demonstrated that lncRNAs are involved in various cellular processes, including proliferation, differentiation, cell death, and metastasis. In addition, aberrant expression of lncRNAs has been discovered in human tumors, where they function as either oncogenes or tumor suppressor genes. Among numerous lncRNAs, we focus on ZNFX1 antisense RNA 1 (ZFAS1), a well-known lncRNA that is aberrant overexpression in various tumors, including melanoma, esophageal squamous cell carcinoma, non-small cell lung cancer, gastric cancer, colon cancer, and Hepatocellular carcinoma, in which it functions as oncogene. In contrast, ZFAS1 is downregulated in breast cancer, which may function as tumor suppressor gene. In this review, we provide an overview of current evidence concerning the role and potential clinical utilities of ZFAS1 in human cancers.

Elliptical Airy beam.

We found a new type of noncircular symmetrical Airy beam called an elliptical Airy beam (EAB). Using a simple single-pixel checkerboard hologram method, we achieved the EAB in an experiment. We observed its unique property of double focusing and the ability of the energy to flow towards the endpoints of the long axis during propagation. These particular properties will have some potential applications.

Cynandione A attenuates neuropathic pain through p38ß MAPK-mediated spinal microglial expression of ß-endorphin.

Cynanchi Wilfordii Radix (baishouwu), a medicinal herb, has been widely used in Asia to treat a variety of diseases or illnesses. Cynandione A isolated from C. Wilfordii is the principle acetophenone and exhibits neuroprotective and anti-inflammatory activities. This study aims to evaluate the antihypersensitivity activities of cynandione A in neuropathy and explored its mechanisms of action. Intrathecal injection of cynandione A dose-dependently attenuated spinal nerve ligation-induced mechanical allodynia and thermal hyperalgesia, with maximal possible effects of 57% and 59%, ED50s of 14.9µg and 6.5µg, respectively. Intrathecal injection of cynandione A significantly increased ß-endorphin levels in spinal cords of neuropathic rats and its treatment concentration-dependently induced ß-endorphin expression in cultured primary microglia (but not in neurons or astrocytes), with EC50s of 38.8 and 20.0µM, respectively. Cynandione A also non-selectively upregulated phosphorylation of mitogen-activated protein kinases (MAPKs), including p38, extracellular signal regulated kinase (ERK1/2), and extracellular signal regulated kinase (JNK) in primary microglial culture; however, cynandione A-stimulated ß-endorphin expression was completely inhibited by the specific p38 activation inhibitor SB203580, but not by the ERK1/2 or JNK activation inhibitors. Knockdown of spinal p38ß but not p38α using siRNA also completely blocked cynandione A-induced ß-endorphin expression in cultured microglial cells. Furthermore, cynandione A-induced antiallodynia in neuropathy was totally inhibited by the microglial inhibitor minocycline, SB203580, anti-ß-endorphin antibody, and µ-opioid receptor antagonist CTAP (but not the κ- or δ-opioid receptor antagonist). These results suggest that cynandione A attenuates neuropathic pain through upregulation of spinal microglial expression ß-endorphin via p38ß MAPK activation.