Results of a Pilot External Quality Assessment Scheme for Genetic Testing of Newborns with Spinal Muscular Atrophy.

BACKGROUND: This study aims to evaluate the ability of laboratories to perform spinal muscular atrophy (SMA) genetic testing in newborns based on dried blood spot (DBS) samples, and to provide reference data and advance preparation for establishing the pilot external quality assessment (EQA) scheme for SMA genetic testing of newborns in China. METHODS: The pilot EQA scheme contents and evaluation principles of this project were designed by National Center for Clinical Laboratories (NCCL), National Health Commission. Two surveys were carried out in 2022, and 5 batches of blood spots were submitted to the participating laboratory each time. All participating laboratories conducted testing upon receiving samples, and test results were submitted to NCCL within the specified date. RESULTS: The return rates were 75.0% (21/28) and 95.2% (20/21) in the first and second surveys, respectively. The total return rate of the two examinations was 83.7% (41/49). Nineteen laboratories (19/21, 90.5%) had a full score passing on the first survey, while in the second survey twenty laboratories (20/20, 100%) scored full. CONCLUSIONS: This pilot EQA survey provides a preliminary understanding of the capability of SMA genetic testing for newborns across laboratories in China. A few laboratories had technical or operational problems in testing. It is, therefore, of importance to strengthen laboratory management and to improve testing capacity for the establishment of a national EQA scheme for newborn SMA genetic testing.

Resatorvid (TAK-242) Ameliorates Ulcerative Colitis by Modulating Macrophage Polarization and T Helper Cell Balance via TLR4/JAK2/STAT3 Signaling Pathway.

Resatorvid (TAK-242), a specific inhibitor of Toll-like receptor-4 (TLR4), has attracted attention for its anti-inflammatory properties. Despite this, few studies have evaluated its effects on ulcerative colitis (UC). This study aimed to investigate the effects of TAK-242 on macrophage polarization and T helper cell balance and the mechanism by which it alleviates UC. Our findings indicated that TLR4 expression was elevated in patients with UC, a mouse model of UC, and HT29 cells undergoing an inflammatory response. TAK­242 treatment reduced apoptosis in TNF-α and LPS-stimulated HT29 cells and alleviated symptoms of dextran sulfate sodium (DSS)­induced colitis in vivo. TAK­242 downregulated TLR4 expression and decreased the secretion of pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß while enhancing IL-10 production. TAK-242 also reduced M1 macrophage polarization and diminished Th1 and Th17 cell infiltration while increasing Th2 cell infiltration and M2 macrophage polarization both in vitro and in vivo. Mechanistically, TAK-242 inhibited the JAK2/STAT3 signaling pathway, an important regulator of macrophage polarization and T helper cell balance. Furthermore, the in vivo and in vitro effects of TAK-242 were partially negated by the administration of the JAK2/STAT3 antagonist AG490, suggesting that TAK-242 inhibits the JAK2/STAT3 pathway to exert its biological activities. Taken together, this study underscores TAK-242 as a promising anti-UC agent, functioning by modulating macrophage polarization and T helper cell balance via the TLR4/JAK2/STAT3 signaling pathway.

Exploring the Prevalence of Tinnitus and Ear-Related Symptoms in China After the COVID-19 Pandemic: Online Cross-Sectional Survey.

BACKGROUND: Tinnitus is a complex and heterogeneous disease that has been identified as a common manifestation of COVID-19. To gain a comprehensive understanding of tinnitus symptoms in individuals following COVID-19 infection, we conducted an online survey called the China Ear Nose and Throat Symptom Survey in the COVID-19 Pandemic (CENTSS) among the Chinese population. OBJECTIVE: Our objective was to investigate tinnitus and ear-related symptoms after COVID-19 infection in the Chinese population, with the aim of providing a solid empirical foundation for improved health care. The findings from CENTSS can contribute to the development of enhanced management strategies for tinnitus in the context of long COVID. By gaining a better understanding of the factors contributing to tinnitus in individuals with COVID-19, health care providers can tailor interventions to address the specific needs of affected patients. Furthermore, this study serves as a basis for research on the long-term consequences of COVID-19 infection and its associated tinnitus symptoms. METHODS: A quantitative, online, cross-sectional survey study design was used to explore the impact of the COVID-19 pandemic on experiences with tinnitus in China. Data were collected through an online questionnaire designed to identify the presence of tinnitus and its impacts. Descriptive statistics were used to analyze individuals' demographic characteristics, COVID-19 infection-related ear symptoms, and the cognitive and emotional implications of tinnitus. Univariable and multivariable logistic regression analyses were used to model the cross-sectional baseline associations between demographic characteristics, noise exposure, educational level, health and lifestyle factors, and the occurrence of tinnitus. RESULTS: Between December 19, 2022, and February 1, 2023, we obtained responses from 1262 Chinese participants representing 24 regions, with an average age of 37 years. Among them, 540 patients (42.8%) reported experiencing ear-related symptoms after COVID-19 infection. Only 114 (9%) of these patients sought medical attention specifically for their ear symptoms, while 426 (33.8%) did not seek hospital care. Tinnitus emerged as the most prevalent and impactful symptom among all ear-related symptoms experienced after COVID-19 infection. Of the respondents, female participants (688/888, 77.78%), younger individuals (<30 years), individuals with lower education levels, participants residing in western China, and those with a history of otolaryngology diseases were more likely to develop tinnitus following COVID-19 infection. CONCLUSIONS: In summary, tinnitus was identified as the most common ear-related symptom during COVID-19 infection. Individuals experiencing tinnitus after COVID-19 infection were found to have poorer cognitive and emotional well-being. Different ear-related symptoms in patients post-COVID-19 infection may suggest viral invasion of various parts of the ear. It is therefore crucial to monitor and manage hearing-related changes resulting from COVID-19 as clinical services resume.

Complete chloroplast genome of sageretia thea (rhamnaceae), an ornamental fruit and medicinal tree.

Sageretia thea (Osbeck) M.C. Johnst (1968) is an important fruit and medicinal species of Rhamnaceae family. The complete chloroplast genome (cp) of Sageretia genus was sequenced and reported for the first time in this study. The cp genome had a total length of 161,352 bp, consisting of a largesingle-copy (LSC) region of 89,802 bp, a small single-copy (SSC) region of 18,914 bp, and a pair of inverted repeat (IR) regions totaling 26,318 bp. The plastid genome contained 129 genes, including 84 protein-coding genes, 37 tRNA genes, 8 rRNA genes. The overall GC content of the genome was found to be 37.10%. Phylogenetic analysis based on comparison with 27 chloroplast genomes revealed that S. thea is closely related to genera Rhamnus and Berchemia. The findings of this study can provide fundamental insights for the conservation, exploitation, and systematic genomic investigation of Rhamnus plants.

The EIF3H-HAX1 axis increases RAF-MEK-ERK signaling activity to promote colorectal cancer progression.

Eukaryotic initiation translation factor 3 subunit h (EIF3H) plays critical roles in regulating translational initiation and predicts poor cancer prognosis, but the mechanism underlying EIF3H tumorigenesis remains to be further elucidated. Here, we report that EIF3H is overexpressed in colorectal cancer (CRC) and correlates with poor prognosis. Conditional Eif3h deletion suppresses colorectal tumorigenesis in AOM/DSS model. Mechanistically, EIF3H functions as a deubiquitinase for HAX1 and stabilizes HAX1 via antagonizing ßTrCP-mediated ubiquitination, which enhances the interaction between RAF1, MEK1 and ERK1, thereby potentiating phosphorylation of ERK1/2. In addition, activation of Wnt/ß-catenin signaling induces EIF3H expression. EIF3H/HAX1 axis promotes CRC tumorigenesis and metastasis in mouse orthotopic cancer model. Significantly, combined targeting Wnt and RAF1-ERK1/2 signaling synergistically inhibits tumor growth in EIF3H-high patient-derived xenografts. These results uncover the important roles of EIF3H in mediating CRC progression through regulating HAX1 and RAF1-ERK1/2 signaling. EIF3H represents a promising therapeutic target and prognostic marker in CRC.

Rational design and synthesis of 2,4-dichloro-6-methyl pyrimidine derivatives as potential selective EGFRT790M/L858R inhibitors for the treatment of non-small cell lung cancer.

Many patients with non-small cell lung cancer (NSCLC) initially benefit from epidermal growth factor receptor (EGFR) targeted therapy. Unfortunately, varying degrees of resistance or side effects eventually develop. Overcoming and preventing the resistance and side effects of EGFR inhibitors has become a hot topic of research today. Based on the previous studies on AZD-9291, we designed and synthesized two series of 2,4-dichloro-6-methylpyrimidine derivatives, 19 compounds in total, as potential inhibitors of the EGFR kinase. The most promising compound, L-18, showed better inhibitory activity (81.9%) and selectivity against EGFRT790M/L858R kinase. In addition, L-18 showed strong antiproliferative activity against H1975 cells with an IC50 value of 0.65 ± 0.06 µM and no toxicity to normal cells (LO-2). L-18 was able to dose-dependently induce the apoptosis of H1975 cells and produced a cell-cycle-blocking effect, and it can also dose-dependently inhibit the migration and invasion of H1975 cells. L-18 also showed in vivo anticancer efficacy in H1975 cells xenograft mice. We also performed a series of in vivo and in vitro toxicological evaluations of compound L-18, which did not cause obvious injury in mice during administration. These results suggest that L-18 may be a promising drug candidate that warrants further investigation.

Effect of propofol and sevoflurane on postoperative fatigue after laparoscopic hysterectomy.

BACKGROUND: Postoperative fatigue syndrome (POFS) is an important factor in postoperative recovery. However, the effect of anesthetic drugs on postoperative fatigue in female patients has been rarely studied. This study compared the effects of maintaining general anesthesia with propofol or sevoflurane on the incidence of POFS in patients undergoing laparoscopic hysterectomy. METHODS: This prospective, single-blind, randomized controlled trial enrolled patients scheduled for laparoscopic hysterectomy. Eligible patients were randomized into the propofol and sevoflurane groups. The primary outcome was the incidence of POFS within 30 Days, defined by a simplified identity consequence fatigue scale (ICFS-10) scores≥24 or Visual Analogue Scale (VAS) scores of fatigues>6. Secondary outcomes were perioperative grip strength, early ambulation and anal exhaust after surgery, and inpatient days. RESULTS: 32 participants were assigned to the propofol group (P) and 33 to the sevoflurane group (S). Incidence of POFS on postoperative D1 was P (8/32) vs. S (10/33) (p = 0.66, 95% confidence interval [CI]: 16.4-27.00); D3 P (2/32) vs. S (5/33) (p = 0.45,95% CI:5.96-23.76). POFS were not found on postoperative D5 and D30. There were no differences in perioperative grip strength, early ambulation and anal exhaust after surgery, and inpatient days between the two groups. CONCLUSIONS: POFS after scheduled laparoscopic hysterectomy was unaffected by anesthesia with propofol vs. sevoflurane. The incidence of POFS was highest on the first postoperative day, at 27.7%, and declined progressively over the postoperative 30 days. Trial registration Chinese Clinical Trial Registry (No. ChiCTR 2,000,033,861), registered on 14/06/2020).

MTTLm6A: A multi-task transfer learning approach for base-resolution mRNA m6A site prediction based on an improved transformer.

N6-methyladenosine (m6A) is a crucial RNA modification involved in various biological activities. Computational methods have been developed for the detection of m6A sites in Saccharomyces cerevisiae at base-resolution due to their cost-effectiveness and efficiency. However, the generalization of these methods has been hindered by limited base-resolution datasets. Additionally, RMBase contains a vast number of low-resolution m6A sites for Saccharomyces cerevisiae, and base-resolution sites are often inferred from these low-resolution results through post-calibration. We propose MTTLm6A, a multi-task transfer learning approach for base-resolution mRNA m6A site prediction based on an improved transformer. First, the RNA sequences are encoded by using one-hot encoding. Then, we construct a multi-task model that combines a convolutional neural network with a multi-head-attention deep framework. This model not only detects low-resolution m6A sites, it also assigns reasonable probabilities to the predicted sites. Finally, we employ transfer learning to predict base-resolution m6A sites based on the low-resolution m6A sites. Experimental results on Saccharomyces cerevisiae m6A and Homo sapiens m1A data demonstrate that MTTLm6A respectively achieved area under the receiver operating characteristic (AUROC) values of 77.13% and 92.9%, outperforming the state-of-the-art models. At the same time, it shows that the model has strong generalization ability. To enhance user convenience, we have made a user-friendly web server for MTTLm6A publicly available at http://47.242.23.141/MTTLm6A/index.php.

Evaluation of combination of ALA-PDT and interferon for cervical low-grade squamous intraepithelial lesion (LSIL).

BACKGROUND: Cervical LSIL is a precancerous disease which requires regular follow-up. High risk patients need active interventions. Interferon and topical PDT have been used in the treatment of cervical LSIL. The aim of this study was to evaluate the combination use of topical PDT and interferon in the treatment of cervical LSIL. MATERIALS AND METHODS: A prospective study was carried out involving 159 women with cervical LSIL and high risk human papillomaviruses (hr-HPV) infection. Patients were divided into three groups. Group 1-receiving interferon suppository only, Group 2-receiving 19 mg/cm2 ALA plus post PDT interferon, and Group 3-receiving 38 mg/cm2 ALA plus post PDT interferon. The primary endpoint was pathological regression. The secondary endpoints were the HPV negative conversion rate and the adverse effects of treatment. RESULTS: At 6-12 months after PDT, for Group 1, the effective rate, CR rate and HPV negative conversion rate was 48.3 %, 43.3 % and 24.0 %, respectively. For Group 2, the effective rate, CR rate and HPV negative conversion rate were 89.3 %, 71.4 %, and 72.4 %, respectively. For Group 3, the effective rate, CR rate and HPV negative conversion rate were 91.5 %, 66.1 %, and 64.4 %, respectively, significantly higher than those of interferon only group. Two ALA dose group study showed similar efficacy. No patient experienced serious adverse effects. CONCLUSIONS: ALA-PDT combined with interferon therapy was feasible and tolerable. Two ALA dose groups showed similar outcomes in treating cervical LSIL.

T6496 targeting EGFR mediated by T790M or C797S mutant: machine learning, virtual screening and bioactivity evaluation study.

Acquired resistance to EGFR is a major impediment in lung cancer treatment, highlighting the urgent need to discover novel compounds to overcome EGFR drug resistance. In this study, we utilized in silico methods and bioactivity evaluation for drug discovery to identify novel active anticancer agents targeting EGFRT790M/L858R and EGFRT790M/C797S/L858R. Firstly, we employed ROC-guided machine learning to retrieve nearly 7,765 compounds from a collection of three libraries (comprising over 220,000 compounds). Next, virtual screening, cluster analysis, and binding model analysis were employed to identify six potential compounds. Additionally, the kinase assay revealed that these six compounds demonstrated higher sensitivity to EGFR than c-Met. Among these compounds, T6496 inhibited both EGFRT790M/L858R and EGFRT790M/C797S/L858R kinases, with an IC50 of 3.30 and 8.72 µM. Furthermore, we evaluated the antitumor effects of the six selected compounds, and compound T6496 exhibited the strongest anticancer activity against H1975 cell lines, with an IC50 value of 2.7 µM. These results suggest that T6496 may mitigate EGFR resistance caused by T790M or C797S mutations. Moreover, the AO staining assay, JC-1 staining, ROS experiment and hemolytic toxicity evaluation revealed that T6496 could induce apoptosis in H1975 cell lines in a time-dependent and concentration-dependent manner, and is a potential compound for further structural optimization.Communicated by Ramaswamy H. Sarma.

ROC guided machine learning, virtual screening and bioevaluation was applied to discover six hit compounds for overcoming EGFR resistance mediated by T790M or C797S.The promising compound T6496 could both inhibit EGFR^T790M/L858R and EGFR^{T790M/C797S/L858R}, with an IC₅₀ of 3.30 and 8.72 µM.In addition, T6496 and AO-365/43489452 show excellent anticancer activity even better than AZD9291.AO staining assay, JC-1 staining, and ROS experiment revealed that compounds T6496 could induce apoptosis in H1975 cell lines in a time-dependent and concentration-dependent manner.

Low serum apolipoprotein A1 level predicts poor prognosis of patients with diffuse large B-cell lymphoma in the real world: a retrospective study.

BACKGROUND: Apolipoprotein A1 (ApoA1) is a member of the apolipoprotein family with diverse functions. It is associated with the pathogenesis and prognosis of several types of tumors. However, the role of serum apolipoprotein A1 (ApoA1) in the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) remains unclear. This study aimed to elucidate its influence on clinical outcomes in patients with DLBCL. METHODS: We retrospectively analyzed a cohort of 1583 consecutive DLBCL patients admitted to the Fujian Medical University Union Hospital between January 2011 and December 2021. 949 newly diagnosed DLBCL patients who met the inclusion criteria were enrolled for statistical analysis. Receiver operating characteristic curve analysis was performed to determine the optimal cut-off value for serum ApoA1 levels for prognostic prediction among patients with DLBCL. The correlations between serum ApoA1 levels and clinical and laboratory parameters were analyzed. Prognostic significance was analyzed using univariate and multivariate Cox proportional hazards models. RESULTS: Newly diagnosed patients with DLBCL demonstrated low serum ApoA1 levels (< 0.925 g/L), had more B symptoms, higher levels of serum lactate dehydrogenase (LDH) (>upper limit of normal), poorer performance status (Eastern Cooperative Oncology Group score of 2-4), higher percentage of advanced stage and non-germinal center B-cell (non-GCB) subtype, more cases of > 1 extranodal site, higher International Prognostic Index (IPI) score (3-5), and higher incidence of relapse or refractory diseases compared with those with high serum ApoA1 levels (≥ 0.925 g/L). Low serum ApoA1 levels were an independent adverse prognostic factor for overall survival (OS) but not progression-free survival (PFS). CONCLUSIONS: Low serum ApoA1 levels were associated with poor treatment response and inferior survival in newly diagnosed patients with DLBCL.

Clinical evaluation of deep learning systems for assisting in the diagnosis of the epiretinal membrane grade in general ophthalmologists.

BACKGROUND: Epiretinal membrane (ERM) is a common age-related retinal disease detected by optical coherence tomography (OCT), with a prevalence of 34.1% among people over 60 years old. This study aims to develop artificial intelligence (AI) systems to assist in the diagnosis of ERM grade using OCT images and to clinically evaluate the potential benefits and risks of our AI systems with a comparative experiment. METHODS: A segmentation deep learning (DL) model that segments retinal features associated with ERM severity and a classification DL model that grades the severity of ERM were developed based on an OCT dataset obtained from three hospitals. A comparative experiment was conducted to compare the performance of four general ophthalmologists with and without assistance from the AI in diagnosing ERM severity. RESULTS: The segmentation network had a pixel accuracy (PA) of 0.980 and a mean intersection over union (MIoU) of 0.873, while the six-classification network had a total accuracy of 81.3%. The diagnostic accuracy scores of the four ophthalmologists increased with AI assistance from 81.7%, 80.7%, 78.0%, and 80.7% to 87.7%, 86.7%, 89.0%, and 91.3%, respectively, while the corresponding time expenditures were reduced. The specific results of the study as well as the misinterpretations of the AI systems were analysed. CONCLUSION: Through our comparative experiment, the AI systems proved to be valuable references for medical diagnosis and demonstrated the potential to accelerate clinical workflows. Systematic efforts are needed to ensure the safe and rapid integration of AI systems into ophthalmic practice.

Structural, functional properties, and in vitro digestibility of sunflower protein concentrate as affected by extraction method: Isoelectric precipitation vs ultrafiltration.

This study was the first to compare the structural features, functional properties and in vitro digestibility of two protein concentrates produced from defatted sunflower meal via two different three-stage processes (chlorogenic acid removal-alkaline extraction-isoelectric precipitation versus chlorogenic acid removal-alkaline extraction-ultrafiltration; concentrates termed AI-SPC and AU-SPC, respectively). Compared with AI-SPC, AU-SPC with a darker brown color had much higher protein recovery yield and purity, much higher solubility at pH 4-7, higher oil-holding capacity, greater emulsifying and foaming capacities at pH 7 and 9, and slightly lower foaming capacity at pH 3. The bioavailability was higher for AU-SPC after oral-gastric-intestinal digestion. Moreover, AI-SPC occurred as clumps/lumps of particles, whilst AU-SPC appeared as flat blocks with continuous surfaces. AU-SPC was more negatively charged, and had a smaller particle size, less ß-sheet, more ß-turn, slightly more α-helix structure. These results confirmed the close relationship between protein production methods and its functional properties and digestibility.

Novel bioactive 2-phenyl-4-aminopyrimidine derivatives as EGFRDel19/T790M/C797S inhibitors for the treatment of non-small cell lung cancer.

Overexpression of the epidermal growth factor receptor (EGFR) has been implicated in the development of non-small-cell lung cancer (NSCLC). Thus, EGFR is an effective drug target for the treatment of NSCLC, and developing fourth-generation EGFR inhibitors to overcome the resistance mediated by T790M/C797S mutations are currently under investigation. In this study, based on the binding model between Angew2017-7634-1 and EGFRT790M/C797S , several series of 2-phenyl-4-aminopyrimidine derivatives were designed and synthesized. The bioactivity of these compounds was evaluated and it is suggested that compound A23 could effectively inhibit the proliferation of Ba/F3-EGFRDel19/T790M/C797S and H1975-EGFRL858R/T790M cells, with an IC50 of 0.22 ± 0.07 and 0.52 ± 0.03 µM, respectively. Meanwhile, the kinase activity of A23 against EGFRL858R/T790M and EGFRDel19/T790M/C797S was also evaluated, with an IC50 of 0.33 and 0.133 µM, respectively. Moreover, compound A23 was further evaluated in the H1975 xenograft models with significant in vivo tumor growth inhibitions of 25.5%, which means that A23 could effectively inhibit the growth of tumor cells and promote the death of tumor cells. As a result, A23 could be identified as a novel potential EGFRDel19/T790M/C797S inhibitor.

Clinical Profile and Outcome Analysis of Ear-Nose-Throat Symptoms in SARS-CoV-2 Omicron Subvariant Infections.

Objective: This study aimed to investigate the clinical characteristics and outcomes of ear-nose-throat (ENT) symptoms in SARS-CoV-2 Omicron infected patients resulting from local transmission. Methods: A convenience sampling network survey was conducted among individuals infected with SARS-CoV-2 to examine the characteristics and progression of ENT symptoms associated with local transmission. The survey comprised 52 questions, and univariable and multivariable logistic regression analyses were employed to assess the rate, severity, and outcome of ENT symptoms across different genders and age groups. Results: Among the 1,366 individuals included in the investigation, a peak in new infections occurred on 20th December, and the majority (78.4%) were female. The most common symptoms reported were coughing (90.6%), nasal congestion (77.2%), and runny nose (74.3%). Otologic symptoms were predominantly represented by tinnitus (29.7%). Conclusion: The rate of specific symptoms showed a significant correlation with age and gender. It is crucial to provide timely medical intervention, especially for female patients. This study offers a comprehensive understanding of the symptom spectrum in individuals infected with the virus, providing valuable insights for the development of targeted symptom management strategies.

In silico screening combined with bioactivity evaluation to identify AMI-1 as a novel anticancer compound by targeting AXL.

Recently, some studies have proven that AXL plays a crucial role in the drug resistance of tumors. At present, no AXL inhibitors on the market and it is essential to discover novel compounds targeting AXL to overcome resistance. In this work, based on the anchor structure, 21,313 compounds were obtained by substructure search from more than 400,000 compounds. Then, the Qvina and Ledock were selected for virtual screening to obtain 17 compounds. Next, four compounds (ARRY614, AMI-1, NG25, and Butein) were selected for bioactivity evaluation after hydrogen bond and cluster analysis. Further activity evaluation suggested that the compound AMI-1 is a novel AXL inhibitor with an IC50 value of 1.13 uM. In addition, molecular dynamics simulation demonstrated that compound AMI-1 contained lower binding energy and more key residues than the other three compounds, showing the best inhibitory activity against AXL. Finally, further MM/PBSA prediction showed that AMI-1 is more sensitive to mutant protein 3IKA than wildtype protein 1M17, which means that the AMI-1 may be helpful to overcome the resistance of EGFRT790M mutations. In conclusion, this work successfully discovered a novel compound with moderate inhibitory activity against AXL by a drug discovery workflow, which also could be applied to discover active compounds for other targets quickly.Communicated by Ramaswamy H. Sarma.

Photic sensitization is mediated by cortico-accumbens pathway in rats with trigeminal neuropathic pain.

Exposure to light stimuli may trigger or exacerbate perception of pain, also known as a common yet debilitating symptom of photophobia in patient with chronic orofacial pain. Mechanism underlying this phenomenon of photic sensitization in neuropathic condition remains elusive. Here, we found that rats developed hypersensitivity to normal light illumination after establishment of chronic constriction injury of infraorbital nerve (ION-CCI) model, which can be attenuated by blocking the exposure of photic stimulation. Additionally, this behavioral phenotype of light-sensitivity impairment was associated with overexpression of anterior cingulate cortex (ACC) c-fos positive neurons, enhancement of neural excitability in the ACC neurons and its excitatory synaptic transmission between nucleus accumbens (NAc). Optogenetic and chemogenic silencing of ACC-NAc pathway improved trigeminal sensitization in responses to light stimuli by decreasing spontaneous pain-like episodes in ION-CCI animals. In contrast, selective activation of ACC-to-NAc circuits enhanced photic hypersensitivity in dark environment. Thus, our data provided novel role of ACC and its projection to NAc in bidirectional modulation of photic sensation, which may contribute to the understanding of photic allodynia in trigeminal neuropathic pain status.

singleCellBase: a high-quality manually curated database of cell markers for single cell annotation across multiple species.

Annotating cells in the analysis of single-cell RNA-seq (scRNA-seq) data is one of the most challenging tasks that researchers are actively addressing. Manual cell annotation is generally considered the gold standard method, although it is labor intensive and independent of prior knowledge. At present, the relationship between high-quality, known marker genes and cell types is very limited, especially for a variety of species other than humans and mice. The singleCellBase is a manually curated resource of high-quality cell types and gene markers associations across multiple species. In details, it offers 9,158 entries spanning a total of 1,221 cell types and linking with 8,740 genes (cell markers), covering 464 diseases/status, and 165 types of tissues across 31 species. The singleCellBase provides a user-friendly interface to the scientific community to browse, search, download and submit records of marker genes and cell types. The resource providing ineluctable prior knowledge required by manual cell annotation, which is valuable to interpret scRNA-seq data and elucidate what cell type or cell state that a cell population represents.

Construction of a novel signature based on immune-related lncRNA to identify high and low risk pancreatic adenocarcinoma patients.

BACKGROUND: Pancreatic adenocarcinoma is one of the most lethal tumors in the world with a poor prognosis. Thus, an accurate prediction model, which identify patients within high risk of pancreatic adenocarcinoma is needed to adjust the treatment and elevate the prognosis of these patients. METHODS: We obtained RNAseq data of The Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma (PAAD) from UCSC Xena database, identified immune-related lncRNAs (irlncRNAs) by correlation analysis, and identified differential expressed irlncRNAs (DEirlncRNAs) between pancreatic adenocarcinoma tissues from TCGA and normal pancreatic tissues from TCGA and Genotype-Tissue Expression (GTEx). Further univariate and lasso regression analysis were performed to construct prognostic signature model. Then, we calculated the areas under curve and identified the best cut-off value to identify high- and low-risk patients with pancreatic adenocarcinoma. The clinical characteristics, immune cell infiltration, immunosuppressive microenvironment, and chemoresistance were compared between high- and low-risk patients with pancreatic adenocarcinoma. RESULTS: We identified 20 DEirlncRNA pairs and grouped the patients by the best cut-off value. We proved that our prognostic signature model possesses a remarkable efficiency to predict prognosis of PAAD patients. The AUC for ROC curve was 0.905 for 1-year prediction, 0.942 for 2-year prediction, and 0.966 for 3-year prediction. Patients in high-risk group have poor survival rate and worse clinical characteristics. We also proved that patients in high-risk groups were in immunosuppressive status and may be resistant to immunotherapy. Anti-cancer drug evaluation was performed based on in-silico predated tool, such as paclitaxel, sorafenib, and erlotinib, may be suitable for PAAD patients in high-risk group. CONCLUSIONS: Overall, our study constructed a novel prognostic risk model based on pairing irlncRNAs, exhibited a promising prediction value in patients with pancreatic adenocarcinoma. Our prognostic risk model may help distinguish PAAD patients suitable for medical treatments.

GRAPE: A multi-modal dataset of longitudinal follow-up visual field and fundus images for glaucoma management.

As one of the leading causes of irreversible blindness worldwide, glaucoma is characterized by structural damage and functional loss. Glaucoma patients often have a long follow-up and prognosis prediction is an important part in treatment. However, existing public glaucoma datasets are almost cross-sectional, concentrating on segmentation on optic disc (OD) and glaucoma diagnosis. With the development of artificial intelligence (AI), the deep learning model can already provide accurate prediction of future visual field (VF) and its progression with the support of longitudinal datasets. Here, we proposed a public longitudinal glaucoma real-world appraisal progression ensemble (GRAPE) dataset. The GRAPE dataset contains 1115 follow-up records from 263 eyes, with VFs, fundus images, OCT measurements and clinical information, and OD segmentation and VF progression are annotated. Two baseline models demonstrated the feasibility in prediction of VF and its progression. This dataset will advance AI research in glaucoma management.