Design of linked-domain protein inhibitors of UBE2D as tools to study cellular ubiquitination.

Ubiquitin (Ub) is a post-translational modification that largely controls proteostasis through mechanisms spanning transcription, translation, and notably, protein degradation. Ub conjugation occurs through a hierarchical cascade of three enzyme classes (E1, E2, and E3s) involving >1000 proteins that regulate the ubiquitination of proteins. The E2 Ub-conjugating enzymes are the midpoint, yet their cellular roles remain under-characterized, partly due to a lack of inhibitors. For example, the cellular roles of the promiscuous E2 UBE2D/UBCH5 are not well described. Here, we develop a highly selective, multivalent, engineered protein inhibitor for the UBE2D family that simultaneously targets the RING- and backside-binding sites. In HeLa cells, these inhibitors phenocopy knockdown of UBE2D by reducing the IC50 to cisplatin and whole-cell proteomics reveal an increased abundance of ~20% of the identified proteins, consistent with reduced Ub degradation and proteotoxic stress. These precision tools will enable new studies probing UBE2D's central role in proteome management.

IL-22 resolves MASLD via enterocyte STAT3 restoration of diet-perturbed intestinal homeostasis.

The exponential rise in metabolic dysfunction-associated steatotic liver disease (MASLD) parallels the ever-increasing consumption of energy-dense diets, underscoring the need for effective MASLD-resolving drugs. MASLD pathogenesis is linked to obesity, diabetes, "gut-liver axis" alterations, and defective interleukin-22 (IL-22) signaling. Although barrier-protective IL-22 blunts diet-induced metabolic alterations, inhibits lipid intake, and reverses microbial dysbiosis, obesogenic diets rapidly suppress its production by small intestine-localized innate lymphocytes. This results in STAT3 inhibition in intestinal epithelial cells (IECs) and expansion of the absorptive enterocyte compartment. These MASLD-sustaining aberrations were reversed by administration of recombinant IL-22, which resolved hepatosteatosis, inflammation, fibrosis, and insulin resistance. Exogenous IL-22 exerted its therapeutic effects through its IEC receptor, rather than hepatocytes, activating STAT3 and inhibiting WNT-ß-catenin signaling to shrink the absorptive enterocyte compartment. By reversing diet-reinforced macronutrient absorption, the main source of liver lipids, IL-22 signaling restoration represents a potentially effective interception of dietary obesity and MASLD.

Likelihood of Laryngeal Involvement in Autoimmune Thyroid Disorder Patients: A Meta-Analysis.

BACKGROUND: The involvement of the larynx in many situations can have a substantial impact on a person's voice, breathing, and general health. Individuals with autoimmune thyroid disorders can experience a variety of conditions affecting the larynx. Autoimmune thyroid disorders, such as Hashimoto's thyroiditis [HT] and Graves' disease [GD], are prevalent conditions affecting the thyroid gland. Beyond their established impact on thyroid function, these disorders have been associated with laryngeal involvement. The current study aims to explore the likelihood of laryngeal involvement in patients with Autoimmune Thyroid Disorders [AITD]. METHOD: This study involved a retrospective analysis of medical records from patients diagnosed with autoimmune thyroid disorders. Inclusion criteria were a confirmed diagnosis through laboratory investigations and clinical assessment. Patients with pre-existing laryngeal pathologies or other conditions affecting the larynx were not considered. We collected data from 4 research articles and 3 clinical trials from Embase, PubMed, and NCBI-Trials portals, focusing on reported laryngeal symptoms. The severity of laryngeal involvement was assessed and categorized based on its extent and impact on vocal function. RESULTS: Preliminary analysis of the collected data indicated a significant proportion of patients with autoimmune thyroid disorders reporting laryngeal symptoms. Among these patients, various manifestations of laryngeal involvement were observed, including vocal changes, hoarseness, and throat discomfort. CONCLUSION: The findings show that laryngeal symptoms may be an underappreciated feature of these diseases, potentially impacting vocal function and quality of life in affected people. Further research is also needed for more precise projections in this direction.

[Identification and expression analysis of members of R2R3-MYB transcription factors family in Artemisia argyi].

The MYB(v-myb avian myeloblastosis viral oncogene homolog) family of transcription factors is the largest class of genes among higher plant transcription factors, which can be divided into four subfamilies, with the R2R3-MYB being the most common subfamily type. R2R3-MYB transcription factors are widely involved in the regulation of organ development and secondary metabolite biosynthesis in plants. To investigate the role of R2R3-MYB family transcription factors in the synthesis of flavonoids and glandular trichome development in Artemisia argyi, this study screened and identified 92 R2R3-MYB transcription factors based on the whole genome data of A. argyi, and predicted their potential functions based on bioinformatics. The results showed that the amino acid lengths of the 92 transcription factors ranged from 168 to 547 aa, with relative molecular weights ranging from 19. 6 to 60. 5 kDa, all of which were hydrophilic proteins. Subcellular localization analysis showed that 89 AaMYB proteins were located in the nucleus, while three proteins were simultaneously located in the nucleus and cytoplasm. According to the classification of Arabidopsis R2R3-MYB family, the 92 A. argyi R2R3-MYB proteins were divided into 26 subfamilies, with similar gene structures within the same subfamily.Cis-acting element prediction results showed that light-responsive elements, methyl jasmonate elements, and abscisic acid elements were widely distributed in the promoter regions of R2R3-MYB genes. Transcriptome expression analysis results showed that the expression of AaMYB60, AaMYB63, and AaMYB86 in leaves was higher than that in stems and roots, indicating that these three transcription factors mainly function in leaves. Additionally, five candidate R2R3-MYB transcription factors involved in A. argyi flavonoid biosynthesis or glandular trichome development were selected through phylogenetic analysis. This study provides important genetic resources for the breeding of superior varieties and germplasm innovation of A. argyi in the future.

miR-141-3p promotes paclitaxel resistance by attenuating ferroptosis via the Keap1-Nrf2 signaling pathway in breast cancer.

Purpose: Breast cancer poses a huge threat to the lives and health of women worldwide. However, drug resistance makes the treatment of breast cancer challenging. This study aims to investigate the effect of miR-141-3p on paclitaxel resistance and its underlying mechanisms in breast cancer. Methods: Using bioinformatics analysis and qRT-PCR to explore the potential molecule miR-141-3p. Specific binding of miR-141-3p to Keap1 was determined by using a dual luciferase reporter assay. qRT-PCR and Western blot were utilized to observe the expression of miR-141-3p, Keap1, Nrf2, SLC7A11 and GPX4. GSH/GSSG content, MDA content and JC-1 assays were used to observe the ferroptosis levels of breast cancer cells. CCK-8 assay was used to observe the cell viability of breast cancer cells. Tumor subcutaneous transplantation experiment was used to understand the effect of miR-141-3p on paclitaxel resistance in breast cancer in vivo. Results: In the present study, miR-141-3p was found to be highly expressed and associated with poor prognosis in breast cancer. miR-141-3p inhibited Keap1 expression, promoted Nrf2 expression, and facilitated paclitaxel resistance in breast cancer cells. Inhibition of miR-141-3p promoted Keap1 expression, inhibited Nrf2 and its downstream SLC7A11-GSH-GPX4 signaling pathway, as well as promoted ferroptosis in cancer cells, and inhibited paclitaxel and RSL3 resistance. ML385 blocks the effect of miR-141-3p on paclitaxel resistance and ferroptosis resistance in breast cancer cells. In vivo, miR-141-3p mimics promoted paclitaxel resistance, whereas miR-141-3p inhibitors inhibited paclitaxel resistance in breast cancer cells. Conclusion: This work revealed that modulation of the Keap1-Nrf2 signaling pathway by miR-141-3p promoted paclitaxel resistance via regulating ferroptosis in breast cancer cells.

Preoperative frailty as a key predictor of short- and long-term outcomes among octogenarians undergoing hepatectomy for hepatocellular carcinoma: a multicenter comprehensive analysis.

BACKGROUND: When considering hepatectomy for elderly HCC patients, it's essential to assess surgical safety and survival benefits. This study investigated the impact of preoperative frailty, assessed with the Clinical Frailty Scale (CFS), on outcomes for octogenarians undergoing HCC hepatectomy. METHODS: A retrospective cohort study of octogenarians who had hepatectomy for HCC between 2010 and 2022 at 16 hepatobiliary centers was conducted. Patients were categorized as frail or non-frail based on preoperative CFS, with frailty defined as CFS ≥5. The primary endpoints were overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS), with perioperative outcomes as secondary endpoints. RESULTS: Among 240 octogenarians, 105 were characterized as being frail. Frail patients had a higher incidence of postoperative 30-day morbidity and postoperative 30-day and 90-day mortality versus non-frail patients. Meanwhile, 5-year OS, RFS and CSS among frail patients were lower compared with non-frail patients. Univariable and multivariable analysis revealed that preoperative frailty was an independent risk factor of postoperative 30-day morbidity (OR: 2.060), OS (HR: 2.384), RFS (HR: 2.190) and CSS (HR: 2.203). CONCLUSION: Preoperative frailty, as assessed by the CFS, was strongly associated with both short-term outcomes and long-term survival among octogenarians undergoing hepatectomy for HCC. Incorporating frailty assessment into the preoperative evaluation may help optimize patient selection and perioperative care.

Protective Effect of Rosavin Against Intestinal Epithelial Injury in Colitis Mice and Intestinal Organoids.

Introduction: Rhodiola species have been utilized as functional foods in Asia and Europe for promoting health. Research has demonstrated that Rhodiola has the potential to alleviate inflammatory bowel disease (IBD) in animal models. However, the specific active components and the underlying mechanism for ameliorating intestinal damage remain unclear. This study aims to explore the relieving effect of Rosavin (Rov), a known active constituent of Rhodiola, in IBD and the regulatory mechanisms. Methods: The therapeutic effect of Rov was evaluated using a murine model of acute colitis induced by dextran sulfate sodium salt (DSS). Inflammatory cytokines and neutrophil activation markers were measured by corresponding kits. Immunohistochemistry, immunofluorescence, TUNEL, and EdU assays were applied to investigate the tight conjunction proteins expression, epithelial marker expression, number of apoptotic cells, and epithelial proliferation, respectively. The protection effect of Rov on gut epithelial injury was assessed using TNF-α-induced intestinal organoids. Additinally, RNA sequencing was applied to observe the genetic alteration profile in these intestinal organoids. Results: Oral administration of Rov significantly attenuated weight loss and restored colon length in mice. Notably, Rov treatment led to decreased levels of pro-inflammatory cytokines and neutrophil activation markers while increasing anti-inflammatory factors. Importantly, Rov restored intestinal despair by increasing the number of Lgr5+ stem cells, Lyz1+ Paneth cells and Muc2+ goblet cells in intestines of colitis mice, displaying reduced epithelial apoptosis and recovered barrier function. In TNF-α-induced intestinal organoids, Rov facilitated epithelial cell differentiation and protected against TNF-α-induced damage. RNA sequencing revealed upregulation in the gene expression associated with epithelial cells (including Lgr5+, Lyz1+ and Muc2+ cells) proliferation and defensin secretion, unveiling the protective mechanisms of Rov on the intestinal epithelial barrier. Discussion: Rov holds potential as a natural prophylactic agent against IBD, with its protective action on the intestinal epithelium being crucial for its therapeutic efficacy.

Crowd Counting Using Meta-Test-Time Adaptation.

Machine learning algorithms are commonly used for quickly and efficiently counting people from a crowd. Test-time adaptation methods for crowd counting adjust model parameters and employ additional data augmentation to better adapt the model to the specific conditions encountered during testing. The majority of current studies concentrate on unsupervised domain adaptation. These approaches commonly perform hundreds of epochs of training iterations, requiring a sizable number of unannotated data of every new target domain apart from annotated data of the source domain. Unlike these methods, we propose a meta-test-time adaptive crowd counting approach called CrowdTTA, which integrates the concept of test-time adaptation into the meta-learning framework and makes it easier for the counting model to adapt to the unknown test distributions. To facilitate the reliable supervision signal at the pixel level, we introduce uncertainty by inserting the dropout layer into the counting model. The uncertainty is then used to generate valuable pseudo labels, serving as effective supervisory signals for adapting the model. In the context of meta-learning, one image can be regarded as one task for crowd counting. In each iteration, our approach is a dual-level optimization process. In the inner update, we employ a self-supervised consistency loss function to optimize the model so as to simulate the parameters update process that occurs during the test phase. In the outer update, we authentically update the parameters based on the image with ground truth, improving the model's performance and making the pseudo labels more accurate in the next iteration. At test time, the input image is used for adapting the model before testing the image. In comparison to various supervised learning and domain adaptation methods, our results via extensive experiments on diverse datasets showcase the general adaptive capability of our approach across datasets with varying crowd densities and scales.

24 h combined esophageal multichannel intraluminal impedance and pH monitoring in children with chronic cough.

BACKGROUND: Chronic cough in children is closely related to gastroesophageal reflux (GER). However, this association has not been adequately studied due to a lack of diagnostic tools. Combined esophageal multichannel intraluminal impedance and pH (MII-pH) monitoring is considered the most accurate method for evaluating the association between symptoms and reflux, but data on its use in children with chronic cough are still lacking. We aimed to assess the association between chronic cough and GER in children through MII-pH monitoring. METHODS: Children with chronic cough (> 4 weeks) who were suspected gastroesophageal reflux disease(GERD) were selected to undergo 24 h MII-pH monitoring at our hospital. Patients were divided into groups according to their age, body position, reflux index (RI) or total reflux events, and the differences between the groups were analyzed. Then the significance and value of 24 h pH and impedance monitoring in chronic cough and the relationship between chronic cough and reflux were discussed. RESULTS: Overall, 426 patients were included. The median age was 12 months (interquartile range: 6-39.5 months), 129 (30.3%) patients had RI > 7% detected by pH-metry, and 290 (68.1%) patients had positive diagnosis based on the impedance data. GER predominantly occurred in the upright position and mostly involved weakly acidic reflux and mixed gas-liquid reflux. There were 14.1% of children in non-acid GER group were SAP positive showing no difference in acid GER group 13.2% (P = 0.88), whereas patients with SAP > 95% in MII positive group (47[16.2%]) is higher than in MII negative group (P < 0.05). CONCLUSION: Twenty four hour MII-pH monitoring is safe, well tolerated in children, but also has a higher detection rate of gastroesophageal reflux. It can find identify weakly acidic reflux, weakly alkaline reflux and reflux events with different physical properties, which can explain the relationship between GER and chronic cough more comprehensively. It provides new approach for exploring the etiology, diagnosis and treatment of children with chronic cough.

Development and Validation of a Novel Multiplex Real-Time PCR Assay for Rapid Detection of Carbapenemase Genes in Carbapenem-Resistant Enterobacterales Isolates and Clinical Samples.

Purpose: Carbapenem-resistant Enterobacterales (CRE) infection is an urgent threat to human health. This study aimed to develop and validate a novel multiplex real-time PCR (multi-qPCR) assay for the detection of the blaKPC, blaNDM, blaIMP, blaOXA-48-like, and blaVIM genes in CRE isolates and clinical samples, as well as to compare it with three phenotypic methods. Methods: The reliability and limit of detection (LOD) of the multi-qPCR assay were evaluated. PCR and DNA sequencing were used as the reference methods to identify carbapenemase genes in CRE isolates and clinical samples. The accuracy of the multi-qPCR assay, modified carbapenem inactivation and EDTA-modified carbapenem inactivation method (mCIMandeCIM), carbapenemase inhibitor-based combined disk test (CDT), and colloidal gold-based immunochromatographic test was compared with the reference methods with 182 isolates of CRE. Furthermore, 112 clinical samples were collected to validate the efficacy of this multi-qPCR assay. Results: The standard deviations (CVs) of intra-assay and inter-assay of the multi-qPCR assay were ≤ 0.53% and ≤ 2.04% for detecting the five major carbapenemase genes, respectively; while the LOD ranged from 2×102 copies/mL to 8×102 copies/mL. PCR and DNA sequencing confirmed 168 out of 182 CRE isolates producing carbapenemase(s): KPC (n = 93), NDM (n = 46), IMP (n = 8), OXA-48-like (n = 14), VIM (n = 1), KPC&NDM (n = 5), and KPC&NDM&IMP (n = 1). The accuracy of mCIMandeCIM, CDT, Colloidal Gold, and the multi-qPCR assay was 96.2%, 89.6%, 100%, and 100% respectively for detecting carbapenemase(s) producers. Moreover, the sensitivity and specificity of the multi-qPCR assay were all 100% for the detection of each carbapenemase gene in clinical samples, compared with PCR and sequencing. Conclusion: For clinical isolate detection, the multi-qPCR assay is comparable to Colloidal Gold, and superior to mCIMandeCIM and CDT; while for clinical samples detection, it also shows excellent performance. Therefore, the multi-qPCR assay has great potential for clinical diagnosis.

Esophageal ulcer and multisystem inflammatory syndrome after COVID-19: A case report.

BACKGROUND: Multisystem inflammatory syndrome in adults (MIS-A) is a rare but severe disease occurring several weeks after severe acute respiratory syndrome coronavirus 2 infection. It develops in adults with inflammation of different organs including the gastrointestinal tract, heart, kidneys, skin and hematopoietic system. CASE SUMMARY: We present a 58-year-old Chinese man diagnosed with MIS-A. His chief complaints were fever, generalized fatigue and anorexia, accompanied with rashes on his back. Further examination showed cardiac, renal and liver injury. He had melena and gastroscopy indicated esophageal ulcer and severe esophagitis. Repeated blood and sputum culture did not show growth of bacteria or fungi. Antibiotic treatment was stopped due to unsatisfactory performance. His condition improved after prednisone and other supportive treatment. CONCLUSION: Gastrointestinal involvement in MIS-A is not uncommon. Intestinal involvement predominates, and esophageal involvement is rarely reported. Esophageal ulcer with bleeding could also be a manifestation of MIS-A.

Genomic Analysis of a Novel Torradovirus "Rehmannia Torradovirus Virus": Two Distinct Variants Infecting Rehmannia glutinosa.

Rehmannia glutinosa, a crucial medicinal plant native to China, is extensively cultivated across East Asia. We used high-throughput sequencing to identify viruses infecting R. glutinosa with mosaic, leaf yellowing, and necrotic symptoms. A novel Torradovirus, which we tentatively named "Rehmannia torradovirus virus" (ReTV), was identified. The complete sequences were obtained through reverse-transcription polymerase chain reaction (RT-PCR), 5' and 3' rapid amplification of cDNA ends, and Sanger sequencing. The amino acid sequence alignment between the ReTV-52 isolate and known Torradovirus species in the Pro-Pol and coat protein regions were 51.3-73.3% and 37.1-68.1%, respectively. Meanwhile, the amino acid sequence alignment between the ReTV-8 isolate and known Torradovirus species in the Pro-Pol and coat protein regions were 52.7-72.8% and 36.8-67.5%, respectively. The sequence analysis classified ten ReTV strains into two variants. The ReTV-52 genome has two RNA segments of 6939 and 4569 nucleotides, while that of ReTV-8 consists of two RNA segments containing 6889 and 4662 nucleotides. Sequence comparisons and phylogenetic analysis showed ReTV strains clustered within the Torradovirus, exhibiting the closet relation to the squash chlorotic leaf spot virus. The RT-PCR results showed a 100% ReTV detection rate in all 60 R. glutinosa samples. Therefore, ReTV should be classified as a novel Torradovirus species. ReTV is potentially dangerous to R. glutinosa, and necessitating monitoring this virus in the field.

Deciphering the Role of Necroptosis-Related Long Non-coding RNAs in Hepatocellular Carcinoma: A Necroptosis-Related lncRNA-Based Signature to Predict the Prognosis of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer, characterized by a high morbidity rate. Long non-coding RNAs (lncRNAs) play an important role in regulating various cellular processes and diseases, including cancer. However, their specific roles and mechanisms in HCC are not fully understood. This study used a multi-cohort design to investigate necroptosis-related lncRNAs (NRLs) in patients with HCC. We curated a list of 1095 NRLs and 838 genes showing differential expression between tumor and normal tissues. Among them, we found 105 NRLs closely associated with the prognosis of HCC patients. The 10 lncRNAs (AC100803.3, AC027237.2, AL158166.1, LINC02870, AC026412.3, LINC02159, AC027097.1, AC139887.4, AC007405.1, AL023583.1) generated by LASSO-Cox regression analysis were used to create a prognostic risk model for HCC and group patients into groups based on risk. The KEGG analysis revealed distinct pathway enrichments in high-risk (H-R) and low-risk (L-R) subgroups. According to GO analysis, this study identified 230 differentially expressed genes (DEGs) that were significantly enriched in specific biological processes. Comparison of immune checkpoint-related genes (MCPGs) between H-R and L-R patients revealed significant differences. Moreover, we established a correlation between the risk scores of patients with liver cancer and their sensitivity to 16 chemotherapeutic agents. Employing protein-protein interaction (PPI) analysis, we identified 10 hub genes that potentially regulate the molecular networks involved in HCC development. This study is a pioneering effort to investigate the roles of NRLs in HCC. It opens a new avenue for potential targeted therapies and provides insights into the molecular mechanisms of HCC.

Respiratory virus infections and adenovirus characteristics during acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease globally, characterized by obstructive ventilatory disorder under pulmonary function tests. Recent years have witnessed a yearly increase in the prevalence of COPD. OBJECTIVE: To investigate the impact of respiratory virus infections on patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and to perform sequencing typing and mutation analysis of viruses with high detection rate. METHODS: A total of 1523 inpatients with AECOPD admitted to our hospital from April 1,2020 to March 30,2022 were collected and divided into two groups: the infected group (n= 532) and the non-infected group (n= 991). The related indexes between the two groups were collected and compared (including clinical characteristics and laboratory tests that blood cell count, PCT, CRP, adenovirus, respiratory syncytial virus, rhinovirus, influenza A virus, influenza B virus, etc.). RESULTS: In the infected group, the proportion of patients with palpitations (49.44% VS 8.07%, P< 0.001), lipid metabolism abnormalities (18.42% VS 39.96%, P< 0.001), heart failure (39.85% VS 29.87%, P< 0.001), disease duration (17.48 ± 7.47 VS 12.45 ± 11.43 d, P< 0.001), and poor prognosis (69.55% VS 17.15%, P< 0.001) were higher than those in the non-infected group; Adenovirus (ADV) accounted for 75.94% (404/532) of all infected viruses. 31 virus strains could be categorized into 16 ADV-C1, one ADV-C5, two ADV-B3, three ADV-B7, two ADV-D17, two ADV-D19, and five ADV-D27, which were similar to the serotypes reported in severe pneumonia. Furthermore, three strains of C1 adenovirus were found to be highly homologous to the original strain AF534906 by sequencing, and the phylogenetic trees of the three main structural genes were all on the same branch as the original strain. Base mutations and amino acid variants were found in each structural gene segment. In clinical data, it's found that patients with mutations are worse than those without mutations. CONCLUSION: Respiratory viruses are common in patients with poor prognosis of AECOPD, especially adenovirus, respiratory syncytial virus. Respiratory virus infections will lead to the deterioration of patients with AECOPD, accompanied by longer treatment cycles and poor prognosis.

5-aminolevulinic acid photodynamic therapy protects against UVB-induced skin photoaging: A DNA-repairing mechanism involving the BER signalling pathway.

Low-dose 5-aminolevulinic acid photodynamic therapy (ALA-PDT) has been used to cope with skin photoaging, and is thought to involve DNA damage repair responses. However, it is still unknown how low-dose ALA-PDT regulates DNA damage repair to curb skin photoaging. We established a photoaging model using human dermal fibroblasts (HDFs) and rat skin. RNA-sequencing (RNA-seq) analysis was conducted to identify differentially expressed genes (DEGs) in HDFs before and after low-dose ALA-PDT treatment, followed by bioinformatics analysis. Senescence-associated ß-galactosidase (SA-ß-gal) staining was employed to assess skin aging-related manifestations and Western blotting to evaluate the expression of associated proteins. A comet assay was used to detect cellular DNA damage, while immunofluorescence to examine the expression of 8-hydroxy-2'-deoxyguanosine (8-oxo-dG) in cells and skin tissues. In both in vivo and in vitro models, low-dose ALA-PDT alleviated the manifestations of ultraviolet B (UVB)-induced skin photoaging. Low-dose ALA-PDT significantly reduced DNA damage in photoaged HDFs. Furthermore, low-dose ALA-PDT accelerated the clearance of the photoproduct 8-oxo-dG in photoaged HDFs and superficial dermis of photoaged rat skin. RNA-seq analysis suggested that low-dose ALA-PDT upregulated the expression of key genes in the base excision repair (BER) pathway. Further functional validation showed that inhibition on BER expression by using UPF1069 significantly suppressed SA-ß-gal activity, G2/M phase ratio, expression of aging-associated proteins P16, P21, P53, and MUTYH proteins, as well as clearance of the photoproduct 8-oxo-dG in photoaged HDFs. Low-dose ALA-PDT exerts anti-photoaging effects by activating the BER signalling pathway.

The prognostic value of pretreatment 18F-FDG PET-CT parameters with peripheral blood markers in patients with de novo metastatic nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: To develop and validate a prognostic nomogram based on pretreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT)radiomics parameters and peripheral blood markers for risk stratification in patients with de novo metastatic nasopharyngeal carcinoma (dmNPC). MATERIALS AND METHODS: A total of 558 patients with dmNPC were retrospectively enrolled between 2011 and 2019. Eligible patients were randomly divided into training and validation cohorts (7:3 ratio). A Cox regression model was used to identify prognostic factors for overall survival (OS). The predictive accuracy and discriminative ability of the prognostic nomogram were determined using the concordance index (C-index) and calibration curve. RESULTS: Independent factors derived from multivariable analysis of the training cohort to predict death were lactate dehydrogenase levels, pretreatment Epstein-Barr virus DNA, total lesion glycolysis of locoregional lesions, number of metastatic lesions, and age, all of which were assembled into a nomogram with (nomogram B) or without PET-CT parameters (nomogram A). The C-index of nomogram B for predicting death was 0.70, which was significantly higher than the C-index values for nomogram A. Patients were then stratified into low- and high-risk groups based on the scores calculated using nomogram B for OS. The median OS was significantly higher in the low-risk group than in the high-risk group (69.60 months [95 % CI: 58.50-108.66] vs. 21.40 months [95 % CI: 19.20-23.90]; p＜0.01). All the results were confirmed in the validation cohort. CONCLUSION: The proposed nomogram including PET-CT parameters yielded accurate prognostic predictions for patients with dmNPC, enabling effective risk stratification for these patients.

PD-L2 Expression in Breast Cancer Promotes Tumor Development and Progression.

Background: This work focused on investigating the role of programmed death ligand 2 (PD-L2) in the progression of breast cancer by utilizing breast cancer specimens and cells. Materials and Methods: The serum levels of soluble PD-L2 (sPD-L2) in breast cancer patients and healthy individuals were analyzed by means of the enzyme-linked immunosorbent assay, and the PD-L2 levels within 416 resected breast cancer specimens were assessed through immunohistochemistry. Concurrently, in vitro cell experiments and in vivo animal experiments were carried out to analyze the relationship between PD-L2 and the invasion and migration of breast cancer. Results: The concentration of sPD-L2 in breast cancer patients significantly increased compared to that in the control groups. Additionally, breast cancer patients with high concentrations of sPD-L2 had higher Ki67 values (≥30%) and tumor grades. PD-L2 was expressed in 79.09% of the cancer samples, which exhibited a positive correlation with the progesterone receptor (PR) and the human epidermal growth factor receptor 2 (HER2). Furthermore, we discovered that knockdown of PD-L2 inhibited the migratory and invasive abilities of both MCF-7 and MDA-MB231 cells. Conclusion: Our findings demonstrated that knockdown of PD-L2 suppressed tumor growth, providing novel insights into important biological functions.

Value of combining targeted emergency nursing with psychological nursing in children with febrile convulsions.

BACKGROUND: Febrile convulsions are a common pediatric emergency that imposes significant psychological stress on children and their families. Targeted emergency care and psychological nursing are widely applied in clinical practice, but their value and impact on the management of pediatric febrile convulsions are unclear. AIM: To determine the impact of targeted emergency nursing combined with psychological nursing on satisfaction in children with febrile convulsions. METHODS: Data from 111 children with febrile convulsions who received treatment at Nantong Maternal and Child Health Care Hospital between June 2021 and October 2022 were analyzed. The control group consisted of 44 children who received conventional nursing care and the research group consisted of 67 children who received targeted emergency and psychological nursing. The time to fever resolution, time to resolution of convulsions, length of hospital stays, Pittsburgh Sleep Quality Index, patient compliance, nursing satisfaction of the parents, occurrence of complications during the nursing process, and parental anxiety and depression were compared between the control and research groups. Parental anxiety and depression were assessed using the Hamilton Rating Scale for Depression (HAMD) and the Hamilton Rating Scale for Anxiety (HAMA). RESULTS: The fever resolution, convulsion disappearance, and hospitalization times were longer in the control group compared with the research group (P < 0.0001). The time to falling asleep, sleep time, sleep quality, sleep disturbance, sleep efficiency, and daytime status scores were significantly better in the research group compared with the control group (P < 0.0001). The HAMD and HAMA scores for parents of children in the research group were lower than the scores in the control group after nursing (P < 0.05). Compliance with treatment of children in the research group was higher than in the control group (P < 0.05). Parental satisfaction with nursing in the research group was higher than in the control group (P < 0.05). The total complication rate of children in the control group was higher than in the research group (P < 0.05). CONCLUSION: Combining psychological nursing with targeted emergency nursing improved the satisfaction of children's families and compliance with treatment and promoted early recovery of clinical symptoms and improvement of sleep quality.

Biodegradation of polystyrene (PS) and polypropylene (PP) by deep-sea psychrophilic bacteria of Pseudoalteromonas in accompany with simultaneous release of microplastics and nanoplastics.

Plastics dumped in the environment are fragmented into microplastics by various factors (UV, weathering, mechanical abrasion, animal chewing, etc.). However, little is known about plastic fragmentation and degradation mediated by deep-sea microflora. To obtain deep-sea bacteria that can degrade plastics, we enriched in situ for 1 year in the Western Pacific using PS as a carbon source. Subsequently, two deep-sea prevalent bacteria of the genus Pseudoalteromonas (Pseudoalteromonas lipolytica and Pseudoalteromonas tetraodonis) were isolated after 6 months enrichment in the laboratory under low temperature (15 °C). Both showed the ability to degrade polystyrene (PS) and polypropylene (PP), and biodegradation accelerated the generation of micro- and nanoplastics. Plastic biodegradation was evidenced by the formation of carboxyl and carboxylic acid groups, heat resistance decrease and plastic weight loss. After 80 days incubation at 15 °C, the microplastic concentration of PS and PP could be up to 1.94 × 107/L and 5.83 × 107/L, respectively, and the proportion of nanoplastics (< 1 µm) could be up to 65.8 % and 73.6 %. The film weight loss were 5.4 % and 4.5 % of the PS films, and 2.3 % and 1.8 % of the PP films by P. lipolytica and P. tetraodonis, respectively; thus after discounting the weight loss of microplastics, the only 3.9 % and 2.8 % of the PS films, and 1.3 % and 0.7 % of the PP films, respectively, were truly degraded by the two bacteria respectively after 80 days of incubation. This study highlights the role of Pseudoalteromonas in fragmentation and degradation of plastics in cold dark pelagic deep sea.

Resurgence of seasonal influenza driven by A/H3N2 and B/Victoria in succession during the 2023-2024 season in Beijing showing increased population susceptibility.

During the COVID-19 pandemic, non-pharmaceutical interventions were introduced to reduce exposure to respiratory viruses. However, these measures may have led to an "immunity debt" that could make the population more vulnerable. The goal of this study was to examine the transmission dynamics of seasonal influenza in the years 2023-2024. Respiratory samples from patients with influenza-like illness were collected and tested for influenza A and B viruses. The electronic medical records of index cases from October 2023 to March 2024 were analyzed to determine their clinical and epidemiological characteristics. A total of 48984 positive cases were detected, with a pooled prevalence of 46.9% (95% CI 46.3-47.5). This season saw bimodal peaks of influenza activity, with influenza A peaked in week 48, 2023, and influenza B peaked in week 1, 2024. The pooled positive rates were 28.6% (95% CI 55.4-59.6) and 18.3% (95% CI 18.0-18.7) for influenza A and B viruses, respectively. The median values of instantaneous reproduction number were 5.5 (IQR 3.0-6.7) and 4.6 (IQR 2.4-5.5), respectively. The hospitalization rate for influenza A virus (2.2%, 95% CI 2.0-2.5) was significantly higher than that of influenza B virus (1.1%, 95% CI 0.9-1.4). Among the 17 clinical symptoms studied, odds ratios of 15 symptoms were below 1 when comparing influenza A and B positive inpatients, with headache, weakness, and myalgia showing significant differences. This study provides an overview of influenza dynamics and clinical symptoms, highlighting the importance for individuals to receive an annual influenza vaccine.