Salvage surgery and conversion surgery for patients with non-small cell lung cancer: A narrative review.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths. With the development of screening, patient selection and treatment strategies, patients' survival outcomes and living quality significantly improved. However, some patients still have local recurrence or residual tumors after receiving definitive therapies. Salvage surgery has been regarded as an effective option for recurrent or residual NSCLC, but its effectiveness remains undetermined. Furthermore, conversion surgery is a special type of salvage surgery for tumors converted from "initially unresectable" to "potentially resectable" status due to a favorable response to systemic treatments. Although conversion surgery is a promising curative procedure for advanced NSCLC, its concept and clinical value remain unfamiliar to clinicians. In this narrative review, we provided an overview of the safety and efficacy of salvage surgery, especially salvage surgery after sublobar resection in early-stage NSCLC. More importantly, we highlighted the concept and value of conversion surgery after systemic treatment in advanced NSCLC to gain some insights into its role in the treatment of lung cancer.

New perspectives in prognostication of hepatocellular carcinoma: The role and clinical implications of transient receptor potential family genes.

The study titled "Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients" is a significant contribution to hepatocellular carcinoma (HCC) research, highlighting the role of transient receptor potential (TRP) family genes in the disease's progression and prognosis. Utilizing data from The Cancer Genome Atlas database, it establishes a new risk assessment model, emphasizing the interaction of TRP genes with tumor proliferation pathways, key metabolic reactions like retinol metabolism, and the tumor immune microenvironment. Notably, the overexpression of the TRPC1 gene in HCC correlates with poorer patient survival outcomes, suggesting its potential as a prognostic biomarker and a target for personalized therapy, particularly in strategies combining immunotherapy and anti-TRP agents.

Cross-linked Sodium Hyaluronate Gel with PLLA-b-PEG Microsphere for Facial Contouring in Chinese: A Retrospective Study.

BACKGROUND: In Asia, the demand for cosmetic facial treatments has surged due to technological advancements, increased social acceptability, and affordability. Poly-L-lactic acid (PLLA) fillers, known for their biocompatibility and biodegradability, have emerged as a popular choice for facial contouring, yet studies specifically addressing their use in Asian populations are scarce. METHODS: This retrospective study examined 30 Chinese patients who underwent facial contouring with PLLA fillers, focusing on product composition, injection techniques, and safety measures. A comprehensive clinical evaluation was performed, including the Global Aesthetic Improvement Scale (GAIS) and Global Impression of Change Scale (GICS) for effectiveness and patient satisfaction, respectively. RESULTS: No significant difference in GAIS scores was observed between injectors and blinded evaluators over a 12-month period, indicating consistent effectiveness. Patient satisfaction remained high, with GICS scores reflecting positive outcomes. The safety profile was favorable, with no serious adverse events reported. The study highlighted the importance of anatomical knowledge to avoid complications, particularly in areas prone to blindness. CONCLUSIONS: PLLA fillers offer a safe, effective option for facial contour correction in the Asian population, achieving high patient satisfaction and maintaining results over time. The study underscores the need for tailored approaches in cosmetic procedures for Asians, considering their unique facial structures and aesthetic goals. Further research with larger, multicenter cohorts is recommended to validate these findings and explore long-term effects. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

[Examination of the Thermal Stability and Swallowing Safety of a Self-Developed Enteral Nutrition Thickening Agent]. / è‡ªåˆ¶è‚ å† è¥å »æ¶²å¢žç¨ å‰‚çš„çƒ­ç¨³å®šæ€§åŠåžå’½å®‰å ¨æ€§æŽ¢ç´¢.

Objective: To experimentally validate the effects of a self-developed heat-stable thickening agent on the textual characteristics of enteral nutrition solutions of standard concentration and its applicability in improving dysphagia. Methods: A gradient of different doses of the self-developed thickening agent (1.0 g, 1.5 g, 2.0 g, 2.5 g, and3.0 g) and three commonly used commercial thickeners were mixed with 23.391 g of a complete nutrition formula powder dissolved in 85 mL of purified water to prepare 100 mL standard concentration nutrition solutions. The textual parameters (cohesiveness, viscosity, thickness, and hardness) of these nutrition solutions were measured using a texture analyzer at various temperature gradients (20 ℃, 40 ℃, 60 ℃, and 80 ℃) to compare their thermal stability. A dysphagia rat model was created via epiglottectomy to explore the effects of the thickener on lung tissue damage scores and levels of inflammatory markers. The rats were divided into a test intervention group, a positive control group, a negative control group, and a blank control group (no surgery and normal feeding after fasting for one day), with 15 rats in each group. After fasting for one day post-surgery, the test intervention group was fed with the standard concentration nutrition solution thickened with the self-developed thickener, while the positive control group was given a standard concentration nutrition solution thickened with product 3, and the negative control group was fed a normal diet. All groups were fed for two weeks with food dyed with food-grade green dye. General conditions, body mass, and food intake were observed and recorded. After two weeks, abdominal aorta blood was collected, and heart, liver, spleen, lung, and kidney tissues were harvested and weighed to calculate the lung tissue organ coefficient. The organ conditions were evaluated using routine H&E staining, and lung damage was semi-quantitatively analyzed based on the Mikawa scoring criteria. Blood supernatants were collected to measure the total serum protein and albumin levels to determine the nutritional status of the rats. The expression of IL-6 and TNF-α genes in lung tissues was measured by RT-qPCR. IL-6 and TNF-α protein expression levels in lung tissues, lung tissue homogenate, and serum were measured by ELISA. The aspiration incidence rate was calculated. Results: Within the dosage range of 1.0 g to 3.0 g, the self-developed thickener in the test samples exhibited superior thermal stability in cohesiveness compared to the three commercially available thickeners, with a statistically significant difference (P<0.01). The differences in the thermal stability of viscosity and hardness between the self-developed thickener and the three commercially available thickeners were not statistically significant. The viscosity stability was optimal for the self-developed thickener, followed by the commercially available thickeners 1 and 3, with thickeners 2 being the least stable, though the differences were not statistically significant (P>0.05). Product 1 showed the best thermal stability in thickness, followed by the self-developed thickener and product 2, while the product 3 exhibited the worst performance, with the difference being statistically significant (P<0.01). The self-developed thickener had the best thermal stability in hardness at temperatures ranging from 20℃ to 80 ℃, followed by products 1 and 2, with product 3 being the least stable. However, the differences were not statistically significant (P>0.05). Animal experiment results indicated that the body weight gain in the positive control group and the test intervention group was lower than that in the blank and negative control groups (P<0.01). The spleen coefficient of the intervention group was lower than that of the positive control group and the blank control group (P<0.01), while the heart, liver, and kidney coefficients were lower than those of the blank control group (P<0.01). The differences in the lung coefficient of the intervention group and those of the other three groups were no statistically significant. Levels of TP and ALB in the test intervention group, the positive control group, and the negative control group were all lower than those in the blank control group, with statistically significant differences (P<0.01). ELISA results showed that serum IL-6 levels in the blank and test intervention groups were lower than those in the negative and positive control groups (P<0.05), while the difference in the other indicators across the four groups were not statistically significant (P>0.05). There were no statistically significant differences among the four groups in terms of lung tissue damage pathology scores, or in the levels of IL-6 and TNF-α gene expression in lung tissues. The aspiration incidence rate was 0% in all groups. Conclusion: The self-developed enteral nutrition thickening agent demonstrated excellent thermal stability and swallowing safety. Further research to explore its application in patients with dysphagia is warranted.

Impact of glucose-containing fluid on acute pancreatitis outcomes: A multicenter retrospective analysis.

INTRODUCTION: Fluid resuscitation reduces mortality and morbidity in acute pancreatitis (AP); however, whether glucose-containing fluids negatively impact AP remains uncertain. We aimed to examine the association between glucose-containing fluids and AP outcomes. METHODS: This multicenter retrospective cohort study included patients diagnosed with AP between January 2015 and December 2018. Glucose density was defined as total glucose content divided by total fluid volume (g/dl) on day 1, and was considered high if the level exceeded the median. Endpoints were early organ failure (OF), including cardiovascular, renal, or respiratory system failure within 7 days; 30-day OF; ICU admission; and AP-related 90-day mortality. Logistic regression models, restricted cubic spline curves, and Cox proportional hazards models were used for statistical analysis. RESULTS: From the database, 1,146 patients with AP were included. Early OF occurred in 8.8% of patients within 7 days. The high glucose-density group (>5 g/dl) had increased risk of early OF (9.7% vs. 8.2%; adjusted odds ratio [aOR], 1.69; 95% confidence interval [CI], 1.03-2.80; P = 0.039), respiratory failure (8.0% vs. 6.2%; aOR, 1.88; 95% CI, 1.09-3.24; P = 0.024), cardiovascular failure (3.4% vs. 2.4%; aOR, 3.59; 95% CI, 1.28-10.0; P = 0.015), and ICU admission (6.8% vs. 5.8%; aOR, 2.06; 95% CI, 1.08-3.94; P = 0.029), with a dose-response effect observed for cardiovascular failure and ICU admission. A significant increase 30-day OF risk (adjusted hazard ratio [aHR], 1.70; 95% CI, 1.19-2.45) was also noted. CONCLUSION: Excess glucose-containing fluid was associated with increased risks of overall, respiratory, and cardiovascular OF and ICU admission in AP.

ABBV-744 alleviates LPS-induced neuroinflammation via regulation of BATF2-IRF4-STAT1/3/5 axis.

Suppression of neuroinflammation using small molecule compounds targeting the key pathways in microglial inflammation has attracted great interest. Recently, increasing attention has been gained to the role of the second bromodomain (BD2) of the bromodomain and extra-terminal (BET) proteins, while its effect and molecular mechanism on microglial inflammation has not yet been explored. In this study, we evaluated the therapeutic effects of ABBV-744, a BD2 high selective BET inhibitor, on lipopolysaccharide (LPS)-induced microglial inflammation in vitro and in vivo, and explored the key pathways by which ABBV-744 regulated microglia-mediated neuroinflammation. We found that pretreatment of ABBV-744 concentration-dependently inhibited the expression of LPS-induced inflammatory mediators/enzymes including NO, TNF-α, IL-1ß, IL-6, iNOS, and COX-2 in BV-2 microglial cells. These effects were validated in LPS-treated primary microglial cells. Furthermore, we observed that administration of ABBV-744 significantly alleviated LPS-induced activation of microglia and transcriptional levels of pro-inflammatory factors TNF-α and IL-1ß in mouse hippocampus and cortex. RNA-Sequencing (RNA-seq) analysis revealed that ABBV-744 induced 508 differentially expressed genes (DEGs) in LPS-stimulated BV-2 cells, and gene enrichment and gene expression network analysis verified its regulation on activated microglial genes and inflammatory pathways. We demonstrated that pretreatment of ABBV-744 significantly reduced the expression levels of basic leucine zipper ATF-like transcription factor 2 (BATF2) and interferon regulatory factor 4 (IRF4), and suppressed JAK-STAT signaling pathway in LPS-stimulated BV-2 cells and mice, suggesting that the anti-neuroinflammatory effect of ABBV-744 might be associated with regulation of BATF2-IRF4-STAT1/3/5 pathway, which was confirmed by gene knockdown experiments. This study demonstrates the effect of a BD2 high selective BET inhibitor, ABBV-744, against microglial inflammation, and reveals a BATF2-IRF4-STAT1/3/5 pathway in regulation of microglial inflammation, which might provide new clues for discovery of effective therapeutic strategy against neuroinflammation.

Moiré fringe imaging of heterostructures by scanning transmission electron microscopy.

A heterostructured crystalline bilayer specimen is known to produce moiré fringes (MFs) in the conventional transmission electron microscopy (TEM). However, the understanding of how these patterns form in scanning transmission electron microscopy (STEM) remains limited. Here, we extended the double-scattering model to establish the imaging theory of MFs in STEM for a bilayer sample and applied this theory to successfully explain both experimental and simulated STEM images of a perovskite PbZrO3/SrTiO3 system. Our findings demonstrated that the wave vectors of electrons exiting from Layer-1 and their relative positions with the atomic columns of Layer-2 should be taken into account. The atomic column misalignment leads to a faster reduction in the intensity of the secondary scattering beam compared to the single scattering beam as the scattering angle increases. Consequently, the intensity distribution of MFs in the bright field (BF)-STEM can be still described as the product of two single atomic images. However, in high angle annular dark field (HAADF)-STEM, it is approximately described as the superposition of the two images. Our work not only fills a knowledge gap of MFs in incoherent imaging, but also emphasizes the importance of the coherent scattering restricted by the real space when analyzing the HAADF-STEM imaging.

Structural basis for activation of somatostatin receptor 5 by cyclic neuropeptide agonists.

Somatostatin receptor 5 (SSTR5) is an important G protein-coupled receptor and drug target for neuroendocrine tumors and pituitary disorders. This study presents two high-resolution cryogenicelectron microscope structures of the SSTR5-Gi complexes bound to the cyclic neuropeptide agonists, cortistatin-17 (CST17) and octreotide, with resolutions of 2.7 Å and 2.9 Å, respectively. The structures reveal that binding of these peptides causes rearrangement of a "hydrophobic lock", consisting of residues from transmembrane helices TM3 and TM6. This rearrangement triggers outward movement of TM6, enabling Gαi protein engagement and receptor activation. In addition to hydrophobic interactions, CST17 forms conserved polar contacts similar to somatostatin-14 binding to SSTR2, while further structural and functional analysis shows that extracellular loops differently recognize CST17 and octreotide. These insights elucidate agonist selectivity and activation mechanisms of SSTR5, providing valuable guidance for structure-based drug development targeting this therapeutically relevant receptor.

Global Clue-Guided Cross-Memory Quaternion Transformer Network for Multisource Remote Sensing Data Classification.

Multisource remote sensing data classification is a challenging research topic, and how to address the inherent heterogeneity between multimodal data while exploring their complementarity is crucial. Existing deep learning models usually directly adopt feature-level fusion designs, most of which, however, fail to overcome the impact of heterogeneity, limiting their performance. As such, a multimodal joint classification framework, called global clue-guided cross-memory quaternion transformer network (GCCQTNet), is proposed for multisource data i.e., hyperspectral image (HSI) and synthetic aperture radar (SAR)/light detection and ranging (LiDAR) classification. First, a three-branch structure is built to extract the local and global features, where an independent squeeze-expansion-like fusion (ISEF) structure is designed to update the local and global representations by considering the global information as an agent, suppressing the negative impact of multimodal heterogeneity layer by layer. A cross-memory quaternion transformer (CMQT) structure is further constructed to model the complex inner relationships between the intramodality and intermodality features to capture more discriminative fusion features that fully characterize multimodal complementarity. Finally, a cross-modality comparative learning (CMCL) structure is developed to impose the consistency constraint on global information learning, which, in conjunction with a classification head, is used to guide the end-to-end training of GCCQTNet. Extensive experiments on three public multisource remote sensing datasets illustrate the superiority of our GCCQTNet with regards to other state-of-the-art methods.

The single-cell opioid responses in the context of HIV (SCORCH) consortium.

Substance use disorders (SUD) and drug addiction are major threats to public health, impacting not only the millions of individuals struggling with SUD, but also surrounding families and communities. One of the seminal challenges in treating and studying addiction in human populations is the high prevalence of co-morbid conditions, including an increased risk of contracting a human immunodeficiency virus (HIV) infection. Of the ~15 million people who inject drugs globally, 17% are persons with HIV. Conversely, HIV is a risk factor for SUD because chronic pain syndromes, often encountered in persons with HIV, can lead to an increased use of opioid pain medications that in turn can increase the risk for opioid addiction. We hypothesize that SUD and HIV exert shared effects on brain cell types, including adaptations related to neuroplasticity, neurodegeneration, and neuroinflammation. Basic research is needed to refine our understanding of these affected cell types and adaptations. Studying the effects of SUD in the context of HIV at the single-cell level represents a compelling strategy to understand the reciprocal interactions among both conditions, made feasible by the availability of large, extensively-phenotyped human brain tissue collections that have been amassed by the Neuro-HIV research community. In addition, sophisticated animal models that have been developed for both conditions provide a means to precisely evaluate specific exposures and stages of disease. We propose that single-cell genomics is a uniquely powerful technology to characterize the effects of SUD and HIV in the brain, integrating data from human cohorts and animal models. We have formed the Single-Cell Opioid Responses in the Context of HIV (SCORCH) consortium to carry out this strategy.

Molecular basis for the activation of PAF receptor by PAF.

Platelet-activating factor (PAF) is a potent phospholipid mediator crucial in multiple inflammatory and immune responses through binding and activating the PAF receptor (PAFR). However, drug development targeting the PAFR has been limited, partly due to an incomplete understanding of its activation mechanism. Here, we present a 2.9-Å structure of the PAF-bound PAFR-Gi complex. Structural and mutagenesis analyses unveil a specific binding mode of PAF, with the choline head forming cation-π interactions within PAFR hydrophobic pocket, while the alkyl tail penetrates deeply into an aromatic cleft between TM4 and TM5. Binding of PAF modulates conformational changes in key motifs of PAFR, triggering the outward movement of TM6, TM7, and helix 8 for G protein coupling. Molecular dynamics simulation suggests a membrane-side pathway for PAF entry into PAFR via the TM4-TM5 cavity. By providing molecular insights into PAFR signaling, this work contributes a foundation for developing therapeutic interventions targeting PAF signal axis.

[Optimized nutrients management improved citrus yield and fruit quality in China: A meta-analysis]. / å »åˆ†ä¼˜åŒ–ç®¡ç†æé«˜æˆ‘å›½æŸ‘æ©˜äº§é‡å’Œå“è´¨çš„æ•´åˆåˆ†æž.

Clarifying current situation of farmers' fertilization and yield in citrus producing areas and the effects of different fertilization measures can provide a scientific basis for improving the yield and quality of citrus in China. We retrieved 92 literatures on citrus fertilization from the CNKI and Web of Science to examine the impacts of nitrogen (N), phosphorus (P or P2O5), and potassium (K or K2O) fertilizer dosage and partial productivity under farmers' conventional fertilization and experts' optimized fertilization, as well as the effects of optimized fertilization measures on citrus yield and quality by using meta-analysis approach. The average conventional application rates of N, P2O5, and K2O were 507.3, 262.2, and 369.3 kg·hm-2 in citrus production in China. Compared with conventional fertilization, optimized fertilization resulted in a reduction of N and P2O5 by 14.7% and 8.3%, an increase in K2O application by 6.6%, which promoted partial productivity of N, P2O5, and K2O fertilizers by 7.8%, 18.4%, and 14.7%, correspondingly. The optimized fertilization resulted in 11.9% and 2.8% increase in fruit yield and single fruit weight, while improved vitamin C content (Vc, 3.1%), total soluble solids (TSS, 5.9%) and total sugar content (TSC, 8.6%). Additionally, it also led to a reduction in titratable acid (TA, -3.4%) and total acid content (TAC, -3.6%), and consequently elevated the TSS/TA (14.0%) and TSC/TAC (9.5%). Among different optimized fertilization methods, the effect of optimized NPK + medium and/or micro element fertilizer on citrus yield and fruit quality was the best, especially NPK decrement ≤25% between optimized NPK measures. The effect of conventional NPK + organic fertilizer was higher than conventional NPK + medium and/or micro element fertilizer. However, different citrus varieties, including mandarins, pomelos, and oranges, showed different responses to optimized fertilization. Optimized fertilization management could synergistically improve citrus yield, fertilizer use efficiency, and fruit quality. Therefore, the strategy of integrated nutrient management1 with reducing NPK fertilizer, balancing medium and/or micro nutrient fertilizer and improving soil fertility by organic fertilizer should be adopted according to local conditions in citrus producing areas of China.

Prognostic factors for patients with pathologic T1-T2N+ esophageal squamous cell carcinoma: A retrospective study with external validation.

BACKGROUND: Lymph node metastasis is significantly associated with a worse prognosis in patients with localized early-stage esophageal squamous cell carcinoma. This study aimed to explore the prognostic factors and develop a nomogram for predicting survival in patients with pathologic T1-2N+ esophageal squamous cell carcinoma. METHODS: Between 2014 and 2022, patients with pT1-2N+ esophageal squamous cell carcinoma who underwent esophagectomy with lymphadenectomy at 2 institutes were reviewed and assigned to training and external validation cohorts. Independent prognostic factors were identified via univariate and multivariate Cox regression analyses. The nomogram model was developed and evaluated by the area under the receiver operating characteristic curve and calibration curve. RESULTS: In total, 268 patients with a median age of 65 years (range, 40-82) were included and assigned to training (n = 190) and external validation (n = 78) cohorts. The Cox proportional hazards model demonstrated that body mass index (P = .031), surgical approach (P < .001), T stage (P = .015), and Clavien-Dindo classification (P < .001) were independent prognostic factors in the training cohort. The nomogram showed good discrimination, with an area under the receiver operating characteristic curve for 1-year, 3-year, and 5-year of 0.810, 0.789, and 0.809 in the training cohort and 0.782, 0.679, and 0.698 in the validation cohort. The calibration curve showed that the predicted survival probability was in good agreement with the actual survival probability. CONCLUSION: Lower body mass index, left surgical approach, T2 stage, and Clavien-Dindo classification grade III to V were related to worse prognosis in patients with pT1-T2N+ esophageal squamous cell carcinoma. The developed nomogram may predict individual survival accurately.

Sex Differences in Anxiety and Depression Conditions among Cancer Patients: A Systematic Review and Meta-Analysis.

(1) Background: Evidence suggested inconsistent results in anxiety and depression scores among female and male cancer patients. The present systematic review and meta-analysis aimed to assess how anxiety and depression conditions among cancer patients vary according to sex. (2) Methods: This systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). The protocol was registered in PROSPERO with id no. CRD42024512553. The search strategy involved combining keywords using Boolean operators, including "Anxiety", "Cancer", and "Depression", across several databases: Embase, PubMed, Scopus, and Web of Science. The outcomes were evaluated using the Hospital Anxiety and Depression Scale (HADS). (3) Results: Data were collected from five studies, enrolling a total of 6317 cancer patients, of whom 2961 were females and 3356 males. For each study, HADS-A and HADS-D scores were considered, also differentiating HADS scores according to cancer typology, and then three different meta-analyses were performed. Generally, females reported significantly higher levels of depression scores than males and, conversely, males reported significantly greater levels of anxiety than females. (4) Conclusions: Previous studies suggested higher rates of depression and anxiety conditions in females than in males, but the present data highlighted controversial findings, since males reported significantly higher levels of anxiety than females. In this scenario, the theoretical approach justified females being more open than males to expressing anxiety or depression conditions. It would be necessary for healthcare professionals to improve effective measures purposed at assessing and mitigating depressive symptoms in cases of advanced cancer, thereby improving their mental health, given the high rates of depression in advanced cancer patients, due to the difficulty level of performing their daily living activities, which deteriorate further over time.

Structural basis for recognition of 26RFa by the pyroglutamylated RFamide peptide receptor.

The neuropeptide 26RFa, a member of the RF-amide peptide family, activates the pyroglutamylated RF-amide peptide receptor (QRFPR), a class A GPCR. The 26RFa/QRFPR system plays critical roles in energy homeostasis, making QRFPR an attractive drug target for treating obesity, diabetes, and eating disorders. However, the lack of structural information has hindered our understanding of the peptide recognition and regulatory mechanism of QRFPR, impeding drug design efforts. In this study, we determined the cryo-EM structure of the Gq-coupled QRFPR bound to 26RFa. The structure reveals a unique assembly mode of the extracellular region of the receptor and the N-terminus of the peptide, and elucidates the recognition mechanism of the C-terminal heptapeptide of 26RFa by the transmembrane binding pocket of QRFPR. The study also clarifies the similarities and distinctions in the binding pattern of the RF-amide moiety in five RF-amide peptides and the RY-amide segment in neuropeptide Y. These findings deepen our understanding of the RF-amide peptide recognition, aiding in the rational design of drugs targeting QRFPR and other RF-amide peptide receptors.

[Impact of the COVID-19 Pandemic on Nurses and an Ecological System Theory-Based Strategy for Reducing This Impact in the Future].

The COVID-19 pandemic led to significant burnout among nurses, resulting in a shortage of nursing staff. Issues related to nursing work have received significant attention recently, and only healthy nurses are capable of providing good quality patient care. The authors employed Bronfenbrenner's Ecological System Theory to analyze the impact of the COVID-19 pandemic on nurses and proposed specific strategies and recommendations to enhance the nursing workplace. Under the Ecological System Theory, several factors, including inadequate preparedness, dangerous working environment, work-family conflicts, discrimination due to public panic, and health damage, contribute to nurse burnout. Whether during or after the COVID-19 pandemic, it is necessary to provide education programs to enhance the professional abilities of nurses, foster policies that promote a positive practice work environment, implement a triage system based on the severity of patients, elevate the image of the nursing profession, monitor the health of nurses, and advocate for transformational leadership. The nursing workplace should help nurses gain greater confidence and improve their ability to handle various workplace challenges. In the future, medical institutions should provide a better work environment for nurses and expect the public to pay more attention to the development of the nursing profession.

[Effects of 4-hydroxy-2(3H)-benzoxazolone on proliferation and apoptosis of pancreatic cancer L3.6 cells].

This study explored the effects of 4-hydroxy-2(3H)-benzoxazolone(HBOA) on the proliferation and apoptosis of pancreatic cancer cells and its molecular mechanism. The L3.6 cells cultured in vitro were treated with HBOA of 0-1.0 mmol·L~(-1). The cell viability was detected by the cell counting kit-8(CCK-8) method, and the half inhibitory concentration(IC_(50)) was analyzed to determine the drug concentration and time. The cell morphology was observed under an inverted microscope and by acridine orange(AO) staining. The ability of proliferation and self-renewal were evaluated through live cell counting and colony formation experiments. The cell cycle progression and cell apoptosis rate were detected by flow cytometry. The morphology of cell apoptosis was observed by scanning electron microscopy. The mRNA expression of proliferating cell nuclear antigen(PCNA), cyclinA1, cyclinA2, cyclin dependent kinase 2(CDK2), and cyclin dependent kinase inhibitor 1A(P21) were determined by qPCR. The level of reactive oxygen species(ROS), lipid peroxide, and mitochondrial membrane potential were measured by flow cytometry. The activity of protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway was detected by Western blot. Compared with the control group, the cells treated with HBOA exhibited a significant decrease in viability. Then the optimal concentration and intervention time of HBOA were determined to be 0.4 mmol·L~(-1), 0.6 mmol·L~(-1), and 48 h. Compared with the control group, groups with HBOA of 0.4 mmol·L~(-1 )and 0.6 mmol·L~(-1) showed a significant suppression in cell proliferation and colony formation ability, down-regulated mRNA of PCNA, cyclinA1, cyclinA2, and CDK2, up-regulated P21 mRNA, S-phase cell cycle arrest, and increased cell apoptosis rate. There was an appearance of apoptotic bodies, increased ROS and lipid peroxide, decreased mitochondrial membrane potential(with a significant decrease in 0.6 mmol·L~(-1) group), and down-regulated p-Akt and p-mTOR proteins. The results show that HBOA inhibits the proliferation of pancreatic cancer L3.6 cells and induces cell apoptosis, which may be related to the increase in reactive oxygen species and the inhibition of the Akt/mTOR pathway.

A Targeted Deep Sequencing Method to Quantify Endogenous Retrovirus Gag Sequence Variants and Open Reading Frames Expressed in Nonobese Diabetic Mice.

Endogenous retroviruses (ERVs) are involved in autoimmune diseases such as type 1 diabetes (T1D). ERV gene products homologous to murine leukemia retroviruses are expressed in the pancreatic islets of NOD mice, a model of T1D. One ERV gene, Gag, with partial or complete open reading frames (ORFs), is detected in the islets, and it contains many sequence variants. An amplicon deep sequencing analysis was established by targeting a conserved region within the Gag gene to compare NOD with T1D-resistant mice or different ages of prediabetic NOD mice. We observed that the numbers of different Gag variants and ORFs are linked to T1D susceptibility. More importantly, these numbers change during the course of diabetes development and can be quantified to calculate the levels of disease progression. Sequence alignment analysis led to identification of additional markers, including nucleotide mismatching and amino acid consensus at specific positions that can distinguish the early and late stages, before diabetes onset. Therefore, the expression of sequence variants and ORFs of ERV genes, particularly Gag, can be quantified as biomarkers to estimate T1D susceptibility and disease progression.

Dimerization and antidepressant recognition at noradrenaline transporter.

The noradrenaline transporter has a pivotal role in regulating neurotransmitter balance and is crucial for normal physiology and neurobiology1. Dysfunction of noradrenaline transporter has been implicated in numerous neuropsychiatric diseases, including depression and attention deficit hyperactivity disorder2. Here we report cryo-electron microscopy structures of noradrenaline transporter in apo and substrate-bound forms, and as complexes with six antidepressants. The structures reveal a noradrenaline transporter dimer interface that is mediated predominantly by cholesterol and lipid molecules. The substrate noradrenaline binds deep in the central binding pocket, and its amine group interacts with a conserved aspartate residue. Our structures also provide insight into antidepressant recognition and monoamine transporter selectivity. Together, these findings advance our understanding of noradrenaline transporter regulation and inhibition, and provide templates for designing improved antidepressants to treat neuropsychiatric disorders.