Polysorbate 80-containing ionizable lipid nanoparticles for mRNA delivery.

Ionizable lipid nanoparticles have demonstrated remarkable success as mRNA vaccine carriers and represent one of the most promising gene drug delivery vehicles. However, polyethylene glycol (PEG), one of the major components, can cause immunogenic reactions, anaphylaxis and increased blood clearance, leading to toxic side effects and reduced efficacy. In this study, we utilize polysorbate 80 (PS80) as a PEG alternative in formulating eGFP mRNA-loaded ionizable lipid nanoparticles (PS80-iLNPs), aiming to enhance stealth properties, uptake efficiency, and biosafety. Our findings revealed that PS80-iLNPs enhanced the stealthiness and resistance to serum interference. Compared to PEG-containing ionizable lipid nanoparticles (PEG-iLNPs), PS80-iLNPs showed a 1.14-fold increase in stealthiness. Moreover, at a total lipid concentration of 50 µg mL-1, PS80-iLNPs exhibited 1.12 times higher cell viability compared to PEG-iLNPs. Notably, under serum interference, PEG-iLNPs showed a 44.97% uptake reduction, whereas PS80-iLNPs exhibited a modest 30.55% decrease, underscoring its superior serum resistance. This work demonstrated that PS80 could serve as a suitable substitute for PEG, thus signifying an excellent basis for the development of PEG-free ionizable lipid nanoparticles.

The links between symptom burden, illness perception, psychological resilience, social support, coping modes, and cancer-related worry in Chinese early-stage lung cancer patients after surgery: a cross-sectional study.

OBJECTIVES: This study aims to investigate the links between the clinical, demographic, and psychosocial factors and cancer-related worry in patients with early-stage lung cancer after surgery. METHODS: The study utilized a descriptive cross-sectional design. Questionnaires, including assessments of cancer-related worry, symptom burden, illness perception, psychological resilience, coping modes, social support and participant characteristics, were distributed to 302 individuals in early-stage lung cancer patients after surgery. The data collection period spanned from January and October 2023. Analytical procedures encompassed descriptive statistics, independent Wilcoxon Rank Sum test, Kruskal-Wallis- H- test, Spearman correlation analysis, and hierarchical multiple regression. RESULTS: After surgery, 89.07% had cancer-related worries, with a median (interquartile range, IQR) CRW score of 380.00 (130.00, 720.00). The most frequently cited concern was the cancer itself (80.46%), while sexual issues were the least worrisome (44.37%). Regression analyses controlling for demographic variables showed that higher levels of cancer-related worry (CRW) were associated with increased symptom burden, illness perceptions, and acceptance-rejection coping modes, whereas they had lower levels of psychological resilience, social support and confrontation coping modes, and were more willing to obtain information about the disease from the Internet or applications. Among these factors, the greatest explanatory power in the regression was observed for symptom burden, illness perceptions, social support, and sources of illness information (from the Internet or applications), which collectively explained 52.00% of the variance. CONCLUSIONS: Healthcare providers should be aware that worry is a common issue for early stage lung cancer survivors with a favorable prognosis. During post-operative recovery, physicians should identify patient concerns and address unmet needs to improve patients' emotional state and quality of life through psychological support and disease education.

Rate and Associated Factors of Fatigue in Chinese Patients with Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Survey.

Purpose: Fatigue was a common symptom of non-alcoholic fatty liver disease (NAFLD), which seriously affected patients' quality of life. The aim of this study was to detect fatigue rate and to evaluate factors associated with fatigue in NAFLD patients. Patients and Methods: A cross-sectional study was carried out from the Huadong Sanatorium between April 2022 and May 2023, and 133 NAFLD patients were included in this study. They completed Fatigue Severity Scale to assess fatigue, the Hospital Anxiety and Depression Scale to estimate psychological status, and the Pittsburgh Sleep Quality Index for sleep quality. Data were analyzed by independent samples t-tests, χ2 tests and logistic regression models. Results: We found that 51.1% of NAFLD patients had fatigue. Exercise, anxiety, depression, subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disorders, daytime dysfunction and overall sleep quality were related to fatigue among NAFLD patients. Moreover, logistic regression models indicated anxiety, habitual sleep efficiency and sleep disorders as important predictors of fatigue. Conclusion: This was the first time to explore demographic, clinical, psychological and sleeping correlated factors for fatigue in Chinese NAFLD patients. Our study showed that more than half of NAFLD patients had fatigue, and anxiety, habitual sleep efficiency and sleep disorders were significantly associated with fatigue in NAFLD. The findings indicated that it was very necessary to pay more attention to fatigue of NAFLD patients, especially those with negative emotions and poor sleep quality by favorable intervention to relieve fatigue symptoms, so as to improve quality of life.

Cascade-targeting polymeric particles eliminate intracellular C. neoformans in fungal infection therapy.

C. neoformans, a life-threatening invasive fungal pathogen, can hijack the pulmonary macrophages as 'Trojan horse', leading to cryptococcal meningitis and recurrence. Combatting these elusive fungi has posed a long-standing challenge. Here, we report an inhaled cascade-targeting drug delivery platform that can sequentially target host cells and intracellular fungi. The delivery system involves encapsulating amphotericin B (AMB) into polymeric particles decorated with AMB, creating a unique surface pattern, denoted as APP@AMB. The surface topology of APP@AMB guides the efficient macrophages internalization and intracellular drugs accumulation. Following endocytosis, the surface-functionalized AMB specifically targets intracellular fungi by binding to ergosterol in the fungal membrane, as demonstrated through co-localization studies using confocal microscopy. Through on-site AMB delivery, APP@AMB displays superior efficacy in eliminating C. neoformans in the lungs and brain compared to free AMB following inhalation in infected mice. Additionally, APP@AMB significantly alleviates the nephrotoxicity associated with free AMB inhalation therapy. Thus, this biocompatible delivery system enabling host cells and intracellular fungi targeting in a cascade manner, provides a new avenue for the therapy of fungal infection.

Severe Venous Calcifications in Phlebosclerotic Colitis and Significantly Decreased Expression in Betaine.

Phlebosclerotic colitis (PC) is a rare type of chronic ischemic colitis. Its etiology is still unknown, and PC is also known as idiopathic mesenteric phlebosclerosis colitis. Currently, many studies have reported that long-term use of Chinese herbal medicine and drinking history are related to its pathogenesis. In the early stage of the lesion, due to insufficient understanding of PC, it is difficult to distinguish it from inflammatory bowel disease and other nonneoplastic intestinal diseases. We reported a case of severe diffuse total colon calcification with multiple misdiagnosis, summarizing and analyzing the clinical pathological characteristics to increase clinical and pathological physicians' understanding of the disease and reduce misdiagnosis. Moreover, for the first time, we conducted metabolomics sequencing on fresh intestinal specimens of PC, in order to explore the possible mechanism of severe calcification in the patient. We found that betaine was significantly decreased in the intestinal specimens of the patient, which is an amino acid that has been shown to improve vascular risk factors, and may be one of the mechanisms underlying severe calcification in the patient.

Development and Prospect of Vacuum High-Pressure Gas Quenching Technology.

As industrial modernization surges forward, the heat treatment industry strives for lower pollution, reduced oxidation and defects, minimized waste, and automatization. This paper reviews the mechanisms, processes, equipment, and simulations of the vacuum gas quenching technology, presenting a comprehensive account of the structure and working principle of a typical vacuum gas quenching furnace. Firstly, the mechanism of the heat transfer process, flow process, and flow-heat transfer-phase transition coupling were summarized. Then, the influences of process parameters on the mechanical properties and distortion of vacuum gas quenched workpieces, as well as the process optimization methods, were discussed. Finally, the advantages of vacuum gas quenching in energy saving, low pollution, and high efficiency were introduced, with the future development directions figured out.

Epidemiological features of SARS-CoV-2 Omicron infection under new control strategy: a cross-sectional study of the outbreak since December 2022 in Sichuan, China.

BACKGROUND: A major shift in the "dynamic zero-COVID" policy was announced by China's National Health Commission on December 7, 2022, and the subsequent immediate large-scale outbreak of SARS-CoV-2 infections in the entire country has caused worldwide concern. This observational cross-sectional study aimed to describe the epidemiological characteristics of this outbreak in Sichuan, China. METHODS: All data were self-reported online by volunteers. We described the epidemic by characterizing the infection, symptoms, clinical duration, severity, spatiotemporal clustering, and dynamic features of the disease. Prevalence ratio (PR), Odds ratios (ORs) and adjusted ORs were calculated to analyze the associations between risk factors and infection and the associations of risk factors with clinical severity using log-binomial and multivariable logistic regression models; 95% confidence intervals (CIs) and Wald test results were reported. The prevalence rates and clinical severity among different subgroups were compared using the Chi-square and trend Chi-square tests. RESULTS: Between January 6 and 12, 2023, 138,073 volunteers were enrolled in this survey, and 102,645 were infected with COVID-19, holding a prevalence rate of 74.34%; the proportion of asymptomatic infections was 1.58%. Log-binomial regression revealed that the risk of infection increased among those living in urban areas. Multivariable logistic regression analysis showed that female sex, chronic diseases, older age and the fewer doses of vaccine received were associated with an increased risk of severe clinical outcomes after infection. We estimated the mean reproduction number during this pandemic was 1.83. The highest time-dependent reproduction number was 4.15; this number decreased below 1 after 11 days from December 7, 2022. Temporal trends revealed a single peak curve with a plateau pattern of incidence during the outbreak, whereas spatiotemporal clustering analysis showed that the onset in 21 cities in the Sichuan province had four-wave peaks. CONCLUSIONS: The peak of the first wave of Omicron infection in Sichuan Province had passed and could be considered a snapshot of China under the new control strategy. There were significant increases in the risk of severe clinical outcomes after infection among females, with chronic diseases, and the elderly. The vaccines have been effective in reducing poor clinical outcomes.

Sex-Specific Contribution of Cardiometabolic Index in Predicting Metabolic Dysfunction-Associated Fatty Liver Disease: Insights from a General Population.

Background and Objective: Evidence suggests that cardiometabolic index (CMI) has been identified as a novel obesity-related index associated with diabetes, hypertension, and cardiovascular disease. Current evidence suggests that the differences in sex hormones and regional fat distribution in both sexes are directly correlated with metabolic dysfunction-associated fatty liver disease (MAFLD) risk. This study aimed to investigate the diagnostic value of CMI in MAFLD in both sexes. Methods: This retrospective study included 6107 subjects who underwent annual health check-ups from March 2021 to January 2022. CMI was calculated by multiplying the ratio of triglycerides and high-density lipoprotein cholesterol (TG/HDL-C) by waist-to-height ratio (WHtR). Multivariable logistic regression analysis and restricted cubic spline were used to investigate the association of CMI and MAFLD risk. Receiver operating characteristic curve analysis was conducted for the exploration of the diagnostic accuracies of obesity-related indicators. Areas under the curves (AUCs) with 95% CIs were calculated. Results: Prevalence of MAFLD increased with elevated quartiles of CMI in both sexes. The median (IQR) age was 46.00 (18.00) years. Multivariate logistic regression analyses showed that higher CMI was independently associated with MAFLD, in which every additional standard deviation (SD) of CMI increased the risk of MAFLD (OR=2.72, 95% CI:2.35-3.15 for males; OR=3.26, 95% CI:2.36-4.51 for females). Subjects in the fourth quartile of CMI had the highest odds of MAFLD for males (OR=15.82, 95% CI:11.84-21.14) and females (OR=22.60, 95% CI:9.52-53.65)(all P for trend<0.001). Besides, CMI had a non-linearity association with MAFLD (all P for non-linearity<0.001). Furthermore, CMI exhibited the largest AUC compared to other obesity-related indexes in terms of discriminating MAFLD in males (AUC=0.796, 95% CI:0.782-0.810) and females (AUC=0.853, 95% CI:0.834-0.872). Conclusion: CMI was a convenient indicator for the screening of MAFLD among Chinese adults. Females with high CMI had a better diagnostic value for MAFLD than males.

Rare synchronous colorectal carcinoma with three pathological subtypes: A case report and review of the literature.

BACKGROUND: Synchronous colorectal carcinomas (SCRC) are two or more primary colorectal carcinomas identified simultaneously or within 6 mo of the initial presentation in a single patient. Their incidence is low and the number of pathological types of SCRC is usually no more than two. It is very unusual that the pathological findings of a patient with SCRC show more than two different pathological subtypes. Here, we report a rare case of SCRC with three pathological subtypes. CASE SUMMARY: A 75-year-old woman who had no previous medical history or family history was admitted to the hospital because of intermittent hematochezia for more than a month. Colonoscopy displayed an irregularly shaped neoplasm of the rectum, a tumor-like lesion causing intestinal stenosis in the descending colon, and a polypoidal neoplasm in the ileocecum. Subsequently, she underwent total colectomy, abdominoperineal resection for rectal cancer, and ileostomy. After operation, the pathological report showed three pathological subtypes including well-differentiated adenocarcinoma of the ascending colon, moderately differentiated adenocarcinoma of the descending colon, and mucinous adenocarcinoma of the rectum. She is now recovering well and continues to be closely monitored during follow-up. CONCLUSION: Preoperative colonoscopy examination, imaging examination, and extensive intraoperative exploration play important roles in reducing the number of missed lesions.

The unmet needs of patients in the early rehabilitation stage after lung cancer surgery: a qualitative study based on Maslow's hierarchy of needs theory.

PURPOSE: This study aimed to explore the unmet needs of lung cancer patients in early rehabilitation, based on Maslow's hierarchy of needs theory. METHODS: Information on the experiences of 20 patients was collected through semi-structured interviews. The interviews were conducted in the surgical nursing clinic within 1 week of discharge from hospital. The data were analysed using a combination of deductive (theory-driven) and inductive (data-driven) methods, using Maslow's Hierarchy of Needs as a framework for identifying and organising themes. RESULTS: Patients had a mean age of 50.92 years (SD 11.88); n = 11 (55%) were female. Major themes aligned with the dimensions of Maslow's hierarchy of needs model. Five major themes with 12 corresponding sub-themes emerged: (1) physiological needs, including "self-care and independence in life", "return to pre-operative status as soon as possible", "increase exercise under specialist guidance" and "reduce cough and pain and improve sleep quality"; (2) safety and security needs, such as "symptom management", "regulation of the emotions of worry and fear" and "access accurate treatment information"; (3) love and belonging needs, including "accompany family members" and "chat with friends";(4)Esteem needs: "live with dignity";(5) Self-actualization, such as "accept and submit to the reality of cancer" and "live meaningfully". CONCLUSIONS: The findings of this study indicated that there were many unmet needs for patients during the early recovery period after lung cancer surgery. An overview of the different areas of need identified in this study may guide future research and development of interventions to improve patients' quality of life during the home rehabilitation phase.

Classic biphasic pulmonary blastoma: A case report and review of the literature from 2000 to 2022.

Classic biphasic pulmonary blastoma (CBPB), a distinct type of lung cancer, is a dual-phasic tumor characterized by the co-existence of low-grade fetal adenocarcinoma and primitive mesenchymal stroma. Accounting for less than 0.1% of surgically removed lung cancers, CBPB commonly presents in individuals during their fourth to fifth decades of life, with smoking as a significant risk factor. The optimal management strategy entails surgical resection, supplemented by chemotherapy to improve prognosis. The frontline chemotherapeutic agents typically include platinum agents and etoposide, with preoperative neoadjuvant chemotherapy potentially enabling operability for initially inoperable cases. In recent years, targeted therapies, such as antiangiogenic agents, have emerged as promising new treatment strategies for CBPB. For patients exhibiting brain metastases or deemed inoperable, radiation therapy proves to be a crucial therapeutic component. CBPB prognosis is adversely affected by factors such as early metastasis, tumor size exceeding 5 cm, and tumor recurrence. In this regard, serological markers have been identified as valuable prognostic indicators. To exemplify, we recount the case of a 44-year-old female patient with CBPB, wherein serum lactate dehydrogenase levels showed significant diagnostic value. This report further incorporates a comprehensive review of CBPB literature from the past 22 years.

Long noncoding RNA XLOC_006786 inhibits the proliferation, invasion and metastasis of osteosarcoma cells through NOTCH3 signaling pathway by targeting miR-491-5p.

Recent research has indicated that Long noncoding RNAs (LncRNAs) are crucial in many disorders, especially tumors. However, the exact role of LncRNA XLOC_006786 (LncRNA-SPIDR-2:1) in malignancies, especially in human osteosarcoma, is unclear. The results of RT‒qPCR, western blotting, CCK-8 assays, and Transwell assays showed that LncRNA XLOC_006786 inhibited osteosarcoma cell proliferation, invasion, and migration, indicating that it may be a tumor suppressor gene in osteosarcoma. We found that LncRNA XLOC_006786 negatively regulated NOTCH3, which is an oncogenic gene in osteosarcoma, as we previously reported. Bioinformatics analysis showed that miR-491-5p may be a direct target of LncRNA XLOC_006786, while NOTCH3 is a key target of miR-491-5p. Then, we verified that LncRNA XLOC_006786 could prevent lung metastatic osteosarcoma in vivo. Taken together, our research showed that LncRNA XLOC_006786 suppresses osteosarcoma proliferation, invasion, and metastasis through the NOTCH3 signaling pathway by targeting miR-491-5p.

Status and factors associated with patient activation and its relationship with HIV clinic outcomes among Yi minority people living with HIV in Liangshan, China: a cross-sectional study.

Introduction: Patient activation is determined by an individual's knowledge, skills and confidence in managing his/her health. It is vital for people living with HIV (PLWH) to enhance their self-management skills and health outcomes, especially those from low- and middle-income regions, since they are at higher risk of worse health outcomes. However, literature from those regions is limited, especially in China. Objectives: This study aimed to explore the status and factors associated with patient activation among Yi minority PLWH in Liangshan, China and to determine whether patient activation is associated with HIV clinic outcomes. Methods: This cross-sectional study included 403 Yi minority people living with HIV in Liangshan between September and October 2021. All participants completed an anonymous survey measuring sociodemographic characteristics, HIV-related information, patient activation and illness perception. Multivariate linear regression and multivariate binary logistic regression were used to explore factors associated with patient activation and the association between patient activation and HIV outcomes, respectively. Results: The Patient Activation Measure (PAM) score was low (mean = 29.8, standard deviation = 4.1). Participants with negative illness perception, low income, and self-rated antiretroviral therapy (ART) effect based on self-perception were most likely to have a lower PAM score (ß = -0.3, -0.2, -0.1, respectively; all p < 0.05); those with having disease knowledge learning experiences and an HIV-positive spouse were more likely to have a higher PAM score (ß = 0.2, 0.2, respectively; both p < 0.001). A higher PAM score (AOR=1.08, 95% CI: 1.02, 1.14) was associated with viral suppression, mediated by gender (AOR=2.25, 95% CI: 1.38, 3.69). Conclusion: Low patient activation level among Yi minority PLWH impacts HIV care. Our findings indicate patient activation is associated with viral suppression for minority PLWH in low- and middle-income settings, suggesting that tailored interventions enhancing patient activation may improve viral suppression.

Gut microbiota alters host bile acid metabolism to contribute to intrahepatic cholestasis of pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is a female pregnancy-specific disorder that is characterized by increased serum bile acid and adverse fetal outcomes. The aetiology and mechanism of ICP are poorly understood; thus, existing therapies have been largely empiric. Here we show that the gut microbiome differed significantly between individuals with ICP and healthy pregnant women, and that colonization with gut microbiome from ICP patients was sufficient to induce cholestasis in mice. The gut microbiomes of ICP patients were primarily characterized by Bacteroides fragilis (B. fragilis), and B. fragilis was able to promote ICP by inhibiting FXR signaling via its BSH activity to modulate bile acid metabolism. B. fragilis-mediated FXR signaling inhibition was responsible for excessive bile acid synthesis and interrupted hepatic bile excretion to ultimately promote the initiation of ICP. We propose that modulation of the gut microbiota-bile acid-FXR axis may be of value for ICP treatment.

GLI1-altered Mesenchymal Tumor Involving the Duodenum: Case Report and Literature Review.

GLI1-altered mesenchymal tumor is an emerging entity with distinctive clinicopathologic features. It shows a distinctive monomorphic round to epithelioid morphology, nested to trabecular pattern of growth, and S100+/SOX10-/SMA-immunophenotype. We report an example of this entity arising in the duodenum. A 31-year-old man presented with anemia for 1 year, a mass in the duodenal bulb was found for 9 days. Histopathologic examination revealed the tumor with distinct multilobulated architecture, a monomorphic appearance of round to epithelioid cells arranged in papillary structures, nests, cords, solid, reticular patterns, and hyalinized stroma surrounding a rich capillary network. The neoplastic cells had amphophilic to light eosinophilic or clear cytoplasm, uniform round nuclei with fine chromatin and inconspicuous nucleoli. Immunohistochemical analysis revealed strong positivity for vimentin, S100, CD56, CyclinD1, and negativity for SOX10, SMA, melan-A, HMB-45, synaptophysin, and a variety of other markers. Based on the morphology and immunophenotype, molecular studies were performed, which revealed the presence of an ACTB::GLI1 fusion transcript, confirming the diagnosis of GLI1-altered mesenchymal tumor.

Erdheim-Chester Disease Involving the Left Uterine Adnexa: Mimicking an Ovarian Carcinoma Clinically.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis (LCH) that results in multiorgan disease involving the skin, bones, lungs, and kidneys. Female reproductive system manifestation of ECD was rare. Herein, we report a case of ECD involving the left ovary and fallopian tube. A 69-year-old woman presented with abdominal pain for 20 days. Magnetic resonance imaging revealed a solid and cystic mass on the left pelvic cavity. Histological examination revealed ovarian and fallopian tube infiltration by abundant histiocytes, with single small nuclei and foamy cytoplasm, reactive small lymphocytes, and plasma cells. Based on histopathological and immunohistochemical findings of positivity for CD68, CD163, and BRAF V600E and negativity for CD1α and S100, the molecular finding of BRAF V600E mutation, the patient was diagnosed with ECD. Positron emission tomography examination did not reveal any other lesions. The patient recovered well 12 months after surgery without any treatment. ECD involving the left fallopian tube and ovary was rare and needed to be differentiated from LCH, Rosai-Dorfman disease (RDD), juvenile xanthogranuloma (JXG), IgG4+-related disease (IgG4+RD), and metastatic signet ring cell carcinoma.

A nomogram prediction model for lymph node metastasis risk after neoadjuvant chemoradiotherapy in rectal cancer patients based on SEER database.

Background: Rectal cancer patients who received neoadjuvant chemoradiotherapy (CRT) may have a lower cancer stage and a better prognosis. Some patients may be able to avoid invasive surgery. It is critical to accurately assess lymph node metastases (LNM) after neoadjuvant chemoradiotherapy. The goal of this study is to identify clinical variables associated with LNM and to develop a nomogram for LNM prediction in rectal cancer patients following nCRT. Methods: From 2010 to 2015, patients were drawn from the Surveillance, Epidemiology, and End Results (SEER) database. To identify clinical factors associated with LNM, the least absolute shrinkage and selection operator (LASSO) aggression and multivariate logistic regression analyses were used. To predict the likelihood of LNM, a nomogram based on multivariate logistic regression was created using decision curve analyses. Reslut: The total number of patients included in this study was 6,388. The proportion of patients with pCR was 17.50% (n=1118), and the proportion of patients with primary tumor pCR was 20.84% (n = 1,331). The primary tumor was pCR in 16.00% (n=213) of the patients. Age, clinical T stage, clinical N stage, and histology were found to be significant independent clinical predictors of LNM using LASSO and multivariate logistic regression analysis. The nomogram was developed based on four clinical factors. The 5-year overall survival rate was 78.9 percent for those with ypN- and 66.3 percent for those with ypN+, respectively (P<0.001). Conclusion: Patients over 60 years old, with clinical T1-2, clinical N0, and adenocarcinoma may be more likely to achieve ypN0. The watch-and-wait (WW) strategy may be considered. Patients who had ypN0 or pCR had a better prognosis.

High aspect ratio plasmonic Au/Ag nanorods-mediated NIR-II photothermally enhanced nanozyme catalytic cancer therapy.

Chemodynamic therapy (CDT) is based on the endogenous generation of cytotoxic hydroxyl free radicals (·OH) with high specificity and selectivity between cancer and normal cells. However, its efficacy is often limited by the relatively deficient catalytic activity of nanozymes in the tumor microenvironment (TME). Therefore, the combination of CDT with other strategy to realize synergistic therapy is necessary. Herein, a versatile plasmonic Au/Ag nanorods (abbreviated as Au/Ag NRs) via anisotropic Ag overgrowth on Au nanobipyramids was rationally devised to achieve synergistic nanozyme catalytic therapy and near infrared II (NIR-II) light induced photothermal therapy (PTT) with the guidance of computed tomography (CT) imaging. As TME contains high concentrations of H+ and H2O2, Au/Ag NRs exhibited peroxidase (POD) activity to catalyze H2O2 to produce ·OH, inducing cancer cell death. Meanwhile, Au/Ag NRs showed a preeminent NIR-II photothermal effect. More importantly, the enhanced ·OH generation by in-situ heating up resulting from PTT could conversely inhibit the expression of heat shock proteins (HSPs) to abate their resistance to PTT, realizing self-augmented synergistic effect. The NIR-II photothermally enhanced nanozyme catalytic cancer therapy validly inhibited the cancer proliferation, as demonstrated via both cell and animal assays. Moreover, ideal high-contrast CT imaging was realized, owing to the X-ray attenuation capability of elemental Au. The multifunctional Au/Ag NRs hold potential in oncotherapy with imaging capability, high efficiency and low side effects.

Optimizing Large-Scale COVID-19 Nucleic Acid Testing with a Dynamic Testing Site Deployment Strategy.

The COVID-19 epidemic has spread worldwide, infected more than 0.6 billion people, and led to about 6 million deaths. Conducting large-scale COVID-19 nucleic acid testing is an effective measure to cut off the transmission chain of the COVID-19 epidemic, but it calls for deploying numerous nucleic acid testing sites effectively. In this study, we aim to optimize the large-scale nucleic acid testing with a dynamic testing site deployment strategy, and we propose a multiperiod location-allocation model, which explicitly considers the spatial-temporal distribution of the testing population and the time-varied availability of various testing resources. Several comparison models, which implement static site deployment strategies, are also developed to show the benefits of our proposed model. The effectiveness and benefits of our model are verified with a real-world case study on the Chenghua district of Chengdu, China, which indicates that the optimal total cost of the dynamic site deployment strategy can be 15% less than that of a real plan implemented in practice and about 2% less than those of the other comparison strategies. Moreover, we conduct sensitivity analysis to obtain managerial insights and suggestions for better testing site deployment in field practices. This study highlights the importance of dynamically deploying testing sites based on the target population's spatial-temporal distribution, which can help reduce the testing cost and increase the robustness of producing feasible plans with limited medical resources.