Geniposide alleviates imiquimod-induced psoriasis-like skin lesions in mice via inhibition of angiogenesis.

In this study, we aimed to evaluate the protective effect of geniposide (GEN) on imiquimod (IMQ)-induced psoriasis-like skin lesions in mice. Firstly, visual changes of psoriatic skin lesions were observed and the severity was recorded using psoriasis area and severity index (PASI) score. Histological changes were assessed by HE staining for epidermal thickness and Masson's staining for collagen fibers. Then, photographs of microvascular inside the skin were taken for macroscopic observation, and microscopic changes associated with angiogenesis were evaluated. Furthermore, expression of angiogenic factors were analyzed by ELISA, immunohistochemistry and immunofluorescence, separately. Lastly, the expression of VEGFR signaling-related proteins was detected by WB. Compared with control, IMQ drove a significant increment of epidermal thicknesses with higher PASI scores and more dermal collagen deposition. IMQ treatment led to abnormal keratinocyte proliferation, increased microvascular inside skin, growing production of angiogenesis-related factors, up-regulated expression of VEGFR1 and VEGFR2, and enhanced phosphorylation of p38. However, GEN significantly ameliorated the psoriatic skin lesions, the epidermal thickness, the formation of collagen fibers, and abnormal keratinocyte proliferation. Importantly, GEN inhibited angiogenesis, the production of angiogenic factors (VEGF-A, Ang-2, TNF-α, and IL-17A), and the proliferation of vascular endothelial cells. Simultaneously, GEN curbed the expression of VEGFR1, VEGFR2, p38, and P-p38 proteins involved in VEGFR signaling. Of note, the suppressive effect of GEN was reversed in the HUVECs with over-expressed VEGFR1 or VEGFR2 related to the cells without transfection. These findings suggest that VEGFR1 and VEGFR2 participate in the anti-angiogenesis of GEN in IMQ-induced psoriasis-like skin lesions in mice.

Knowledge and Practices Regarding Human Papillomavirus and Cervical Cancer Screening Among Women in Low-Income Areas of China: A Cross-Sectional Study.

BACKGROUND: Persistent human papillomavirus (HPV) infection is the primary cause of cervical cancer. However, this can be prevented through vaccination and screening. This study aimed to clarify the relationship between behavior, knowledge, and attitude toward cervical cancer and regular screening and HPV infection among women in Lueyang County. METHODS: Women who underwent cervical cancer screening at the outpatient department of a maternal and child health center between September and December 2021 were invited to participate. In total, 2,303 women completed the questionnaire. Women who underwent regular or irregular screening were 1:1 matched for age. Differences in knowledge of HPV and attitudes toward HPV vaccination among different populations were assessed. Logistic regression analysis was performed to identify the factors influencing HPV infection. RESULTS:  In total, 417 pairs of women who underwent regular and irregular screening were successfully matched. Multivariate logistic regression results indicated that age is a risk factor for HPV infection (OR=1.056 95%CI: [1.031 1.082]), while regular screening acts as a protective factor against HPV infection (OR=0.174 95%CI: [0.117 0.259]). Additionally, regular screening was associated with a higher level of knowledge about HPV among women compared to those who did not undergo regular screening (p<0.001). CONCLUSIONS:  Women in Lueyang County have low levels of knowledge regarding HPV and cervical cancer. Regular screening is a protective factor against HPV infection. The regular screening group demonstrates a higher level of HPV knowledge compared with the irregular screening group. These findings highlight the importance of regular screening and the need to strengthen public health education.

Gasless transvaginal natural orifice transluminal endoscopic surgery for hysterectomy and salpingectomy on a robot platform with flexible devices in a porcine model.

In this report, we described a new technique of gasless V-NOTES for hysterectomy and salpingectomy on a robotic platform with flexible devices in a porcine model. As a result, the gynecological procedures were successfully completed. The total operative time was 110 min, while the docking time was 10 min. The estimated blood loss was estimated to be 10 mL with no intraoperative complications. It revealed that gasless V-NOTES for hysterectomy and salpingectomy on a robotic platform with flexible devices appeared to be feasible and safe in the porcine model and has the potential for clinical use in human beings.

Aerobic exercise suppresses cognitive injury in patients with Alzheimer's disease by regulating long non-coding RNA TUG1.

BACKGROUND: Alzheimer's disease (AD) is the primary reason for disability of the elderly. This article studied the diagnostic possibility of TUG1 and its potential mechanism in the regulation of aerobic exercise (AE) on AD. METHODS: 77 AD patients undertook a three-month-long cycling exercise, and 77 healthy controls were recruited. Polymerase Chain Reaction amplification was applied to assess the expression of TUG1 and miR-129-5p. The diagnostic possibility was manifested by the receiver operating characteristic (ROC) curve. Spearman correlation analyzed the interrelationships between TUG1 and AD. In vivo, the APP/PS1 double transgenic mouse models of AD were included for rescue experiments. Morris water maze (MWM) was performed to assess cognitive function of AD mice. RESULTS: The content of TUG1 was ascended in AD patients and was diminished after AE. The increase of TUG1 indicated the high risk of the occurrence of AD. TUG1 was closely connected to the cognitive assessment tools of AD patients. The TUG1/ miR-129-5p axis was the regulator of the regulation of AE in AD mice. CONCLUSION: TUG1 was involved in AD development and targeted miR-129-5p to participate in the regulation of AE.

CircTLK1: A novel regulator involved in VSMC phenotypic switching and the developmental process of atherosclerosis.

Phenotypic switching of vascular smooth muscle cells (VSMCs) is essential for atherosclerosis development. Circular RNA (circRNA) is a specific non-coding RNA that is produced as a closed-loop structure in mammals, and its specific expression pattern is closely related to its cell type and tissue. To clarify the roles of circTLK1 in VSMC phenotypic switching, we performed qRT-PCR, immunoblotting, and immunostaining. qRT-PCR revealed that circTLK1 was upregulated in both mouse models of atherosclerosis in vivo and PDGF (platelet-derived growth factor)-BB-induced VSMCs in vitro. Furthermore, the overexpression of circTLK1 promoted PDGF-BB-induced VSMC phenotypic switching. Conversely, experiments performed in vivo demonstrate that the knockdown of SMC-specific circTLK1 led to a reduction in the development of atherosclerosis. The relationship between circTLK1 and miR-513a-3p and Krüppel-like factor 4 (KLF4) was detected by RNA immunoprecipitation (RIP), luciferase reporter assay, RNA pull-down, and RNA fluorescence in situ hybridization (RNA FISH). Mechanistically, circTLK1 acted as a sponge for miR-513a-3p, leading to the upregulation of KLF4, a key transcription factor for phenotypic switching. Targeting the circTLK1/miR-513a-3p/KLF4 axis may provide a potential therapeutic strategy for atherosclerosis.

Translation and psychometric testing of the Chinese version of the Perinatal Missed Care Survey.

Objective: This study aimed to translate and evaluate the psychometric properties of the Perinatal Missed Care Survey in China. Methods: The Perinatal Missed Care Survey was translated according to the guidelines of the cross-cultural debugging scale recommended by the American Academy of Orthopaedic Surgeons Evidence-Based Medicine Committee, including forward translation, back translation, cultural adaption, and content validation, and its Chinese version was used in a cross-sectional study conducted from February to April in 2023. A total of 491 midwives from 14 different level hospitals in southwest China were recruited through a convenience sampling method. The discrimination ability of the items was tested through item analysis, and construct validity was assessed through exploratory factory and confirmatory factor analyses. The content validity index and Cronbach's α coefficients evaluated content validity and reliability, respectively. Results: The Chinese version's item-total correlation coefficients ranged from 0.641 to 0.866 in part A and from 0.644 to 0.819 in part B (P < 0.001). Parts A and B's scale-level content validity indexes were 0.95, and the item-level content validity indexes were from 0.86 to 1.00. The three common factors of part A (necessary care, basic care, and postnatal care) and part B (communication, labor resources, and material resources) were extracted, accounting for 70.186% and 71.984% of the total variance, respectively. Confirmatory factor analysis indicated that the good fit of the three-factor models was acceptable. The Cronbach's α coefficients were 0.968 (part A) and 0.940 (part B). Conclusion: The Chinese version of the Perinatal Missed Care Survey is a reliable and valid instrument for assessing nursing care missed by midwives during labor and birth and the reasons it was missed. Studies with large sample sizes are needed to verify the instrument's applicability in China.

SENP3 attenuates foam cell formation by deSUMOylating NLRP3 in macrophages stimulated with ox-LDL.

SUMO-specific protease 3 (SENP3) participates in the removal of SUMOylation and maintains the balance of the SUMO system, which ensures normal functioning of substrates and cellular activities. In the present study, we found that SENP3 expression was significantly reduced in ox-LDL-stimulated macrophages. SENP3 overexpression suppressed and SENP3 knockdown promoted macrophage foam cell formation. Moreover, SENP3 inhibited cholesterol uptake, CD36 expression, and NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome activation in ox-LDL-stimulated macrophages. Ox-LDL-stimulated NLRP3 SUMOylation was reduced by SENP3. Blocking NLRP3 SUMOylation inhibited foam cell formation and NLRP3 inflammasome activation. Thus, this study revealed that SENP3 inhibits macrophage foam cell formation by deSUMOylating NLRP3 and regulating NLRP3 inflammasome activation, which may provide a potentially innovative approach to treatment of atherosclerosis.

Effectiveness and safety of nirmatrelvir-ritonavir in kidney transplant recipients with severe kidney dysfunction infected with COVID-19.

Transplant patients face an elevated risk of coronavirus disease 2019 (COVID-19) morbidity and mortality and commonly encounter renal dysfunction. Nirmatrelvir is primarily excreted through the kidneys. The dosage of nirmatrelvir/ritonavir (NR) needs to be adjusted according to the degree of renal function impairment. Nevertheless, NR is not recommended for patients with severe renal impairment (estimated glomerular filtration rate < 30 mL/min) due to a dearth of associated research. In this study, we focus on kidney transplant patients and document and analyze the experiences of using NR in individuals with severe kidney dysfunction. This was a retrospective multicenter study that included transplant recipients hospitalized for COVID-19 in five major tertiary hospitals in China from December 2022 to June 2023. The outcomes consisted of the disease progression rate by day 28, individual disease progression events, safety outcomes, information on adverse events (AEs), and the blood drug concentrations of immunosuppressants. Data were presented with descriptive statistics. All analyses were performed using SPSS version 22. In total, 40 patients were included in the analysis. Considering the potential interaction between drugs, all patients temporarily discontinued their immunosuppressants during the NR treatment. None of the 32 moderate patients experienced disease progression. However, among the eight patients with critical COVID-19, unfortunately, two of them died. During the medication period, four patients experienced a total of six AEs associated with NR. None of them experienced AEs with a maximum grade of ≥3. Blood drug concentrations of immunosuppressants were monitored in 22 of 40 patients, and the blood drug concentrations of immunosuppressants did not show a significant increase, but some patients experienced lower blood drug concentrations. Our findings supported the use of NR therapy for the treatment of COVID-19 in transplant patients with severe renal insufficiency. A modified dose of NR was well-tolerated.

Targeting heat shock protein 47 alleviated doxorubicin-induced cardiotoxicity and remodeling in mice through suppression of the NLRP3 inflammasome.

AIM: Doxorubicin-induced cardiotoxicity (DIC) is an increasing problem, occurring in many cancer patients receiving anthracycline chemotherapy, ultimately leading to heart failure (HF). Unfortunately, DIC remains difficult to manage due to an ignorance regarding pathophysiological mechanisms. Our work aimed to evaluate the role of HSP47 in doxorubicin-induced HF, and to explore the molecular mechanisms. METHODS AND RESULTS: Mice were exposed to multi-intraperitoneal injection of doxorubicin (DOX, 4mg/kg/week, for 6 weeks continuously) to produce DIC. HSP47 expression was significantly upregulated in serum and in heart tissue in DOX-treated mice and in isolated cardiomyocytes. Mice with cardiac-specific HSP47 overexpression and knockdown were generated using recombinant adeno-associated virus (rAVV9) injection. Importantly, cardiac-specific HSP47 overexpression exacerbated cardiac dysfunction in DIC, while HSP47 knockdown prevented DOX-induced cardiac dysfunction, cardiac atrophy and fibrosis in vivo and in vitro. Mechanistically, we identified that HSP47 directly interacted with IRE1α in cardiomyocytes. Furthermore, we provided powerful evidence that HSP47-IRE1α complex promoted TXNIP/NLRP3 inflammasome and reinforced USP1-mediated NLRP3 ubiquitination. Moreover, NLRP3 deficiency in vivo conspicuously abolished HSP47-mediated cardiac atrophy and fibrogenesis under DOX condition. CONCLUSION: HSP47 was highly expressed in serum and cardiac tissue after doxorubicin administration. HSP47 contributed to long-term anthracycline chemotherapy-associated cardiac dysfunction in an NLRP3-dependent manner. HSP47 therefore represents a plausible target for future therapy of doxorubicin-induced HF.

Impact of gasless vNOTES vs. traditional vNOTES on hemodynamic profiles and outcomes in patients with benign gynecological disease: study protocol of a randomized controlled trial.

BACKGROUND: Literature regarding the advantages of gasless vNOTES is insufficient. The aim of our study is to compare gasless vNOTES vs. traditional vNOTES on hemodynamic profiles and outcomes in patients with benign gynecological disease. We hypothesize that compared with those in the traditional vNOTES group, hemodynamic profiles will be changed less during gasless vNOTES, while safety can be promised. METHODS: This is a single-center, prospective, single-blind, randomized controlled clinical trial, which has been approved by the Institutional Review Board of Chengdu Women's and Children's Hospital on September 27, 2022. One hundred and twenty patients will be recruited and randomly assigned to either the traditional vNOTES group or the gasless vNOTES group in a 1:1 ratio. For patients allocated to the traditional vNOTES group, after insertion of one port through the vagina, CO2 gas is infused with a pressure of 12-14 mmHg; while for those allocated to the gasless vNOTES group, a special device is used as an abdominal wall-lifting device to facilitate gasless surgery. CO2 pneumoperitoneum will not be used during the whole gasless vNOTES procedure. The primary outcome is vital signs at different time points. The secondary outcomes include surgical conversion rate, duration of surgery and anesthesia, anesthetic consumption, intraoperative estimated blood loss, VAS and PONV scores at postoperative 2 h and 24 h, administration of vasopressor drugs from the beginning of general anesthesia induction to 15 min after endotracheal intubation, including times, dosage, and type, intraoperative and postoperative complications, time of first getting out of bed after surgery, and time of first eating after surgery, including light drink. DISCUSSION: This is the first randomized controlled trial to compare the impacts of gasless vNOTES vs. traditional vNOTES on hemodynamic profiles and outcomes in patients with benign gynecological disease. If a favorable effect and safety of gasless vNOTES for hemodynamic profiles and outcomes in patients are shown, gasless vNOTES would be an optimal treatment option for patients with benign gynecological disease. TRIAL REGISTRATION: The trial was registered at https://www.chictr.org.cn/showproj.html?proj=182441 with registration No. ChiCTR2200064779 on Oct 17, 2022.

Efficacy and Safety of Distal Radial Artery Approach for Coronary Angiography: A Retrospective Study.

BACKGROUND: The distal radial artery approach has been employed as a potential alternative technique for coronary angiography. Nevertheless, its clinical implementation is significantly constrained by the narrow diameter of the radial artery. A comprehensive investigation of the efficacy and safety of the distal radial artery approach for coronary angiography is lacking. The objective of this study is to investigate the impact of the distal radial artery approach for coronary angiography and transradial artery access for interventional diagnosis and treatment. In addition, the effectiveness and safety of the distal radial artery approach for coronary artery angiography will be analyzed, for the wider adoption of this technique in clinical practice. METHODS: A total of 68 patients with coronary heart disease (CHD) who underwent coronary catheterization via the left distal radial artery approach from December 2020 to December 2022 using the Distal radial artery approach (TRA) comprised the case-control study group. Seventy-three CHD patients who underwent routine left Transradial Artery Access coronary catheterization were selected as the Regular TRA group during the same period. Clinical data including age, body mass index (BMI), gender, CHD risk factors, routine drug treatment, ultrasonic-related indicators and operation-related indicators were collected from electronic medical records and the catheterization database from the two groups of patients. RESULTS: The diameter and Endothelium-dependent vasodilation (noe FMD) of puncture vessels in the Distal TRA group were significantly lower than those in the Regular radial artery approach (TRA) group (p-value < 0.05). After a period of 48 hours following the catheterization, the puncture vessel diameter and flow-mediated dilation (FMD) of the Distal TRA group were significantly lower compared to those of the Regular TRA group (p-value < 0.05). The effectiveness of transradial artery access was then compared between the two groups. It was determined that the Distal TRA group exhibited significantly higher values in terms of the Visual Analog Scale (VAS) score, puncture time, and heparin usage, in comparison to the Regular TRA group (p-value < 0.05). The occurrence rates of local hematoma, mediastinal hematoma, retroperitoneal hematoma, pseudoaneurysm, arteriovenous fistula, vagal reflex, vasospasm, blood transfusion, and other complications among patients in the Distal TRA group were comparable to those in the Regular TRA group (p-value > 0.05). The incidence of puncture and X-ray radiation in the Distal TRA group was found to be marginally higher compared to the Regular TRA group. This study suggests that the safety profile of patients undergoing coronary artery catheterization via the distal radial artery is relatively higher than those undergoing the procedure via the transradial artery, although the difference was not statistically significant (p-value > 0.05). CONCLUSIONS: The Distal radial artery approach can be used for conducting comprehensive coronary interventional diagnosis and treatment procedures, offering benefits such as reduced postoperative compression time, better hemostasis through the distal radial artery approach, and enhanced patient comfort. This approach demonstrates favorable efficacy and safety, making it a suitable routine puncture method for clinical treatment.

Diagnostic value of α1-MG and URBP in early diabetic renal impairment.

Aims/Introduction: Diabetic kidney disease (DKD) is defined as diabetes with impaired renal function, elevated urinary albumin excretion, or both. DKD is one of the most common microvascular complications of diabetes and plays an important role in the cause of end-stage renal disease (ESRD). About 5% of people with type 2 diabetes (T2DM) already have kidney damage at the time they are diagnosed, but other triggers of renal insufficiency, such as obesity, hyperlipidemia, glomerular atherosclerosis are often present, making it difficult to define "diabetic kidney disease" or "diabetic nephropathy" precisely in epidemiology or clinical practice. Therefore, the aim of this study is to identify diabetic patients with CKD at an early stage, and evaluate the value of tubular injury markers including α1-microglobulin (α1-MG), ß2-microglobulin (ß2-MG), N-acetyl-beta-D-glucosaminidase (NAG) and Urinary retinol binding protein (URBP) in the development of diabetes to DKD. Materials and methods: We recruited a total of 182 hospitalized patients with T2DM in the First Affiliated Hospital of Zhengzhou University from February 2018 to April 2023. We collected basic clinical characteristics and laboratory biochemical parameters of the patients. Based on their levels of urinary albumin creatinine ratio (UACR) and glomerular filtration rate (GFR), patients were divided into DM group (UACR≤30 mg/g and eGFR≥90 mL/min/1.73 m2, n = 63) and DKD group (UACR>30 mg/g or eGFR<90 mL/min/1.73 m2, n = 119) excluding other causes of chronic kidney disease. We further developed diagnostic models to improve the ability to predict the risk of developing DKD by screening potential risk factors using univariate and multivariate logistic regression analysis. Calibration plots and curve analysis were used to validate the model and clinical usefulness. Next, we screened patients with relatively normal estimated glomerular filtration rate (eGFR) (≥90 mL/min/1.73 m2) to investigate whether tubular injury markers could accurately predict the risk of DKD in patients with normal renal function. We defined the rate of GFR decline as a prognostic indicator of renal function in patients and collected the information of the re-hospitalized DKD patients to determine whether the relevant indicators had an impact on the renal prognosis. Results: The patients with DKD had higher levels of tubular injury markers than patients with DM. URBP, α1-MG, eGFR were statistically different in both univariate and multivariate logistic regression analyses and displayed great predictive power after modeling with an area under curve of 0.987. The calibration curve showed medium agreement. Decision curve showed it would add more net benefits for clinical decision. After adjusting eGFR and serum creatinine (Scr), URBP was demonstrated to be associated with early renal function impairment. Conclusion: Tubular injury markers play an important role in early diabetic renal function impairment.

Multiple Isothermal Amplification Coupled with CRISPR-Cas14a for the Naked-eye and Colorimetric Detection of Aflatoxin B1.

Aflatoxin B1 (AFB1) is highly toxic and challenging to remove, posing significant risks to both human health and economic development. Therefore, there is an urgent need to develop rapid, simple, and sensitive detection technologies. In this study, we introduce a naked-eye and colorimetric method based on multiple isothermal amplifications coupled with CRISPR-Cas14a and investigate its biosensing properties. This technique utilizes composite nanoprobes (MAPs) comprising magnetic nanoparticles and gold nanoparticles. AFB1 is efficiently identified through an aptamer competition process facilitated by magnetic nanoparticles , which triggers multiple isothermal amplification. This converts trace amounts of the toxin into a large quantity of DNA signal. Upon specific activation of the CRISPR-Cas14a complex, the MAPs are cleaved, resulting in significant changes in both color and colorimetric signal. The method demonstrates acceptable sensitivity, with a detection limit of 31.90 pg mL-1 and a wide detection range from 0.05 to 10 ng mL-1. Furthermore, the assay exhibits satisfactory specificity and high accuracy when it is applied to practical samples. Our approach offers a universal sensing platform with potential applications in food safety, environmental monitoring, and clinical diagnostics.

Protective effects of GuanXinNing tablet (GXNT) on diabetic encephalopathy in zucker diabetic obesity (ZDF) rats.

BACKGROUND: Diabetic encephalopathy (DE) is a complication of diabetes that leads to cognitive and behavioral decline. Utilizing safe and effective complementary and alternative medications for its management is a wise choice. Previous studies have shown that GuanXinNing Tablet (GXNT), an oral preparation primarily derived from two Chinese herbs, Salvia miltiorrhiza Bge. and Ligusticum chuanxiong Hort., exerts a beneficial neuroprotective effect. In this study, we explored the protective effects of GXNT on DE in male Zucker diabetic fatty (ZDF) rats induced by a high-fat diet, aiming to ascertain its significance and potential mechanisms. METHODS: ZDF rats were induced to develop type 2 diabetes (T2DM) with DE by a high-fat diet and treated with GXNT for 8 weeks until they were 20 weeks old. Throughout the experiment, the animals' vital parameters, such as body weight, were continuously monitored. Cognitive function was evaluated using the Y maze test. Biochemical kits were employed to analyze blood glucose, lipids, and vascular endothelial-related factors. Cerebrovascular lesions were assessed using magnetic resonance angiography (MRA) imaging. Brain lesions were evaluated using hematoxylin and eosin (H&E) staining and ultrastructure observation. IgG and albumin (ALB) leakage were detected using immunofluorescence. RESULTS: GXNT demonstrated an enhancement in the overall well-being of the animals. It notably improved cognitive and behavioral abilities, as demonstrated by extended retention time in the novel heterogeneous arm during the Y-maze test. GXNT effectively regulated glucose and lipid metabolism, reducing fasting and postprandial blood glucose, glycated hemoglobin (HbA1c), and total cholesterol (TC) levels. Additionally, it exhibited a protective effect on the vascular endothelium by reducing the serum TXB2/PGI2 ratio while elevating NO and PGI2 levels. Moreover, GXNT ameliorated stenosis and occlusion in cerebral vessel branches, increased the number of microvessels and neurons around the hippocampus, and improved microvascular occlusion in the cerebral cortex, along with addressing perivascular cell abnormalities. Immunofluorescence staining showed a decrease in the fluorescence intensity of IgG and ALB in the cerebral cortex. CONCLUSIONS: GXNT demonstrated a highly satisfactory protective effect on DE in ZDF rats. Its mechanism of action could be based on the regulation of glucolipid metabolism and its protective effect on the vascular endothelium.

A novel strategy for therapeutic drug monitoring: application of biosensors to quantify antimicrobials in biological matrices.

Over the past few years, therapeutic drug monitoring (TDM) has gained practical significance in antimicrobial precision therapy. Yet two categories of mainstream TDM techniques (chromatographic analysis and immunoassays) that are widely adopted nowadays retain certain inherent limitations. The use of biosensors, an innovative strategy for rapid evaluation of antimicrobial concentrations in biological samples, enables the implementation of point-of-care testing (POCT) and continuous monitoring, which may circumvent the constraints of conventional TDM and provide strong technological support for individualized antimicrobial treatment. This comprehensive review summarizes the investigations that have harnessed biosensors to detect antimicrobial drugs in biological matrices, provides insights into the performance and characteristics of each sensing form, and explores the feasibility of translating them into clinical practice. Furthermore, the future trends and obstacles to achieving POCT and continuous monitoring are discussed. More efforts are necessary to address the four key 'appropriateness' challenges to deploy biosensors in clinical practice, paving the way for personalized antimicrobial stewardship.

CD300ld on neutrophils is required for tumour-driven immune suppression.

The immune-suppressive tumour microenvironment represents a major obstacle to effective immunotherapy1,2. Pathologically activated neutrophils, also known as polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), are a critical component of the tumour microenvironment and have crucial roles in tumour progression and therapy resistance2-4. Identification of the key molecules on PMN-MDSCs is required to selectively target these cells for tumour treatment. Here, we performed an in vivo CRISPR-Cas9 screen in a tumour mouse model and identified CD300ld as a top candidate of tumour-favouring receptors. CD300ld is specifically expressed in normal neutrophils and is upregulated in PMN-MDSCs upon tumour-bearing. CD300ld knockout inhibits the development of multiple tumour types in a PMN-MDSC-dependent manner. CD300ld is required for the recruitment of PMN-MDSCs into tumours and their function to suppress T cell activation. CD300ld acts via the STAT3-S100A8/A9 axis, and knockout of Cd300ld reverses the tumour immune-suppressive microenvironment. CD300ld is upregulated in human cancers and shows an unfavourable correlation with patient survival. Blocking CD300ld activity inhibits tumour development and has synergistic effects with anti-PD1. Our study identifies CD300ld as a critical immune suppressor present on PMN-MDSCs, being required for tumour immune resistance and providing a potential target for cancer immunotherapy.

Metabolic characteristics of voriconazole - Induced liver injury in rats.

Voriconazole (VOR) - induced liver injury is a common adverse reaction, and can lead to serious clinical outcomes. It is of great significance to describe the metabolic characteristics of VOR - induced liver injury and to elucidate the potential mechanisms. This study investigated the changes of plasma metabolic profiles in a rat model of VOR - induced liver injury by non - targeted metabolomics. Correlation analysis was performed between differentially expressed metabolites and plasma liver function indexes. The metabolites with strong correlation were determined for their predictive performance for liver injury using receiver operating characteristic (ROC) curve analysis. Potential biomarkers were then screened combined with liver pathological scores. Finally, the expression level of genes that involved in lipid metabolism were determined in rat liver to verify the mechanism of VOR - induced liver injury we proposed. VOR - induced liver injury in rats was characterized by plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation, the lipid droplets accumulation in liver, as well as inflammation and fibrosis. Significant changes of plasma metabolites were observed, with a decrease in lipid metabolites accounting for over 50% of all changed metabolites, and alterations of cholesterol and bile acids metabolites. The decrease of 3 phosphatidylcholine (PC) in plasma could indicate the occurrence of VOR - induced liver injury. Decreased fatty acids (FA) oxidation and bile acid excretion might be the potential mechanisms of VOR - induced liver injury. This study provided new insights into the molecular characterization of VOR - induced liver injury.

Identification and Characterization of a Novel Nanobody Against Human CTGF to Reveal Its Antifibrotic Effect in an in vitro Model of Liver Fibrosis.

Background: No agents are currently available for the treatment or reversal of liver fibrosis. Novel antifibrotic therapies for chronic liver diseases are thus urgently needed. Connective tissue growth factor (CTGF) has been shown to contributes profoundly to liver fibrogenesis, which makes CTGF as a promising target for developing antifibrotic agents. Methods: In this study, we identified a novel nanobody (Nb) against human CTGF (anti-CTGF Nb) by phage display using an immunized camel, which showed high affinity and specificity in vitro. LX-2 cells, the immortalized human hepatic stellate cells, were induced by transforming growth factor beta1 (TGFß1) as an in vitro model of liver fibrosis to verify the antifibrotic activity of the anti-CTGF Nb. Results: Our data demonstrated that anti-CTGF Nb effectively alleviated TGFß1-induced LX-2 cell proliferation, activation, and migration, and promoted the apoptosis of activated LX-2 cells in response to TGFß1. Moreover, the anti-CTGF Nb remarkably reduced the levels of TGFß1, Smad2, and Smad3 expression in LX-2 stellate cells stimulated by TGFß1. Conclusion: Taken together, we successfully identified a novel Nb against human CTGF, which exhibited antifibrotic effects in vitro by regulating the biological functions of human stellate cells LX-2.

Selective Reduction of NO into N2 Catalyzed by Rh1-Doped Cluster Anions RhCe2O3-5.

Catalytic conversion of toxic nitrogen oxide (NO) and carbon monoxide (CO) into nitrogen (N2) and carbon dioxide (CO2) is imperative under the weight of the increasingly stringent emission regulations, while a fundamental understanding of the nature of the active site to selectively drive N2 generation is elusive. Herein, in combination with state-of-the-art mass-spectrometric experiments and quantum-chemical calculations, we demonstrated that the rhodium-cerium oxide clusters RhCe2O3-5- can catalytically drive NO reduction by CO and give rise to N2 and CO2. This finding represents a sharp improvement in cluster science where N2O is commonly produced in the rarely established examples of catalytic NO reduction mediated with gas-phase clusters. We demonstrated the importance of the unique chemical environment in the RhCe2O3- cluster to guide the substantially improved N2 selectivity: a triatomic Lewis "acid-base-acid" Ceδ+-Rhδ--Ceδ+ site is proposed to strongly adsorb two NO molecules as well as the N2O intermediate that is attached on the Rh atom and can facilely dissociate to form N2 assisted by both Ce atoms.

Recall Bias in the Assessment of Cough for Patients Discharged from Lung Surgery.

Purpose: This study aimed to evaluate the presence of recall bias when patients retrospectively report cough scores. Patients and Methods: Patients who underwent lung surgery between July 2021 and November 2021 were recruited for this study. We retrospectively assessed the severity of cough within the past 24 hours and the past 7 days using a 0-10 numerical rating scale. Recall bias was defined as the difference between the scores reported on the two assessments. Patients were grouped based on the longitudinal change in cough scores from pre-operation to 4 weeks after discharge using group-based trajectory models. Using generalized estimating equation to explore the factors influencing recall bias. Results: Overall, 199 patients were analyzed and demonstrated the three distinct trajectories of post-discharge cough: high (21.1%), medium (58.3%), and low (20.6%). Significant recall bias was found in week 2 for the high-trajectory patients (6.26 vs 5.10, P<0.01) and in week 3 for the medium-trajectory patients (2.88 vs 2.60, P=0.01). Among all recall bias, 41.8% were of underestimation, and 21.7% of overestimation. The high trajectory group (ß=1.14, P<0.01) and measurement interval (ß=0.36, P<0.01) were risk factors for underestimation, while post-discharge time (ß=-0.57, P<0.01) and measurement interval (ß=-0.13, P=0.02) were protective factors for overestimation. Conclusion: Retrospective assessment of post-discharge cough in patients who underwent lung surgery will introduce recall bias, with a tendency of underestimation. The high-trajectory group, interval time and post-discharge time are influencing factors of recall bias. For patients with severe cough at discharge, a shorter recall periods should be employed for monitoring, due to the large bias that results from a longer recall period.