Glycyrrhetinic acid blocks SARS-CoV-2 infection by activating the cGAS-STING signalling pathway.

BACKGROUND AND PURPOSE: Traditional Chinese medicine (TCM) played an important role in controlling the COVID-19 pandemic, but the scientific basis and its active ingredients are still weakly studied. This study aims to decipher the underlying anti-SARS-CoV-2 mechanisms of glycyrrhetinic acid (GA). EXPERIMENTAL APPROACH: GA's anti-SARS-CoV-2 effect was verified both in vitro and in vivo. Homogeneous time-resolved fluorescence assays, biolayer interferometry technology, and molecular docking were employed to examine interactions of GA with human stimulator of interferon genes (hSTING). Immunofluorescence staining, western blot, and RT-qPCR were used to investigate nuclear translocation of interferon regulatory factor 3 (IRF3) and levels of STING target genes. Pharmacokinetics of GA was studied in mice. KEY RESULTS: GA could directly bind to Ser162 and Tyr240 residues of hSTING, thus up-regulating downstream targets and activation of the STING signalling pathway. Such activation is crucial for limiting the replication of SARS-CoV-2 Omicron in Calu-3 cells and protecting against lung injury induced by SARS-CoV-2 Omicron infection in K18-ACE2 transgenic mice. Immunofluorescence staining and western blot indicated that GA increased levels of phosphorylated STING, phosphorylated TANK-binding kinase-1, and cyclic GMP-AMP synthase (cGAS). Importantly, GA increased nuclear translocation of IRF3. Pharmacokinetic analysis of GA in mice indicated it can be absorbed into circulation and detected in the lung at a stable level. CONCLUSION AND IMPLICATIONS: Activation of the cGAS-STING pathway through the GA-STING-IRF3 axis is essential for the antiviral activity of GA in mice, providing new insights into the potential translation of GA for treating SARS-CoV-2 in patients.

Experimental Study of Mechanical Properties and Theoretical Models for Recycled Fine and Coarse Aggregate Concrete with Steel Fibers.

With diminishing natural aggregate resources and increasing environmental protection efforts, the use of recycled fine aggregate is a more sustainable approach, although challenges persist in achieving comparable mechanical properties. Exploration into the incorporation of steel fibers with recycled aggregate has led to the development of steel-fiber-reinforced recycled aggregate concrete. This study investigates the shrinkage performance and compressive constitutive relationship of steel fiber recycled concrete with different steel fibers and recycled aggregate dosages. Initially, based on different replacement rates of recycled coarse aggregate and different volume contents of steel fiber, experimental results demonstrate that as the replacement rate of recycled coarse aggregate increases, shrinkage also increases, while the addition of steel fiber can mitigate this effect. An empirical shrinkage model for steel fiber recycled concrete under natural curing conditions is also proposed. Subsequently, based on the uniaxial compression test, findings indicate that with an increasing replacement rate of recycled fine aggregate, the peak stress and elastic modulus of concrete decrease, accompanied by an increase in peak strain, and the addition of steel fiber limits concrete crack development and enhances its brittleness while the peak stress and strain of recycled fine aggregate concrete are enhanced. However, the steel fiber volume percentage has a negligible effect on the elastic modulus. A constitutive relationship for concrete considering the effects of recycled fine aggregate and steel fiber is also proposed. This finding provides foundational support for the influence patterns of steel fiber dosage and recycled aggregate ratio on the mechanical properties of steel fiber recycled concrete.

A comprehensive review on the recent advances for 5-aminolevulinic acid production by the engineered bacteria.

5-Aminolevulinic acid (5-ALA) is a non-proteinogenic amino acid essential for synthesizing tetrapyrrole compounds, including heme, chlorophyll, cytochrome, and vitamin B12. As a plant growth regulator, 5-ALA is extensively used in agriculture to enhance crop yield and quality. The complexity and low yield of chemical synthesis methods have led to significant interest in the microbial synthesis of 5-ALA. Advanced strategies, including the: enhancement of precursor and cofactor supply, compartmentalization of key enzymes, product transporters engineering, by-product formation reduction, and biosensor-based dynamic regulation, have been implemented in bacteria for 5-ALA production, significantly advancing its industrialization. This article offers a comprehensive review of recent developments in 5-ALA production using engineered bacteria and presents new insights to propel the field forward.

Introducing Triplex Forming Oligonucleotide into Loop-Mediated Isothermal Amplification for Developing a Lateral Flow Biosensor for Streptococci Detection.

Loop-mediated isothermal amplification (LAMP) technology is extensively utilized for the detection of infectious diseases owing to its rapid processing and high sensitivity. Nevertheless, conventional LAMP signaling methods frequently suffer from a lack of sequence specificity. This study integrates a triplex-forming oligonucleotide (TFO) probe into the LAMP process to enhance sequence specificity. This TFO-LAMP technique was applied for the detection of Group B Streptococcus (GBS). The TFO probe is designed to recognize a specific DNA sequence, termed the TFO targeting sequence (TTS), within the amplified product, facilitating detection via fluorescent instrumentation or lateral flow biosensors. A screening method was developed to identify TFO sequences with high affinity to integrate TFO into LAMP, subsequently incorporating a selected TTS into an LAMP primer. In the TFO-LAMP assay, a FAM-labeled TFO is added to target the TTS. This TFO can be captured by an anti-FAM antibody on lateral flow test strips, thus creating a nucleic acid testing biosensor. The efficacy of the TFO-LAMP assay was confirmed through experiments with specimens spiked with varying concentrations of GBS, demonstrating 85% sensitivity at 300 copies and 100% sensitivity at 30,000 copies. In conclusion, this study has successfully developed a TFO-LAMP technology that offers applicability in lateral flow biosensors and potentially other biosensor platforms.

Implementation of an Automated Antibiotic Time-out at a Comprehensive Cancer Center.

Background: Antimicrobial stewardship programs can optimize antimicrobial use and have been federally mandated in all hospitals. However, best stewardship practices in immunocompromised patients with cancer are not well established. Methods: An antimicrobial time out, in the form of an email, was sent to physicians caring for hospitalized patients reaching 5 days of therapy for targeted antimicrobials (daptomycin, linezolid, tigecycline, vancomycin, imipenem/cilastatin, meropenem) in a comprehensive cancer center. Physicians were to discontinue the antimicrobial if unnecessary or document a rationale for continuation. This is a quasi-experimental, interrupted time series analysis assessing antimicrobial use during the following times: period 1 (before time-out: January 2007-June 2010) and period 2 (after time-out: July 2010-March/2015). The primary antimicrobial consumption metric was mean duration of therapy. Days of therapy per 1000 patient-days were also assessed. Results: Implementation of the time-out was associated with a significant decrease in mean duration of therapy for the following antimicrobials; daptomycin: -0.89 days (95% confidence interval [CI], -1.38 to -.41); linezolid: -0.89 days (95% CI, -1.27 to -.52); meropenem: -0.97 days (95% CI, -1.39 to -.56); tigecycline: -1.41 days (95% CI, -2.19 to -.63); P < .001 for each comparison. Days of therapy/1000 patient-days decreased significantly for meropenem (-43.49; 95% CI, -58.61 to -28.37; P < .001), tigecycline (-35.47; 95% CI, -44.94 to -26.00; P < .001), and daptomycin (-9.47; 95% CI, -15.25 to -3.68; P = .002). Discussion: A passive day 5 time-out was associated with reduction in targeted antibiotic use in a cancer center and could potentially be successfully adopted to several settings and electronic health records.

Functional assessment of a novel biallelic MYH3 variation causing CPSKF1B (contractures, pterygia, and spondylocarpotarsal fusion syndrome1B).

BACKGROUND: The MYH3-associated myosinopathies comprise a spectrum of rare neuromuscular disorders mainly characterized by distal arthrogryposis with or without other features like pterygia and vertebrae fusion. CPSKF1B (contractures, pterygia, and spondylocarpotarsal fusion syndrome1B) is the only known autosomal recessiveMYH3-associated myosinopathy so far, with no more than two dozen cases being reported. MATERIALS AND METHODS: A boy with CPSKF1B was recruited and subjected to a comprehensive clinical and imaging evaluation. Genetic detection with whole-exome sequencing (WES) was performed on the patient and extended family members to identify the causative variation. A series of in silico and in vitro investigations were carried out to verify the pathogenicity of the two variants of the identified compound heterozygous variation. RESULTS: The patient exhibited moderate CPSKF1B symptoms including multiarticular contractures, webbed neck, and spondylocarpotarsal fusion. WES detected a compound heterozygous MYH3 variation consisting of two variants, namely NM_002470.4: c.3377A>G; p. (E1126G) and NM_002470.4: c.5161-2A>C. It was indicated that the NM_002470.4: c.3377A>G; p. (E1126G) variant mainly impaired the local hydrogen bond formation and impacted the TGF-B pathway, while the NM_002470.4: c.5161-2A>C variant could affect the normal splicing of pre-mRNA, resulting in the appearance of multiple abnormal transcripts. CONCLUSIONS: The findings of this study expanded the mutation spectrum of CPSKF1B, provided an important basis for the counseling of the affected family, and also laid a foundation for the functional study of MYH3 mutations.

Impact of age, sex, and thyroid autoimmunity on the association between selenium intake and type 2 diabetes mellitus.

BACKGROUND: The association between dietary selenium(Se) intake and type 2 diabetes mellitus (T2DM) remains controversial. The present study aimed to investigate this association using data from the National Health and Nutrition Examination Survey (NHANES) database for the years 2007-2012. METHODS: Three thousand seventy three individuals aged 20 years and above were eligible for inclusion in this cross-sectional study. The average age of the participants was 50.74 years and the proportions of males and females were nearly equal (49.12% vs. 50.88%). The odds ratios (OR) of the association between dietary Se intake (log2-transformed) and T2DM were examined through the multivariate logistic regression model. Subgroup analyses were conducted based on age, sex, and thyroid autoimmunity to assess the potential impact of these variables on the relationship. Fitted smoothing curves and threshold effect analysis were conducted to describe the nonlinear relationship. RESULTS: In the fully adjusted model, a significant positive association between Se intake and T2DM was observed (OR = 1.49, 95% CI: 1.16, 1.90, p = 0.0017). After stratifying the data by age, sex, and thyroid autoimmunity, a significant positive association between Se intake and T2DM was observed in individuals under 65 years of age, males, and those with negative thyroid autoimmunity. A two-segment linear regression model was analyzed for sex stratification, revealing a threshold effect in males with an inflection point of 90.51 µg, and an inverted U-shaped relationship in females with an inflection point of 109.90 µg, respectively. CONCLUSIONS: The present study found a positive relationship between Se intake and the prevalence of T2DM. This association is particularly significant in younger individuals, males, and those with negative thyroid autoimmunity. Our results should be validated in future large prospective studies in different populations.

Constructing Efficient CuO-Based CO Oxidation Catalysts with Large Specific Surface Area Mesoporous CeO2 Nanosphere Support.

CeO2 is an outstanding support commonly used for the CuO-based CO oxidation catalysts due to its excellent redox property and oxygen storage-release property. However, the inherently small specific surface area of CeO2 support restricts the further enhancement of its catalytic performance. In this work, the novel mesoporous CeO2 nanosphere with a large specific surface area (~190.4 m2/g) was facilely synthesized by the improved hydrothermal method. The large specific surface area of mesoporous CeO2 nanosphere could be successfully maintained even at high temperatures up to 500 °C, exhibiting excellent thermal stability. Then, a series of CuO-based CO oxidation catalysts were prepared with the mesoporous CeO2 nanosphere as the support. The large surface area of the mesoporous CeO2 nanosphere support could greatly promote the dispersion of CuO active sites. The effects of the CuO loading amount, the calcination temperature, mesostructure, and redox property on the performances of CO oxidation were systematically investigated. It was found that high Cu+ concentration and lattice oxygen content in mesoporous CuO/CeO2 nanosphere catalysts greatly contributed to enhancing the performances of CO oxidation. Therefore, the present mesoporous CeO2 nanosphere with its large specific surface area was considered a promising support for advanced CO oxidation and even other industrial catalysts.

FTO genotype and body mass index reduction in childhood obesity interventions: A systematic review and meta-analysis.

Numerous guidelines have called for personalized interventions to address childhood obesity. The role of fat mass and obesity-associated gene (FTO) in the risk of childhood obesity has been summarized. However, it remains unclear whether FTO could influence individual responses to obesity interventions, especially in children. To address this, we systematically reviewed 12,255 records across 10 databases/registers and included 13 lifestyle-based obesity interventions (3980 children with overweight/obesity) reporting changes in body mass index (BMI) Z-score, BMI, waist circumference, waist-to-hip ratio, and body fat percentage after interventions. These obesity-related outcomes were first compared between children carrying different FTO genotypes (rs9939609 or its proxy) and then synthesized by random-effect meta-analysis models. The results from single-group interventions showed no evidence of associations between FTO risk allele and changes in obesity-related outcomes after interventions (e.g., BMI Z-score: -0.01; 95% CI: -0.04, 0.01). The results from controlled trials showed that associations between the FTO risk allele and changes in obesity-related outcomes did not differ by intervention/control group. To conclude, the FTO risk allele might play a minor role in the response to obesity interventions among children. Future studies might pay more attention to the accumulation effect of multiple genes in the intervention process among children.

Dysregulation of mitochondrial dynamics mediated aortic perivascular adipose tissue-associated vascular reactivity impairment under excessive fructose intake.

Excessive fructose intake presents the major risk factor for metabolic cardiovascular disease. Perivascular adipose tissue (PVAT) is a metabolic tissue and possesses a paracrine function in regulating aortic reactivity. However, whether and how PVAT alters vascular function under fructose overconsumption remains largely unknown. In this study, male Sprague-Dawley rats (8 weeks old) were fed a 60% high fructose diet (HFD) for 12 weeks. Fasting blood sugar, insulin, and triglycerides were significantly increased by HFD intake. Plasma adiponectin was significantly enhanced in the HFD group. The expression of uncoupling protein 1 (UCP1) and mitochondrial mass were reduced in the aortic PVAT of the HFD group. Concurrently, the expression of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and mitochondrial transcription factor A (TFAM) were suppressed. Furthermore, decreased fusion proteins (OPA1, MFN1, and MFN2) were accompanied by increased fission proteins (FIS1 and phospho-DRP1). Notably, the upregulated α-smooth muscle actin (α-SMA) and osteocalcin in the PVAT were concurrent with the impaired reactivity of aortic contraction and relaxation. Coenzyme Q10 (Q, 10 mg/100 mL, 4 weeks) effectively reversed the aforementioned events induced by HFD. Together, these results suggested that the dysregulation of mitochondrial dynamics mediated HFD-triggered PVAT whitening to impair aortic reactivity. Fortunately, coenzyme Q10 treatment reversed HFD-induced PVAT whitening and aortic reactivity.

Gene variants and the response to childhood obesity interventions: A systematic review and meta-analysis.

BACKGROUND: Multiple lifestyle-based childhood obesity interventions have been conducted to address childhood obesity, but individual's response to the universal intervention approach varied greatly. Whether gene variants related to children and adolescents' varied responses to obesity interventions remained unclear. AIMS: To determine the associations of gene variants with the changes in obesity- and metabolism-related indicators after obesity interventions in children and adolescents. METHODS: Ten databases and registers (including grey literature) were searched. The lifestyle-based obesity interventions in children and adolescents (≤18 years) that reported the changes in obesity- (body mass index (BMI), BMI Z-score, waist circumference (WC), waist-to-hip ratio (WHR), etc) and metabolism-related (glucose, cholesterol, etc) indicators by genotype after interventions were included. Our primary outcome was the mean difference of the changes in BMI Z-score by genotype after interventions, and secondary outcomes were changes in the remaining obesity- and metabolism-related indicators after interventions. We used the random-effects model to synthesize the results. RESULTS: This review included 50 studies (15,354 children and adolescents with overweight/obesity) covering 102 genes and 174 single nucleotide polymorphisms (SNPs). Approximately three-quarters of SNPs showed no evidence of association with the changes in obesity- or metabolic-related indicators after interventions. One quarter of SNPs were minorly associated with the changes in the BMI Z-score (median effect size: 0.001) with little clinical significance. Only 6 (12 %) studies focused on the accumulated effect of multiple gene variants. CONCLUSIONS: Gene variants that have been explored appear to play a minor role in lifestyle-based obesity interventions in children and adolescents. More high-quality studies based on the design of randomized controlled trials are needed to examine the accumulated effect of multiple gene variants in childhood obesity interventions. PROSPERO REGISTRY NUMBER: This systematic review and meta-analysis was registered at PROSPERO as CRD42022312177.

Pregnancy and Progression of Differentiated Thyroid Cancer: A Propensity Score-Matched Retrospective Cohort Study.

CONTEXT AND OBJECTIVE: Differentiated thyroid cancer (DTC) is very common in women of reproductive age. However, it remains unclear whether pregnancy is associated with DTC progression before surgical treatment. METHODS: This retrospective cohort study, conducted at the Peking University Third Hospital in Beijing, China between January 2012 and December 2022, included 311 eligible women aged 20 to 45 years. To control for potential confounders, we first used propensity score matching (PSM) to match the pregnant group (n = 48) with the nonpregnant group (n = 154) on age, tumor size, tumor type, and Hashimoto's thyroiditis status at baseline, and then used Cox proportional risk models stratified by the matched pairs to estimate the association of pregnancy with DTC progression. RESULTS: After PSM, the pregnant and nonpregnant groups were well comparable at baseline (standardized difference < 10% and P > .05). Over an average observation period of 2.5 years, we observed no difference between the pregnant group and the matched nonpregnant group in DTC progression-free survival (hazard ratio [HR] = 0.96; 95% CI, 0.56 to 1.65; P = .895), tumor enlargement-free survival (HR = 0.99; 95% CI, 0.56 to 1.76; P = .969) or lymph node metastasis-free survival (LNM) (HR = 0.67; 95% CI, 0.21 to 2.13; P = .498). The postoperative pathological characteristics also showed no significant difference between the pregnant and nonpregnant groups (P > .05). CONCLUSION: Pregnancy seemed to be irrelevant to DTC progression-free survival before surgical treatment. Further prospective cohort studies are needed to translate this finding into clinical practice.

Study on the prevention and nursing intervention of infection after flap transfer for hand trauma.

To analyze the factors associated with infection after flap transfer for hand trauma and use them to develop nursing strategies and observe the effects of their application. Eighty-two patients admitted to our hospital for flap transfer for hand trauma from January 2020 to May 2020 were selected for the retrospective analysis. Logistic regression analysis was performed to analyze the factors associated with postoperative infections to develop care strategies. Another 88 patients admitted for flap transfer for hand trauma from September 2020 to June 2021 were retrospectively analyzed and divided into the observation (n = 44) and control groups (n = 44) according nursing strategies that they received. The operative time, intraoperative bleeding, incision healing time, first postoperative time to get out of bed on their own and hospital stay were compared between the 2 groups. The patients postoperative adverse effects and flap survival rates were also counted. visual analogue score, total active motion, manual muscle test, Barthel index, self-rating anxiety scale, self-rating depression scale scores were used to assess patients pain, hand function recovery and psychology before and after treatment. Logistic regression analysis manifested that postoperative bed rest time, affected limb immobilization, and pain were independent factors affecting postoperative infection after flap transfer (P < .05). After using targeted care strategies, the observation group had dramatically shorter operative time, intraoperative bleeding, incision healing time, time to first postoperative bed release on their own, and hospital stay, less postoperative pain and adverse effects, and higher flap survival rate than the control group (P < .05). Total active motion, manual muscle test, and Barthel index were higher in the observation group than in the control group after treatment, while self-rating anxiety scale and self-rating depression scale scores were lower than in the control group (P < .05). Finally, total satisfaction was higher in the observation group than in the control group (P < .05). Postoperative bedtime, fixation of the affected limb, and pain are independent factors affecting postoperative infection after flap transfer for hand trauma. Implementing infection prevention care strategies based on these factors can effectively improve the safety of flap transfer, reduce the possibility of infection, and shorten the recovery period of patients, which has high clinical application value.

Piezoelectric ceramic sensor-based structural health monitoring of diagonally braced H-shaped steel structures.

In this study, we propose a piezoelectric ceramic sensor-based health monitoring method to monitor the stress state of diagonally braced H-shaped steel structures. Loading experiments were carried out on diagonally braced H-shaped steel under different working conditions. Subsequently, the amplitude and energy of piezoelectric signals under these two working conditions were compared and analyzed, and finite element analysis was performed using ABAQUS software to verify the results. The experimental results showed that with an increase in the web height or load, the time-domain waveform energy index of the H-shaped steel increased. Under different working conditions, such as a diagonally braced H-shaped steel member with a web height of 10 cm, when the pressure value was less than 10 N/mm2, the energy index increased by approximately 15.98% for every 1 N/mm2 increase in the pressure. When the pressure value was greater than 10 N/mm2 and less than 15 N/mm2, the energy index increased by approximately 1% for every 1 N/mm2 increase in pressure. Further, the energy index increased by approximately 8.4% for every 1 cm increase in the height of the web. Simultaneously, it can be seen from the results of the finite element analysis that the stress and strain at the induction position of the piezoelectric ceramic sensor increased with an increase in the external pressure. The study of structural health monitoring for diagonally braced H-shaped steel structures holds significant importance in ensuring the safety and reliability of these structures, achieving predictive maintenance, evaluating structural performance and energy efficiency, and optimizing structural maintenance.

The association of personality traits with childhood obesity: A systematic review and meta-analysis.

BACKGROUND: A growing body of evidence has revealed an association between personality traits and obesity, but the findings regarding this association among children remain mixed. The aim of this review was to systematically summarize the literature regarding the associations between personality traits and childhood obesity. METHODS: The study has been registered on PROSPERO (CRD42022306529). We searched a total of 8 databases up to July 1, 2023, to identify both published studies and grey literature written in English. Personality traits were classified into five dimensions based on the widely used Five-Factor Model. We conducted random effects meta-analyses to quantitatively synthesize the data. Newcastle-Ottawa Scale was used to assess the quality of included studies. RESULTS: A total of 7 studies were included. The pooled correlation coefficient of 2 studies was -0.09 (95 % CI: -0.17 to 0.00; I2 = 0 %) and the pooled standardized mean difference of 3 studies was -0.08 (95 % CI: -0.13 to -0.03; I2 = 66 %), indicating that conscientiousness was negatively associated with childhood obesity. No consistent patterns were found in the associations between the other 4 dimensions of personality traits and BMI/obesity in children. LIMITATIONS: Our findings should be interpreted with caution due to the exclusion of non-English studies, the limited generalizability to Eastern population, and the scarcity body of evidence for present topic. CONCLUSIONS: Low conscientiousness has been found to be consistently associated with childhood obesity. Causal associations of personality traits with the risk of childhood obesity remain to be clarified in future studies.

The Association of Pregnancy with Disease Progression in Patients Previously Treated for Differentiated Thyroid Cancer: A Propensity Score-Matched Retrospective Cohort Study.

Background: Differentiated thyroid cancer (DTC) is increasingly common in women of reproductive age. However, whether pregnancy increases the risk of DTC progression/recurrence after treatment remains controversial. The study aimed to assess the association of pregnancy with risk of progression in patients previously treated for DTC. Methods: This was a retrospective cohort study following 123 pregnant women and 1376 nonpregnant women at Peking University Third Hospital after initial treatment for DTC between January 2012 and December 2022. To control the effect of confounding, we carefully matched pregnancy (n = 107) and nonpregnancy groups (n = 298) in terms of baseline characteristics by using propensity score matching (PSM). Results: At baseline, the pregnancy and nonpregnancy groups were balanced in all matched variables. At follow-up, the percentage of DTC progression in the two groups was 12 (11.8%) and 47 (15.8%), respectively. Regression models showed no evidence of association of pregnancy with the risk of progression (odds ratio: 0.74 and 95% confidence interval: 0.37-1.50; p = 0.404), and remained consistent across long/short follow-up and other subgroup variables. We found that the shorter the time interval between treatment and pregnancy, the higher the risk of DTC progression (ptrend = 0.019). Conclusions: The risk of DTC progression in pregnant women was not higher than that in the well-matched, nonpregnant women. For young women previously treated for DTC, disease progression might not be a concern for their future pregnancy plan, but it seems safer to wait at least 1 year before pregnancy compared with immediate pregnancy.

The working experience of medical staff in the hospital-wide bed-sharing mode: A qualitative study.

AIM: The purpose of this study was to provide a comprehensive understanding of the attitudes and experiences of the medical staff regarding the hospital bed-sharing model. DESIGN: The present research was a qualitative study. METHODS: This qualitative study used in-depth individual interviews with 7 doctors, 10 clinical nurses and 3 head nurses, which were then transcribed and analysed thematically. RESULTS: The study identified six overall themes. Issues were raised about the efficient utilization of hospital bed resources, greater challenges for nursing work, adjustment of doctors' work modes, barriers to communication between doctors, nurses, and patients, potential medical risks, and differentiation of patients' medical experience. IMPLICATIONS FOR NURSING MANAGEMENT: Hospital administrators and nurse managers should work together to solve the challenges that medical staff face, including strengthening nursing training, improving medical-nursing collaboration models, standardizing and effective communication strategies, and improving patient experiences.

PD-L1 dimerisation induced by biphenyl derivatives mediates anti-breast cancer activity via the non-immune PD-L1-AKT-mTOR/Bcl2 pathway.

Recent studies on biphenyl-containing compounds, a type of PD-1/PD-L1 blocker which binds to PD-L1 and induces dimerisation, have focussed on its immune function. Herein, 10 novel biphenyl derivatives were designed and synthesised. The results of the CCK-8 showed that compounds have different anti-tumour activities for tumour cells in the absence of T cells. Particularly, 12j-4 can significantly induce the apoptosis of MDA-MB-231 cells (IC50 = 2.68 ± 0.27 µM). In further studies, 12j-4 has been shown to prevent the phosphorylation of AKT by binding to cytoplasmic PD-L1, which induces apoptosis in MDA-MB-231 cells through non-immune pathways. The inhibition of AKT phosphorylation restores the activity of GSK-3ß, ultimately resulting in the degradation of PD-L1. Besides, in vivo study indicated that 12j-4 repressed tumour growth in nude mice. As these biphenyls exert their anti-tumour effects mainly through non-immune pathways, they are worthy of further study as PD-L1 inhibitors.