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Abstract Tracheopericardial fistula is an extremely rare clinical condition caused by lung disease penetrating the tracheal wall and extending to the pericardial cavity, forming a fistula between the airway and the pericardial cavity. Since the pericardial cavity communicates with the respiratory tract, gases, airway secretions and pathogens can enter the cavity, leading to pneumopericardium, effusion and abscess. In severe cases, it can result in cardiac tamponade and cardiogenic shock. Only a few cases of TPF have been reported in the literature. In this report, a 72-year-old man with recurrent lung cancer presented with fever, chest tightness and chest pain. Electrocardiogram showed ST-segment elevation in multiple leads, resembling an acute myocardial infarction. Emergency coronary angiography did not reveal significant stenosis. Further examination with chest computed tomography and bronchoscopy revealed pericardial effusion and a tracheal fistula, leading to the final diagnosis of TPF as a complication of lung cancer. This case aims to enhance understanding and recognition of this clinical entity to reduce misdiagnosis.

Abstract Radiotherapy (RT) is a crucial treatment for colorectal cancer (CRC) patients, but it often fails to induce systemic antitumor immunity. CD73, an immunomodulatory factor, is upregulated after RT and associated with poor prognosis in CRC patients. This study aims to elucidate the mechanisms driving RT-induced CD73 upregulation in CRC and investigate how combining RT with CD73 blockade stimulates immune responses and induces abscopal effects. Findings revealed that RT-induced CD73 upregulation is mediated by the ataxia telangiectasia and Rad3-related (ATR) pathway and correlated with RT tolerance, as demonstrated through flow cytometry, immunofluorescence, and Western Blotting. Using flow cytometry and multicolor immunofluorescence, experiments demonstrated that in CRC subcutaneous tumor models, combination therapy reduces the infiltration of myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and regulatory T cells (Tregs) while increasing dendritic cells (DCs) and CD8 + T cells, resulting in superior antitumor responses. Additionally, results from flow cytometry, Western Blot, and RNA sequencing demonstrated that combination therapy enhances the antigen-presenting ability of DCs and activates tumor antigen-specific CD8 + T cells, improving their function and delaying their depletion. The activation of the cGAS-STING and IFN-I pathways is crucial for this effect. In summary, the integration of RT with CD73 blockade effectively reverses the immunosuppressive TME and invigorates CD8 + T cell-driven, specific antitumor immune responses. These insights shed fresh light on the mechanisms governing the synergistic modulation of immunity by RT and CD73 blockade in CRC, offering promising avenues for the advancement of therapeutic strategies against CRC.

Abstract Background The purpose of this network meta-analysis was to assess the impact of different protective ventilatory strategies on postoperative pulmonary complications (PPCs). Methods Several databases were searched for randomized controlled trials (RCTs) that were published before October 2023 in a network meta-analysis. We assessed the effect of different lung-protective ventilation strategies on the incidence of PPCs using Bayesian network meta-analysis. Results We included 58 studies (11610 patients) in this meta-analysis. The network meta-analysis showed that low tidal volumes (LTVs) combined with iPEEP and recruitment manoeuvres (RM) was associated with significantly lower incidence of PPCs [HTVs: OR = 0.38, 95%CrI (0.19, 0.75), LTVs: OR = 0.33, 95%CrI (0.12, 0.82)], postoperative atelectasis[HTVs: OR = 0.2, 95%CrI (0.08, 0.48), LTVs: OR = 0.47, 95%CrI (0.11, 0.93)], and pneumonia[HTVs: OR = 0.22, 95%CrI (0.09, 0.48), LTVs: OR = 0.27, 95%CrI (0.08,0.89)] than was High tidal volumes (HTVs) or LTVs. LTVs combined with medium-to-high PEEP and RM were associated with significantly lower incidence of postoperative atelectasis, and pneumonia. Conclusion LTVs combined with iPEEP and RM decreased the incidence of PPCs, postoperative atelectasis, and pneumonia in noncardiac surgery patients. Individual PEEP-guided ventilation was the optimal lung protection ventilation strategy. The quality of evidence is moderate. Trial registration PROSPERO identifier CRD42023399485.

Abstract Imaging and characterizing the dynamics of cellular adhesion in blood samples is of fundamental importance in understanding biological function. In vitro microscopy methods are widely used for this task but typically require diluting the blood with a buffer to allow for transmission of light. However, whole blood provides crucial signaling cues that influence adhesion dynamics, which means that conventional approaches lack the full physiological complexity of living microvasculature. We can reliably image cell interactions in microfluidic channels during whole blood flow by motion blur microscopy (MBM) in vitro and automate image analysis using machine learning. MBM provides a low cost, easy to implement alternative to intravital microscopy, for rapid data generation where understanding cell interactions, adhesion, and motility is crucial. MBM is generalizable to studies of various diseases, including cancer, blood disorders, thrombosis, inflammatory and autoimmune diseases, as well as providing rich datasets for theoretical modeling of adhesion dynamics.

Abstract Background The remarkable advancements in surgical techniques over recent years have shifted the clinical focus from merely reducing mortality to enhancing the quality of postoperative recovery. The duration of a patient’s hospital stay serves as a crucial indicator in evaluating postoperative recovery and surgical outcomes. This study aims to identify predictors of the length of hospital stay for children who have undergone corrective surgery for Ebstein Anomaly (EA). Methods We conducted a retrospective cohort study on children (under 18 years of age) diagnosed with EA who were admitted for corrective surgery between January 2009 and November 2021 at Fuwai Hospital. The primary outcome was the Time to Hospital Discharge (THD). Cox proportional hazard models were utilized to identify predictors of THD. In the context of time-to-event analysis, discharge was considered an event. In cases where death occurred before discharge, it was defined as an extended THD, input as 100 days (exceeding the longest observed THD), and considered as a non-event. Results A total of 270 children were included in this study, out of which three died in the hospital. Following the Cox proportional hazard analysis, six predictors of THD were identified. The hazard ratios and corresponding 95% confidence intervals were as follows: age, 1.030(1.005,1.055); C/R > 0.65, 0.507(0.364,0.707); Carpentier type C or D, 0.578(0.429,0.779); CPB time, 0.995(0.991,0.998); dexamethasone, 1.373(1.051,1.795); and transfusion, 0.680(0.529,0.875). The children were categorized into three groups based on the quartile of THD. Compared to children in the ≤ 6 days group, those in the ≥ 11 days group were associated with a higher incidence of adverse outcomes. Additionally, the duration of mechanical ventilation and ICU stay, as well as hospital costs, were significantly higher in this group. Conclusion We identified six predictors of THD for children undergoing corrective surgery for EA. Clinicians can utilize these variables to optimize perioperative management strategies, reduce adverse complications, improve postoperative recovery, and reduce unnecessary medical expenses.

Abstract Zika virus, a mosquito-borne arbovirus, has repeatedly caused large pandemics with symptoms worsening from mild and self-limiting diseases to Guillain–Barré syndrome in adults and fetal microcephaly in newborns. In recent years, Zika virus diseases have posed a serious threat to human health. The shortage of susceptible small animal models makes it difficult to study pathogenic mechanisms and evaluate potential therapies for Zika virus infection. Therefore, we chose immunocompromised mice (AG129 mice) deficient in IFN-α/β and IFN-γ receptors, which can abolish the innate immune system that prevents Zika virus infection early. AG129 mice were infected with the Zika virus, and this mouse model exhibited replication dynamics, tissue tropism, pathological lesion and immune activation of the Zika virus. Our results suggest that the inoculum dose of Zika virus can affect the viral replication dynamics, cytokine responses and survival rate in AG129 mice. By testing the potential antiviral drug favipiravir, several critical indicators, including replication dynamics and survival rates, were identified in AG129 mice after Zika virus infection. It is suggested that the model is reliable for drug evaluation. In brief, this model provides a potential platform for studies of the infectivity, virulence, and pathogenesis of the Zika virus. Moreover, the development of an accessible mouse model of Zika virus infection will expedite the research and deployment of therapeutics and vaccines.

The micaceous weathered granitic soil (WGS) is frequently encountered in civil engineering worldwide, unfortunately little information is available regarding how mica affects the physico-mechanical behaviors of WGS. This study prepares reconstituted WGS with different mica contents by removing natural mica in the WGS, and then mixes it with commercial mica powders. The geotechnical behavior as well as the microstructures of the mixtures are characterized. The addition of mica enables the physical indices of WGS to be specific combinations of coarser gradation and high permeability but high Atterberg limits. However, high mica content in WGS was found to be associated with undesirable mechanical properties, including increased compressibility, disintegration, and swelling potential, as well as poor compactability and low effective frictional angle. Microstructural analysis indicates that the influence of mica on the responses of mixtures originates from the intrinsic nature of mica as well as the particle packing being formed within WGS. Mica exists in the mixture as stacks of plates that form a spongy structure with high compressibility and swelling potential. Pores among the plates give the soil high water retention and high Atterberg limits. Large pores are also generated by soil particles with bridging packing, which enhances the permeability and water-soil interactions upon immersion. This study provides a micro-level understanding of how mica dominates the behavior of WGS and provides new insights into the effective stabilization and improvement of micaceous soils.

Objective Myelodysplastic syndrome (MDS) is a malignant clonal disorder of hematopoietic stem cells which is characterized by morphologic dysplasia. However, the pathological characteristics of megakaryocytes (MKs) in MDS patients with gene mutation are not well established.

Key Clinical Message Adult‐onset immunodeficiency (AOID) is an emerging acquired immunodeficiency, characterized by multiple opportunistic infections including non‐tuberculous mycobacterium (NTM) due to the presence of anti‐IFN‐γ autoantibody (AIGA). This case highlights the challenges of accurate diagnosis of monoclonal gammaglobulinemia with NTM infection and favorable outcomes of anti‐plasma cell therapy in AOID. Abstract Adult‐onset immunodeficiency (AOID) is an emerging acquired immunodeficiency due to anti‐IFN‐γ autoantibody (AIGA) with low morbidity, frequent disseminated infections, a prolonged course, difficult diagnosis and treatment, and a poor prognosis. Here, we report a patient with positive AIGA and monoclonal gammaglobulinemia who was mimicking symptomatic multiple myeloma and resulting in a non‐tuberculous mycobacterial (NTM) infection. While he achieved an excellent therapeutic effect with anti‐plasma cell therapy, it also serves as a warning that monoclonal gammaglobulinemia with NTM infection is easily misdiagnosed as symptomatic multiple myeloma, and the screening for AIGA should not be ignored in patients with NTM infection.

This research aims to assess the predictors that impact the online learning experiences (OLEs) of undergraduate sports students amid the Coronavirus Disease 2019 (COVID-19) outbreak utilizing the Community of Inquiry (CoI) framework. An online survey was employed using the cluster sampling method to systematically examine the associations among the variables related to the OLE of sports students. A sample size of 402 undergraduate sports students from two universities in China was chosen and surveyed. Exploratory factor analysis was conducted to assess the validity of the questionnaires and model adequacy. Finally, a multiple linear regression analysis was performed to explore the associations of the study constructs. The results revealed that open communication, social presence, design and organization, and facilitation possess significant potential in predicting students’ OLE. This demonstrates the paramountcy of transparent communication, directs focus towards the indispensability of fostering a sense of reception and admiration among sports students, and highlights educators' sway in shaping their students' holistic and positive educational encounters. The scalability of our study highlights its potential to contribute valuable insights for developing national-level policies and educational strategies for this demographic.

Abstract Background To explore the perceptions and experience of oral health management among rural older people in China. Methods Qualitative methodologies were used in this study. Face-to-face semi-structured interviews were conducted. Thirteen older adults in rural areas were purposively sampled at two metropolitan hospitals in Hunan, China. The data were transcribed and thematically analyzed, and MAXQDA software was used to assist with coding. Results Three overarching major themes and ten sub‑themes capturing the perceptions and experience of oral health management among rural older people were identified. Three themes emerged from the thematic analysis: oral health cognitive bias, poor management behaviors, and limited oral health services. Oral health management as a whole is negative, oral health behaviors are poor, oral health service utilization is limited. Conclusions Based on these findings, there is great scope here for improving the current status of oral health for rural older people around awareness, behavior, and access. Oral health education, improved oral health services and primary oral health promotion are warranted.

Objective The unloading-induced upheaval deformation resulting from river excavation above metro shield tunnels may affect metro tunnel normal operation. Therefore, it is necessary to study the deformation effects of soft soil area river excavation on underlying metro tunnels and formulate control measures for metro tunnel deformation. Method The general overview of a case project is presented, and finite element method is conducted on its field-measured data analysis to validate the reasonability of the soil constitutive model and parameters. Based on the characteristic soft soil profile and soil parameters of Ningbo region stratum, a simplified soil mass model is established. The impact of changes in river excavation width, depth and the burial depth of soft soil layers on the deformation of underlying metro tunnels is analyzed sequentially. Two deformation control measures of gantry-type soil reinforcement and gantry-type beam-slab reinforcement, are introduced. A comparative analysis is performed between the finite element calculation results considering the control deformation measures and the baseline model. Result & Conclusion During soil reinforcement and river excavation stages, the deformation of underlying metro tunnel manifested as settlement and upheaval, respectively. When maintaining the same cross-sectional area for river excavation, reducing the river excavation depth and increasing the river excavation width are conducive to minimizing underlying metro tunnel deformation. Vertical displacement of the metro tunnel is primarily influenced by the rebound deformation of the soil below it. The gantry-type beam-slab reinforcement measure exhibits a noticeable control effect on metro tunnel upheaval deformation.

Abstract In the early 1990s, China introduced into its civil legal system the punitive damages system derived from the Anglo-American legal tradition, marking a significant legislative breakthrough among civil law countries. Currently, China is one of the countries with the greatest pressure to reduce emissions in the world, and more effective legal tools are needed for environmental governance. Therefore, in China’s Civil Code, which came into effect in January 2021, punitive damages for environmental torts were established, enabling the imposition of additional compensation for severe environmental pollution and ecological damage incidents and thus enhancing the deterrent effect of environmental laws. The construction of punitive damages for environmental torts in China has significant positive implications, but the provisions of the system are not perfect, leading to some confusion in its judicial practice. The United States has a very systematic and mature experience in the construction of punitive damages for environmental torts, which is worthy of reference for China. From a comparative research perspective, China’s punitive damages for environmental torts should particularly focus on issues such as expanding its scope of application, clarifying rules for determining compensation amounts, addressing issues of concurrent liability and optimizing related legislation.

Abstract Introduction The impact of immunosuppression on prognosis of carbapenem-resistant organism (CRO) bloodstream infection (BSI) remains unclear. The aim of this study was to clarify the relationship between immunosuppression and mortality of CRO-BSI and to identify the risk factors associated with mortality in immunosuppressed patients. Methods This retrospective study included 279 patients with CRO-BSI from January 2018 to March 2023. Clinical characteristics and outcomes were compared between the immunosuppressed and immunocompetent patients. The relationship between immunosuppression and 30-day mortality after BSI onset was assessed through logistic-regression analysis, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Factors associated with mortality in immunosuppressed patients were analyzed using multivariable logistic regression analysis. Results A total of 88 immunocompetent and 191 immunosuppressed patients were included, with 30-day all-cause mortality of 58.8%. Although the 30-day mortality in immunosuppressed patients was significantly higher than in immunocompetent patients (46.6% vs. 64.4%, P = 0.007), immunosuppression was not an independent risk factor for mortality in multivariate logistic regression analysis (odds ratio [OR] 3.53, 95% confidence interval [CI] 0.74–18.89; P = 0.123), PSM (OR 1.38, 95% CI 0.60–3.18; P = 0.449,) or IPTW (OR 1.40, 95% CI 0.58–3.36; P = 0.447). For patients with CRO-BSI, regardless of immune status, appropriate antibiotic therapy was associated with decreased 30-day mortality, while Charlson comorbidity index (CCI), intensive care unit (ICU)-acquired infection and thrombocytopenia at CRO-BSI onset were associated with increased mortality. Conclusion Despite the high mortality rate of CRO-BSI, immunosuppression did not affect the mortality. Appropriate antibiotic therapy is crucial for improving the prognosis of CRO-BSI, regardless of the immune status.

Abstract Tertiary lymphoid structure (TLS) contributes to the anti-tumor immune response, and predicts the prognosis of colorectal cancer patients. However, the potential impact of TLS in shaping the immune status of rectal adenocarcinoma, and the intrinsic relationship between TLS and neoadjuvant therapies (neoTx) remain unclear. We performed hematoxylin-eosin staining, immunohistochemical and biomolecular analyses to investigate TLS and tumor-infiltrating lymphocytes (TILs) in 221 neoTx-treated and 242 treatment-naïve locally advanced rectal cancer (LARC) patients. High TLS density was significantly associated with the absence of vascular invasion, a lower neutrophil-to-lymphocyte ratio, increased TLS maturity, a longer recurrence-free survival (RFS) (hazard ratio [HR] 0.2985 95% confidence interval [CI] 0.1894–0.4706, p

SARS-CoV-2 ancestral strain-induced immune imprinting poses great challenges to updating vaccines for new variants. Studies showed that repeated Omicron exposures could override immune imprinting induced by inactivated vaccines but not mRNA vaccines, a disparity yet to be understood. Here, we analyzed the immune imprinting alleviation in inactivated vaccine (CoronaVac) cohorts after a long-term period following breakthrough infections (BTI). We observed in CoronaVac-vaccinated individuals who experienced BA.5/BF.7 BTI, the proportion of Omicron-specific memory B cells (MBCs) substantially increased after an extended period post-Omicron BTI, with their antibodies displaying enhanced somatic hypermutation and neutralizing potency. Consequently, the neutralizing antibody epitope distribution encoded by MBCs post-BA.5/BF.7 BTI after prolonged maturation closely mirrors that in BA.5/BF.7-infected unvaccinated individuals. Together, these results indicate the activation and expansion of Omicron-specific naïve B cells generated by first-time Omicron exposure helped to alleviate CoronaVac-induced immune imprinting, and the absence of this process should have caused the persistent immune imprinting seen in mRNA vaccine recipients.

A multitude of functional mutations continue to emerge on the N-terminal domain (NTD) of the spike protein in SARS-CoV-2 Omicron subvariants. Understanding the immunogenicity of Omicron NTD and the properties of antibodies elicited by it is crucial for comprehending the impact of NTD mutations on viral fitness and guiding vaccine design. In this study, we find that most of NTD-targeting antibodies isolated from individuals with BA.5/BF.7 breakthrough infection (BTI) are ancestral (wild-type or WT)-reactive and non-neutralizing. Surprisingly, we identified five ultra-potent neutralizing antibodies (NAbs) that can only bind to Omicron but not WT NTD. Structural analysis revealed that they bind to a unique epitope on the N1/N2 loop of NTD and interact with the receptor-binding domain (RBD) via the light chain. These Omicron-specific NAbs achieve neutralization through ACE2 competition and blockage of ACE2-mediated S1 shedding. However, BA.2.86 and BA.2.87.1, which carry insertions or deletions on the N1/N2 loop, can evade these antibodies. Together, we provided a detailed map of the NTD-targeting antibody repertoire in the post-Omicron era, demonstrating their vulnerability to NTD mutations enabled by its evolutionary flexibility, despite their potent neutralization. These results revealed the function of the indels in the NTD of BA.2.86/JN.1 sublineage in evading neutralizing antibodies and highlighted the importance of considering the immunogenicity of NTD in vaccine design.

ABSTRACTAlthough fecal microbiota composition is considered to preserve relevant and representative information for distal colonic content, it is evident that it does not represent microbial communities inhabiting the small intestine. Nevertheless, studies investigating the human small intestinal microbiome and its response to dietary intervention are still scarce. The current study investigated the spatio-temporal dynamics of the small intestinal microbiome within a day and over 20 days, as well as its responses to a 14-day synbiotic or placebo control supplementation in 20 healthy subjects. Microbial composition and metabolome of luminal content of duodenum, jejunum, proximal ileum and feces differed significantly from each other. Additionally, differences in microbiota composition along the small intestine were most pronounced in the morning after overnight fasting, whereas differences in composition were not always measurable around noon or in the afternoon. Although overall small intestinal microbiota composition did not change significantly within 1 day and during 20 days, remarkable, individual-specific temporal dynamics were observed in individual subjects. In response to the synbiotic supplementation, only the microbial diversity in jejunum changed significantly. Increased metabolic activity of probiotic strains during intestinal passage, as assessed by metatranscriptome analysis, was not observed. Nevertheless, synbiotic supplementation led to a short-term spike in the relative abundance of genera included in the product in the small intestine approximately 2 hours post-ingestion. Collectively, small intestinal microbiota are highly dynamic. Ingested probiotic bacteria could lead to a transient spike in the relative abundance of corresponding genera and ASVs, suggesting their passage through the entire gastrointestinal tract. This study was registered to http://www.clinicaltrials.gov, NCT02018900.

BackgroundLing-gui-zhu-gan (LGZG) formula has been demonstrated to effectively ameliorate the clinical symptoms of patients with obesity or metabolic syndrome. This study aimed to explore both the effect and the underlying mechanisms of LGZG against obesity.MethodsMale C57BL/6N mice were randomized into four groups (n = 8): normal control (NC), obese (OB), metformin (Met), and LGZG. After 8 weeks of gavage administration, the pharmacological effects of LGZG on obesity and metabolism were investigated using biochemical parameters, histomorphological examination, and lipidomics techniques. Pivotal factors associated with white adipose tissue browning were evaluated using quantitative real-time polymerase chain reaction and western blotting.ResultsThe results revealed that LGZG reduced the levels of obesity markers, including body weights, body fat mass and food intake in obese mice. Further evaluations highlighted that LGZG restored glucose homeostasis and significantly improved insulin sensitivity in obese mice. Importantly, LGZG could adjust serum lipid profiles and regulate the lipidomic spectrum of intestinal contents, with noticeable shifts in the levels of certain lipids, particularly diacylglycerols and monoacylglycerols. Histopathological examinations of LGZG-treated mice also revealed more favorable adipose tissue structures than their obese counterparts. Furthermore, we found that LGZG upregulated the expression of several key thermogenesis-related factors, such as UCP1, PRDM16, PGC-1α, PPARα, PPARγ, CTBP1, and CTBP2 in white adipose tissues.ConclusionOur findings position LGZG as a novel strategy for preventing obesity and improving metabolic health.

Objectives This systematic review and meta-analysis examined whether the lymphocyte-to-monocyte ratio (LMR) can serve as an indicator for predicting the prognosis of patients with resectable pancreatic cancer. Patients and Methods This meta-analysis was registered with PROSPERO: CRD42023461260. A systematic literature search was conducted in the PubMed, Embase, Cochrane, and Web of Science databases up to September 2023 to assess whether LMR can predict the prognosis of patients with resectable pancreatic cancer. The outcomes measured included subgroup analyses of overall survival (OS) with hazard ratios (HR) and confidence intervals of geographical region, patient population, and LMR threshold. A sensitivity analysis was also performed for OS and HR and confidence intervals were calculated for recurrence-free survival (RFS). Results A total of 14 eligible articles, comprising 4,019 patients, were included in the comprehensive analysis. The results of this comprehensive analysis indicate that LMR is a robust predictor of OS, demonstrating strong prognostic significance (HR = 0.55, 95% CI [0.44–0.69], I2 = 79%, P < 0.00001). This predictive significance extended to various types of pancreatic cancer, such as pancreatic ductal adenocarcinoma (HR = 0.73, 95% CI [0.57–0.93], I2 = 46%, P = 0.01), pancreatic neuroendocrine neoplasms (HR = 0.81, 95% CI [0.66–0.99], P = 0.04) and other subtypes (HR = 0.40, 95% CI [0.22–0.72], I2 = 89%, P < 0.00001), but not to pancreatic head cancer (HR = 0.46, 95% CI [0.16–1.13], I2 = 59%, P = 0.12). LMR retained its predictive value across different regions, including Asia (HR = 0.62, 95% CI [0.47–0.76], I2 = 68%, P < 0.0001), Europe (HR = 0.78, 95% CI [0.67–0.91], I2 = 0%, P = 0.002), and the Americas (HR = 0.14, 95% CI [0.08–0.24], I2 = 0%, P < 0.00001). Notably, both LMR cut-off values greater than or equal to three (HR = 0.62, 95% CI [0.47–0.82], I2 = 67%, P = 0.0009) and less than three (HR = 0.47, 95% CI [0.32–0.69], I2 = 85%, P = 0.0001) exhibited prognostic significance. The sensitivity analysis for OS confirmed the strong predictive value of LMR, whereas LMR did not exhibit predictive significance for RFS (HR = 0.35, 95% CI [0.09–1.32], I2 = 95%, P = 0.12). In both subgroups categorized by Newcastle-Ottawa Scale (NOS) scores of ≥7 (HR = 0.66, 95% CI [0.54–0.80], I2 = 53%, P = 0.04) and

Lactate levels in humans reveal intensity and duration of exertion and provide a critical readout for the severity of life-threatening illnesses such as pediatric sepsis. Using the lactate oxidase enzyme (Lox) from Aerococcus viridians, we demonstrated its functionality for lactate electrochemical sensing in physiological fluids in a lab setting. The structure and dynamics of LOx were validated by crystallography, X-ray scattering, and hydroxyl radical protein footprinting. This provided a validated protein template for understanding and designing an enzyme-based electrochemical sensing elements. Using this template, LOx enzyme variants were generated and compared. Comparison of the variants demonstrates that one exhibits effective lactate sensing at significantly reduced operating voltages. Additionally, we demonstrate that the four hexahistidine-tags on each enzyme tetramer are sufficient for immobilization to create a durable, functional sensor, with no need for a covalent attachment, enabling self-immobilization and eliminating the need for additional immobilization steps. The functionality of the LOx enzyme variants was verified at physiological lactate concentrations in both human serum (0–4 mM) and artificial sweat (0–100 mM) using 3-electrode setups for analysis of the three variants in parallel. Accuracy of measurement in both artificial sweat and human serum were high. Employing a microfluidic flow cell, we successfully monitored varying lactate levels in physiological fluids continuously over a 2h period. Overall, this optimized LOx enzyme, which self-immobilizes onto gold sensing electrodes, facilitates efficient and reliable lactate detection and continuous monitoring at reduced operating voltages suitable for further development towards commercial use.

Summary: Microbiota play a critical role in the development and training of host innate and adaptive immunity. We present the cellular landscape of the upper airway, specifically the larynx, by establishing a reference single-cell atlas, while dissecting the role of microbiota in cell development and function at single-cell resolution. We highlight the larynx’s cellular heterogeneity with the identification of 16 cell types and 34 distinct subclusters. Our data demonstrate that commensal microbiota have extensive impact on the laryngeal immune system by regulating cell differentiation, increasing the expression of genes associated with host defense, and altering gene regulatory networks. We uncover macrophages, innate lymphoid cells, and multiple secretory epithelial cells, whose cell proportions and expressions vary with microbial exposure. These cell types play pivotal roles in maintaining laryngeal and upper airway health and provide specific guidance into understanding the mechanism of immune system regulation by microbiota in laryngeal health and disease.

Abstract Background The Enhanced Recovery After Cardiac Surgery (ERACS) programs are comprehensive multidisciplinary interventions to improve patients’ recovery. The application of the ERAS principle in pediatric patients has not been identified completely. Methods This study is a multicenter, stepwise design, cluster randomized controlled trial. 3030 patients presenting during control and intervention periods are eligible if they are aged from 28 days to 6 years old and awaiting elective correction surgery of congenital heart disease with cardiopulmonary bypass. 5 centers are randomly assigned to staggered start dates for one-way crossover from the control phase to the intervention phase. In the intervention periods, patients will receive a bundle strategy including preoperative, intraoperative, and postoperative approaches. During the control phase, patients receive the usual care. The primary outcome consists of major adverse cardiac and cerebrovascular events (MACCEs), postoperative pulmonary complications (PPCs), and acute kidney injury (AKI). Discussion This study aims to explore whether the bundle of ERAS measurements could improve patients’ recovery in congenital heart surgery. Trial registration http://www.clinicaltrials.gov . (NCT05914103).

Abstract Background Modern medicine emphasizes that medical professionals engage in interprofessional collaboration to better meet the diverse needs of patients from physical, psychological, and social perspectives. As nursing students are the future reserve of the clinical nursing workforce, nursing educators worldwide should pay close attention to nursing students’ interprofessional learning attitudes and take responsibility for training qualified interprofessional nursing personnel. However, little is known about the relationship between nursing students' readiness for interprofessional learning and academic self-efficacy. Thus, this study aims to investigate the level of readiness for interprofessional learning and academic self-efficacy among nursing students, and to explore the relationship between the two. Methods A cross-sectional survey was conducted with a sample of 741 undergraduate nursing students pursuing four-year degrees from a school in Jinan, Shandong Province, China from November to December 2021. The social-demographic questionnaire, Readiness for Interprofessional Learning Scale, and Academic Self-efficacy Scale were used for data collection. Descriptive statistics used to analyze the data included: Cronbach's alpha, t-test, one-way ANOVA, Pearson’s correlation, and multiple linear regression analysis. Results Readiness for interprofessional learning mean score was (3.91 ± 0.44) and mean academic self-efficacy was (3.47 ± 0.42). Significant differences were found in the research variables according to participants’ sex, grade, choice of nursing profession, and frequency of communication with health-related major students in studies (p

Abstract Background The relationship between obesity and non-Hodgkin’s lymphoma (NHL) was controversial, which may be due to the crudeness definition of obesity based on body mass index (BMI). As obesity and metabolic abnormalities often coexist, we aimed to explore whether the classification of obesity based on metabolic status can help to evaluate the real impact of obesity on the readmission of NHL. Methods In this retrospective cohort study, utilizing the 2018 Nationwide Readmissions Database, we identified NHL-related index hospitalizations and followed them for non-elective readmission. The patients with NHL were classified as metabolically healthy non-obese (MHNO) and obese (MHO) and metabolically unhealthy non-obese (MUNO) and obese (MUO). Readmission rates for each phenotype were calculated at 30-day intervals. Multiple COX regression was used to analyze the association of metabolic-defined obesity with 30-day, 90-day, and 180-day readmission rates in patients with NHL. Results There were 22,086 index hospitalizations with NHL included. In the multivariate COX regression, MUNO was associated with increased 30-day (HR = 1.113, 95% CI 1.036–1.195), 90-day (HR = 1.148, 95% CI 1.087–1.213), and 180-day readmission rates (HR = 1.132, 95% CI 1.077–1.189), and MUO was associated with increased 30-day (HR=1.219, 95% CI: 1.081-1.374), 90-day (HR = 1.228, 95% CI 1.118–1.348), and 180-day readmission rates (HR = 1.223, 95% CI 1.124–1.33), while MHO had no associations with readmission rates. Conclusions The presence of metabolic abnormalities with or without obesity increased the risk of non-selective readmission in patients with NHL. However, obesity alone had no associations with the risk of non-selective readmission, suggesting that interventions for metabolic abnormalities may be more important in reducing readmissions of NHL patients.

This study aimed to determine the effects of tributyrin on growth performance, gastrointestinal tract development, ruminal bacteria and volatile fatty acid (VFA) formation. Thirty healthy weaned Small-Tailed Han female lambs at 3 months old with BW 27.5 ± 4.1 kg (mean ± SD) were randomly assigned to five groups of six lambs each, and each group received tributyrin at 0, 0.5, 1.0, 2.0 and 4.0 g/kg in feed. Weights were measured before the start and end of the study. After 15 d adaptation, DMI, feed, faeces and urine were recorded every week. Lambs were sacrificed at d 75. Compared to lambs fed no tributyrin, lambs fed 4.0 g/kg tributyrin had higher average daily BW gain (P = 0.04) and DMI (P

AbstractContext Fructus Ligustri Lucidi (FLL), a commonly used herb of traditional Chinese medicine (TCM), is the fruit of Ligustrum lucidum Ait. (Oleaceae). The ethanol extract of FLL is a potential candidate for preventing and treating postmenopausal osteoporosis (PMOP) by nourishing the liver and kidneys.Objective This study determines whether an ethanol extract of FLL has anti-osteoporotic effects in ovariectomized (OVX) mice and explores the underlying mechanism.Materials and methods The OVX model of eight-week-old C57BL/6J female mice was taken, and ovariectomy was used as PMOP. Mice were divided into five groups: sham-operated group (n = 10), OVX group (n = 10), OVX + E2 group (n = 10; 0.039 mg/kg), OVX + FLL group (n = 10; 2 g/kg) and OVX + FLL group (n = 10; 4 g/kg). Mice were treated by gavage with FLL or CMCNa once daily for 8 weeks. We harvested uteri, femur, and tibias from mice; bone mineral density (BMD) and bone microstructure were obtained by X-ray absorptiometry and micro-CT. Furthermore, the effect of FLL on the balance of osteoblast and adipocyte differentiation was investigated using bone marrow mesenchymal stem cells (BMMSCs).Results The results indicated that FLL did not affect OVX-induced estradiol reduction. Compared with OVX mice, FLL significantly increased BMD (63.54 vs. 61.96), Conn. D (86.46 vs. 57.00), and left tibial strength (13.91 vs. 11.27), decreased Tb. Sp (0.38 vs. 0.44) and body fat content (4.19% vs. 11.24%). FLL decreased osteoclast activity and enhanced RUNX2 expression; inhibited perilipin peroxisome proliferator-activated receptor gamma (PPARγ) expression and adipocyte differentiation from BMMSCs.Conclusions FLL prevented additional bone loss and improved bone microstructure in OVX mice by modulating bone and fat balance, suggesting that FLL might be a therapeutic agent for PMOP.

DNase II, identified in 1947 and named in 1953, is an acidic DNA endonuclease prevalent across organisms and crucial for normal growth. Despite its expression in nearly all human tissues, as well as its biological significance, DNase II’s detailed functions and corresponding mechanisms remain unclear. Although many groups are trying to figure this out, progress is very limited. It is very hard to connect its indispensability with its DNA cleavage activity. In this study, we find that DNase II secreted to saliva can digest RNA in mildly acidic conditions, prompting us to hypothesize that salivary DNase II might digest RNA in the stomach. This finding is consistent with the interesting discovery reported in 1964 that RNA could inhibit DNase II’s activity, which has been largely overlooked. This RNA digestion activity is further confirmed by using purified DNase II, showing activity to digest both DNA and RNA effectively. Here, we suggest redesignating DNase II as DNase II (RNase). The biological functions of DNase II are suggested to recycle intracellular RNA or digest external nucleic acids (both RNA and DNA) as nutrients. This discovery may untangle the mystery of DNase II and its significant biofunctions.

In this study, sixteen Sprague Dawley (SD) female rats and eight SD male rats were co-housed to mate. Pregnant SD female rats were fed with a control diet or an MA diet. Breast milk, maternal ileum, and intestinal samples of the offspring were collected at the day of birth and ten days afterwards. The results showed that the impact of MA was more obvious on the microbiota of mature milk (p = 0.066) than on that of colostrum. In addition, MA additive did not significantly affect maternal ileal microbiota, but affected offsprings’ colonic microbiota significantly ten days after birth (p = 0.035). From the day of giving birth to ten days afterwards, in addition to the increase in microbial richness and diversity, at genus level, the dominant bacteria of breastmilk changed from Pseudomonas veronii to Bacillus and Lactococcus. Different from breastmilk microbiota, ten days after giving birth, the maternal ileal microbiota and the offsprings’ intestinal microbiota were dominated by Lactobacillus. Instead of ileal microbiota, offsprings’ colonic microbiota is a key action site of maternal MA additive. Therefore, the current findings have significant implications for the development of maternal feed aimed at modulating the intestinal microbiota of offspring, ultimately leading to improved health outcomes for both mothers and their offspring.

Benzene is a known contributor to human leukaemia through its toxic effects on bone marrow cells, and epigenetic modification is believed to be a potential mechanism underlying benzene pathogenesis. However, the specific roles of N6-methyladenosine (m6A), a newly discovered RNA post-transcriptional modification, in benzene-induced hematotoxicity remain unclear. In this study, we identified self-renewing malignant proliferating cells in the bone marrow of benzene-exposed mice through in vivo bone marrow transplantation experiments and Competitive Repopulation Assay. Subsequent analysis using whole transcriptome sequencing and RNA m6A methylation sequencing revealed a significant upregulation of RNA m6A modification levels in the benzene-exposed group. Moreover, RNA methyltransferase METTL14, known as a pivotal player in m6A modification, was found to be aberrantly overexpressed in Lin-Sca-1+c-Kit+ (LSK) cells of benzene-exposed mice. Further analysis based on the GEO database showed a positive correlation between the expression of METTL14, mTOR, and GFI and benzene exposure dose. In vitro cellular experiments, employing experiments such as western blot, q-PCR, m6A RIP, and CLIP, validated the regulatory role of METTL14 on mTOR and GFI1. Mechanistically, continuous damage inflicted by benzene exposure on bone marrow cells led to the overexpression of METTL14 in LSK cells, which, in turn, increased m6A modification on the target genes’ (mTOR and GFI1) RNA. This upregulation of target gene expression activated signalling pathways such as mTOR-AKT, ultimately resulting in malignant proliferation of bone marrow cells. In conclusion, this study offers insights into potential early targets for benzene-induced haematologic malignant diseases and provides novel perspectives for more targeted preventive and therapeutic strategies.

Abstract Finding a real thermoelectric (TE) material that excels in various aspects of TE performance, mechanical properties, TE power generation, and cooling is challenging for its commercialization. Herein, we report a novel multifunctional Ge0.78Cd0.06Pb0.1Sb0.06Te material with excellent TE performance and mechanical strength, which is utilized to construct candidate TE power generation and cooling devices near room temperature. Specifically, the effectiveness of band convergence, combined with optimized carrier concentration and electronic quality factor, distinctly boosts the Seebeck coefficient, thus greatly improving the power factor. Advanced electron microscopy observation indicates that complex multi‐scale hierarchical structures and strain field distributions lead to ultra‐low lattice thermal conductivity, and also effectively enhance mechanical properties. High ZT ~ 0.6 at 303 K, average ZTave ~ 1.18 from 303 to 553 K, and Vickers hardness of ~200 Hv in Ge0.78Cd0.06Pb0.1Sb0.06Te are obtained synchronously. Particularly, a 7‐pair TE cooling device with a maximum ΔT of ~45.9 K at Th = 328 K, and a conversion efficiency of ~5.2% at Th = 553 K is achieved in a single‐leg device. The present findings demonstrate a unique approach to developing superior multifunctional GeTe‐based alloys, opening up a promising avenue for commercial applications.

BackgroundThe simultaneous occurrence of Branchial Cleft Cyst (BCC) and Papillary Thyroid Carcinoma (PTC) represents an unusual malignant tumor, with cases featuring associated lymph node metastasis being particularly rare. This combination underscores an increased potential for metastasis, and the assessment of neck masses, particularly on the lateral aspect, may inadvertently overlook the scrutiny of the thyroid. Therefore, healthcare providers should exercise vigilance, especially in patients over the age of 40, regarding the potential for neck masses to signify metastasis from thyroid malignancies. Currently, surgical intervention stands as the primary effective curative method, while the postoperative administration of radioactive iodine therapy remains a topic of ongoing debate.Case reportIn the presented case, a 48-year-old male patient with a right neck mass underwent surgical intervention. The procedure included the excision of the right neck mass, unilateral thyroidectomy with isthmus resection, and functional neck lymph node dissection under tracheal intubation and general anesthesia. Postoperative pathology findings revealed the coexistence of a BCC with metastatic PTC in the right neck mass, as well as papillary carcinoma in the right thyroid lobe. Lymph node metastasis was observed in the central and levels III of the right neck.ConclusionThe rare amalgamation of a BCC with PTC and concurrent lymph node metastasis underscores the invasive nature of this malignancy. Healthcare professionals should be well-acquainted with its clinical presentation, pathological characteristics, and diagnostic criteria. A multidisciplinary approach is strongly recommended to enhance patient outcomes.

Abstract Macrophage therapy for liver fibrosis is on the cusp of meaningful clinical utility. Due to the heterogeneities of macrophages, it is urgent to develop safer macrophages with a more stable and defined phenotype for the treatment of liver fibrosis. Herein, a new macrophage‐based immunotherapy using macrophages stably expressing a pivotal cytokine from Toxoplasma gondii, a parasite that infects ≈ 2 billion people is developed. It is found that Toxoplasma gondii macrophage migration inhibitory factor‐transgenic macrophage (Mφtgmif) shows stable fibrinolysis and strong chemotactic capacity. Mφtgmif effectively ameliorates liver fibrosis and deactivates aHSCs by recruiting Ly6Chi macrophages via paracrine CCL2 and polarizing them into the restorative Ly6Clo macrophage through the secretion of CX3CL1. Remarkably, Mφtgmif exhibits even higher chemotactic potential, lower grade of inflammation, and better therapeutic effects than LPS/IFN‐γ‐treated macrophages, making macrophage‐based immune therapy more efficient and safer. Mechanistically, TgMIF promotes CCL2 expression by activating the ERK/HMGB1/NF‐κB pathway, and this event is associated with recruiting endogenous macrophages into the fibrosis liver. The findings do not merely identify viable immunotherapy for liver fibrosis but also suggest a therapeutic strategy based on the evolutionarily designed immunomodulator to treat human diseases by modifying the immune microenvironment.

Summary: Consumption of fructo- (FOS) and galacto-oligosaccharides (GOS) has health benefits which have been linked in part to short-chain fatty acids (SCFA) production by the gut microbiota. However, detailed knowledge of this process in the human intestine is lacking. We aimed to determine the acute fermentation kinetics of a FOS:GOS mixture in healthy males using a naso-intestinal catheter for sampling directly in the ileum or colon. We studied the fate of SCFA as substrates for glucose and lipid metabolism by the host after infusion of 13C-SCFA. In the human distal ileum, no fermentation of FOS:GOS, nor SCFA production, or bacterial cross-feeding was observed. The relative composition of intestinal microbiota changed rapidly during the test day, which demonstrates the relevance of postprandial intestinal sampling to track acute responses of the microbial community toward interventions. SCFA were vividly taken up and metabolized by the host as shown by incorporation of 13C in various host metabolites.

Objective: Penile vascular anomalies (PVAs) or hemangioma can arouse patient concern about aesthetics and cause symptoms like bleeding and sexual dysfunction. However, its low incidence and the deficiency of large-volume studies hinder urologists from making informed decisions. This study aimed to investigate the clinical features and treatment experience of PVAs at the Seventh Medical Center of PLA General Hospital, Beijing, China. Furthermore, by systematically analysis of studies on PVAs in Chinese people, we aimed to provide novel insights on the management of this condition. Methods: We retrospectively investigated clinical features and pathology of surgery-treated PVAs at our center. Moreover, by systemically reviewing the literature from PubMed and the three largest medical databases (China National Knowledge Infrastructure, Wan Fang, and Chinese Medical Journal Database) in China, we analyzed the clinical features and various therapies of PVAs in Chinese people. Results: Between March 1, 2018 and March 1, 2023, a total of 356 cases with vascular anomalies were treated with surgery at out center. Only seven (2.0%) cases had lesions involving the perineum and external genitalia. All the seven cases were pathologically benign and demonstrated no recurrence over a follow-up period of 1–52 months (median 14 months). A total of 410 cases from 44 studies were selected in the cumulative analysis. Most patients (92.4%) diagnosed with PVAs were asymptomatic, and 68.8% of the patients were treated with sclerotherapy. As to the pathology, 57.1% were venous malformation. Conclusion: The most common PVA is venous malformation and the majority of patients are asymptomatic. Sclerotherapy and laser have emerged as viable options for treating small lesions. Surgery still has its role in treating large lesions and obtaining pathology. Although PVAs often relapse or demand multiple treatments, the prognosis is favorable.

Abstract Background Tetralogy of Fallot (TOF) is a common cyanotic congenital heart malformation that carries a high risk of right-to-left shunting. Anemia is characterized by decreased hemoglobin (Hb) levels that can affect tissue oxygen delivery and impact postoperative recovery in patients. Chronic hypoxia caused by right-to-left shunting of TOF could lead to compensatory increases in Hb to maintain systemic oxygen balance. This study aims to investigate whether preoperative Hb and blood oxygen saturation (SpO2) can predict adverse outcomes in children undergoing corrective surgery for TOF. Methods This retrospective study included patients under 18 years of age who underwent corrective surgery for TOF at Fuwai Hospital between January 2016 and December 2018. Adverse outcomes, including in-hospital death, extracorporeal membrane oxygenation implantation, ICU stay > 30 days, and severe complications, were considered as the primary outcome. Univariable and multivariable logistic analyses were performed to identify independent risk factors for adverse outcomes. Propensity score-matched (PSM) analysis was also conducted to minimize the confounding factors. Results A total of 596 children were included in the study, of which 64 (10.7%) experienced adverse outcomes. Hb*SpO2

Intracerebral haemorrhage (ICH) is a lethal cerebrovascular disorder with a high mortality and morbidity. Although it is a major public health problem, there is no effective treatment for ICH. After ICH, the primary and secondary mechanisms are mentioned when discussing brain injury. The transcription factor, nuclear factor-kappa B (NF-kB), is an important regulator of inflammatory responses. The role of platelet factor 4 (PF4) in ICH is unclear. To study the effect of PF4 on inflammatory response of rats in ICH, a rat model of striatum ICH was established by injecting autologous blood from the autogenous femoral artery into the right striatum of rats. Forty-eight hours after ICH, the expression of PF4, NF-kB (P-P65) and inflammatory changes in rats were determined with WB and ELISA. Heme was used to induce PC12 cell damage, simulate the ICH model in vitro, and detect PF4, P-P65 and striatal inflammatory changes. Short hairpin RNA (shRNA-PF4) was used to knock-down the expression of PF4 in PC12 cells to detect changes in inflammatory factors. The results showed that 48 hours after surgery, the behavioural score of cerebral haemorrhage was the lowest. The expression of PF4 and P-P65 in the striatum of the ICH group was significantly higher compared with the sham surgery group. The expression of interleukin (IL)-6 and IL-1b in the ICH group was also greatly improved. After inhibiting NF-kB expression, PF4 expression was decreased. In short, ICH enhances the expression of PF4, which induces an inflammatory response in rats with cerebral haemorrhage through the NF-kB signalling pathway. Reducing the expression of PF4 can attenuate the inflammatory response.

Hepatocellular carcinoma (HCC) has a very high incidence and fatality rate, and in most cases, it is already at an advanced stage when diagnosed. Therefore, early prevention and detection of HCC are two of the most effective strategies. However, the methods recommended in the practice guidelines for the detection of HCC cannot guarantee high sensitivity and specificity except for the liver biopsy, which is known as the “gold standard”. In this review, we divided the detection of HCC into pre-treatment diagnosis and post-treatment monitoring, and found that in addition to the traditional imaging detection and liver biopsy, alpha fetoprotein (AFP), lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), protein induced by vitamin K absence or antagonist-II (PIVKA-II) and other biomarkers are excellent biomarkers for HCC, especially when they are combined together. Most notably, the emerging liquid biopsy shows great promise in detecting HCC. In addition, lactic dehydrogenase (LDH), suppressor of cytokine signaling (SOCS) and other relevant biomarkers may become promising biomarkers for HCC post-treatment monitoring. Through the detailed introduction of the diagnostic technology of HCC, we can have a detailed understanding of its development process and then obtain some enlightenment from the diagnosis, to improve the diagnostic rate of HCC and reduce its mortality.

The efficient preparation of single-stranded DNA (ssDNA) rings, as a macromolecular construction approach with topological features, has aroused much interest due to the ssDNA rings’ numerous applications in biotechnology and DNA nanotechnology. However, an extra splint is essential for enzymatic circularization, and by-products of multimers are usually present at high concentrations. Here, we proposed a simple and robust strategy using permuted precursor (linear ssDNA) for circularization by forming an intramolecular dynamic nick using a part of the linear ssDNA substrate itself as the template. After the simulation of the secondary structure for desired circular ssDNA, the linear ssDNA substrate is designed to have its ends on the duplex part (≥5 bp). By using this permuted substrate with 5′-phosphate, the splint-free circularization is simply carried out by T4 DNA ligase. Very interestingly, formation of only several base pairs (2–4) flanking the nick is enough for ligation, although they form only instantaneously under ligation conditions. More significantly, the 5-bp intramolecular duplex part commonly exists in genomes or functional DNA, demonstrating the high generality of our approach. Our findings are also helpful for understanding the mechanism of enzymatic DNA ligation from the viewpoint of substrate binding.

Muscadine grapes are characterized by their large and abundant seeds and hard and thick skins that contain significant amounts of dietary fiber (DF). The current study investigated the chemical constituents, molecular architecture, and physicochemical attributes of DF derived from Muscadine grapes (Granny Val and Alachua) and compared them with those derived from Shine Muscat and Kyoho. Using a combined enzymatic method, the total dietary fiber (TDF) was extracted and divided into two parts: soluble dietary fiber (SDF) and insoluble dietary fiber (IDF). TDF (mainly IDF, with a small fraction of SDF) was dominated by cellulose, followed by pectin and hemicellulose. In addition, Granny Val and Alachua had a significantly higher abundance of TDF and IDF compared with Shine Muscat and Kyoho. Moreover, Shine Muscat had significantly the highest abundance of SDF among the four grape varieties. Of note, IDF from Granny Val and Alachua exhibited a complex and dense texture on its surface, and notably outperformed Shine Muscat and Kyoho in terms of cholesterol, fatty acid, heavy metal adsorption, and antioxidant activity. Collectively, Muscadine grapes, i.e., Granny Val and Alachua in the current study, possessed elevated DF levels (predominantly IDF), and their enhanced bioactivity underscored their potential as a potential food ingredient for further use.

Abstract Autophagy is one of the underlying causes of resistance to many antitumor drugs, including cisplatin (DDP). The low‐density lipoprotein receptor (LDLR) is a regulator of ovarian cancer (OC) progression. However, whether LDLR regulates DDP resistance in OC via autophagy‐related pathways remains unclear. LDLR expression was measured by quantitative real‐time PCR, western blot (WB) and IHC staining. A Cell Counting Kit 8 assay was employed to evaluate DDP resistance and cell viability, and flow cytometry was used to assess apoptosis. WB analysis was employed to evaluate the expression of autophagy‐related proteins and PI3K/AKT/mTOR signaling pathway proteins. The autophagolysosomes and the fluorescence intensity of LC3 were observed by transmission electron microscopy and immunofluorescence staining, respectively. A xenograft tumor model was established to explore the role of LDLR in vivo. LDLR was highly expressed in OC cells, which was correlated with disease progression. In DDP‐resistant OC cells, high LDLR expression was related to DDP resistance and autophagy. Downregulation of LDLR repressed autophagy and growth in DDP‐resistant OC cell lines by activating the PI3K/AKT/mTOR pathway, and these effects were eliminated by an mTOR inhibitor. In addition, LDLR knockdown also reduced OC tumor growth by suppressing autophagy associated with the PI3K/AKT/mTOR pathway. LDLR promoted autophagy‐mediated DDP resistance in OC associated with the PI3K/AKT/mTOR pathway, indicating that LDLR might be a new target to prevent DDP resistance in OC patients.

Abstract Previous studies provide evidence for an association between modifications of the gut microbiota in early life and the development of food allergies. We studied the faecal microbiota composition (16S rRNA gene amplicon sequencing) and faecal microbiome functionality (metaproteomics) in a cohort of 40 infants diagnosed with cow’s milk allergy (CMA) when entering the study. Some of the infants showed outgrowth of CMA after 12 months, while others did not. Faecal microbiota composition of infants was analysed directly after CMA diagnosis (baseline) as well as 6 and 12 months after entering the study. The aim was to gain insight on gut microbiome parameters in relation to outgrowth of CMA. The results of this study show that microbiome differences related to outgrowth of CMA can be mainly identified at the taxonomic level of the 16S rRNA gene, and to a lesser extent at the protein-based microbial taxonomy and functional protein level. At the 16S rRNA gene level outgrowth of CMA is characterized by lower relative abundance of Lachnospiraceae at baseline and lower Bacteroidaceae at visit 12 months.

Abstract Near‐infrared (NIR) light is well‐suited for the optical imaging and wireless phototherapy of malignant diseases because of its deep tissue penetration, low autofluorescence, weak tissue scattering, and non‐invasiveness. Rare earth nanoparticles (RENPs) are promising NIR‐responsive materials, owing to their excellent physical and chemical properties. The 4f electron subshell of lanthanides, the main group of rare earth elements, has rich energy‐level structures. This facilitates broad‐spectrum light‐to‐light conversion and the conversion of light to other forms of energy, such as thermal and chemical energies. In addition, the abundant loadable and modifiable sites on the surface offer favorable conditions for the functional expansion of RENPs. In this review, the authors systematically discuss the main processes and mechanisms underlying the response of RENPs to NIR light and summarize recent advances in their applications in optical imaging, photothermal therapy, photodynamic therapy, photoimmunotherapy, optogenetics, and light‐responsive drug release. Finally, the challenges and opportunities for the application of RENPs in optical imaging and wireless phototherapy under NIR activation are considered.

Breast angiosarcoma is a rare and highly aggressive malignancy with a poor prognosis. It can occur spontaneously or be associated with factors such as radiation therapy or chronic lymphedema. The etiology and pathogenesis of this disease are still unclear, the clinical symptoms and imaging findings lack specificity, and the pathological morphology is diverse, which is easy to be confused with other diseases. There is no clear guideline for surgical treatment. Although the optimal surgical approach remains unclear, the ultimate goal is surgical excision with optimal margins, which remains the primary method of treatment. In clinical practice, the choice of the surgical approach should be made by considering the tumor size, pathological type, and patient preferences. In clinical practice, the selection of surgical methods should be carried out with comprehensive consideration of tumor size, pathological types and patients' wishes. There is no clear consensus on whether radiotherapy and chemotherapy should be carried out after surgery, and its optimal program and efficacy are uncertain. This article reviews the etiology, clinical manifestations, pathological features, imaging findings, treatment, prognosis and other aspects of breast angiosarcoma, so as to strengthen clinicians' overall understanding of this disease and avoid missed diagnosis and misdiagnosis.

The larynx undergoes significant age and sex-related changes in structure and function across the lifespan. Emerging evidence suggests that laryngeal microbiota influences immunological processes. Thus, there is a critical need to delineate microbial mechanisms that may underlie laryngeal physiological and immunological changes. As a first step, the present study explored potential age and sex-related changes in the laryngeal microbiota across the lifespan in a murine model. We compared laryngeal microbial profiles of mice across the lifespan (adolescents, young adults, older adults and elderly) to determine age and sex-related microbial variation on 16s rRNA gene sequencing. Measures of alpha diversity and beta diversity were obtained, along with differentially abundant taxa across age groups and biological sexes. There was relative stability of the laryngeal microbiota within each age group and no significant bacterial compositional shift in the laryngeal microbiome across the lifespan. There was an abundance of short-chain fatty acid producing bacteria in the adolescent group, unique to the laryngeal microbiota; taxonomic changes in the elderly resembled that of the aged gut microbiome. There were no significant changes in the laryngeal microbiota relating to biological sex. This is the first study to report age and sex-related variation in laryngeal microbiota. This data lays the groundwork for defining how age-related microbial mechanisms may govern laryngeal health and disease. Bacterial compositional changes, as a result of environmental or systemic stimuli, may not only be indicative of laryngeal-specific metabolic and immunoregulatory processes, but may precede structural and functional age-related changes in laryngeal physiology.

BackgroundBy comparing the three lateral approaches to thyroidectomy, the feasibility and clinical effects were analyzed, and the advantages of the lateral approach were summarized.MethodsFrom January 2022 to January 2023, 52 patients with thyroid cancer admitted to our department were selected and subjected to Lateral approach for thyroidectomy. Among them, 31 patients underwent thyroidectomy via the supraclavicular approach, 13 patients underwent endoscopic thyroidectomy via the subclavicular approach, and 8 patients underwent endoscopic thyroidectomy via the axillary approach. The basic conditions, surgical conditions, complications, postoperative pain scores and postoperative satisfaction of patients in the three approach surgery groups were recorded and analyzed.ResultsThere were no significant differences among the three approach groups in terms of patient characteristics, number of central lymph node dissections, intraoperative blood loss, postoperative drainage volume, duration of drainage tube placement, length of hospital stay, postoperative pain, satisfaction, and complications. However, the operation time was longest in the subclavicular approach group, followed by the axillary approach group, and shortest in the supraclavicular approach group. The total hospitalization cost was highest in the axillary approach group, followed by the subclavicular approach group, and lowest in the supraclavicular approach group.ConclusionThe lateral approach for thyroidectomy is deemed a safe and effective method. The three different approach paths gradually increase in length, allowing for the accumulation of anatomical experience. This approach has a shorter learning curve for clinical doctors and is a favorable choice for patients seeking aesthetic benefits.

Background. Allergic rhinitis (AR) is a common chronic respiratory disease that has become a global health problem. miRNAs play an important role in multiple immune and inflammatory diseases, including AR. In this work, the mechanism by which miR-224-5p regulates AR in vivo and in vitro was examined. Methods. Human nasal epithelial cells (HNEpCs) were used to establish an AR cell model induced by Der P1, and C57BL/6 mice were used to establish an AR animal model induced by OVA (ovalbumin). RT-qPCR was used to determine the level of miR-224-5p; western blot analysis was used to determine GATA3; ELISA was used to determine the levels of OVA-specific IgE, IFN-γ, IL-4, IL-5, and IL-13; flow cytometry was used to determine the differentiation of Th1 and Th2 cells; and HE and PAS staining was used to observe the histopathological alterations in the mouse nasal mucosa and spleen. Results. miR-224-5p was downregulated in nasal mucosa from mice with AR and an AR cell model. Overexpressed miR-224-5p can improve AR development and attenuate AR symptoms by regulating GATA3-mediated Th1/Th2 responses. Conclusion. miR-224-5p attenuates allergic reactions in mice with AR by regulating the Th1/Th2 response.

ABSTRACTMetal oxide nanorods exhibit promising potential as reinforcement fillers in various polymer matrices, but their application in the Multi Jet Fusion (MJF) technique is rarely reported. In this work, surface-modified zinc oxide nanorods (SMZnO) were synthesized and incorporated into polyamide 12 (PA12) powder to enhance the mechanical properties of the MJF-printed parts. Compared to ZnO, SMZnO exhibited better dispersion, resulting in markedly enhanced mechanical performances. The ultimate tensile strength and the Young's modulus of the MJF-printed SMZnO/PA12 nanocomposites were 62.02 MPa and 2.28 GPa in the X orientation and 64.07 MPa and 2.34 GPa in the Y orientation, equivalent to 27.85%, 59.44%, 29.12%, and 54.97% increments, respectively. The flexural strength and modulus demonstrated similar improvements in the X and Y orientations, confirming the uniform mechanical enhancement effect of homogenously distributed SMZnO. This work provides a novel and facile approach for the additive manufacturing of polymeric nanocomposites with superior mechanical performance.

Multi Jet Fusion (MJF) has attracted extensive attention because of its ability to print support-free complex structures. However, the mechanical properties of MJF-printed polymer parts are still unsatisfactory for certain industrial requirements. Herein, by leveraging the fibre reinforcement effect and high specific strength of polyimide (PI) fibres, this work developed PI/polyamide 12 (PA12) composites with largely enhanced mechanical performance via MJF. Specifically, the tensile strength and modulus were increased by 43% and 42%, and the flexural strength and modulus were improved by 39% and 46%, respectively, compared to those of the neat PA12 parts. Furthermore, the incorporation of lightweight PI fibres endowed the composites with high specific tensile strength (67.60 kN·m/kg) and specific flexural strength (93.70 kN·m/kg), which are superior to those of MJF-printed PA12 composites reinforced with other fibres. This work provides new insights into enhancing the mechanical performance of lightweight parts printed by MJF and other powder-based techniques.

ABSTRACTMultiple clinical and epidemiological studies have shown an interconnection between coronavirus disease 2019 (COVID-19) and diabetes, but experimental evidence is still lacking. Understanding the interplay between them is important because of the global health burden of COVID-19 and diabetes. We found that C57BL/6J mice were susceptible to the alpha strain of SARS-CoV-2. Moreover, diabetic C57BL/6J mice with leptin receptor gene deficiency (db/db mice) showed a higher viral load in the throat and lung and slower virus clearance in the throat after infection than C57BL/6J mice. Histological and multifactor analysis revealed more advanced pulmonary injury and serum inflammation in SARS-CoV-2 infected diabetic mice. Moreover, SARS-CoV-2 infected diabetic mice exhibited more severe insulin resistance and islet cell loss than uninfected diabetic mice. By RNA sequencing analysis, we found that diabetes may reduce the collagen level, suppress the immune response and aggravate inflammation in the lung after infection, which may account for the greater susceptibility of diabetic mice and their more severe lung damage after infection. In summary, we successfully established a SARS-CoV-2 infected diabetic mice model and demonstrated that diabetes and COVID-19 were risk factors for one another.