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Abstract The downregulation of Cadm4 (Cell adhesion molecular 4) is a prominent feature in demyelination diseases, yet, the underlying molecular mechanism remains elusive. Here, we reveal that Cadm4 undergoes specific palmitoylation at cysteine-347 (C347), which is crucial for its stable localization on the plasma membrane (PM). Mutation of C347 to alanine (C347A), blocking palmitoylation, causes Cadm4 internalization from the PM and subsequent degradation. In vivo experiments introducing the C347A mutation (Cadm4-KI) lead to severe myelin abnormalities in the central nervous system (CNS), characterized by loss, demyelination, and hypermyelination. We further identify ZDHHC3 (Zinc finger DHHC-type palmitoyltransferase 3) as the enzyme responsible for catalyzing Cadm4 palmitoylation. Depletion of ZDHHC3 reduces Cadm4 palmitoylation and diminishes its PM localization. Remarkably, genetic deletion of ZDHHC3 results in decreased Cadm4 palmitoylation and defects in CNS myelination, phenocopying the Cadm4-KI mouse model. Consequently, altered Cadm4 palmitoylation impairs neuronal transmission and cognitive behaviors in both Cadm4-KI and ZDHHC3 knockout mice. Importantly, attenuated ZDHHC3-Cadm4 signaling significantly influences neuroinflammation in diverse demyelination diseases. Mechanistically, we demonstrate the predominant expression of Cadm4 in the oligodendrocyte lineage and its potential role in modulating cell differentiation via the WNT-β-Catenin pathway. Together, our findings propose that dysregulated ZDHHC3-Cadm4 signaling contributes to myelin abnormalities, suggesting a common pathological mechanism underlying demyelination diseases associated with neuroinflammation.

Abstract With childhood hypertension emerging as a global public health concern, understanding its associated factors is crucial. This study investigated the prevalence and associated factors of hypertension among Chinese children. This cross-sectional investigation was conducted in Pinghu, Zhejiang province, involving 2,373 children aged 8–14 years from 12 schools. Anthropometric measurements were taken by trained staff. Blood pressure (BP) was measured in three separate occasions, with an interval of at least two weeks. Childhood hypertension was defined as systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) ≥ age-, sex-, and height-specific 95th percentile, across all three visits. A self-administered questionnaire was utilized to collect demographic, socioeconomic, health behavioral, and parental information at the first visit of BP measurement. Random forest (RF) and multivariable logistic regression model were used collectively to identify associated factors. Additionally, population attributable fractions (PAFs) were calculated. The prevalence of childhood hypertension was 5.0% (95% confidence interval [CI]: 4.1–5.9%). Children with body mass index (BMI) ≥ 85th percentile were grouped into abnormal weight, and those with waist circumference (WC) > 90th percentile were sorted into central obesity. Normal weight with central obesity (NWCO, adjusted odds ratio [aOR] = 5.04, 95% CI: 1.96–12.98), abnormal weight with no central obesity (AWNCO, aOR = 4.60, 95% CI: 2.57–8.21), and abnormal weight with central obesity (AWCO, aOR = 9.94, 95% CI: 6.06–16.32) were associated with an increased risk of childhood hypertension. Childhood hypertension was attributable to AWCO mostly (PAF: 0.64, 95% CI: 0.50–0.75), followed by AWNCO (PAF: 0.34, 95% CI: 0.19–0.51), and NWCO (PAF: 0.13, 95% CI: 0.03–0.30). Our results indicated that obesity phenotype is associated with childhood hypertension, and the role of weight management could serve as potential target for intervention.

The ATP-binding cassette (ABC) transporter superfamily comprises membrane proteins that efflux various substrates across extra- and intracellular membranes. Among them, ABCB1, ABCG2, and ABCC1 are directly linked to tumor multidrug resistance (MDR). This review provides an overview of the current understanding on the novel mechanisms and functions of ABCB1, ABCG2, and ABCC1 transporters in tumor MDR, discusses the latest strategies to target these transporters, and explores further opportunities to overcome MDR.

Artificial tracheal substitutes encounter significant challenges during long-segmental tracheal defects (LSTD) reconstruction, notably early postoperative anastomotic stenosis and tracheal chondromalacia. Mitigating early anastomotic stenosis by creating a compliant sutureless substitute is pivotal. Enhancing its chondrogenic capacity is equally critical for sustained healthy tracheal cartilage regeneration. This study proposes a self-healing hydrogel for sutureless tracheal anastomosis to mitigate anastomotic stenosis, enriched with kartogenin (KGN) and transforming growth factor-β1 (TGFβ1) to bolster chondrogenic properties. Initially, two precursor solutions were prepared: 1) aldehyde-modified hyaluronic acid with sulfonation and β-cyclodextrin-CHO loaded with KGN; 2) hydrazide-grafted gelatin loaded with TGFβ1. Coextrusion of these solutions resulted in a gelated G + TGFβ1/sH-CD + KGN hydrogel, characterized by a robust covalent bonding network of acylhydrazones between hydrazide and aldehyde groups, imparting excellent self-healing properties. The G + TGFβ1/sH-CD + KGN hydrogels, showcasing favorable cytocompatibility, excellent injectability, and rapid gelation, were loaded with bone marrow stem cells. These were customized into O-shaped rings and assembled into a malleable tracheal substitute using our established ring-to-tube method. This resultant compliant substitute facilitated sutureless anastomosis of LSTD in a rabbit model, attributed to the Schiff base reaction between the hydrogel's carbonyl group and the tissue's amino group. Notably, the tracheal substitute reduced early postoperative anastomotic stenosis, maintained tracheal patency, alleviated sputum blockage, promoted reepithelization, and increased the survival rate of the experimental rabbits. The sustained release of chondrocytokines resulted in excellent tracheal cartilage regeneration. Employing chondrocytokines-loaded hydrogels with self-healing properties represents a significant advancement in sutureless tracheal anastomosis and tracheal cartilage regeneration, holding promising potential in inhibiting early postoperative anastomotic stenosis and tracheal chondromalacia when treating LSTD.

Abstract BackgroundChildren’s lives are increasingly mediated by digital technologies, yet evidence regarding the associations between internet use and depression is far from comprehensive and remains unclear. ObjectiveThis study aimed to investigate the dose-response association between internet use, including use time and addiction behaviors, and depressive symptoms among children and adolescents in Zhejiang Province. MethodsData were collected from a school-based health survey China Common Disease and Risk Factor Surveillance Among Students, encompassing 21,336 students in Zhejiang Province. The daily internet use time, internet addiction (IA) behaviors, and depressive symptoms were assessed with questionnaires. Logistic regression models were used to explore the associations of internet use time and IA behaviors with depressive symptoms among children and adolescents. Restricted cubic spline curves were used to determine the dose-response associations. ResultsA total of 6225 (29.2%) students had depressive symptoms. Compared to those reporting no internet use, boys using the internet for >2 hours/day (odds ratio [OR] 1.53, 95% CI 1.34‐1.74) and girls using internet for 1.1‐2 hours/day (OR 1.22, 95% CI 1.06‐1.39) and >2 hours/day (OR 1.70, 95% CI 1.50‐1.93) were at higher risks of depressive symptoms. A significant J-shaped association was identified between internet use time and depressive symptoms among children and adolescents, especially in boys and primary school students (nonlinear PP ConclusionsFindings suggested that excessive internet use time and IA behaviors were significantly associated with an increased risk of depressive symptoms, highlighting the importance of interventions to regulate and educate about adequate internet use during childhood and adolescence.

Introduction Overactive bladder (OAB) affects approximately 500 million people worldwide, with a higher prevalence in women than in men, significantly impacting the quality of life of female patients. Treatment options for OAB are currently limited. Previous research has proposed that electroacupuncture could be a viable treatment for OAB in women, but there is a lack of high-quality clinical evidence. This study aims to evaluate the effectiveness of electroacupuncture as a safe and efficient non-pharmacological treatment for female OAB by comparing it with solifenacin succinate.Methods and analysis This study is a multicentre, single-blind, double-dummy randomised controlled non-inferiority clinical trial involving 204 eligible female participants with OAB. Participants will be randomly assigned in a 1:1 ratio to either the electroacupuncture group (receiving electroacupuncture and placebo) or the solifenacin succinate group (receiving sham electroacupuncture and solifenacin succinate). Each participant will undergo 12 sessions of electroacupuncture (or sham electroacupuncture) treatment and solifenacin succinate (or placebo) treatment over a 4-week period. The primary outcome measure will be the percentage change in the number of micturition episodes every 24 hours at week 4 compared with baseline. Secondary outcomes will include a percentage reduction in the number of micturition episodes every 24 hours at 2th, 8th and 16th weeks of the trial, Overactive Bladder Symptom Score, number of urinary incontinence and urgency episodes every 24 hours based on a 3-day voiding diary, OAB Questionnaire, Generalised Anxiety Disorder Scale-7, King’s Health Questionnaire and Participant Self-evaluation of Therapeutic Effects. Adverse events will be monitored throughout the study. Efficacy analyses will be conducted on both the intention-to-treat population and the per-protocol set population.Ethics and dissemination Ethical approval has been obtained from the Medical Ethics Committee of Longhua Hospital Shanghai University of Traditional Chinese Medicine (approval number: 2022LCSY097). Each participant will sign a written informed consent before randomisation. The results of this study will be published in a peer-reviewed journal.Trial registration number NCT05798403.

Abstract It is generally recognized that tumor cells proliferate more rapidly than normal cells. Due to such an abnormally rapid proliferation rate, cancer cells constantly encounter the limits of insufficient oxygen and nutrient supplies. To satisfy their growth needs and resist adverse environmental events, tumor cells modify the metabolic pathways to produce both extra energies and substances required for rapid growth. Realizing the metabolic characters special for tumor cells will be helpful for eliminating them during therapy. Cell death is a hot topic of long-term study and targeting cell death is one of the most effective ways to repress tumor growth. Many studies have successfully demonstrated that metabolism is inextricably linked to cell death of cancer cells. Here we summarize the recently identified metabolic characters that specifically impact on different types of cell deaths and discuss their roles in tumorigenesis.

Breast cancer remains one of the predominant malignancies worldwide. In the context of inoperable advanced or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer, systemic management primarily relies on HER2-targeting monoclonal antibodies. With the successful development of anti-HER2 antibody-drug conjugates (ADCs), these agents have been increasingly integrated into therapeutic regimens for metastatic breast cancer. Here, we present the case of a 42-year-old female patient with HER2-positive pulmonary metastatic breast cancer who underwent an extensive treatment protocol. This protocol included chemotherapy, radiation therapy, hormonal therapy, surgical intervention on the breast, and anti-HER2 therapies. The anti-HER2 therapies involved both singular and dual targeting strategies using trastuzumab and the ADC disitamab vedotin (RC48) over an 8-year period. After experiencing disease progression following HER2-targeted therapy with RC48, the patient achieved noticeable partial remission through a therapeutic regimen that combined trastuzumab deruxtecan (DS8201) and tislelizumab. The data suggest a promising role for DS8201 in managing advanced stages of HER2-amplified metastatic breast cancer, especially in cases that demonstrate progression after initial HER2-directed therapies using ADCs. Furthermore, its combination with anti-PD-1 agents enhances therapeutic efficacy by augmenting the anti-tumoral immune response.

Abstract Background DNA N6-methyladenosine (6mA), as an important epigenetic modification, widely exists in bacterial genomes and participates in the regulation of toxicity, antibiotic resistance, and antioxidant. With the continuous development of sequencing technology, more 6mA sites have been identified in bacterial genomes, but few studies have focused on the distribution characteristics of 6mA at the whole-genome level and its association with gene expression and function. Results This study conducted an in-depth analysis of the 6mA in the genomes of two pathogenic bacteria, Aeromonas veronii and Helicobacter pylori. The results showed that the 6mA was widely distributed in both strains. In A. veronii, 6mA sites were enriched at 3’ end of protein-coding genes, exhibiting a certain inhibitory effect on gene expression. Genes with low 6mA density were associated with cell motility. While in H. pylori, 6mA sites were enriched at 5’ end of protein-coding genes, potentially enhancing gene expression. Genes with low 6mA density were closely related to defense mechanism. Conclusions This study elucidated the distribution characteristics of 6mA in A. veronii and H. pylori, highlighting the effects of 6mA on gene expression and function. These findings provide valuable insights into the epigenetic regulation and functional characteristics of A. veronii and H. pylori.

Abstract Diabetic retinopathy is a common microvascular complication of diabetes and a leading cause of blindness. Pyroptosis has emerged as a mechanism of cell death involved in diabetic retinopathy pathology. This study explored the role of GSDME-mediated pyroptosis and its regulation by TNFSF15 in diabetic retinopathy. We found GSDME was upregulated in the progression of diabetic retinopathy. High glucose promoted GSDME-induced pyroptosis in retinal endothelial cells and retinal pigment epithelial cells, attributed to the activation of caspase-3 which cleaves GSDME to generate the pyroptosis-executing N-terminal fragment. TNFSF15 was identified as a binding partner and inhibitor of GSDME-mediated pyroptosis. TNFSF15 expression was increased by high glucose but suppressed by the caspase-3 activator Raptinal. Moreover, TNFSF15 protein inhibited high glucose- and Raptinal-induced pyroptosis by interacting with GSDME in retinal cells. Collectively, our results demonstrate TNFSF15 inhibits diabetic retinopathy progression by blocking GSDME-dependent pyroptosis of retinal cells, suggesting the TNFSF15-GSDME interaction as a promising therapeutic target for diabetic retinopathy.

Abstract Background Revascularization and restoration of normal pulp-dentin complex are important for tissue-engineered pulp regeneration. Recently, a unique periodontal tip-like endothelial cells subtype (POTCs) specialized to dentinogenesis was identified. We have confirmed that TPPU, a soluble epoxide hydrolase (sEH) inhibitor targeting epoxyeicosatrienoic acids (EETs) metabolism, promotes bone growth and regeneration by angiogenesis and osteogenesis coupling. We hypothesized that TPPU could also promote revascularization and induce POTCs to contribute to pulp-dentin complex regeneration. Here, we in vitro and in vivo characterized the potential effect of TPPU on the coupling of angiogenesis and odontogenesis and investigated the relevant mechanism, providing new ideas for pulp-dentin regeneration by targeting sEH. Methods In vitro effects of TPPU on the proliferation, migration, and angiogenesis of dental pulp stem cells (DPSCs), human umbilical vein endothelial cells (HUVECs) and cocultured DPSCs and HUVECs were detected using cell counting kit 8 (CCK8) assay, wound healing, transwell, tube formation and RT-qPCR. In vivo, Matrigel plug assay was performed to outline the roles of TPPU in revascularization and survival of grafts. Then we characterized the VEGFR2 + POTCs around odontoblast layer in the molar of pups from C57BL/6 female mice gavaged with TPPU. Finally, the root segments with DPSCs mixed with Matrigel were implanted subcutaneously in BALB/c nude mice treated with TPPU and the root grafts were isolated for histological staining. Results In vitro, TPPU significantly promoted the migration and tube formation capability of cocultured DPSCs and HUVECs. ALP and ARS staining and RT-qPCR showed that TPPU promoted the osteogenic and odontogenic differentiation of cultured cells, treatment with an anti-TGF-β blocking antibody abrogated this effect. Knockdown of HIF-1α in HUVECs significantly reversed the effect of TPPU on the expression of angiogenesis, osteogenesis and odontogenesis-related genes in cocultured cells. Matrigel plug assay showed that TPPU increased VEGF/VEGFR2-expressed cells in transplanted grafts. TPPU contributed to angiogenic-odontogenic coupling featured by increased VEGFR2 + POTCs and odontoblast maturation during early dentinogenesis in molar of newborn pups from C57BL/6 female mice gavaged with TPPU. TPPU induced more dental pulp-like tissue with more vessels and collagen fibers in transplanted root segment. Conclusions TPPU promotes revascularization of dental pulp regeneration by enhancing migration and angiogenesis of HUVECs, and improves odontogenic differentiation of DPSCs by TGF-β. TPPU boosts the angiogenic–odontogenic coupling by enhancing VEGFR2 + POTCs meditated odontoblast maturation partly via upregulating HIF-1α, which contributes to increasing pulp-dentin complex for tissue-engineered pulp regeneration.

PARP inhibitors (PARPi) are a kind of cancer therapy that targets poly (ADP-ribose) polymerase. PARPi is the first clinically approved drug to exert synthetic lethality by obstructing the DNA single-strand break repair process. Despite the significant therapeutic effect in patients with homologous recombination (HR) repair deficiency, innate and acquired resistance to PARPi is a main challenge in the clinic. In this review, we mainly discussed the underlying mechanisms of PARPi resistance and summarized the promising solutions to overcome PARPi resistance, aiming at extending PARPi application and improving patient outcomes.

Abstract Bladder cancer, a prevalent and heterogeneous malignancy, necessitates the discovery of pertinent biomarkers to enable personalized treatment. The mammalian target of rapamycin complex 1 (mTORC1), a pivotal regulator of cellular growth, metabolism, and immune response, exhibits activation in a subset of bladder cancer tumors. In this study, we explore the prognostic significance of mTORC1 signaling in bladder cancer through the utilization of bioinformatics analysis. Our investigation incorporates transcriptomic, somatic mutation, and clinical data, examining the mTORC1 score of each sample, as well as the enrichment of differentially expressed genes (DEGs), differentiation characteristics, immunological infiltration, and metabolic activity. Our findings reveal that elevated mTORC1 levels serve as an adverse prognostic indicator for bladder cancer patients, exhibiting a significant association with Basal-type bladder cancer. Patients with heightened mTORC1 activation display heightened levels of pro-carcinogenic metabolism. Additionally, these individuals demonstrate enhanced response to immunotherapy. Finally, we develop an mTORC1-related signature capable of predicting the prognosis of bladder cancer patients.The signature offers novel mTORC1-related biomarkers and provides fresh insights into the involvement of mTORC1 in the pathogenesis of bladder cancer.

Introduction Studies on economic evaluations of the 13-valent pneumococcal conjugate vaccine (PCV13) have been increasing over the last decade. No systematic reviews have synthesized the evidence of economic evaluations of the PCV13. Areas covered We systematically searched the literature which published on peer-reviewed journals from January 2010 to June 2022. The literature search was conducted in the following electronic databases: PubMed, Web of Science, Embase, the Cochrane Library, CNKI, Wanfang database, VIP database. We identified 1827 records from the database search. After excluding 511 duplicates, 1314 records were screened, of which 156 records were retained for the full-text reviews. A total of 44 studies were included in the review. Among the included studies, 33 studies were economic evaluations of PCV13 among children, and 11 studies were conducted among adults. The literature search initiated in April, 2022, and updated in June 2022. Expert opinion Vaccination with PCV13 was found to significantly reduce the mortality and morbidity of pneumococcal diseases and was cost-effective compared to no vaccine or several other pneumococcal vaccines (e.g. PCV10, PPV23). Future research is advised to expand economic evaluations of PCV13 combined with dynamic model to enhance methodologic rigor and prediction accuracy.

Th2 polarization is essential for the pathogenesis of allergic rhinitis (AR). Th2 polarization's mechanism requires further understanding. IL-4 is the primary cytokine involved in Th2 response. Fibroblasts play a role in immune regulation. This study aims to elucidate the role of nasal mucosal fibroblast-derived IL-4 in the induction of Th2 responses. Nasal mucosal tissues were obtained from surgically removed samples from patients with nasal polyps, whether with or without AR. Fibroblasts were isolated from the tissues by flow cytometry cell sorting, and analyzed by RNA sequencing (RNAseq). The data from RNAseq showed that nasal fibroblasts expressed genes of GATA3, CD80, CD83, CD86, STAT6, IL2, IL4, IL5, IL6, IL13 and costimulatory factor. The data were verified by RT-qPCR. The level of gene activity was positively correlated with those of AR-related cytokines present in nasal secretions. Nasal fibroblasts release IL-4 upon activation. Nasal fibroblasts had the ability to transform naive CD4 + T cells into Th2 cells, which can be eliminated by inhibiting IL-4 receptor or CD28 in CD4 + T cells. To sum up, nasal mucosal fibroblasts produce IL-4, which can induce Th2 cell development. The data implicate that nasal fibroblasts are involved in the pathogenesis of nasal allergy.

The factors that determine fibrosis progression or normal tissue repair are largely unknown. We previously demonstrated that autophagy inhibition-mediated epithelial–mesenchymal transition (EMT) in human alveolar epithelial type II (ATII) cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine signaling. Here, we report that liver kinase B1 (LKB1) inactivation in ATII cells inhibits autophagy and induces EMT as a consequence. In IPF lungs, this is caused by the down-regulation of CAB39L, a key subunit within the LKB1 complex. 3D co-cultures of ATII cells and MRC5 lung fibroblasts coupled with RNA sequencing (RNA-seq) confirmed that paracrine signaling between LKB1-depleted ATII cells and fibroblasts augmented myofibroblast differentiation. Together, these data suggest that reduced autophagy caused by LKB1 inhibition can induce EMT in ATII cells and contribute to fibrosis via aberrant epithelial–fibroblast crosstalk.

Summary: Cerebrospinal fluid (CSF) samples are commonly collected via lumbar puncture (LP) in both clinical and research settings for measurement of biomarkers of Alzheimer’s disease (AD). To determine the effects of LP on CSF AD biomarkers, we collected CSF samples at seven different time points after an LP in rhesus monkeys. We find that amyloid-beta (Aβ) and Tau levels increased significantly on day 1, peaked on day 3, and returned to baseline on day 10 after LP. The NFL levels increased significantly on day 5, peaked on day 10, and returned to baseline after day 30. The increased AD biomarker levels were mainly due to CSF outflow and deep intrathecal invasion during LP. Therefore, if LPs are repeated within a short period of time, prior LP can affect Aβ and Tau levels within 10 days and NFL levels within 30 days, which may lead to clinical misdiagnosis or incorrect scientific conclusions.

Abstract Cancer-associated cachexia is a multi-organ weight loss syndrome, especially with a wasting disorder of adipose tissue and skeletal muscle. Small extracellular vesicles (sEVs) serve as emerging messengers to connect primary tumour and metabolic organs to exert systemic regulation. However, whether and how tumour-derived sEVs regulate white adipose tissue (WAT) browning and fat loss is poorly defined. Here, we report breast cancer cell-secreted exosomal miR-204-5p induces hypoxia-inducible factor 1A (HIF1A) in WAT by targeting von Hippel-Lindau (VHL) gene. Elevated HIF1A protein induces the leptin signalling pathway and thereby enhances lipolysis in WAT. Additionally, exogenous VHL expression blocks the effect of exosomal miR-204-5p on WAT browning. Reduced plasma phosphatidyl ethanolamine level is detected in mice lack of cancer-derived miR-204-5p secretion in vivo. Collectively, our study reveals circulating miR-204-5p induces hypoxia-mediated leptin signalling pathway to promote lipolysis and WAT browning, shedding light on both preventive screenings and early intervention for cancer-associated cachexia.

Aiming to address the dual complexities that current scientific research institutes face in both management work and research tasks, parallel scientific research institutes were proposed.Parallel scientific research institutes were constructed based on the virtual-real interactive parallel intelligence theory, which leveraged digital construction technologies based on digital twins and metaverse, distributed governance technologies based on blockchain and decentralized autonomous organizations and operations (DAOs), intelligent decision-making technologies based on big data and foundation models, as well as scientific innovation paradigms based on decentralized science (DeSci) and artificial intelligence for science (AI4S).Their core goal was to form a prescriptive scheme for scientific research institute transformation driven by complex science, thereby constructing a trustworthy, reliable, usable, efficient and effective intelligent research organizational and operational ecosystem.The systematic design and key technologies of parallel scientific research institutes were introduced, their main characteristics and advantages were described, and their typical application scenarios were explored.Parallel scientific research institutes go beyond the simple digital transformation of scientific research institutes, and emphasize a higher level of intelligent transformation, promoting the sustainable and healthy development of scientific research institutes.

Abstract Multiple studies have shown that extracellular vesicles (EVs) play a key role in the process of information transfer and material transport between cells. EVs are classified into different types according to their sizes, which includes the class of exosomes. In comparison to normal EVs, tumor-derived EVs (TDEs) have both altered components and quantities of contents. TDEs have been shown to help facilitate an environment conducive to the occurrence and development of tumor by regulation of glucose, lipids and amino acids. Furthermore, TDEs can also affect the host metabolism and immune system. EVs have been shown to have multiple clinically useful properties, including the use of TDEs as biomarkers for the early diagnosis of diseases and using the transport properties of exosomes for drug delivery. Targeting the key bioactive cargoes of exosomes could be applied to provide new strategies for the treatment of tumors. In this review, we summarize the finding of studies focused on measuring the effects of TDE on tumor-related microenvironment and systemic metabolism. Video Abstract

Abstract Background Doxorubicin (Dox) has been recommended in clinical guidelines for the standard-of-care treatment of breast cancer. However, Dox therapy faces challenges such as hypoxia, acidosis, H2O2-rich conditions and condensed extracellular matrix in TME as well as low targeted ability. Methods We developed a nanosystem H-MnO2-Dox-Col NPs based on mesoporous manganese dioxide (H-MnO2) in which Dox was loaded in the core and collagenase (Col) was wrapped in the surface. Further the H-MnO2-Dox-Col NPs were covered by a fusion membrane (MP) of inflammation-targeted RAW264.7 cell membrane and pH-sensitive liposomes to form biomimetic MP@H-MnO2-Dox-Col for in vitro and in vivo study. Results Our results shows that MP@H-MnO2-Dox-Col can increase the Dox effect with low cardiotoxicity based on multi-functions of effective penetration in tumor tissue, alleviating hypoxia in TME, pH sensitive drug release as well as targeted delivery of Dox. Conclusions This multifunctional biomimetic nanodelivery system exhibited antitumor efficacy in vivo and in vitro, thus having potential for the treatment of breast cancer.

Macrolide antibiotics are widely used antibacterial agents that are associated with autophagy inhibition. This study aimed to investigate the association between macrolide antibi-otics and malignant tumors, as well as the effect on autophagy, reactive oxygen species (ROS) accumulation and integrated stress response (ISR). The meta-analysis indicated a modestly higher risk of cancer in macrolide antibiotic ever-users com-pared to non-users. Further experiments showed that macro-lides block autophagic flux by inhibiting lysosomal acidification. Additionally, azithromycin, a representative macrolide antibi-otic, induced the accumulation of ROS, and stimulated the ISR and the activation of transcription factor EB (TFEB) and TFE3 in a ROS-dependent manner. Finally, animal experiments confirmed that azithromycin promoted tumor progression in vivo, which could be receded by N-acetylcysteine, an inhibitor of ROS and ISR. Overall, this study reveals the potential role of macrolide antibiotics in malignant progression and highlights the need for further investigation into their effects.

The cultivation of drip-irrigated rice has resulted in lower yields. However, the decrease in rice yield under drip irrigation and its relationship with the existing water and N regime have not been fully explained. Research and development of optimized water and N-management techniques are crucial for increasing rice yield under drip irrigation. In this study, two irrigation treatments were set: conventional drip irrigation (DIO) and drip irrigation with water stress (DIS). Each irrigation treatment contained four N rates: urea N 240 kg ha−1 (LN), urea N 300 kg ha−1 (MN), urea N 360 kg ha−1 (HN), and ammonium sulfate N 300 kg ha−1 (AN). The soil’s ammonium and nitrate contents were measured on the 2nd and 28th days after N application at panicle initiation stage. At anthesis, the aboveground and root biomass of rice were measured. In heading and maturity stage the N content of aboveground was measured and the yield, yield components, and NPFP were assessed at maturity stage. The results showed the following: (1) On the second day after N application, the contents of soil NO3−-N and NH4+-N in the 0–10 cm soil layer were highest for both the DIO and DIS. On the 28th day after N application, the soil NO3−-N content was highest at the 20–40 cm depth, while the soil NH4+-N content was still highest at the 0–10 cm depth. (2) The aboveground and root biomass in DIO treatment were significantly higher than in DIS. Furthermore, the root biomass at the 0–10 cm depth was significantly greater than at the 10–50 cm depth for both the DIO and DIS treatments. In the DIO treatment, the root biomass at the 10–50 cm depth was significantly higher with the HN and AN treatments compared to MN. However, in the DIS treatment, the root biomass at the 10–50 cm depth did not show significant differences between the MN, HN, and AN. (3) N accumulation in rice was significantly higher for the DIO treatment compared to the DIS treatment. Under the same irrigation treatment, the N accumulation in rice was highest in the AN and lowest in the LN. The PrNTA and PrNTC in DIS were significantly higher than in DIO, while the PoNAA and PoNAC were significantly lower in DIS. (4) The number of panicles, spikelets per panicle, seed-setting rate, 1000-grain weight, and grain yield were significantly lower in DIS. Under the DIS, these parameters were not significantly different among the MN, HN, and AN. In the DIO, the seed-setting rate, 1000-grain weight, and yield were not significantly different between the HN and AN, but were significantly higher than in the MN and LN. (5) NPFP was significantly higher in the DIO compared to the DIS. Among the different N rates, NPFP was highest with the AN treatment and lowest with the LN. In summary, under drip irrigation, there was a mismatch between soil mineral N and the distribution of rice roots, leading to reduced N accumulation and utilization in rice, ultimately impacting yield formation. Increasing N application and soil ammonium nutrition can improve rice yield under drip irrigation. However, optimizing N fertilizer management may not increase rice yield further when irrigation is further limited.

Oxidative stress is a key factor leading to profound neurological deficits following spinal cord injury (SCI). In this study, we present the development and potential application of an iridium (iii) complex, (CpxbiPh) Ir (N^N) Cl, where CpxbiPh represents 1-biphenyl-2,3,4,5-tetramethyl cyclopentadienyl, and N^N denotes 2-(3-(4-nitrophenyl)-1H-1,2,4-triazol-5-yl) pyridine chelating agents, to address this challenge through a mechanism governed by the regulation of an antioxidant protein. This iridium complex, IrPHtz, can modulate the Oxidation Resistance 1 (OXR1) protein levels within spinal cord tissues, thus showcasing its antioxidative potential. By eliminating reactive oxygen species (ROS) and preventing apoptosis, the IrPHtz demonstrated neuroprotective and neural healing characteristics on injured neurons. Our molecular docking analysis unveiled the presence of π stacking within the IrPHtz-OXR1 complex, an interaction that enhanced OXR1 expression, subsequently diminishing oxidative stress, thwarting neuroinflammation, and averting neuronal apoptosis. Furthermore, in in vivo experimentation with SCI-afflicted mice, IrPHtz was efficacious in shielding spinal cord neurons, promoting their regrowth, restoring electrical signaling, and improving motor performance. Collectively, these findings underscore the potential of employing the iridium metal complex in a novel, protein-regulated antioxidant strategy, presenting a promising avenue for therapeutic intervention in SCI.

Age-related hearing loss (ARHL) is a prevalent condition affecting millions of individuals globally. This study investigated the role of the cell survival regulator Bcl2 in ARHL through in vitro and in vivo experiments and metabolomics analysis. The results showed that the lack of Bcl2 in the auditory cortex affects lipid metabolism, resulting in reduced synaptic function and neurodegeneration. Immunohistochemical analysis demonstrated enrichment of Bcl2 in specific areas of the auditory cortex, including the secondary auditory cortex, dorsal and ventral areas, and primary somatosensory cortex. In ARHL rats, a significant decrease in Bcl2 expression was observed in these areas. RNAseq analysis showed that the downregulation of Bcl2 altered lipid metabolism pathways within the auditory pathway, which was further confirmed by metabolomics analysis. These results suggest that Bcl2 plays a crucial role in regulating lipid metabolism, synaptic function, and neurodegeneration in ARHL; thereby, it could be a potential therapeutic target. We also revealed that Bcl2 probably has a close connection with lipid peroxidation and reactive oxygen species (ROS) production occurring in cochlear hair cells and cortical neurons in ARHL. The study also identified changes in hair cells, spiral ganglion cells, and nerve fiber density as consequences of Bcl2 deficiency, which could potentially contribute to the inner ear nerve blockage and subsequent hearing loss. Therefore, targeting Bcl2 may be a promising potential therapeutic intervention for ARHL. These findings provide valuable insights into the molecular mechanisms underlying ARHL and may pave the way for novel treatment approaches for this prevalent age-related disorder.

Abstract Background Non-alcoholic steatohepatitis (NASH) had not yet been approved therapy. Electro-acupuncture (EA) has been reported to have potential efficacy. However, high-quality clinical evidence was still lacking. Methods NASH patients were randomized and allocated to either sham acupuncture (SA) or EA group in a 1:1 ratio, with the patient blinded. Each patient received 36 sessions of SA or EA treatment over 12 weeks, followed by additional 4 weeks. The primary outcome was the changes in relative liver fat content measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF). Results A total of 60 patients were enrolled. From baseline to week 12, the reduction of relative liver fat content measured by MRI-PDFF in the EA group (− 33.6%, quantile range: − 52.9%, − 22.7%) was significantly more significant than that in the SA group (− 15.8%, quantile range: − 36.1%, − 2.7%) (p = 0.022). Furthermore, the EA group had more patients who achieved MRI-PDFF to 30% reduction at week 12 (53.3% vs. 25.9%, p = 0.035). EA treatment also significantly reduced body weight (− 3.0 vs. + 0.1 kg, p = 0.034) and BMI (− 1.5 vs. − 0.2 kg/m2, p = 0.013) at week 16. Except for AST (− 27.4 vs. − 16.2 U/L, p = 0.015), other biochemical varieties, including ALT, fasting-glucose, cholesterol, and triglyceride, showed no statistically significant difference. Both groups measured no significant changes in liver stiffness by magnetic resonance elastography (MRE). There were no serious adverse events in either group. Conclusions Twelve weeks of EA effectively and safely reduces relative liver fat content in NASH patients. Further multicenter randomized controlled studies are needed. Trial registration Chinese Clinical Trial Registry, ChiCTR2100046617. Registered 23 May 2021, http://www.chictr.org.cn/edit.aspx?pid=127023&htm=4

Abstract Background Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, anovulation, and polycystic ovaries. Electroacupuncture (EA) can effectively improve hyperandrogenism and increase ovulation frequency in patients with PCOS. Pieces of suggest that androgen activity in the brain is associated with impaired steroid negative feedback in such patients. Studies have shown that EA regulated androgen receptor (AR) expression and local factor levels (such as anti-Müllerian hormone and inhibin B) in the ovary of PCOS rats. However, few studies have explored the effect of EA on androgen activity in the brain. Objective This study investigated the effect of EA on the kisspeptin-gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) neural circuit and sex hormone receptor expression in the hypothalamus of PCOS rats. Methods PCOS signs were induced by letrozole administration, and the induced rats were treated with low-frequency EA at Guan Yuan acupoint (CV4). The effect of EA on PCOS-like signs was evaluated by observing changes in the body weight, ovarian quality, ovarian morphology, and serum sex hormone levels in rats. To explore the mechanism of the effect of EA on PCOS-like signs, the neuropeptide content of the kisspeptin-GnRH/LH neural circuit was assessed using enzyme-linked immunosorbent assay(ELISA); AR and estrogen receptor α (ERα) coexpression on kisspeptin/neurokinin B/dynorphin (KNDy) neurons was determined via triple-label immunofluorescence; and protein and mRNA expression of Kiss1, Ar, Esr1, and kisspeptin receptor (Kiss1r) was evaluated via western blotting and Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Results The results revealed that the estrous cycle of rats in the EA treatment group recovered, and their body and ovary weight reduced; ovarian morphology improved; serum testosterone and LH levels significantly decreased; and kisspeptin, GnRH, and dynorphin levels in hypothalamic arcuate nucleus significantly decreased. Compared with controls, the number of AR/Kiss1-positive cells increased, number of ERα/Kiss1-positive cells decreased, and protein and mRNA expression of Kiss1, Ar, and Kiss1r significantly increased in PCOS rats. However, EA treatment reversed these changes and reduced the expression of Kiss1, Ar, and Kiss1r significantly. Conclusion Improvement in the reproductive hallmarks of PCOS rats via EA may be achieved by regulating the kisspeptin-GnRH/LH circuit via androgen activity attenuation. Thus, the results provide an experimental basis for acupuncture as an adjuvant medical therapy on PCOS.

Abstract Background As the second cause of cancer death in women, breast cancer has become a worldwide priority. Previous studies based on tumour cell lines demonstrated that arachidonic acid (AA) and its metabolites promote cancer development. However, recent studies based on the tumour microenvironment revealed the antitumour effect of AA metabolism. Therefore, it is essential to reevaluate and elucidate the effect of AA metabolism on breast cancer. Methods Raw data were obtained from The Cancer Genome Atlas (TCGA), Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and Gene Expression Omnibus (GEO) databases. The AA metabolic score of each sample, enrichment of differentially expressed genes (DEGs) and immune infiltration were analysed by bioinformatics. Cox regression and least absolute shrinkage and selection operator regression were performed to establish an AA metabolism prognostic signature. An AA metabolism related nomogram for predicting the survival probability of patients was built. Result AA metabolism was related to good prognosis in the TCGA-BRCA and METABRIC cohort. DEGs enrichment suggested that the upregulated DEGs of the high AA metabolism group were significantly enriched in immune-related pathways. The high AA metabolism group was infiltrated with more CD8+ T cells and activated NK cells. An AA metabolic signature (SPINK8, KLRB1, APOD and PIGR) was constructed for breast cancer prognosis. Conclusion The study indicated that a high level of AA metabolism may be a biomarker for good prognosis in breast cancer, providing a possible explanation for the discouraging effect of cyclooxygenase inhibitors in cancer therapy. Moreover, a novel AA metabolic prognostic signature was constructed in the study, providing a novel strategy for breast cancer.

BackgroundNewly developed catheter ablation (CA) techniques, such as laser balloon ablation (LBA) and cryoballoon ablation (CBA), have been introduced in recent years and emerged as valuable alternatives to conventional radiofrequency CA strategies for paroxysmal atrial fibrillation (PAF) patients. However, evidence comparing LBA and CBA remain controversial. Thus, we conducted this meta-analysis to assess the efficacy and safety between these two techniques.MethodsScientific databases (PubMed, Embase) and relevant websites (the Cochrane Library, ClinicalTrials.gov) were systematically searched from inception to March 2023. The primary outcomes of interest were the AF recurrence and the procedure-related complications. Secondary outcomes included procedural time, fluoroscopy time, and left atrial (LA) dwell time.ResultsSeven clinical trials with a total of 637 patients were finally enrolled. No significant differences were found between LBA and CBA in terms of AF recurrence [16.3% vs. 22.7%, odds ratio (OR) = 0.66, 95% confidence interval (CI): 0.42–1.05, p = 0.078] or total procedural-related complications (8.4% vs. 6.4%, OR = 1.33, 95% CI: 0.71–2.51, p = 0.371). LBA had a significantly longer procedural time [weighted mean difference (WMD) = 38.03 min, 95% CI: 13.48–62.58 min, p = 0.002] and LA dwell time (WMD = 46.67 min, 95% CI: 14.63–78.72 min, p = 0.004) than CBA, but tended to have shorter fluoroscopy time.ConclusionsLBA and CBA treatment have comparable efficacy and safety for PAF patients. LBA was associated with longer procedural and LA dwell times compared with CBA. Further large-scale studies are warranted to compare these two techniques with the newest generations.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=426513, identifier (CRD42023426513).

BackgroundStress urinary incontinence (SUI) is a common condition that can severely affect women’s life quality. Electroacupuncture (EA) has been proved to be an optional treatment for SUI, but the tolerance of EA becomes a factor affecting efficiency, which should not be ignored and needs to be solved urgently. The purpose of this study is to find out whether the use of alternating acupoints combination can solve this problem or not and provide an optimization of EA treatment for female SUI.MethodsThis multi-center randomized controlled trial will enroll 360 patients with SUI. They will be randomly assigned to one of the three groups—sacral acupoints group (sacral group), abdominal acupoints group (abdominal group), or alternating acupoints group (alternating group)—at a 1:1:1 ratio. The patients will receive 18 sessions of EA treatment and will be followed up for 48 weeks after the treatment. The primary outcome measure of the study is the change of urine leakage at week 6. The secondary outcomes include the incontinence episode frequency (IEF), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), severity of SUI, patient self-evaluation of therapeutic effects, weekly usage of urine pads, ultrasonography of pelvic floor, specialty therapies for SUI, evaluation of discomfort during EA treatment, patient acceptability evaluation and adverse events related to intervention.DiscussionThis trial is specifically designed to offer an optimized EA treatment for female SUI, aiming to enhance their quality of life.Clinical trial registration: ClinicalTrials.gov, identifier ID:NCT05635669.

Abstract Background: Acute kidney injury (AKI) caused by cisplatin is common and has a higher incidence of multiple use, resulting in a poor short- and long-term prognosis for patients. There is currently no good pre-medication AKI risk assessment tool. The aim of this study is to establish an AKI risk assessment nomogram for patients with multiple cisplatin applications. Methods: This study was a retrospective analysis of patients who were treated with non-first-time cisplatin chemotherapy regimen in Changzhou second people's Hospital affiliated to Nanjing Medical University from January 2016 to January 2022. All data of the development group were used to screen the impact factors of AKI via univariate and multivariate analyses. A nomogram was developed based on these impact factors and verified with verification group. The area under the curve (AUC) of receiver-operating characteristic (ROC) curve, calibration curves, and decision curve analyses (DCAs) were used to evaluate the nomogram. Results: Among the 256 patients enrolled in 450 cycles of chemotherapy, 282 were in the development cohort (97 AKI), and 168 were in the validation cohort (61 AKI). Multivariate logistic regression revealed that age, hypertension, diabetes, sCysC, uKim1 and a single dose of cisplatin were independently associated with AKI. The results showed that our model yielded satisfied diagnostic performance with an AUC value of 0.887 and 0.906 using the development group and on verification group. The calibration plots and DCA showed the superior clinical applicability of the nomogram. These results were verified in the validation cohort. Conclusion: A nomogram combining functional (sCysC) and tubular (uKim1) injury biomarkers with conventional clinical factors might assess the risk of AKI after multiple cycles of cisplatin chemotherapy.

Aim to deal with the problem of data, trust and timeliness asymmetry faced by modern organizational management from the root, a novel organizational management model towards Web 3.0 namely crypto management was proposed.It was enabled by blockchain technology and smart contracts based on it, supported by the federated data, organized in the form of DAO (decentralized autonomous organization), and driven by the incentive mechanism with NFT (non-fungible token) as the core.The primary goal of crypto management was to realize trustable, reliable and usable real-time management decision-making under the premise of data security and privacy protection.The framework of crypto management was formulated, its core components and implementation mode were discussed, and its operation process using the example of personnel performance management was also introduced.Towards the end, the potential future works in this emerging new area were discussed.

ObjectiveTo evaluate the clinical value of systemic immune-inflammation index (SII) based on peripheral blood neutrophil, lymphocyte, and platelet count in evaluating the subtype and severity of depression in patients with depressive disorder.MethodsThis retrospective cohort study was conducted in the Third People’s Hospital of Fuyang City from January 1, 2020 to December 31, 2022. The data included sociodemographic information at admission, clinical data, discharge diagnosis and inflammatory markers. Patients were divided into low SII group and high SII group according to the optimal threshold of SII determined by receiver operating characteristic curve (ROC curve). Binary logistic regression was used to analyze the correlation between moderate/major depression and SII level.ResultsCompared to the low SII group, the high SII group had a higher age level (χ2 = 7.663, p = 0.006), more smokers (χ2 = 9.458, p = 0.002), more moderate/major depression patients (χ2 = 45.645, p

BackgroundWeb-based forums provide a space for communities of interest to exchange ideas and experiences. Nurse professionals used these forums during the COVID-19 pandemic to share their experiences and concerns. ObjectiveThe objective of this study was to examine the nurse-generated content to capture the evolution of nurses’ work concerns during the COVID-19 pandemic. MethodsWe analyzed 14,060 posts related to the COVID-19 pandemic from March 2020 to April 2021. The data analysis stage included unsupervised machine learning and thematic qualitative analysis. We used an unsupervised machine learning approach, latent Dirichlet allocation, to identify salient topics in the collected posts. A human-in-the-loop analysis complemented the machine learning approach, categorizing topics into themes and subthemes. We developed insights into nurses’ evolving perspectives based on temporal changes. ResultsWe identified themes for biweekly periods and grouped them into 20 major themes based on the work concern inventory framework. Dominant work concerns varied throughout the study period. A detailed analysis of the patterns in how themes evolved over time enabled us to create narratives of work concerns. ConclusionsThe analysis demonstrates that professional web-based forums capture nuanced details about nurses’ work concerns and workplace stressors during the COVID-19 pandemic. Monitoring and assessment of web-based discussions could provide useful data for health care organizations to understand how their primary caregivers are affected by external pressures and internal managerial decisions and design more effective responses and planning during crises.

The tumor-adipose microenvironment (TAME) is a universal microecosystem, that is characterized by the dysfunction of lipid metabolism, such as excessive free fatty acids (FFAs). Macrophages are the most abundant immune cell type within TAME, although their diversity in the TAME is not clear. We first reveal that infiltration of M2-like macrophages in the TAME is associated with poor survival in breast cancer. To explore lipid-associated alterations in the TAME, we also detected the levels of FFAs transporters including fatty acid binding proteins (FABPs) and fatty acid transport protein 1 (FATP1). The results indicated that expression of fatty acid transporters in the TAME is tightly linked to the function of macrophages and predicts survival in breast cancer. To explore the impact of FFAs transporters on the function of macrophages, we performed single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics. Consequently, we identified a special subpopulation of macrophages defined as lipid-associated macrophages (LAMs), highly expressed macrophage markers (CD163, SPP1 and C1QC), genes involved in lipid metabolism (FABP3, FABP4, FABP5, LPL and LIPA) and some lipid receptors (LGALS3 and TREM2). Functionally, LAMs were characterized by a canonical functional signature of M2-like macrophages, lipid accumulation and enhancing phagocytosis, and they were mostly distributed in tumor-adipose junctional regions. Finally, the allograft cancer mouse models confirmed that LAMs depletion in the TAME synergizes the antitumorigenic effects of anti-PD1 therapy. In summary, we defined a novel subtype of macrophages in the TAME, that has unique features and clinical outcomes.

The incidence rate of nasopharyngeal carcinoma (NPC) is the highest among the malignant tumors of otorhinolaryngology, posing a huge burden to public health. Long noncoding RNAs (lncRNAs) exert an important role in tumorigenesis and the progression of various cancers. The present study found that HOXC-AS1 was highly expressed in NPC and in NPC cell lines, suggesting a critical role of HOXC-AS1 in NPC progression. In addition, the abundance of HOXC-AS1 was negatively correlated with the prognosis of NPC. To molecularly dissect the mechanism of HOXC-AS1 in NPC progression, we knocked down the expression of HOXC-AS1 in HNE1 and C666-1 cells. Then, we employed CCK8, colony-formation experiment and Transwell to investigate how the cell performed when HOXC-AS1 was knocked down. It could be observed that HOXC-AS1 knockdown decreases cell proliferation, migration and invasion, but induces cell apoptosis in NPC. We found that HOXC-AS1 could sponge miR-4651 subsequently binding FOXO6 and inhibiting its expression. Therefore, HOXC-AS1/miR-4651/FOXO6 may form a competing endogenous RNA (ceRNA) network that promotes NPC progression. In conclusion, our study demonstrates that HOXC-AS1 promotes NPC progression by sponging miR-4651 and regulating FOXO6 expression, thus providing potential pharmaceutical targets for developing new NPC treatments.

Abstract Background Social support is an important health determinant and may affect dietary behaviors. The purpose of this study was to examine the relations between perceived social support and the Chinese Diet Balance Index-16 (DBI-16) among ethnic minority groups in Southwest China. Methods This cross-sectional study was conducted between May 2019 and August 2020 among six ethnic minority groups native to Yunnan Province (n = 3564). Perceived social support from family, friends and significant others were measured with the Multi-dimensional Scale of Perceived Social Support (MSPSS). Dietary data were obtained using a 100-item Food Frequency Questionnaire (FFQ) and a lifestyle questionnaire. Lower Bound Score (LBS), Higher Bound Score (HBS) and Diet Quality Distance (DQD) which represent inadequate, excessive and unbalanced food intake respectively were calculated to measure the compliance with the recommendations of the Dietary Guidelines for Chinese 2016. Results One thousand four hundred ninety-six men and two thousand sixty-eight women were included. 51.2% of the subjects had moderate or high levels of inadequate intake; 21.3% had moderate or high levels of excessive intake; and 74.0% had moderate or high levels of unbalanced dietary intake. With potential confounders adjusted, support from family was negatively associated with inadequate intake, while support from friends was positively associated with inadequate and excessive intake. No significant associations were found between perceived social support from significant others and diet quality indicators. Conclusions An unbalanced diet is common among adults of the ethnic minority groups in Yunnan Province, Southwest China. Social support should be taken into account in designing nutrition interventions rather than focusing solely on individuals.

Research on elemental 2D materials has been experiencing a renaissance in the past few years. Of particular interest is tellurium (Te), which possesses many exceptional properties for nanoelectronics, photonics, and beyond. Nevertheless, the lack of a scalable approach for the thickness engineering and the local properties modulation remains a major obstacle to unleashing its full device potential. Herein, a solution-processed oxidative etching strategy for post-growth thickness engineering is proposed by leveraging the moderate chemical reactivity of Te. Large-area ultrathin nanosheets with well-preserved morphologies could be readily obtained with appropriate oxidizing agents, such as HNO2, H2O2, and KMnO4. Compared with the conventional physical thinning approaches, this method exhibits critical merits of high efficiency, easy scalability, and the capability of site-specific thickness patterning. The thickness reduction leads to substantially improved gate tunability of field-effect transistors with an enhanced current switching ratio of ∼103, promoting the applications of Te in future logic electronics. The response spectrum of Te phototransistors covers the full range of short-wave infrared wavelength (1–3 μm), and the room-temperature responsivity and detectivity reach 0.96 AW-1 and 2.2 × 109 Jones at the telecom wavelength of 1.55 μm, together with a favorable photocurrent anisotropic ratio of ∼2.9. Our study offers a new approach to tackling the thickness engineering issue for solution-grown Te, which could help realize the full device potential of this emerging p-type 2D material.

Abstract Metabolic reprogramming in tumor‐immune interactions is emerging as a key factor affecting pro‐inflammatory carcinogenic effects and anticancer immune responses. Therefore, dysregulated metabolites and their regulators affect both cancer progression and therapeutic response. Here, we describe the molecular mechanisms through which microenvironmental, systemic, and microbial metabolites potentially influence the host immune response to mediate malignant progression and therapeutic intervention. We summarized the primary interplaying factors that constitute metabolism, immunological reactions, and cancer with a focus on mechanistic aspects. Finally, we discussed the possibility of metabolic interventions at multiple levels to enhance the efficacy of immunotherapeutic and conventional approaches for future anticancer treatments.

Abstract Preoperative staging of suspicious axillary lymph nodes (ALNs) allows patients to be triaged to ALN dissection or to sentinel lymph node biopsy (SLNB). Ultrasound-guided fine needle aspiration (FNA) and cytology of ALN is moderately sensitive but its clinical utility relies heavily on the cytologist’s experience. We proposed that the 5-h automated GeneXpert system-based prototype breast cancer detection assay (BCDA) that quantitatively measures DNA methylation in ten tumor-specific gene markers could provide a facile, accurate test for detecting cancer in FNA of enlarged lymph nodes. We validated the assay in ALN-FNA samples from a prospective study of patients (N = 230) undergoing SLNB. In a blinded analysis of 218 evaluable LN-FNAs from 108 malignant and 110 benign LNs by histology, BCDA displayed a sensitivity of 90.7% and specificity of 99.1%, achieving an area under the ROC curve, AUC of 0.958 (95% CI: 0.928–0.989; P

Non-fungible token (NFT) based on blockchain is a kind of digital asset ownership recorded on blockchain, which is unique, irreplaceable and indivisible.It has been widely used in collectibles, encrypted artworks and games.Firstly, the concepts, characteristics and development processes of NFT were mainly introduced, and its core elements and typical application fields were analyzes.The problems and risks faced by NFT in the aspects of property right, value, technology and supervision were also pointed out.After that, the related literatures on NFT were reviewed, and the research issues of NFT in value evaluation, transaction mode and pricing were proposed.Finally, the trend of NFT driven digital capitalization was prospected.

Erigeron annuus (L.) Pers. (annual, daisy or tall fleabane) is an annual herb native to North America but has been introduced and naturalized worldwide. In this study, its complete chloroplast (cp) genome was assembled from Illumina sequencing reads. The cp genome is 153,177 bp long with an A + T-biased base composition. It encodes a panel of 113 genes, including 80 protein-coding, 29 tRNA, and four rRNA genes. Nineteen genes are completely or partially duplicated, while 17 genes possess one or two introns. Phylogenetic analysis suggested E. annuus is mostly closely related to Erigeron canadensis L. and that the two genera Conyza and Erigeron are not mutually monophyletic.

Background CC chemokine receptor 9 (CCR9), an organ-specific chemokine receptor, interacts with its exclusive ligand CCL25 to promote tumor proliferation and metastasis. However, the effect of CCR9 on salivary adenoid cystic carcinoma (SACC) malignant behavior remains unknown. This study aimed to investigate the specific molecular mechanism by which CCR9/CCL25 modulates malignant progression in SACC. Methods Immunohistochemistry staining and RT–qPCR analyses were performed to detect the correlation of CCR9 expression and tumor progression-associated markers in SACC. In vitro, SACC cell proliferation and apoptosis were evaluated using Cell Counting Kit-8 and colon formation, and cell migration and invasion were detected by wound healing and transwell assays. Vercirnon was used as an inhibitor of CCR9, and LY294002 was used as an inhibitor of the PI3K/AKT pathway in this study. Western blot and RT–qPCR assays were carried out to measure the downstream factors of the interaction of CCL25 and CCR9. The effect of CCL25 on the development of SACC in vivo was examined by a xenograft tumor model in nude mice following CCL25, Vercirnon and LY294002 treatment. Results CCR9 was highly expressed in SACC compared with adjacent salivary gland tissues, and its level was associated with tumor proliferation and metastases. CCL25 enhanced cell proliferation, migration, and invasion through its interaction with CCR9 and exerted an antiapoptotic effect on SACC cells. Targeting CCR9 via Vercirnon significantly reduced the phosphorylation level of AKT induced by CCL25. CCL25/CCR9 could activate its downstream factors through the PI3K/AKT signaling pathway, such as cyclin D1, BCL2 and SLUG, thus promoting SACC cell proliferation, antiapoptosis, invasion and metastasis. The in vivo data from the xenograft mouse models further proved that CCL25 administration promoted malignant tumor progression by activating the PI3K/AKT pathway. Conclusion The interaction of CCL25 and CCR9 promotes tumor growth and metastasis in SACC by activating the PI3K/AKT signaling pathway, offering a promising strategy for SACC treatment.

ObjectiveEarly detection of scoliosis is of great significance to patients with scoliosis and the whole society. This paper aims to learn the prevalence of scoliosis screening positive among students in primary and secondary schools and to explore the influencing factors.MethodsIn 2019, a stratified cluster sampling technique was employed in this school-based cross-sectional study. The sampling covers all prefecture-level cities in Zhejiang Province. Based on the whole class, at least 80 students in each grade of primary school, junior high school, and senior high school were selected. Physical examination and scoliosis screening were performed in the school-based investigation. The distribution of demographic characteristics and nutritional status of children and adolescents with scoliosis screening positive were explored.ResultsA total of 45,547 students were screened. The overall prevalence of children and adolescents with scoliosis screening positive were 3.9%. Higher prevalence of scoliosis screening positive was found in students living in urban area (4.1%), women students (4.1%), students with low weight (5.3%) (p < 0.05), and the prevalence increased with age (p < 0.05). In logistic analysis, we found age (OR = 1.145; 95% Cis: 1.128, 1.162), gender (OR = 1.118; 95% Cis: 1.016, 1.230) and low weight (OR = 1.48; 95% Cis: 1.25, 1.751) were the influencing factors for prevalence of scoliosis screening positive (p < 0.05).ConclusionsThere were no disparities between living areas, but there was a significant difference between genders, among different ages, and among different nutritional statuses of children and adolescents with or without scoliosis screening positive. In multi-analysis, age, gender, and low weight were the influencing factors for the prevalence of scoliosis screening positive. Age and gender-specific scoliosis screening strategies and nutritional public health policies for children and adolescents are needed.

Abstract Cancer-associated adipocytes (CAAs), as a main component of the tumor-adipose microenvironment (TAME), have various functions, including remodeling the extracellular matrix and interacting with tumor cells or infiltrated leukocytes through a variety of mutual signals. Here, we summarize the primary interplay among CAAs, the immune response and cancer with a focus on the mechanistic aspects of these relationships. Finally, unifying our understanding of CAAs with the immune cell function may be an effective method to enhance the efficacy of immunotherapeutic and conventional treatments.

Abstract Aims The purpose of this study was to examine the reported ritual practices (dealing with the deceased's remains, wake, funeral, burial and celebration) of White non‐Hispanic, Black non‐Hispanic and Hispanic/Latino adults in their country of origin or ethnic or cultural group in the United States following the death of a loved one. Design This descriptive study is a secondary analysis from a longitudinal mixed‐methods study that examined parents' health and functioning following the death of a child. Methods Adult parents whose child died in neonatal intensive care units or paediatric intensive care units were recruited from four hospitals and from death records. Data were collected from 61 adult parents at 7 and 13 months postinfant/child death using semi‐structured interviews about the child's death. Only those parents who responded to questions about usual death practices in their country of origin or cultural group were included in the data analysis. Results Thirty‐two adults from 14 countries reported practices in their country or cultural group after a loved one's death including keeping the front door closed, walking funeral processions with a band playing, the deceased in a car accompanied by family and friends, fireworks, making home altars for deceased spirits with food and water for adults, toys and candy for children and no TV or radio for sometime. Relevance to clinical practice For community health nurses, understanding these practices is important in being sensitive and appropriate around the death. Asking the family about specific practices they hope to carry out and noting this in the family's record will help alert providers to the family's wishes at this challenging time.

Breast cancer susceptibility gene 1 (BRCA1) is a tumor suppressor gene, which is mainly involved in the repair of DNA damage, cell cycle regulation, maintenance of genome stability, and other important physiological processes. Mutations or defects in the BRCA1 gene significantly increase the risk of breast, ovarian, prostate, and other cancers in carriers. In this review, we summarized the molecular functions and regulation of BRCA1 and discussed recent insights into the detection and treatment of BRCA1 mutated breast cancer.

Abstract Background Starch in the lotus seed contains a high proportion of amylose, which endows lotus seed a promising property in the development of hypoglycemic and low-glycemic index functional food. Currently, improving starch content is one of the major goals for seed-lotus breeding. ADP-glucose pyrophosphorylase (AGPase) plays an essential role in regulating starch biosynthesis in plants, but little is known about its characterization in lotus. Results We describe the nutritional compositions of lotus seed among 30 varieties with starch as a major component. Comparative transcriptome analysis showed that AGPase genes were differentially expressed in two varieties (CA and JX) with significant different starch content. Seven putative AGPase genes were identified in the lotus genome (Nelumbo nucifera Gaertn.), which could be grouped into two subfamilies. Selective pressure analysis indicated that purifying selection acted as a vital force in the evolution of AGPase genes. Expression analysis revealed that lotus AGPase genes have varying expression patterns, with NnAGPL2a and NnAGPS1a as the most predominantly expressed, especially in seed and rhizome. NnAGPL2a and NnAGPS1a were co-expressed with a number of starch and sucrose metabolism pathway related genes, and their expressions were accompanied by increased AGPase activity and starch content in lotus seed. Conclusions Seven AGPase genes were characterized in lotus, with NnAGPL2a and NnAGPS1a, as the key genes involved in starch biosynthesis in lotus seed. These results considerably extend our understanding on lotus AGPase genes and provide theoretical basis for breeding new lotus varieties with high-starch content.