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Abstract RNA degradation using ribonuclease targeting chimeras (RiboTACs) is a promising approach for cancer therapy. However, potential off-target degradation is a serious issue. Here, a RiboTAC is designed for tumor microenvironment triggered activation. The tumor microenvironment activated RiboTAC (TaRiboTAC) incorporates two pre-miR-21 binders, a near-infrared fluorophore IR780, an RGD targeting peptide and a phenylboronic acid caged ribonuclease recruiter. The caged ribonuclease recruiter is embedded in the molecule and exposed in acidic pH, the phenylboronic acid cage is removed by H2O2 making the TaRiboTAC responsive to the acidic and high H2O2 levels in the tumor microenvironment. It is shown the TaRiboTAC targets tumor tissue and degrades pre-miR-21. The degradation of pre-miR-21 by TaRiboTACs significantly increases the radiotherapeutic susceptibility of cancer cells achieving efficient suppression of human lung adenocarcinoma A549 tumors in living mice.

ABSTRACT Background The optimal exercise regimen for alleviating sarcopenia remains uncertain. This study aimed to investigate the efficacy of high‐intensity interval training (HIIT) over moderate‐intensity continuous training (MICT) in ameliorating sarcopenia. Methods We conducted a randomized crossover trial to evaluate plasma proteomic reactions to acute HIIT (four 4‐min high‐intensity intervals at 70% maximal capacity alternating with 4 min at 30%) versus MICT (constant 50% maximal capacity) in inactive adults. We explored the relationship between a HIIT‐specific protein relative to MICT, identified via comparative proteomic analysis, eukaryotic translation elongation factor 1 epsilon 1 (EEF1E1) and sarcopenia in a paired case–control study of elderly individuals (aged over 65). Young (3 months old) and aged (20 months old) mice were randomized to sedentary, HIIT and MICT groups (five sessions/week for 4 weeks; n = 8 for each group). Measurements included skeletal muscle index, hand grip strength, expression of atrophic markers Atrogin1 and MuRF1 and differentiation markers MyoD, myogenin and MyHC‐II via western blotting. We examined the impact of EEF1E1 siRNA and recombinant protein on D‐galactose‐induced myoblast senescence, measuring senescence‐associated β‐galactosidase and markers like p21 and p53. Results The crossover trial, including 10 sedentary adults (32 years old, IQR 31–32) demonstrated significant alterations in the abundance of 21 plasma proteins after HIIT compared with MICT. In the paired case–control study of 84 older adults (84 years old, IQR 69–81; 52% female), EEF1E1 was significantly increased in those with sarcopenia compared to those without (14.68 [95%CI, 2.02–27.34] pg/mL, p = 0.03) and was associated with skeletal muscle index (R2 = 0.51, p

Abstract Background Determining the optimal timing of surgical intervention for Neonatal necrotizing enterocolitis (NEC) poses significant challenges. This study develops a predictive model using the long short-term memory network (LSTM) with a focal loss (FL) to identify infants at risk of developing Bell IIB + NEC early and issue timely surgical warnings. Methods Data from 791 neonates diagnosed with NEC are gathered from the Neonatal Intensive Care Unit (NICU), encompassing 35 selected features. Infants are categorized into those requiring surgical intervention (n = 257) and those managed medically (n = 534) based on the Mod-Bell criteria. A fivefold cross-validation approach is employed for training and testing. The LSTM algorithm is utilized to capture and utilize temporal relationships in the dataset, with FL employed as a loss function to address class imbalance. Model performance metrics include precision, recall, F1 score, and average precision (AP). Results The model tested on a real dataset demonstrated high performance. Predicting surgical risk 1 day in advance achieved precision (0.913 ± 0.034), recall (0.841 ± 0.053), F1 score (0.874 ± 0.029), and AP (0.917 ± 0.025). The 2-days-in-advance predictions yielded (0.905 ± 0.036), recall (0.815 ± 0.057), F1 score (0.857 ± 0.035), and AP (0.905 ± 0.029). Conclusion The LSTM model with FL exhibits high precision and recall in forecasting the need for surgical intervention 1 or 2 days ahead. This predictive capability holds promise for enhancing infants’ outcomes by facilitating timely clinical decisions.

Objective: To investigate the diagnosis and treatment of T lymphoblastic lymphoma (T-LBL) progressing into acute monocytic leukemia (AML-M5b) and explore possible pathogenic mechanisms. Methods: Comprehensive diagnosis and evaluation of the patient's disease status were conducted through lymph node biopsy, bone marrow aspiration and biopsy, PET/CT, immunohistochemistry, flow cytometry, fusion gene detection, and whole-exome sequencing (WES) based on the clinical manifestations at different stages. Results: The lymph node biopsy revealed Ki67 positivity at 80 % and expression of TDT, CD4, CD8, CD3, and CD5. The PET/CT scan showed increased FDG metabolism at multiple sites. Based on relevant tests and examination results, the patient was diagnosed with T-LBL (stage IV; IPI score, 3). After three cycles of chemotherapy, abnormal immature monocytes were detected using bone marrow flow cytometry, suggesting an acute progression from T-LBL to AML-M5b. Chromosomal karyotype analysis revealed t(9; 11)(p22; q23) and the MLL-AF9 fusion gene. WES analysis identified mutations in several genes, among which mutations in SET domain-containing protein 2 and CBL may be associated with the occurrence of acute myeloid leukemia. The patient died 1 month after AML-M5b diagnosis. Conclusion: Patients with T-LBL progression to AML have a poor prognosis and shorter overall survival. Hence, exploring the pathogenic mechanisms and reasons for disease progression has significant implications for finding effective treatment modalities and prolonging patient survival.

Background: Plants of the genus Orthosiphon (Lamiaceae) have been widely employed in traditional and ethnic medicines for the treatment of various diseases, including diabetes, kidney stones, edema, rheumatism, hepatitis, hypertension, and urinary tract disorders. Purpose: This review summarized the research progresses in botany, traditional uses, phytochemistry, and pharmacological activities on plants of the genus Orthosiphon. Additionally, this review described the shortcomings of studies on these species, thus serving as the basis of further researches and development of these traditional herbal medicines. Method: Orthosiphon-related information was collected from the online databases, such as Google Scholar, SciFinder, Web of Science, Elsevier, PubMed and China Knowledge Resource Integrated (CNKI). Results: Plants of the genus Orthosiphon are widely distributed in African, Australia, South Asian, and Southeast Asian, and in China. Phytochemical investigations on Orthosiphon species have revealed the presence of various compounds, mainly including phenolic acids, flavonoids, diterpenoids, triterpenoids, sesquiterpenoids, and chromenes. Previous reports have demonstrated the diverse pharmacological properties of extracts and constituents derived from Orthosiphon, such as anti-cancer, anti-diabetic, anti-inflammatory, antioxidant, hepatoprotective, analgesic, and nephroprotective effects. However, previous researches on this genus were somewhat limited and skewed towards a few species, with a particular emphasis on O. aristatus, O. wulfenioides, O. thymiflorus and O. rubicundus (D. Don) Benth, which might be attributed to the ethnopharmacological background, geographical constraints, and the distribution of these species. In the future, more investigations on other species of the genus Orthosiphon are needed. Conclusion: This study provided a comprehensive overview of the ethnopharmacological, phytochemical, and pharmacological progresses related to the genus of Orthosiphon. Despite substantial bias in attention among various species of the genus Orthosiphon, its potential as health food and therapeutic agents is evident. The genus is an underexplored source of bioactive compounds with potential in various therapeutic areas. This review laid the groundwork for further investigation and development of these traditional herbal remedies.

Today, cancer has become one of the leading global tragedies. It occurs when a small number of cells in the body mutate, causing some of them to evade the body’s immune system and proliferate uncontrollably. Even more irritating is the fact that patients with cancers frequently relapse after conventional chemotherapy and radiotherapy, leading to additional suffering. Scientists thereby presume that cancer stem cells (CSCs) are the underlying cause of metastasis and recurrence. In recent years, it was shown that not only can chemotherapy and radiotherapy underperform in the treatment of breast cancer, but they can also increase the number of breast cancer stem cells (BCSCs) that transform regular breast cancer cells into their own population. Such data somewhat support the aforementioned hypothesis. Meanwhile, our understanding of the extracellular matrix (ECM) has changed considerably over the last decade. A lot of studies have bit by bit complemented human knowledge regarding how the ECM greatly shapes the behaviors of BCSCs. In this review, we highlighted the influence on BCSCs exerted by different critical components and biochemical properties of ECM.

Abstract COVID-19 associated pulmonary aspergillosis (CAPA) had been reported, and raised concern about this secondary infection due to the high mortality. This study aimed to investigate the risk factors for CAPA. The enrolled 114 COVID-19 patients were further divided into CAPA group and non-CAPA group. Demographic characteristics, underlying diseases, laboratory parameters and therapeutic schedule between the two groups were compared to identify the independent risk factors for CAPA by univariate analysis and multivariable logistic regression analysis. Sensitivity and specificity of independent risk factors were confirmed by receiver operating characteristic (ROC) curve analysis. Univariate analysis showed that renal transplant, IL-6 and CRP levels, decreased CD4 + T cell and CD8 + T cell, duration of antibiotics therapy, and prolonged mechanical ventilation were risk factors for development of CAPA. These factors were further analyzed by multivariable logistic regression analysis and the results indicated that elevated IL-6 level, decreased CD4 + T cell and prolonged mechanical ventilation could be recognized as independent risk factors for CAPA in COVID-19 patients. Identification of these risk factors is essential to initiate antifungal therapy as soon as possible to improve outcome of patients with CAPA.

Abstract Background Cervical cancer, encompassing squamous cell carcinoma and endocervical adenocarcinoma (CESC), presents a considerable risk to the well-being of women. Recent studies have reported that squalene epoxidase (SQLE) is overexpressed in several cancers, which contributes to cancer development. Methods RNA sequencing data for SQLE were obtained from The Cancer Genome Atlas. In vitro experiments, including colorimetry, colony formation, Transwell, RT-qPCR, and Western blotting were performed. Furthermore, a transplanted CESC nude mouse model was constructed to validate the tumorigenic activity of SQLE in vivo. Associations among the SQLE expression profiles, differentially expressed genes (DEGs), immune infiltration, and chemosensitivity were examined. The prognostic value of genetic changes and DNA methylation in SQLE were also assessed. Results SQLE mRNA expression was significantly increased in CESC. ROC analysis revealed the strong diagnostic ability of SQLE toward CESC. Patients with high SQLE expression experienced shorter overall survival. The promotional effects of SQLE on cancer cell proliferation, metastasis, cholesterol synthesis, and EMT were emphasized. DEGs functional enrichment analysis revealed the signaling pathways and biological processes. Notably, a connection existed between the SQLE expression and the presence of immune cells as well as the activation of immune checkpoints. Increased SQLE expressions exhibited increased chemotherapeutic responses. SQLE methylation status was significantly associated with CESC prognosis. Conclusion SQLE significantly affects CESC prognosis, malignant behavior, cholesterol synthesis, EMT, and immune infiltration; thereby offering diagnostic and indicator roles in CESC. Thus, SQLE can be a novel therapeutic target in CESC treatment.

Abstract People affected by psychotic, depressive and developmental disorders are at a higher risk for alcohol and tobacco use. However, the further associations between alcohol/tobacco use and symptoms/cognition in these disorders remain unexplored. We identified multimodal brain networks involving alcohol use (n = 707) and tobacco use (n = 281) via supervised multimodal fusion and evaluated if these networks affected symptoms and cognition in people with psychotic (schizophrenia/schizoaffective disorder/bipolar, n = 178/134/143), depressive (major depressive disorder, n = 260) and developmental (autism spectrum disorder/attention deficit hyperactivity disorder, n = 421/346) disorders. Alcohol and tobacco use scores were used as references to guide functional and structural imaging fusion to identify alcohol/tobacco use associated multimodal patterns. Correlation analyses between the extracted brain features and symptoms or cognition were performed to evaluate the relationships between alcohol/tobacco use with symptoms/cognition in 6 psychiatric disorders. Results showed that (1) the default mode network (DMN) and salience network (SN) were associated with alcohol use, whereas the DMN and fronto-limbic network (FLN) were associated with tobacco use; (2) the DMN and fronto-basal ganglia (FBG) related to alcohol/tobacco use were correlated with symptom and cognition in psychosis; (3) the middle temporal cortex related to alcohol/tobacco use was associated with cognition in depression; (4) the DMN related to alcohol/tobacco use was related to symptom, whereas the SN and limbic system (LB) were related to cognition in developmental disorders. In summary, alcohol and tobacco use were associated with structural and functional abnormalities in DMN, SN and FLN and had significant associations with cognition and symptoms in psychotic, depressive and developmental disorders likely via different brain networks. Further understanding of these relationships may assist clinicians in the development of future approaches to improve symptoms and cognition among psychotic, depressive and developmental disorders.

Abstract Objective Patients with Postherpetic Neuralgia (PHN) often exhibit depressive-like symptoms, significantly impacting their quality of life. Esketamine, known for its analgesic properties, has also been recognized for its rapid antidepressant effects. However, its efficacy in the treatment of PHN requires further exploration. This study aims to evaluate the impact of intravenous patient-controlled analgesia(PICA) with esketamine on depressive mood in PHN patients. Methods This retrospective study analyzed PHN patients hospitalized and treated at the affiliated hospital of Southwest Medical University from June 2021 to March 2023. Patients were divided into the esketamine group (E group) and the sufentanil group (S group) based on their treatment regimens. Primary outcomes included pain numerical rating scale(NRS), depression patient health questionaire-9(PHQ-9), and anxiety generalized anxiety disorder-7(GAD-7) scores measured before treatment, and at 3 days, 7 days, 1 month, 2 months, and 3 months post-treatment. Results A total of 83 patients were included in the analysis. Before treatment, there were no statistically significant differences in pain NRS, depression PHQ-9, and anxiety GAD-7 scores between the two groups (P > 0.05). Compared to before treatment, significant reductions in pain NRS scores were observed at all post-treatment time points in both groups (P 0.05). The E group exhibited significantly lower depression PHQ-9 scores than the S group at 3 days and 7 days post-treatment (P 0.05). Anxiety GAD-7 scores were significantly lower in the E group compared to the S group at 3 days, 7 days post-treatment (P 0.05). Conclusion Both PICA with esketamine and sufentanil alleviated pain equally in PHN patients. However, PICA with esketamine specifically improved early symptoms of anxiety and depression.

The benefits of urban green spaces for human beings have become increasingly evident amid global urbanisation, which has exacerbated health issues. However, the effects of different characteristics of urban green spaces, such as vegetation structure, species and colour, on human health and well-being remain poorly understood. This study addressed this gap using a mixed design (between-subjects and within-subjects) and a 2 × 2 × 2 factorial design to combine structural diversity, species richness and colour diversity of vegetation. Participants experienced virtual scenes created on Mars to assess preference and perceived restoration. Through analysis of variance (ANOVA), beneficial features of urban green space and formulated equations using a linear regression model to explain the joint effects of these characteristics were identified. Results indicate that rich structure, species and colours of vegetation significantly enhance preferences and perceived restoration, with colour having the greatest impact ─ 2.55 times greater than structural diversity and species richness. However, the superposition of multiple features does not mean ‘the more the merrier’, as binary and ternary interactions can have synergistic and erosive roles. Therefore, medium complexity is most beneficial for improving health and well-being. Overall, urban green space construction should consider multiple dimensions for a harmonious relationship between humans and nature, promoting sustainable development.

The emergence of antimicrobial resistance (AMR) is a principal global health crisis projected to cause 10 million deaths annually worldwide by 2050. While the Gram-negative bacteria Escherichia coli is commonly found as a commensal microbe in the human gut, some strains are dangerously pathogenic, contributing to the highest AMR-associated mortality. Strains of E. coli that can translocate from the gastrointestinal tract to distal sites, called extraintestinal E. coli (ExPEC), are particularly problematic and predominantly afflict women, the elderly, and immunocompromised populations. Despite nearly 40 years of clinical trials, there is still no vaccine against ExPEC. One reason for this is the remarkable diversity in the ExPEC pangenome across pathotypes, clades, and strains, with hundreds of genes associated with pathogenesis including toxins, adhesins, and nutrient acquisition systems. Further, ExPEC is intimately associated with human mucosal surfaces and has evolved creative strategies to avoid the immune system. This review summarizes previous and ongoing preclinical and clinical ExPEC vaccine research efforts to help identify key gaps in knowledge and remaining challenges.

Abstract The efficient co‐production of H2 and CH4 via anaerobic digestion (AD) requires separate stages, as it cannot yet be achieved in one step. Lactic acid bacteria (LAB) (Limosilactobacillus) release H2 and acetate by enhancing hydrolysis, potentially increasing CH4 production with simultaneous H2 accumulation. This study investigated the enhanced effect of one‐step co‐production of H2 and CH4 in AD by LAB and elucidated its enhancement mechanisms. The results showed that 236.3 times increase in H2 production and 7.1 times increase in CH4 production are achieved, resulting in profits of 469.39 USD. Model substrates lignocellulosic straw, sodium acetate, and H2 confirmes LAB work on the hydrolysis stage and subsequent sustainable volatile fatty acid production during the first 6 days of AD. In this stage, the enrichment of Limosilactobacillus carrying bglB and xynB, the glycolysis pathway, and the high activity of protease, acetate kinase, and [FeFe] hydrogenase, jointly achieved rapid acetate and H2 accumulation, driving hydrogenotrophic methanogenesis dominated. From day 7 to 24, with enriched Methanosarcina, and increased methenyltetrahydromethanopterin hydrogenase activity, continuously produced acetate led to the mainly acetoclastic methanogenesis shift from hydrogenotrophic methanogenesis. The power generation capacity of LAB‐enhanced AD is 333.33 times that of China's 24,000 m3 biogas plant.

Colorectal cancer (CRC) has a postoperative recurrence rate of up to 50%. Local treatment at the surgical site offers a new strategy to prevent recurrence, minimizing systemic side effects. However, these treatments often face issues like poor stability, insufficient targeting, and significant local side effects. Research shows glucose starvation can induce disulfidptosis, a novel cell death pathway, in CRC cells, suitable for precise intervention in residual tumor cells postsurgery. This study develops a biocompatible 2D therapeutic platform using amyloid‐like protein nanofilm technology for precise local synergistic intervention in disulfidptosis and photodynamic therapy (PDT) after CRC surgery. The nanofilm boasts excellent drug‐loading capacity, enzyme activity retention, ultrathin dimensions, wet adhesion, and biocompatibility. A model simulating incomplete tumor resection post‐CRC surgery shows that the GCI@nanofilm effectively inhibits recurrence through an enzyme‐catalyzed cascade reaction inducing disulfidptosis and synergizing with PDT. In summary, GCI@nanofilm overcomes multiple challenges in local postsurgical intervention, providing a foundation for precise and efficient treatment of residual tumors.

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV). Previous studies have indicated that SFTS patients have a high mortality rate, which may be related to cytokine storm and immune dysfunction. In our study, we analyzed differences in cytokines and lymphocyte subsets between severe and non-severe SFTS patients, with the aim of identifying predictors of severity. Methods We retrospectively analyzed demographic characteristics, clinical data, cytokine profiles, and lymphocyte subsets from 96 laboratory confirmed SFTS patients between April 2021 and August 2023. Results A total of 96 SFTS patients were enrolled, with a mean age of 65.05 (± 7.92) years old. According to our grouping criteria, 35 (36.5%) of these patients were classified as severe group, while 61 (63.5%) were classified as non-severe group. Univariate analysis revealed that age, interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), interferon-α (IFN-α), CD4 + T cell, and CD8 + T cell counts were risk predictors for the severity of SFTS. Further multivariable logistic regression analysis confirmed age, IL-6 levels, and CD4 + T cell counts as independent predictors of SFTS severity. Conclusions Severe SFTS patients may experience cytokine storms and immune dysfunction. Aging, elevated levels of IL-6, and decreased CD4 + T cell count may serve as independent predictors for the severity of SFTS.

Abstract Two-dimensional materials with ultrahigh in-plane thermal conductivity are ideal for heat spreader applications but cause significant thermal contact resistance in complex interfaces, limiting their use as thermal interface materials. In this study, we present an interfacial phonon bridge strategy to reduce the thermal contact resistance of boron nitride nanosheets-based composites. By using a low-molecular-weight polymer, we are able to manipulate the alignment of boron nitride nanosheets through sequential stacking and cutting, ultimately achieving flexible thin films with a layer of arc-like structure superimposed on perpendicularly aligned ones. Our results suggest that arc-like structure can act as a phonon bridge to lower the contact resistance by 70% through reducing phonon back-reflection and enhancing phonon coupling efficiency at the boundary. The resulting composites exhibit ultralow thermal contact resistance of 0.059 in2 KW−1, demonstrating effective cooling of fast-charging batteries at a thickness 2-5 times thinner than commercial products.

Abstract Background Bioconversion of plant biomass into biofuels and bio-products produces large amounts of lignin. The aromatic biopolymers need to be degraded before being converted into value-added bio-products. Microbes can be environment-friendly and efficiently degrade lignin. Compared to fungi, bacteria have some advantages in lignin degradation, including broad tolerance to pH, temperature, and oxygen and the toolkit for genetic manipulation. Results Our previous study isolated a novel ligninolytic bacterial strain Erwinia billingiae QL-Z3. Under optimized conditions, its rate of lignin degradation was 25.24% at 1.5 g/L lignin as the sole carbon source. Whole genome sequencing revealed 4556 genes in the genome of QL-Z3. Among 4428 protein-coding genes are 139 CAZyme genes, including 54 glycoside hydrolase (GH) and 16 auxiliary activity (AA) genes. In addition, 74 genes encoding extracellular enzymes are potentially involved in lignin degradation. Real-time PCR quantification demonstrated that the expression of potential ligninolytic genes were significantly induced by lignin. 8 knock-out mutants and complementary strains were constructed. Disruption of the gene for ELAC_205 (laccase) as well as EDYP_48 (Dyp-type peroxidase), ESOD_1236 (superoxide dismutase), EDIO_858 (dioxygenase), EMON_3330 (monooxygenase), or EMCAT_3587 (manganese catalase) significantly reduced the lignin-degrading activity of QL-Z3 by 47–69%. Heterologously expressed and purified enzymes further confirmed their role in lignin degradation. Fourier transform infrared spectroscopy (FTIR) results indicated that the lignin structure was damaged, the benzene ring structure and groups of macromolecules were opened, and the chemical bond was broken under the action of six enzymes encoded by genes. The abundant enzymatic metabolic products by EDYP_48, ELAC_205 and ESOD_1236 were systematically analyzed via liquid chromatography–mass spectrometry (LC–MS) analysis, and then provide a speculative pathway for lignin biodegradation. Finally, The activities of ligninolytic enzymes from fermentation supernatant, namely, LiP, MnP and Lac were 367.50 U/L, 839.50 U/L, and 219.00 U/L by orthogonal optimization. Conclusions Our findings provide that QL-Z3 and its enzymes have the potential for industrial application and hold great promise for the bioconversion of lignin into bioproducts in lignin valorization.

Abstract Background The neck management of clinical-nodal negative (cN0) oral squamous cell carcinoma (OSCC) remains controversial. Elective neck dissection (END) and observation are the main strategies, but it is still not clear who could benefit the most from END. The purpose of this study was to clarify the potential clinical factors that affect the therapeutic value of END and to explore the actual characteristics associated with benefit from END. Methods Patients with cN0 OSCC were identified in the SEER database from 2000 to 2019. 5-year Overall survival (OS) and disease-specific survival (DSS) were analyzed using the Kaplan‒Meier method, and the hazard ratios (HRs) for survival were estimated using the Cox regression model. Multiple subgroup analyses of DSS and OS among different factors, comparing END and No END, were performed. Results A total of 17,019 patients with cN0 OSCC were included. The basic survival analysis and Cox regression model showed that END increased the probability of 5-year DSS and OS and was an independent prognostic factor. However, among patients who underwent only primary tumor surgery, no significant differences were found between the END and No END groups in 5-year DSS (P = 0. 585) and OS (P = 0.465). Further subgroup analysis showed that primary sites and T stage, but not other factors, might influence the benefit of END. Significant differences were found for T1 (P

Abstract Abiotic stresses are major factors constraining the growth, development and productivity of tomato (Solanum lycopersicum), the most cultivated vegetable crop worldwide. Uridine diphosphate glycosyltransferases (UDPGTs or UGTs) are essential enzymes that utilize 5-uridine diphosphate as a glycosyl donor molecule to facilitate the catalysis of glycosylation reactions across diverse substrates, thereby playing a pivotal role in conferring abiotic stress tolerance. Currently, there is a limited understanding of the structure and functions of the UDPGT gene family in tomato. In this work, 106 members of the SlUDPGT gene family were identified through in silico analysis, besides, their protein sequence properties, phylogenetic relationships, gene structure, chromosomal distribution, cis-acting elements, tissue expression and hormone- and stress-induced expression were comprehensively investigated. The expression of representative SlUDPGTs under abiotic stress and exogenous hormone treatments, including salt, polyethylene glycol, methyl viologen, gibberellic acid, jasmonic acid, abscisic acid and brassinolide, was investigated through qRT‒PCR analysis. Numerous cis-acting elements linked to stress and hormone signaling were present in the promoter regions of SlUDPGTs. According to microarray data, most SlUDPGT genes were responsive to hormones and abiotic stresses, while certain SlUDPGTs were specifically differentially expressed under Botrytis cinerea and tomato spotted wilt virus infection. Additionally, diverse expression profiles of SlUDPGTs were observed in various tissues and developmental stages. Furthermore, CRISPR/Cas9-mediated knockout of SlUDPGT52 led to enhanced drought tolerance due to enhanced reactive oxygen species (ROS) scavenging. These findings lay the foundations for the future functional characterization of specific UDPGT gene family members, assisting the biotechnology-mediated improvement of tomato and other horticultural crops.

Highlights A core-sheath structured coaxial composite fiber with highly aligned and densely stacked boron nitride nanosheets arrangements in the sheath was successfully fabricated. The coaxial fibers have an ultrahigh axial Herman orientation parameter of 0.81, thermal conductivity of 17.2 W m−1 K−1, and tensile strength of 192.5 MPa. The coaxial fibers exhibit intensively potential applications in the wearable thermal management textile.

Urban green space serves as an important restorative environment for alleviating the physiological and psychological stress of residents, results which are primarily achieved through visual perception. However, air pollution results in decreased visibility, affects visual perception, and thus redues the positive effects of the experience of using the green space environment.There is a limited number of related studies. Therefore, based on the Stress Reduction Theory (SRT), this study constructed 12 groups of green space environments with different degrees of visibility and compared the physiological (SCL, α-EEG / β-EEG) and psychological (TMD) restorative effects of the participants in different environments by using photo elicitation. Combined with the perception and preference of green space, the impact of air pollution on the restoration received from the environment was explored. The results show that: (1) Visibility and green space type can affect the level of green space recovery. When the visibility is poor, the semi-open and semi-closed green spaces resulted in the best recovery; (2) When the visibility is reduced, the participants' perception of the eight types of Perceived Sensory Dimensions (PSDs) is generally reduced, and the type of green space is related to the perception of air quality; (3) As visibility decreased, participants' preference for green spaces significantly decreased; and (4) Visibility will affect green space perception and preference, thus affecting its recovery. This study provides a basis and reference for the design and construction of a higher quality restorative green space environment to effectively account for air pollution problems.

BackgroundMetagenomic next-generation sequencing (mNGS) is a novel non-invasive and comprehensive technique for etiological diagnosis of infectious diseases. However, its practical significance has been seldom reported in the context of hematological patients with high-risk febrile neutropenia, a unique patient group characterized by neutropenia and compromised immune responses.MethodsThis retrospective study evaluated the results of plasma cfDNA sequencing in 164 hematological patients with high-risk febrile neutropenia. We assessed the diagnostic efficacy and clinical impact of mNGS, comparing it with conventional microbiological tests.ResultsmNGS identified 68 different pathogens in 111 patients, whereas conventional methods detected only 17 pathogen types in 36 patients. mNGS exhibited a significantly higher positive detection rate than conventional methods (67.7% vs. 22.0%, P < 0.001). This improvement was consistent across bacterial (30.5% vs. 9.1%), fungal (19.5% vs. 4.3%), and viral (37.2% vs. 9.1%) infections (P < 0.001 for all comparisons). The anti-infective treatment strategies were adjusted for 51.2% (84/164) of the patients based on the mNGS results.ConclusionsmNGS of plasma cfDNA offers substantial promise for the early detection of pathogens and the timely optimization of anti-infective therapies in hematological patients with high-risk febrile neutropenia.

Abstract Background Cervical cancer is and will remain to be an important health problem in China, especially with an increasing proportion of younger patients who has more specific needs. In China, surgery to remove tumor burden followed by postoperative treatment with radiotherapy and chemotherapy based on clinicopathologic factors may be the best choice for stages IB3 and IIA2 patients. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology. The current trial is designed to evaluate whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stages IB3 and IIA2) patient survival under stringent operation standards and consistent surgical oncologic principles. This paper reports the rationale, design, and implementation of the trial. Methods/design This is an investigator-initiated, prospective, randomized, open, blinded endpoint (PROBE) controlled trial. A total of 1104 patients with stage IB3 and IIA2 cervical cancer will be enrolled over a period of 3 years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed up for at least 5 years. The primary end point will be 5-year overall survival, and secondary endpoints include 5-year progression-free survival, recurrence, and quality of life measurements. Discussion The study results will provide more convincing evidence-based information for stages IB3 and IIA2 cervical cancer patients and their gynecologic cancer surgeons in their choice of surgical method. Trial registration ClinicalTrials.gov, NCT04939831 , retrospectively registered on 25 June 2021.

Abstract Switching to normal diet (ND) is the regular therapy for high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD). Intermittent fasting (IF) is a unique treatment which may exhibits better therapeutic efficacy. Thus, we aim to investigate the therapeutic effects of these treatments and exploring the mechanisms. In the present study, NAFLD mouse model was induced by a 10-week HFD. Thereafter, mice adopted continued HFD, ND, or IF for the next 12 weeks. Finally, the liver was then harvested to assess lipid deposition, lipid metabolism, apoptosis, and autophagy, while blood was collected to determine blood glucose and insulin. The results showed that IF and ND treatment improved lipid deposition and metabolic disorder of NAFLD mice; the increasing body weight, liver weight, and HOMA-IR index of HFD mice were also alleviated by IF and ND. Furthermore, IF and ND treatment activated the macrophage migration inhibitory factor (MIF)/AMPK pathway and regulated its downstream autophagy and apoptosis. However, the efficacy of IF was better than ND. Both IF and ND activates MIF signaling and alleviate the lipotoxicity of NAFLD while IF therapy is more effective than ND. The different MIF up-regulation might be the underlying mechanism of why IF benefits more than ND.

Abstract Background Nutcracker syndrome (NCS) caused by left renal vein (LRV) entrapment, is one of the most common causes of orthostatic proteinuria. In stereotype, orthostatic proteinuria is often accompanied by left renal vein obstruction and is found in young and underweight individuals. Here, we report a rare case with orthostatic proteinuria in an old obese female caused by a rare type of congenital inferior vena cava (IVC) interruption. Case presentation A 65-year-old obese woman, who suffered from fluctuated proteinuria, had been misdiagnosed as chronic glomerulitis for 30 years. Instead of having any sign of NCS, she had a unique type of IVC interruption. Most venous blood from infrarenal IVC and right kidney drained into her LRV, and then through the expanded communicating vessel, drained into the left ascending lumbar vein which extended as hemiazygos vein. To the best of our knowledge, this is one of the first cases reported of orthostatic proteinuria attributed to the subsequent hemodynamic irregularity caused by IVC interruption without nutcracker phenomenon. Conclusion Adult-onset orthostatic proteinuria is relatively rare, hard to be recognized and could be misdiagnosed as chronic glomerulonephritis. The case provided a novel differential diagnostic condition for those who suffered from fluctuated proteinuria of unknown causes.

Traditional cement epoxy pavements suffer from inherent limitations such as terrible tribological properties, poor wear resistance, and weak impact resistance, presenting significant challenges to ensure the safety and continuous operation of urban roads. As a solution, high-performance cement epoxy composite grouting materials have emerged as the preferred option for engineering construction and road maintenance. In this study, CSP/epoxy cement (CSEC) composite materials were prepared by emulsion polymerization. The thermal properties of the materials were characterized, revealing that CSP enhances the thermal properties of epoxy cement (EC) to a certain extent. Furthermore, the frictional properties of CSEC composite materials and pure epoxy cement under different normal loads were investigated. The results indicated that the CSEC composite material exhibited a slight increase in friction coefficient and a notable decrease in wear rate compared to pure epoxy cement (EC). Specifically, the wear rate of CSEC decreased by 14.4% at a load of 20 N, highlighting the enhanced frictional performance facilitated by CSP. Mechanistic analysis attributed the improvement to the unique core-shell structure of CSP, which imparted higher impact resistance and eliminated alleviate residual stresses at the friction interface. This structural advantage further enhanced the wear resistance of materials, making it a promising choice for improving the durability and safety of urban road surfaces.

The over-utilizing of nitrogen fertilizers in paddy wetlands potentially threatens to the surrounding waterbody, and a deep understanding of the community and function of microorganisms is crucial for paddy non-point source pollution control. In this study, top soil samples (0–15 cm) of paddy wetlands under groundwater's irrigation at different depths (H1: 6.8 m, H2: 13.7 m, H3: 14.8 m, H4: 15.6 m, H5: 17.0 m, and H6: 17.8 m) were collected to investigate microbial community and function differences and their interrelation with soil properties. Results suggested some soil factor differences for groundwater's irrigation at different depths. Deep-groundwater's irrigation (H2-H6) was beneficial to the accumulation of various electron acceptors. Nitrifying-bacteria Ellin6067 had high abundance under deep groundwater irrigation, which was consistent with its diverse metabolic capacity. Meanwhile, denitrifying bacteria had diverse distribution patterns. Iron-reducing bacteria Geobacter was abundant in H1, and Anaeromyxobacter was abundant under deep groundwater irrigation; both species could participate in Fe-anammox. Furthermore, Geobacter could perform dissimilatory nitrate reduction to ammonia using divalent iron and provide substrate supply for anammox. Intrasporangium and norank_f_Gemmatimonadacea had good chromium- and vanadium-reducting potentials and could promote the occurrence of anammox. Low abundances of methanotrophs Methylocystis and norank_f_Methyloligellaceae were associated with the relatively anoxic environment of paddy wetlands, and the presence of aerobic methane oxidation was favorable for in-situ methane abatement. Moisture, pH, and TP had crucial effects on microbial community under phylum- and genus-levels. Microorganisms under shallow groundwater irrigation were highly sensitive to environmental changes, and Fe-anammox, nitrification, and methane oxidation were favorable under deep groundwater irrigation. This study highlights the importance of comprehensively revealing the microbial community and function of paddy wetlands under groundwater's irrigation and reveals the underlying function of indigenous microorganisms in agricultural non-point pollution control and greenhouse gas abatement.

BackgroundChimeric antigen receptor T (CAR-T) cell immunotherapy is becoming one of the most promising treatments for hematological malignancies, however, complications such as cytokine release syndrome (CRS) seriously threaten the lives of patients. Interleukin 6(IL-6) monoclonal antibody is the common and useful treatment of CRS, however, it is not clear whether prophylactic use IL-6 monoclonal antibody before CAR-T therapy can reduce the incidence of CRS.PurposeThis study aims to systematically evaluate whether the prophylactic use of IL-6 monoclonal antibody can reduce the incidence of CRS.Data sources and methodsWe searched the PubMed, Embase, web of Science, and Cochrane Library databases for studies that reported the prophylactic use of IL-6 monoclonal antibody in the treatment of CRS-related complications of CAR-T cell immunotherapy before December 2022. The literature is screened according to the established inclusion and exclusion criteria, relevant data are extracted, and the quality of the literature is evaluated using the scale Cochrane bias risk assessment tool, and the Review Manager 5.3 is used to draw for related charts. Since the two experimental data only provide the median, the maximum and minimum values of the data, the mean and standard (Standard Deviation, SD) are calculated by this document Delai, and finally use Review Manager for data processing, and STATA software for supplementation.ResultsA total of 2 trials with a total of 37 participants were included in this study. Meta-analysis showed that compared with no use of IL-6 monoclonal antibody to prevent CRS, IL-6 monoclonal antibody was given to patients at 8 mg/kg one hour before CAR-T cell infusion, which reduced the incidence of CRS [RR: 0.41 95% confidence interval (0.20, 0.86) I[2] = 0.0% P = 0.338 z = −2.369 (p = 0.018)]. In subgroup analysis, compared with those who did not use IL-6 monoclonal antibody to prevent CRS, IL-6 monoclonal antibody was given to patients at 8 mg/kg one hour before CAR-T cell infusion, which reduced lactate dehydrogenase (LDH)[MD: −617.21, 95% confidence interval (−1104.41, −130.01) I[2] = 0% P = 0.88 Z = 2.48 (P = 0.01)], prophylactic use of IL-6 monoclonal antibody has a significant effect on reducing peak C-reactive protein (CRP) after CAR-T therapy [MD: −11.58, 95% confidence interval (−15.28, −7.88) I[2] = 0.0% P = 0.73 z = 6.14 (p < 0.00001)].ConclusionThe prophylactic use of IL-6 monoclonal antibody can significantly reduce the incidence of CRS complications after CAR-T therapy, can also reduce LDH vaule and peak CRP vaule after CAR-T therapy.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023487662, identifier CRD42023487662.

There are abundant tight sandstone gas resources in the Sichuan Basin, which are the important objects of reserve and production increase and large-scale development. Due to their discontinuous sandbody distribution, narrow channels, and strong horizontal and vertical heterogeneity, however, conventional fracturing technologies cannot achieve the ideal stimulation effect here. In order to address this difficulty, this paper dissects the geology engineering characteristics of tight sandstone gas reservoirs in the western Sichuan Basin. Starting from the seepage mechanics theory, the concept of “multi-scale high-density” tight gas fracturing technology is put forward by fully referring to the experience of previous multi-round reservoir stimulation in the western Sichuan Basin and the idea of unconventional volume fracturing technology. In addition, its conceptual connotation, key technologies and implementation effects are illustrated. The following research results are obtained. First, the seepage characteristics make it necessary for the efficient production of tight gas reserves to increase fracture density and stimulated reservoir volume (SRV). Second, the “multi-scale high-density” fracturing technology emphasizes the rationality of high-density hydraulic fracture creation and the matching of multi-scale fracture flow capacity, and aims at establishing a multi-level fracture system with effective and steady gas flow in tight reservoirs through fracturing. Third, the “wide, dense, support, stable, and precise” fracturing technology is applied to improve single well production and estimated ultimate recovery (EUR). Fourth, the engineering practice of “multi-scale high-density” fracturing technology in the tight reservoirs of Jurassic Shaximiao Formation and Triassic Xujiahe Formation in the ZJ Gas Field realizes the average single well production rate of 15.6 × 104 m3/d, which is 1.96 times higher than that before the stimulation. Obviously, it provides powerful support for the operation of the ZJ Gas Field into a giant gas field with the reserves of 100 billion cubic meters. In conclusion, the formation of the concept and key technologies of “multi-scale high-density” fracturing technology effectively supports the efficient development of tight gas in the western Sichuan Basin and points out the following research direction of tight gas reservoir stimulation. The research results provide reference and guidance for the large-scale benefit development of tight gas in China.

Abstract Background Despite the extensive research on data mining algorithms, there is still a lack of a standard protocol to evaluate the performance of the existing algorithms. Therefore, the study aims to provide a novel procedure that combines data mining algorithms and simplified preprocessing to establish reference intervals (RIs), with the performance of five algorithms assessed objectively as well. Methods Two data sets were derived from the population undergoing a physical examination. Hoffmann, Bhattacharya, Expectation Maximum (EM), kosmic, and refineR algorithms combined with two-step data preprocessing respectively were implemented in the Test data set to establish RIs for thyroid-related hormones. Algorithm-calculated RIs were compared with the standard RIs calculated from the Reference data set in which reference individuals were selected following strict inclusion and exclusion criteria. Objective assessment of the methods is implemented by the bias ratio (BR) matrix. Results RIs of thyroid-related hormones are established. There is a high consistency between TSH RIs established by the EM algorithm and the standard TSH RIs (BR = 0.063), although EM algorithms seems to perform poor on other hormones. RIs calculated by Hoffmann, Bhattacharya, and refineR methods for free and total triiodo-thyronine, free and total thyroxine respectively are close and match the standard RIs. Conclusion An effective approach for objectively evaluating the performance of the algorithm based on the BR matrix is established. EM algorithm combined with simplified preprocessing can handle data with significant skewness, but its performance is limited in other scenarios. The other four algorithms perform well for data with Gaussian or near-Gaussian distribution. Using the appropriate algorithm based on the data distribution characteristics is recommended.

Abstract Background Regular sleep is very important for human health; however, the short-term and long-term effects of nightshift with sleep deprivation and disturbance on human metabolism, such as oxidative stress, have not been effectively evaluated based on a realistic cohort. We conducted the first long-term follow-up cohort study to evaluate the effect of nightshift work on DNA damage. Methods We recruited 16 healthy volunteers (aged 33 ± 5 years) working night shifts at the Department of Laboratory Medicine at a local hospital. Their matched serum and urine samples were collected at four time points: before, during (twice), and after the nightshift period. The levels of 8-oxo-7,8-dihydroguanosine (8-oxoG) and 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG), two important nucleic-acid damage markers, were accurately determined based on a robust self-established LC‒MS/MS method. The Mann–Whitney U or Kruskal–Wallis test was used for comparisons, and Pearson’s or Spearman’s correlation analysis was used to calculate the correlation coefficients. Results The levels of serum 8-oxodG, estimated glomerular filtration rate-corrected serum 8-oxodG, and the serum-to-urine 8-oxodG ratio significantly increased during the nightshift period. These levels were significantly higher than pre-nightshift work level even after 1 month of discontinuation, but no such significant change was found for 8-oxoG. Moreover, 8-oxoG and 8-oxodG levels were significantly positively associated with many routine biomarkers, such as total bilirubin and urea levels, and significantly negatively associated with serum lipids, such as total cholesterol levels. Conclusion The results of our cohort study suggested that working night shifts may increase oxidative DNA damage even after a month of discontinuing nightshift work. Further studies with large-scale cohorts, different nightshift modes, and longer follow-up times are needed to clarify the short- and long-term effects of night shifts on DNA damage and find effective solutions to combat the negative effects.

Abstract Introduction Adoptive cellular therapy with tumor‐infiltrating lymphocytes (TIL) has demonstrated promising clinical benefits in several solid tumors, but the efficacy of this therapy might be compromised by the “prone‐to‐exhaustion” phenotype of TIL and poor persistence in vivo. This calls for a robust expansion process to produce a large number of cells for clinical usage while at the same time maintaining favorable anti‐tumor function and memory phenotype. Previous studies showed that the PI3K‐AKT signaling pathway plays a key role in the regulation of T cell activation, differentiation and memory formation. Method We modulated the PI3K‐AKT pathway in TIL isolated from cervical and ovarian cancer by application of AKT or PI3K inhibitors or CRISPR knockout of AKT1 and/or AKT2, and characterized their effects on TIL phenotype and effector function. Mechanistic study was further performed with RNA‐seq analysis of AKT1/2 KO TIL in comparison to control TIL. Result The inhibition of either PI3K or AKT led to an increase in the population of effector CD8+ T cells with upregulation of activation markers, elevated CD39−CD69− memory T cells, and significantly enhanced cytotoxicity when cocultured with tumor cell lines and patient‐derived tumor samples. Moreover, dual knockout of AKT1 and AKT2 largely phenocopies the functional impact of AKT or PI3K inhibition on TIL. This result was further validated by RNA‐seq analysis indicating that AKT1/2 ablation primarily regulates T cell differentiation and function‐related programs. Conclusion Modulation of PI3K‐AKT signaling represents a promising strategy to enhance TIL stemness and cytotoxicity and improve the clinical outcome of current TIL‐based therapy to treat solid tumors.

Manipulating molecular self-assembly and disassembly in vivo may permit temporal control of drug delivery and release. Here, the authors report a fluorogenic cisplatin prodrug for cancer theranostics by leveraging stimuli-triggered in situ self-assembly and intracellular disassembly processes.

Objectives: Circ_003686 is a novel_circRNA with abnormally low expression found in the samples of multiple myeloma bone disease (MBD) patients. The current research intended to investigate the effects of novel_circ_003686 in osteogenesis-induced differentiation of bone marrow mesenchymal stem cells (BMSCs) in MBD. Methods: BMSCs were extracted from MBD patients and normal participants, the pcDNA3.1 encoding the circ_003686 (ov-circ_003686), miR-142-5p-mimic/inhibitor and siRNA oligonucleotides targeting insulin like growth factor 1 (IGF1, si-IGF1) were applied to intervene circ_003686, miR-142-5p and IGF1 levels, respectively. Results: Results showed that ov-circ_003686 could mediate the osteogenesis-induced differentiation of MBD-BMSC, and luciferase assay and RIP experiments confirmed that circ_003686 could bind to miR-142-5p. MiR-142-5p-inhibitor helped osteogenesis-induced differentiation, while miR-142-5p-mimic inhibited osteogenesis-induced differentiation and reversed the promoting effect of ov-circ_003686, suggesting that circ_003686/miR-142-5p axis participated in osteogenesis-induced differentiation of MBD-BMSC. In addition, miR-142-5p binds to the target gene IGF1 and negatively adjust its expression. Si-IGF1 significantly inhibited the osteogenesis-induced differentiation and reversed the promotion effects of miR-142-5p-inhibitor and ov-circ_003686. Moreover, circ_003686/miR-142-5p/IGF1 axis meaningfully regulates protein expressions in the PI3K/AKT pathway. Conclusion: In conclusion, this research confirmed that circ_003686 regulated the osteogenesis-induced differentiation of MBD-BMSC by sponging miR-142-5p and mediating IGF1, and the PI3K/AKT pathway may also be involved.

ABSTRACTPharmaceutical companies have recently focused on accelerating the timeline for initiating first-in-human (FIH) trials to allow quick assessment of biologic drugs. For example, a stable cell pool can be used to produce materials for the toxicology (Tox) study, reducing time to the clinic by 4–5 months. During the coronavirus disease 2019 (COVID-19) pandemic, the anti-COVID drugs timeline from DNA transfection to the clinical stage was decreased to 6 months using a stable pool to generate a clinical drug substrate (DS) with limited stability, virus clearance, and Tox study package. However, a lean chemistry, manufacturing, and controls (CMC) package raises safety and comparability risks and may leave extra work in the late-stage development and commercialization phase. In addition, whether these accelerated COVID-19 drug development strategies can be applied to non-COVID projects and established as a standard practice in biologics development is uncertain. Here, we present a case study of a novel anti-tumor drug in which application of “fast-to-FIH” approaches in combination with BeiGene’s de-risk strategy achieved successful delivery of a complete CMC package within 10 months. A comprehensive comparability study demonstrated that the DS generated from a stable pool and a single-cell-derived master cell bank were highly comparable with regards to process performance, product quality, and potency. This accomplishment can be a blueprint for non-COVID drug programs that approach the pace of drug development during the pandemic, with no adverse impact on the safety, quality, and late-stage development of biologics.

Within urban green spaces, spontaneous groundcovers, as potential alternatives for traditional lawns, have garnered attention due to their ecological adaptability. However, little attention has been paid to whether spontaneous groundcovers can serve as suitable replacements for lawns in terms of the aesthetic values and human preferences for each. Based on questionnaires accompanied by photo elicitation, this study explored the perceptions of and preferences for seven kinds of lawns and six kinds of spontaneous groundcovers in China. The effects of social backgrounds on people’s perceptions of and preferences for ground covers were also analyzed. The results indicated a general equivalence in preferences for the lawn and spontaneous groundcover. The Taraxacum mongolicum – Cynodon dactylon – Conyza canadensis community was significantly preferred most among all of the selected ground covers. Spontaneous groundcovers were regarded as more natural, wild, variable, and species-richer compared to lawns, while lawns were perceived as better kept than spontaneous groundcovers. Ground covers were preferred which were perceived to have high ecological aesthetic value and low wildness. Industry and attention to herbaceous plants mostly affected human perceptions and preferences among the social background factors, and gender, age, education level, and occupation also had significant effects. The results thus provide the support for the application of spontaneous groundcovers in moderately developed cities, but such application should consider the comprehensive development of ecological aesthetic value and the applicability of different groups of residents.

Background The chronic kidney disease-mineral and bone disorder（CKD-MBD) is known to be associated with increased mortality in dialysis patients, but whether current global guidelines for CKD-MBD, which were primarily developed from hemodialysis, are suitable for peritoneal dialysis (PD) patients practice require further investigation.Methods This is a single-center retrospective cohort study. In total 491 prevalent PD patients (median follow-ups: 34 months) from Peking Union Medical College Hospital (PUMCH) from January 2004 to December 2017 were included and followed until 30 June 2018. In the first dialysis year, the average levels of serum calcium, albumin-corrected calcium (CorCa), phosphorus, and parathyroid hormone (PTH) levels were the interested predictors in Cox proportional regression model.Results Of these PD patients (age 58 ± 17 years), 52% were male and 36% had diabetic nephropathy. In Cox regression over first-year mean parameters, PTH

Despite advances in immunotherapy for the treatment of cancers, not all patients can benefit from programmed cell death ligand 1 (PD-L1) immune checkpoint blockade therapy. Anti-PD-L1 therapeutic effects reportedly correlate with the PD-L1 expression level; hence, accurate detection of PD-L1 expression can guide immunotherapy to achieve better therapeutic effects. Therefore, based on the high affinity antibody Nb109, a new site-specifically radiolabeled tracer, 68Ga-NODA-cysteine, aspartic acid, and valine (CDV)-Nb109, was designed and synthesized to accurately monitor PD-L1 expression. The tracer 68Ga-NODA-CDV-Nb109 was obtained using a site-specific conjugation strategy with a radiochemical yield of about 95% and radiochemical purity of 97%. It showed high affinity for PD-L1 with a dissociation constant of 12.34 ± 1.65 nM. Both the cell uptake assay and positron emission tomography (PET) imaging revealed higher tracer uptake in PD-L1-positive A375-hPD-L1 and U87 tumor cells than in PD-L1-negative A375 tumor cells. Meanwhile, dynamic PET imaging of a NCI-H1299 xenograft indicated that doxorubicin could upregulate PD-L1 expression, allowing timely interventional immunotherapy. In conclusion, this tracer could sensitively and dynamically monitor changes in PD-L1 expression levels in different cancers and help screen patients who can benefit from anti-PD-L1 immunotherapy.

Abstract Background Currently, the direct method is the main approach for establishment of reference interval (RI). However, only a handful of studies have described the effects of sample size on establishment of RI and estimation of sample size. We describe a novel approach for estimation of the sample size when establishing RIs using the transformed parametric and non-parametric methods. Methods A total of 3,697 healthy participants were enrolled in this study. We adopted a two-layer nested loop sample size estimation method to determine the effects of sample size on RI, using thyroid-related hormone as an example. The sample size was selected as the calculation result when the width of the confidence interval (CI) of the upper and lower limit of the RI were both stably

BackgroundDiabetes is prevalent worldwide and is associated with cardiovascular disease (CVD). Furthermore, due to the insulin resistance, diabetic populations are vulnerable to liver fibrosis, which increases the risk of CVD. Fibrosis-4 index (FIB-4)—a non-invasive biomarker for liver fibrosis—is crucial in predicting CVD among patients with liver diseases. However, the association between FIB-4, death, and CVD in the US diabetic population has not yet been investigated.MethodWe conducted a cross-sectional study using the data from the National Health and Nutrition Examination Survey (NHANES) 1999–2008. The mortality status was obtained from the National Death Index through December 31, 2015. Participants were divided into survivor and mortality group to compare the basic characteristics. The association between FIB-4, death, and CVD was analyzed using the restricted cubic spline method and Cox proportional hazards models. In stratified analysis, Participants were stratified based on age, sex, BMI, hypertension, or eGFR respectively.ResultsThe participants (N = 3,471) were divided into survivor (N = 1,785) and mortality groups (N = 1,632), with the mortality group exhibiting significantly higher FIB-4 values. Moreover, the risk of all-cause mortality (HR 1.24; 95% CI, 1.17–1.32) and CVD mortality (HR 1.17; 95% CI, 1.04–1.31) increased with each FIB-4 SD increase after adjusting for all covariates. However, except for myocardial infarction, FIB-4 had no significant effect on the incidence of the other three CVD subtypes (congestive heart failure, coronary heart disease, and angina pectoris). In stratified analysis, we found that the effect of FIB-4 on CVD mortality was influenced by age, and FIB-4 is a risk factor for people older than 60 years (HR 1.14; 95% CI, 1.01–1.29).ConclusionUsing data from NHANES 1999–2008, FIB-4 was found to be associated with all-cause and CVD mortality in the diabetic population, and this association was significantly affected by age. However, FIB-4 only affected the incidence of myocardial infarction. Future work should investigate the association between FIB-4 and CVD in the diabetic population.

ObjectiveOur aim was to analyze the trends and hotspots on glial fibrillary acidic protein (GFAP) within the area of Alzheimer’s disease (AD) by using a bibliometric method, which is currently missing.MethodsAll articles and reviews on GFAP within the area of AD from inception to December 31, 2022, were searched from the Web of Science Core Collection. Full records were derived, imported into Microsoft Excel, and analyzed by BIBLIOMETRC, VOSviewer, and CiteSpace.ResultsIn total, 2,269 publications, including 2,166 articles, were ultimately included. The number of publications from 81 countries/regions and 527 academic journals increased annually. The top three prolific countries and institutions were the USA, China, and England, the University of Gothenburg (Sweden), Federal University of Rio Grande do Sul (Brazil), and UCL Queen Square Institute of Neurology (England). Henrik Zetterberg from the University of Gothenburg, Kaj Blennow from the University of Gothenburg, and Alexei Verkhratsky from the University of Manchester were the top three prolific and cited authors; Journal of Alzheimer’s Disease, Brain Research, and Neuroscience contributed the most publications. The top key areas of research included “molecular, biology, and genetics” and “molecular, biology, and immunology,” and the top published and linked meaningful keywords included oxidative stress, inflammation/neuroinflammation, microglia, hippocampus, amyloid, cognitive impairment, tau, and dysfunction.ConclusionBased on the bibliometric analysis, the number of publications on GFAP within the area of AD has been rapidly increasing, especially in the past several years. Oxidative stress and inflammation are research hotspots, and GFAP in body fluids, especially blood, could be used for large-scale screening for AD.

Abstract Background A retrospective study and a randomized controlled trial published in a high quality journal in late 2018 have shown that laparoscopic radical hysterectomy (RH) was associated with worse survival than abdominal RH among patients with early stage cervical cancer. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology, therefore this conclusion is pivotal. The current trial is designed to reconfirm whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stage IA1 with LVSI, IA2) patient survival under stringent operation standards and consistent tumor-free technique. This paper reports the rationale, design, and implementation of the trial. Methods This is an investigator-initiated, prospective, randomized, open, blinded endpoint (PROBE) controlled trial. A total of 690 patients with stage IA1 (with intravascular), and IA2 cervical cancer will be enrolled over a period of three years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed-up for at least five years. The primary endpoint will be 5-year progression-free survival. Secondary endpoints will include 5-year overall survival rates, recurrence rates, operation time, intraoperative blood loss, surgery-related complications, and quality of life. Discussion The results of the trial will provide valuable evidence for guiding clinical decision of choosing appropriate treatment strategies for stage IA1 (LVSI) and stage IA2 cervical cancer patients. Trial registration ClinicalTrials.gov ( NCT04934982 , Registered on 22 June 2021).

Abstract Background A retrospective study and a randomized controlled trial published in late 2018 have shown that laparoscopic radical hysterectomy (RH) was associated with worse survival than abdominal RH among patients with early-stage cervical cancer. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology; therefore, this conclusion is pivotal. The current trial is designed to reconfirm whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stages IB1, IB2, and IIA1) patient survival under stringent operation standards and consistent surgical oncologic principles. Methods/design This is an investigator-initiated, Prospective, Randomized, Open, Blinded End-point (PROBE)-controlled non-inferiority trial. A total of 780 patients with stage IB1, IB2, and IIA1 cervical cancer will be enrolled over a period of 3 years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed up for at least 5 years. The primary endpoint will be 5-year progression-free survival, and secondary endpoints include 5-year overall survival, recurrence, and quality of life measurements. Discussion The debate on laparoscopic versus abdominal RH is still ongoing, and high-quality evidences are needed to guide clinical practice. The study results will provide more convincing evidence-based information for early-stage cervical cancer patients and their gynecologic cancer surgeons in their choice of surgical method. Trial registration ClinicalTrials.gov NCT04929769 . Registered on 18 June 2021

Background: Metastatic Breast Cancer (MBC) patients often feel their symptom-related needs are unmet, despite visiting their doctors up to once a week. Novel approaches are needed to address symptoms without requiring additional appointments. Technology based symptom management approaches to address symptoms have not been well tested. Methods: Nurse AMIE (Addressing Metastatic Individuals Everyday) is a technology based supportive care platform that provides guideline-concordant symptom management interventions in response to patient reported symptoms. We have previously successfully implemented a tablet version of Nurse AMIE. However, some eligible patients chose not to participate because they were overwhelmed by the technology. To address this barrier, we translated the Nurse AMIE platform to the Amazon Echo Show, which allowed for voice-based interactions. Forty-two MBC patients were randomized 1:1 to receive the Nurse AMIE for Echo Show immediately for six months, or to receive the same intervention for three months, after a three month delay. The primary outcome was change in physical distress over three months, and secondary outcomes included feasibility, acceptability, patient reported outcomes and usability. Conclusions: Results from the Nurse AMIE for Echo Show trial will identify the feasibility, acceptability, and preliminary effects of the Nurse AMIE for Echo Show on patient reported outcomes. Untested novel technologies, particularly voice-based artificial intelligence devices may an effective and scalable vehicle through which we can deliver supportive care interventions. Clinicaltrials.gov identifier: NCT04673019.

Ecological restoration of today's urban soils is a global challenge. Soil quality improvement through groundcover is one of the practical ways in urban ecological restoration practice, and the selection of suitable groundcover types is the key to successful soil ecological restoration. Spontaneous groundcover and lawn, as the two typical urban groundcovers, are mostly used for urban soil restoration. However, few studies have quantified and compared their effects on improving soil quality in urban environments, making it difficult to make scientific choices in practice. Furthermore, the improving mechanism of groundcovers on soil quality is still not quite clear. First, root biomass is commonly considered to be a direct factor affecting soil quality, however, most of the current studies focus on the relationship between a single soil quality index and root mass, and few studies systematically explore the relationship between soil quality index and root mass. Second, species richness and functional group are two main differences in species composition between autochthonous groundcover and lawn, one of which must be the driving factor for the difference in soil improvement effect. At present, there are inconsistent results on whether the driving factors of groundcover for soil quality improvement are species richness or functional groups. In order to explore the above problems, this study sets up a comparative experiment in the urban environment. this study. Twelve typical groundcovers (including six urban groundcovers and six lawns) covering five functional groups (grass (G), forbs (F) and grass (L), G + F and G + F + L) were selected for experiments. Soil quality indicators including nitrogen (N), phosphorus (P), potassium (K), boron (B), iron (Fe), soil organic carbon (SOC), catalase (CAT), root biomass and species richness were tested, and the soil quality index (SQI) reflecting soil quality was calculated. The results showed that the soil quality index (SQI) of autochthonous groundcover was 35 % higher than that of lawn, and the contents of N, P, K and SOC in autochthonous groundcover were significantly higher than those in lawn. N, P, SOC, CAT showed a response to the root mass of groundcovers. Among all the indicators, only CAT was significantly correlated with groundcover species richness, while N, P, K, and SOC were significantly dependent on their functional diversity, and showed significant differences in different functional combinations. This study shows that the improvement effect of urban autochthonous groundcover on soil quality is significantly better than that of lawn. Functional groups may be the driving factors for the change of groundcover soil quality. Different functional groups may affect the root system of groundcover through compensation effect, thus affecting soil quality, which ultimately leads to the difference in the improvement effect of spontaneous groundcover and lawn on soil quality. This study provides a theoretical basis for the application of groundcover and lawn in urban soil ecological restoration in the future. In the practice of ecological restoration, if the goal is to improve soil quality, groundcover will be a more sensible choice than lawn. At the same time, attention should be paid to the diversity of functional groups to maximize the benefits of soil ecological restoration.

In practice, it is difficult to represent both biodiversity and recreational values in urban green spaces, mostly due to the lack of knowledge concerning people's biodiversity perceptions and recreational preferences. This study investigated the relationship between biodiversity, perceived biodiversity and recreational preference in urban green spaces in a Chinese urban environmental context. A compound factor was used to assess the actual biodiversity in biotopes while visitor-employed photography (VEP) was adopted to collect the perceptions of biodiversity and recreational preferences of participants, who were professional teachers and college students. Kruskal-Wallis tests were applied to compare the perceived biodiversity and recreational preferences across different biotopes. The reasons for which participants identified biodiversity or preferred the biotopes were also analyzed through binary logistic regression models and Kruskal-Wallis tests. Lastly, the differences between perception and recreational preference as effects of ecological knowledge were analyzed by Mann-Whitney tests. The results indicated that the participants could identify the biodiversity in different biotopes and preferred the water biotope. Landscape content was the most important environmental factor contributing to both the perception and recreational preference trends. The teachers focused more on spatial configurations while students noticed greater management in the biotopes. The study explored and identified people's attitudes and recreational preferences towards biodiversity in urban green spaces in China, and discussed balanced strategies for biodiversity conservation and recreation.