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Abstract Background Since the outbreak of the Coronavirus Disease 2019 (COVID-19), front-line nurses have faced not only daily work stress but also a high risk of infection and excessive workload, leading to unsatisfactory professional quality of life (ProQOL). This study aimed to explore whether self-compassion (SC) and benefit finding (BF) play a chain mediating role between work stress and ProQOL among Chinese nurses during the COVID-19 pandemic. Methods From March to April 2022, a sample of 13,936 Chinese nurses was recruited through snowball sampling. Demographic information, work stress, SC, BF, and ProQOL were assessed. The SPSS 25.0 software and Amos 24.0 software were used for statistical analysis. The bootstrap method was employed to construct and examine the chain mediating structural equation model. Results The ProQOL level of Chinese nurses during the COVID-19 pandemic was moderate. The overall fit indices for the compassion satisfaction (CS), burnout (BO), and secondary traumatic stress (STS) models were satisfactory (χ²/df = 2.486, 3.256, 2.553, RMSEA = 0.011, 0.014, 0.011, the GFI, AGFI, NFI, and CFI values were all above 0.90). Work stress had direct effects on CS, BO, and STS (β=–0.171, 0.334, 0.222, P

Abstract Background Multiple myeloma (MM) often causes renal tubular damage, such as the light chain cast nephropathy (LCCN) and the light chain proximal tubulopathy (LCPT). The excessive light chains deposited in the proximal and distal tubules usually manifest with different characteristics, leading to a rare coexistence of the two pathological conditions. Here we report a unique case of a patient with multiple myeloma (MM) who presented with acute kidney injury (AKI) due to dual conditions of λ light chain-restricted non-crystalline LCPT and LCCN. This report reviews the clinical presentation and histological findings, comparing them with previously published cases. Case presentation A 49-year-old male patient was admitted with a chief complaint of “fatigue, loss of appetite for 40 days and elevated blood creatinine for 10 days.” In serum and urine, the λ light chain level and the ratio of κ to λ free light chain were 1235 mg/dl and 93.25 mg/dl, 0.0022 and 0.0316, respectively. Additionally, serum protein electrophoresis showed an M-spike with monoclonal IgD-λ. Bone marrow puncture revealed 30.5% primitive naive plasma cells, indicative of IgD-λ MM. Light microscopy of kidney biopsy specimen showed periodic acid-Schiff (PAS)-negative cytoplasm in some proximal tubules and PAS-negative casts with a rigid appearance in some distal tubule lumens. On immunofluorescence, these proximal tubular epithelial cells cytoplasm and casts stained exclusively with λ-light chains. Electron microscopy did not reveal any crystalline inclusions. Given the clinical and bone marrow puncture findings, the overall pathological presentation was LCPT with LCCN secondary to IgD-λ MM. After chemotherapy and dialysis, the patient’s condition was improved and he was tracked in follow-ups. Conclusion In some tubular renal injuries caused by MM, the morphological changes are subtle and often overlooked. In this paper, we present a rare case of LCPT with LCCN showing λ restriction in patient with MM. Through the clinicopathological analysis of patients, the understanding of the disease can be deepened and the diagnosis rate improved.

Abstract Despite the widespread advocacy for the integration of arts and humanities (A&H) into science, technology, engineering, and mathematics (STEM) education on an international scale, teachers face numerous obstacles in practically integrating A&H into STEM teaching (IAT). To tackle the challenges, a comprehensive five-stage framework for teacher professional development programs focussed on IAT has been developed. Through the use of a qualitative case study approach, this study outlines the shifts in a participant teacher’s self-efficacy following their exposure to each stage of the framework. The data obtained from interviews and reflective analyses were analyzed using a seven-stage inductive method. The findings have substantiated the significant impact of a teacher professional development program based on the framework on teacher self-efficacy, evident in both individual performance and student outcomes observed over eighteen months. The evolution of teacher self-efficacy in IAT should be regarded as an open and multi-level system, characterized by interactions with teacher knowledge, skills and other entrenched beliefs. Building on our research findings, an enhanced model of teacher professional learning is proposed. The revised model illustrates that professional learning for STEAM teachers should be conceived as a continuous and sustainable process, characterized by the dynamic interaction among teaching performance, teacher knowledge, and teacher beliefs. The updated model further confirms the inseparable link between teacher learning and student learning within STEAM education. This study contributes to the existing body of literature on teacher self-efficacy, teacher professional learning models and the design of IAT teacher professional development programs.

To prepare different types of lutein nanostructured lipid carriers (LNLs) using chitosan (CS), chitosan-epigallocatechin gallate covalent (C-CS-EGCG), and chitosan-epigallocatechin gallate ester non-covalent (Non-C-CS-EGCG) modifications combined with high-pressure microfluidization. A simulated colonic digestion model was established to investigate the stability and interaction with gut microbiota of these modified lutein nanostructured lipid carriers. Results showed that after 24 hours of simulated in vitro colonic fermentation, the lutein content in CS-LNLs significantly decreased (P

Ulcerative colitis (UC) is characterized by chronic inflammatory processes of the intestinal tract of unknown origin. Current treatments lack understanding on how to effectively alleviate oxidative stress, relieve inflammation, as well as modulate gut microbiota for maintaining intestinal homeostasis synchronously. In this study, a novel drug delivery system based on a metal polyphenol network (MPN) was constructed via metal coordination between epigallocatechin gallate (EGCG) and Fe3+. Curcumin (Cur), an active polyphenolic compound, with distinguished anti-inflammatory activity was assembled and encapsulated into MPN to generate Cur-MPN. The obtained Cur-MPN could serve as a robust reactive oxygen species modulator by efficiently scavenging superoxide radical (O2•-) as well as hydroxyl radical (·OH). By hitchhiking yeast microcapsule (YM), Cur-MPN was then encapsulated into YM to obtain CM@YM. Our findings demonstrated that CM@YM was able to protect Cur-MPN to withstand the harsh gastrointestinal environment and enhance the targeting and retention abilities of the inflamed colon. When administered orally, CM@YM could alleviate DSS-induced colitis with protective and therapeutic effects by scavenging ROS, reducing pro-inflammatory cytokines, and regulating the polarization of macrophages to M1, thus restoring barrier function and maintaining intestinal homeostasis. Importantly, CM@YM also modulated the gut microbiome to a favorable state by improving bacterial diversity and transforming the compositional structure to an anti-inflammatory phenotype as well as increasing the content of short-chain fatty acids (SCFA) (such as acetic acid, propionic acid, and butyric acid). Collectively, with excellent biocompatibility, our findings indicate that synergistically regulating intestinal microenvironment will be a promising approach for UC.

Platycodon grandiflorus stands as one of the most extensively utilized traditional Chinese medicinal herbs, with triterpenoids and their derivatives serving as its primary medicinal components. Oxido squalene cyclase (OSC), serving as a crucial enzyme in the triterpenoid synthesis pathway, has the capability to enzymatically generate significant quantities of sterols and triterpenoid intermediates. While the OSC gene family has been identified in numerous species, bioinformatics research on this family remains scant. Presently, the specific members of this gene family in Platycodon grandiflorus have yet to be definitively determined. In this study, we successfully identified a total of 15 PgOSC genes within the genome of Platycodon grandiflorus by conducting homology comparisons. These genes were discovered to be unevenly distributed across the five chromosomes of the species, organized in the form of gene clusters. Subsequently, we conducted a thorough analysis of the OSC gene family’s evolutionary relationship by constructing a phylogenetic tree. Other characteristics of PgOSC family members, including gene structure, conserved motifs, protein three-dimensional structure, subcellular localization, and cis-acting elements were thoroughly characterized. Furthermore, We analyzed the expression of PgOSC gene in different tissues of Platycodon grandiflorus by qRT-PCR, and found that the expression of PgOSC genes in root was higher than that in stem and leaf. Upon comparing the effects of salt, heat, and drought treatments, we observed a significant induction of PgOSC gene expression in Platycodon grandiflorus specifically under salt stress conditions. In summary, this study comprehensively identified and analyzed the OSC gene family, aiming to provide basic biological information for exploring the members of PgOSC gene family.

Tartaric acid is one of the characteristic acids in wine, playing a crucial role in wine characteristics. However, superabundant tartaric acid will form insoluble salts and precipitate in the form of crystals, affecting consumers' purchasing appetite. Therefore, tartaric stability is also one of the important indices for controlling the wine quality. At present, the main processing methods for tartaric stability include cold stabilization, ion exchange treatment, electrodialysis and the addition of exogenous components (gum arabic, metatartaric acid, carboxymethyl cellulose, mannoprotein and potassium polyaspartate). This review summarizes and analyzes the origin of tartaric acid in wine, factors influencing the tartaric stability, detection methods, treatments for tartaric stabilization, and the effects of these methods on the sensory quality of wine. Comparing the effects of these methods on wine quality can provide a basis for the further study of tartaric stabilization methods in order to select an appropriate tartaric stabilization method.

Musk deer (Moschus spp.) are widely known for its musk and are globally endangered as a result of poaching, habitat loss, and fragmentation. To facilitate restoration of the alpine musk deer (M. chrysogaster) in existing areas, reliable estimates of population size and influencing factors are essential to assess effectiveness of conservation interventions, particularly for isolated musk deer populations in patches. In this paper, we used line transect and camera trap data collected from 2020 to 2022 in the Helan mountains to assess the population status and characterized the influencing factors of alpine musk deer. Our findings indicate that musk deer are patchily distributed in three areas of high elevation, with the population limited to less than 200 individuals, remaining below historic levels (compared to 1995). There was a significant positive correlation between the role of sympatric species on musk deer, with red fox (Vulpes vulpes), badger (Meles meles) and blue eared-pheasant (Crossoptilon auritum) having a significant effect on the out-modeled pathway. Variable but insignificant effects of anthropogenic activities were observed across all species categories, which could be due to mutual adaptation over time. Our results imply that the recovery of sensitive population in island-like habitats remains challenging and may be exacerbated by limited environment and resources. Our study underscores the necessity of establishing ecological corridors to enhance habitat connectivity for alpine musk deer, undertaking conservation genetics research on isolated populations, controlling stray dogs to maintain interspecific balance, and implementing electronic fencing to mitigate human disturbance and resource competition. This study provides basic information for understanding the population status of alpine musk deer and offers insights for conservation efforts.

Abstract Purpose Observational studies and clinical validation have suggested a link between thyroid dysfunction and an elevated ovarian cancer (OC) risk. However, whether this association indicates a cause-and-effect relationship remains uncertain. We aimed to investigate the plausible causal impact of thyroid dysfunction on OC through a Mendelian randomization (MR) study. Methods Genome-wide association study (GWAS) data for thyrotropin (TSH), free thyroxine (FT4), hypothyroidism, and hyperthyroidism were obtained as exposures and those for OC (N = 199,741) were selected as outcomes. Inverse variance-weighted method was used as the main estimation method. A series of sensitivity analyses, including Cochran’s Q test, MR-Egger intercept analysis, forest plot scatter plot, and leave-one-out test, was conducted to assess the robustness of the estimates. Results Genetic prediction of hyperthyroidism was associated with a potential increase in OC risk (odds ratio = 1.094, 95% confidence interval: 1.029–1.164, p = 0.004). However, no evidence of causal effects of hypothyroidism, TSH, and FT4 on OC or reverse causality was detected. Sensitivity analyses demonstrated consistent and reliable results, with no significant estimates of heterogeneity or pleiotropy. Conclusions This study employed MR to establish a correlation between hyperthyroidism and OC risk. By genetically predicting OC risk in patients with hyperthyroidism, our research suggests new insights for early prevention and intervention of OC.

Abstract The aim of this study is to assess the relationship between dietary intake of fatty acids and the age-related macular degeneration (AMD) in the United States population. Adult participants of the 2005–2008 National Health and Nutrition Examination Survey (NHANES) were included in this nationwide cross-sectional study. Dietary fatty acid intake was obtained from two 24-h dietary recall interviews. The intake of dietary fatty acids was analyzed as a continuous and categorical variable. AMD status was assessed using nonmydriatic fundus photographs. Univariate and multivariate logistic regression analyses were used to assess the association between dietary fatty acid intake and AMD. The unweighted population included 4702 individuals of whom 374 had AMD. After adjusting for relevant variables, each 1 unit increase (1 mg/1000 kcal) intake of EPA (OR: 0.996, 95% CI: 0.993–0.996, P = 0.018), DPA (OR: 0.976, 95% CI: 0.962–0.990, P = 0.002), and DHA (OR: 0.996, 95% CI: 0.994–0.999, P = 0.003) were significantly decreased odds of any AMD. The highest versus lowest quartile of EPA (OR: 0.476, P for trend

Abstract Background Cepharanthin® alone or in combination with glucocorticoid (GC) has been used to treat chronic immune thrombocytopenia (ITP) since the 1990s. Cepharanthine (CEP) is one of the main active components of Cepharanthin®. The purpose of this study was to investigate the effects of CEP on GC pharmacodynamics on immune cells and analyse the possible action mechanism of their interactions. Methods Peripheral blood mononuclear cells (PBMCs), T lymphocytic leukemia MOLT-4 cells and daunorubicin resistant MOLT-4 cells (MOLT-4/DNR) were used to evaluate the pharmacodynamics and molecular mechanisms. Drug pharmacodynamics was evaluated by WST-8 assay. P-glycoprotein function was examined by rhodamine 123 assay. CD4+CD25+Foxp3+ regulatory T cells and Th1/Th2/Th17 cytokines were detected by flow cytometry. P-glycoprotein expression and GC receptor translocation were examined by Western blot. Results CEP synergistically increased methylprednisolone (MP) efficacy with the suppressive effect on the cell viability of PBMCs. 0.3 and 1 μM of CEP significantly inhibited P-glycoprotein efflux function of CD4+ cells, CD8+ cells, and lymphocytes (P

Abstract Sensory-motor interactions in the auditory system play an important role in vocal self-monitoring and control. These result from top-down corollary discharges, relaying predictions about vocal timing and acoustics. Recent evidence suggests such signals may be two distinct processes, one suppressing neural activity during vocalization and another enhancing sensitivity to sensory feedback, rather than a single mechanism. Single-neuron recordings have been unable to disambiguate due to overlap of motor signals with sensory inputs. Here, we sought to disentangle these processes in marmoset auditory cortex during production of multi-phrased ‘twitter’ vocalizations. Temporal responses revealed two timescales of vocal suppression: temporally-precise phasic suppression during phrases and sustained tonic suppression. Both components were present within individual neurons, however, phasic suppression presented broadly regardless of frequency tuning (gating), while tonic was selective for vocal frequencies and feedback (prediction). This suggests that auditory cortex is modulated by concurrent corollary discharges during vocalization, with different computational mechanisms.

Objective This study aimed to investigate the effect of the soluble Klotho (sKlotho)/Wnt/β-catenin signaling pathway on vascular calcification in rat models of chronic kidney disease (CKD) and the intervention effect of Shenyuan granules.Methods Rats with 5/6 nephrectomy and high phosphorus feeding were used to establish the vascular calcification model. The rats were given gradient doses of Shenyuan granules aqueous solution and calcitriol solution by gavage for 8 weeks, which were divided into experimental group and positive control group.Results The 5/6 nephrectomy combined with high phosphorus feeding induced thoracic aortic calcification in rats. Shenyuan granules intervention increased the serum sKlotho level, inhibited the mRNA and protein expression of Wnt1, β-catenin, and Runx2 in the thoracic aorta, and alleviated thoracic aortic media calcification in rats.Conclusion Shenyuan granules may partially regulate the Wnt/β-catenin signaling pathway via serum sKl to interfere with the expression of Runx2, thereby improving vascular calcification in CKD.

Ovarian cancer (OCa) is a common malignancy in women, and the role of cuproptosis and its related genes in OCa is unclear. Using the GSE14407 dataset, we analyzed the expression and correlation of cuproptosis-related genes (CRGs) between tumor and normal groups. From the TCGA-OV dataset, we identified 20 cuproptosis-related long non-coding RNAs (CuLncs) associated with patient survival through univariate Cox analysis. OCa patients were divided into early-stage and late-stage groups to analyze CuLncs expression. Cluster analysis classified patients into two clusters, with Cluster1 having a poorer prognosis. Significant differences in “Lymphatic Invasion” and “Cancer status” were observed between clusters. Seven CRGs showed significant expression differences, validated using the human protein atlas (HPA) databases. Immune analysis revealed a higher ImmuneScore in Cluster1. GSEA identified associated signaling pathways. LASSO regression included 11 CuLncs to construct and validate a survival prediction model, classifying patients into high-risk and low-risk groups. Correlations between riskScore, Cluster phenotype, ImmuneScore, and immune cell infiltration were explored. Cell experiments showed that knocking down AC023644.1 decreases OCa cell viability. In conclusion, we constructed an accurate prognostic model for OCa based on 11 CuLncs, providing a basis for prognosis assessment and potential immunotherapy targets.

The combined use of immune checkpoint inhibitors and tyrosine kinase inhibitors (ICI/TKI) is an effective treatment strategy for some cancers. A better understanding of the potential additive toxicity for ICI/TKI combinations is needed to inform patient and provider treatment decisions. We aim to evaluate the safety of ICI/TKI combinations for individuals with renal cell or endometrial carcinoma. This rapid systematic review (SR) protocol follows PRISMA guidelines. A systematic search will be designed, peer reviewed and executed by experienced information specialists (Cochrane Central, MEDLINE, Embase) to identify published SRs and primary studies published since the most recent SR search. Randomized, quasi- or non-randomized controlled trials and comparative cohort studies are eligible if they compare ICI/TKI combinations to monotherapy or standard of care in participants with renal cell or endometrial carcinoma. The primary outcome is grade ≥ 3 treatment-related adverse-effects. Studies will be screened, selected, extracted and assessed for risk of bias by a single reviewer and checked completely by a second. Where feasible and appropriate, we will pool studies separately by design and indication using meta-analysis and test robustness of effects using prespecified subgroup and sensitivity analyses. Results will be summarized descriptively and presented in tables and figures. (PROSPERO ID: CRD42023416388). • This will be a comprehensive systematic review of the additive toxicity arising from the combined use of ICI/TKIs in patients with renal-cell or endometrial carcinoma. • We will consider treatment-related, treatment-emergent adverse events (Grade 3 or higher). • Identified safety profile may be used to inform patient or provider treatment decisions.

Neural network quantization represents weights and activations with few bits, greatly reducing the overhead of multiplications. However, due to the recursive accumulation operations, high-precision accumulators are still required in multiply-accumulate (MAC) units to avoid overflow, incurring significant computational overhead. This constraint limits the efficient deployment of quantized NNs on resource-constrained platforms. To address this problem, we present a novel framework named CANET, which adapts the 8-bit quantized model to execute MAC operations with 8-bit accumulators. CANET not only employs 8-bit carry-aware accumulators to represent overflow data correctly, but also adaptively learns the optimal format per layer to minimize truncation errors. Meanwhile, a weight-oriented reordering method is developed to reduce the transfer length of the carry. CANET is evaluated on three networks in the ImageNet classification task, where comparable performance with state-of-the-art methods is realized. Finally, we implement the proposed architecture on a custom hardware platform, demonstrating a reduction of 40% in power and 49% in area compared with the MAC unit with 32-bit accumulators.

Abstract Backgrounds Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare but lethal cardiac ion channelopathy. Delayed diagnosis and misdiagnosis remain a matter of concern due to its rarity and insufficient recognition of this disorder, particularly in developing countries like China. Aims and methods We reported six catecholaminergic polymorphic ventricular tachycardia (CPVT) children diagnosed in our center along with a comprehensive review of Chinese pediatric CPVT patients reported in domestic and overseas literature between January 2013 and December 2021 to provide an essential reference for physicians to deepen their understanding of pediatric CPVT. Results A total of 95 children with CPVT, including our six patients from 21 medical centers were identified. The median age of symptom onset is 8.7 ± 3.0 years. Diagnosis occurred at a median age of 12.9 ± 6.8 years with a delay of 4.3 ± 6.6 years. Selective beta-blockers (Metoprolol and Bisoprolol) were prescribed for 38 patients (56.7%) and 29 (43.3%) patients received non-selective beta-blocker (Propranolol and Nadolol) treatment. Six patients accepted LCSD and seven received ICD implantation at the subsequent therapy. A total of 13 patients died during the disease course. Of the 67 patients with positive gene test results, variants in RYR2 were 47 (70.1%), CASQ2 were 11 (16.4%), and RYR2 accompanied SCN5A were 7 (10.4%). Patients with CASQ2 gene mutations presented with younger symptom onset age, higher positive family history rate and better prognosis than those with RYR2 mutations. Conclusion Chinese pediatric patients with CPVT had a poorer prognosis than other cohorts, probably due to delayed/missed diagnosis, non-standard usage of beta-blockers, unavailability of flecainide, and a lower rate of LCSD and ICD implantation.

Gastric cancer (GC) imposes a heavy burden on global public health, and microRNAs (miRNAs) play a crucial role in the diagnosis and treatment of GC. Therefore, it is necessary to clarify the hotspots and frontiers in the field of miRNAs in GC to guide future research. A total of 2,051 publications related to miRNAs in GC from January 2013 to December 2023 were searched from the Web of Science Core Collection database. CiteSpace was used to identify research hotspots and delineate developmental trends. In the past decade, China, Nanjing Medical University, and Ba Yi were the most contributing research country, institute, and author in this field, respectively. The role of miRNAs as biomarkers in GC, the mechanism of miRNAs in the progression of GC, and the impact of the mutual effects between miRNAs and Helicobacter pylori on GC have been regarded as the research hotspots. The mechanisms of miRNAs on glucose metabolism and the application of the roles of circular RNAs as miRNA sponges in GC treatment will likely be frontiers. Overall, this study called for strengthened cooperation to identify targets and therapeutic regimes for local specificity and high-risk GC types, and to promote the translation of research results into clinical practice.

D-dimer is a very important biomarker about sepsis, pulmonary thromboembolism and atherosclerosis, thus designing effective and sensitive method for its detection is of great significance. Herein, by synthesizing β-cyclodextrin-carbon nanotube nanohybrid (CNTs-CD) as the carrier to assemble the initial antibody (Ab1) of D-dimer, immobilizing secondary antibody (Ab2) and sulfydryl ferrocene (Fc) on the nanogold (Au) particles surface as the signaling amplifier (Ab2-Au-Fc), a low cost, simple, sensitive and effective sandwich-like electrochemical immunosensing (SEI) platform of D-dimer was proposed in this work for the first time. Briefly, CNTs shows large specific area and superior electroconductivity, and CD provides high host guest recognition ability that could bound with Ab1; meanwhile, the Fc probe offers stable current response which are proportionable positively to the level of D-dimer. Under the best conditions, the designed SEI platform exhibits prominent analytical performances for D-dimer: low detection limit of 3.0 ng mL−1 and large linearity of 10.0–800.0 ng mL−1. In addition, the selectivity, stability and reproducibility as well as real applications of the proposed SEI assay were evaluated and the obtained results are satisfactory.

Abstract Background Surgical treatment has been increasingly performed in Hirayama disease (HD) patients to limit excessive neck flexion and restore cervical lordosis. However, postoperative recurrence of cervical lordosis loss may restart the progress of HD. Many studies have demonstrated a relationship between neck muscle strength and cervical lordosis, and it is widely accepted that leisure-time physical activity (LTPA) can increase muscle strength. However, there are few reports about the correlation between LTPA and maintenance of postoperative cervical curvature. Objective To quantify the cervical lordosis and motor function before and after operation in HD patients and to analyze the impact of postoperative LTPA levels on the changes in these measurements. Methods C2-7 Cobb were measured in 91 HD patients before, 2–5 days and approximately 2 years after operation. Motor unit number estimation (MUNE) and handgrip strength (HGS) were performed in all patients before and approximately 2 years after operation, and both cross-sectional area and fatty infiltration of posterior cervical muscles were measured in 62 patients. Long-form international Physical Activity Questionnaire and its different domains was administered to all patients at postoperative 2-year assessments. Results The C2-7 Cobb was larger immediately and approximately 2 years after operation than that at preoperative assessment (P

Abstract Background Platycodon grandiflorus (Jacq.) A. DC is a famous traditional Chinese medicine in China and an authentic medicine in Inner Mongolia. It has been traditionally used as an expectorant in cough and also has anti-inflammatory and other pharmacological effects. As a homologous plant of medicine and food, P. grandiflorus is widely planted in Northeast China. Soil salinity isa limiting factor for its cultivation. In this study, we comprehensively described the physiological characteristics of P. grandiflorus and combined transcriptomics and metabolomics to study the response of roots of P. grandiflorus to salt stress. Results Overall, 8,988 differentially expressed genes were activated and significantly altered the metabolic processes. In total, 428 differentially abundant metabolites were affected by salt stress. After moderate and severe salt stress, most of the differentially abundant metabolites were enriched in the L-phenylalanine metabolic pathway. Through the comprehensive analysis of the interaction between key genes and metabolites, the main pathways such as lignin compound biosynthesis and triterpene saponin biosynthesis were completed. The relative content of compounds related to lignin biosynthesis, such as caffeic acid, coniferin, and syringing, increased under salt stress, and the related genes such as PAL, C4H, and the key enzyme gene UGT72E2 were activated to adapt to the salt stress. Platycodon saponin is one of the major triterpene saponins in P. grandiflorus, and Platycodin D is its most abundant major bioactive component. Under severe salt stress, Platycodin D level increased by nearly 1.77-fold compared with the control group. Most of the genes involved insynthetic pathway of Platycodin D, such as HMGCR, GGPS, SE, and LUP, were upregulated under salt stress. Conclusion Salt stress led to a decrease in the biomass and affected the activities of antioxidant enzymes and contents of osmotic regulators in the plant. These results provided not only novel insights into the underlying mechanisms of response of P. grandiflorus to salt stress but also a foundation for future studies on the function of genes related to salt tolerance in the triterpenoid saponin biosynthesis pathway.

Abstract Vocal communication is essential for social behaviors in humans and non-human primates. While the frontal cortex is crucial to human speech production, its role in vocal production in non-human primates has long been questioned. It is unclear whether activities in the frontal cortex represent diverse vocal signals used in non-human primate communication. Here we studied single neuron activities and local field potentials (LFP) in the frontal cortex of male marmoset monkeys while the animal engaged in vocal exchanges with conspecifics in a social environment. We found that both single neuron activities and LFP were modulated by the production of each of the four major call types. Moreover, neural activities showed distinct patterns for different call types and theta-band LFP oscillations showed phase-locking to the phrases of twitter calls, suggesting a neural representation of vocalization features. Our results suggest important functions of the marmoset frontal cortex in supporting the production of diverse vocalizations in communication.

Estradiol (E2) and related estrogens are emerging environmental contaminants that may adversely affect the health of humans, animals, and ecosystems. Many aptamers have been reported for the detection of E2, and our lab recently selected a series of high-affinity and short DNA aptamers that showed various binding orientations to E2, leading to different selectivity patterns. In this work, we report that using SYBR Green I (SGI) as a fluorescence probe, up to 200% fluorescence increase was achieved upon titration of E2 to these aptamers. Such enhancement was the highest among all reported small molecule binding aptamers using SGI for signal generation, although some metal-binding DNA can achieve even higher enhancement. By gradually shortening the stem region of an E2 binding aptamer, we concluded that the enhanced fluorescence was from the aptamer binding pocket upon target binding instead of from the duplexed stem region. Comparison was also made with a few other aptamers including those for caffeine, quinine, uric acid and cortisol, and none of them showed more than 20% fluorescence change. Using the SGI method, the detection limit was calculated to be 2.4 nM E2. We attributed the large fluorescence enhancement to the hydrophobic nature of E2 and the high-affinity binding of the aptamers. This study provides insights into the aptamers that can use SGI for their binding assays and biosensor development.

We report 2 rare cases of male breast cancer with bloody nipple discharge. Patient 1, a 32-year-old male, presented with a bloody nipple discharge from the left breast. Diagnostic workup revealed papillary ductal carcinoma in situ. Patient 1 underwent bilateral mastectomy with left axillary sentinel lymph node biopsy and has been doing well ever since. Patient 2, a 70-year-old male with concomitant metastatic prostate cancer, presented with a palpable right breast mass and with initially serous, then bloody nipple discharge. Diagnostic workup revealed invasive ductal carcinoma with ductal carcinoma in situ of the right breast. Patient 2 received aromatase inhibitor therapy prior to right total mastectomy with SLN biopsy followed by adjuvant tamoxifen therapy. Patient 2 recovered without complication for 2 years until metastatic disease recurrence was detected. This case report's purpose is to increase awareness and enhance understanding of the presentation, diagnosis, treatment, and outcomes of rare malignant pathologies.

With the advancement of living standards, the role of healthy diets in maintaining well-being has gained prominence. The concept of “medicinal fruits and vegetables” has attracted much research attention recently. Medicinal fruits and vegetables are rich in nutrients and high in edible value, and are also necessary for people's daily diet. In order to better exert the effect of medicinal fruits and vegetables and prolong their shelf life, this paper reviews the effects of common thermal processing methods (boiling, steaming, microwaving, hot air drying, and pasteurization) on the bioactive compounds and pharmacological activities of medicinal fruits and vegetables. It is found that different heat treatment methods have their own advantages and disadvantages, and microwave drying has greater advantages in comparison. Through the summary of the thermal processing methods of medicinal fruits and vegetables, it is expected to provide a theoretical reference for its rational utilization in the field of fruits and vegetables and the improvement of thermal processing methods.

Objective: To elucidate the chemical profile of Xanthocerais lignum’s extracts of different polarities and their impact on rheumatoid arthritis (RA), we identified anti-RA markers and predicted their action mechanisms. Methods: A collagen-induced arthritis rat model was established, and UPLC-Q-Exactive Orbitrap MS technology was employed to analyze and identify the chemical constituents within the alcohol extract of Xanthocerais lignum and its various extraction fractions, as well as their translocation into the bloodstream. Serum spectrum–effect correlation analysis was utilized to elucidate the pharmacodynamic material basis of Xanthocerais lignum against RA and to screen for Q-Markers. Finally, the potential anti-RA mechanisms of the Q-Markers were predicted through compound-target interaction data and validated using molecular docking techniques. Results: We identified 71 compounds, with flavan-3-ols and flavanones as key components. Of these, 36 were detected in the bloodstream, including 17 original and 19 metabolized forms. Proanthocyanidin A2, dihydroquercetin, catechin, and epicatechin (plus glucuronides) showed potential anti-RA activity. These compounds, acting as Q-Markers, may modulate ERK, NF-κB, HIF-1α, and VEGF in the HIF-1 pathway. Conclusions: This research clarifies Xanthocerais lignum’s pharmacodynamic material basis against RA, identifies 4 Q-Markers, and offers insights into their mechanisms, aiding quality assessment and lead compound development for RA treatment.

Abstract Objective To determine the efficacy of cataract surgeries in blindness prevention programs in Chongqing. Methods During February–December 2019, we prospectively enrolled 487 patients (592 eyes) undergoing cataract surgery during blindness prevention programs in 6 Chongqing district/county hospitals (experimental group) and 481 patients (609 eyes) undergoing cataract surgery in the First Affiliated Hospital of Chongqing Medical University (controls). Uncorrected visual acuity (UCVA), refractive status, best corrected visual acuity (BCVA), slit lamp examination, and visual function/quality of life (VF-QOL) questionnaire scores were evaluated preoperatively, and at 1 and 6 months postoperatively. Results In the experimental group, UCVA, BCVA, and VF-QOL scores at 1 and 6 months were better than the preoperative values (P 0.5 logMAR) in the experimental group were uncorrected refractive errors (33.0%), PCO (29.5%), and fundus diseases (33.9%). Conclusion Cataract surgeries in blindness prevention programs in Chongqing significantly improved visual acuity, VF, and QOL, but underperformed compared to surgeries in the tertiary teaching hospital.

Abstract. Background:. This study aimed to develop a comprehensive instrument for evaluating and ranking clinical practice guidelines, named Scientific, Transparent and Applicable Rankings tool (STAR), and test its reliability, validity, and usability. Methods:. This study set up a multidisciplinary working group including guideline methodologists, statisticians, journal editors, clinicians, and other experts. Scoping review, Delphi methods, and hierarchical analysis were used to develop the STAR tool. We evaluated the instrument's intrinsic and interrater reliability, content and criterion validity, and usability. Results:. STAR contained 39 items grouped into 11 domains. The mean intrinsic reliability of the domains, indicated by Cronbach's α coefficient, was 0.588 (95% confidence interval [CI]: 0.414, 0.762). Interrater reliability as assessed with Cohen's kappa coefficient was 0.774 (95% CI: 0.740, 0.807) for methodological evaluators and 0.618 (95% CI: 0.587, 0.648) for clinical evaluators. The overall content validity index was 0.905. Pearson's r correlation for criterion validity was 0.885 (95% CI: 0.804, 0.932). The mean usability score of the items was 4.6 and the median time spent to evaluate each guideline was 20 min. Conclusion:. The instrument performed well in terms of reliability, validity, and efficiency, and can be used for comprehensively evaluating and ranking guidelines.

Abstract Background Psychomotor alterations are a common symptom in patients with major depressive disorder (MDD). The primary motor cortex (M1) plays a vital role in the mechanism of psychomotor alterations. Post-movement beta rebound (PMBR) in the sensorimotor cortex is abnormal in patients with motor abnormalities. However, the changes in M1 beta rebound in patients with MDD remain unclear. This study aimed to primarily explore the relationship between psychomotor alterations and PMBR in MDD. Methods One hundred thirty-two subjects were enrolled in the study, comprising 65 healthy controls (HCs) and 67 MDD patients. All participants performed a simple right-hand visuomotor task during MEG scanning. PMBR was measured in the left M1 at the source reconstruction level with the time–frequency analysis method. Retardation factor scores and neurocognitive test performance, including the Digit Symbol Substitution Test (DSST), the Making Test Part A (TMT-A), and the Verbal Fluency Test (VFT), were used to measure psychomotor functions. Pearson correlation analyses were used to assess relationships between PMBR and psychomotor alterations in MDD. Results The MDD group showed worse neurocognitive performance than the HC group in all three neurocognitive tests. The PMBR was diminished in patients with MDD compared to HCs. In a group of MDD patients, the reduced PMBR was negatively correlated with retardation factor scores. Further, there was a positive correlation between the PMBR and DSST scores. PMBR is negatively associated with the TMT-A scores. Conclusion Our findings suggested that the attenuated PMBR in M1 could illustrate the psychomotor disturbance in MDD, possibly contributing to clinical psychomotor symptoms and deficits of cognitive functions.

BackgroundAldehyde dehydrogenase (ALDH) scavenges toxic aldehyde molecules by catalyzing the oxidation of aldehydes to carboxylic acids. Although ALDH gene family members in various plants have been extensively studied and were found to regulate plant response to abiotic stress, reports on ALDH genes in the common bean (Phaseolus vulgaris L.) are limited. In this study, we aimed to investigate the effects of neutral (NS) and basic alkaline (AS) stresses on growth, physiological and biochemical indices, and ALDH activity, ALDH gene expression of common bean. In addition, We used bioinformatics techniques to analyze the physical and chemical properties, phylogenetic relationships, gene replication, collinearity, cis-acting elements, gene structure, motifs, and protein structural characteristics of PvALDH family members.ResultsWe found that both NS and AS stresses weakened the photosynthetic performance of the leaves, induced oxidative stress, inhibited common bean growth, and enhanced the antioxidative system to scavenge reactive oxygen species. Furthermore, we our findings revealed that ALDH in the common bean actively responds to NS or AS stress by inducing the expression of PvALDH genes. In addition, using the established classification criteria and phylogenetic analysis, 27 PvALDHs were identified in the common bean genome, belonging to 10 ALDH families. The primary expansion mode of PvALDH genes was segmental duplication. Cis-acting elemental analysis showed that PvALDHs were associated with abiotic stress and phytohormonal responses. Gene expression analysis revealed that the PvALDH gene expression was tissue-specific. For instance, PvALDH3F1 and PvALDH3H1 were highly expressed in flower buds and flowers, respectively, whereas PvALDH3H2 and PvALDH2B4 were highly expressed in green mature pods and young pods, respectively. PvALDH22A1 and PvALDH11A2 were highly expressed in leaves and young trifoliates, respectively; PvALDH18B2 and PvALDH18B3 were highly expressed in stems and nodules, respectively; and PvALDH2C2 and PvALDH2C3 were highly expressed in the roots. PvALDHs expression in the roots responded positively to NS–AS stress, and PvALDH2C3, PvALDH5F1, and PvALDH10A1 were significantly (P < 0.05) upregulated in the roots.ConclusionThese results indicate that AS stress causes higher levels of oxidative damage than NS stress, resulting in weaker photosynthetic performance and more significant inhibition of common bean growth. The influence of PvALDHs potentially modulates abiotic stress response, particularly in the context of saline–alkali stress. These findings establish a basis for future research into the potential roles of ALDHs in the common bean.

An improved understanding of the factors associated with suicidal attempts in youth suffering from depression is crucial for the identification and prevention of future suicide risk. However, there is limited understanding of how neural activity is modified during the process of decision-making. Our study aimed to investigate the neural responses in suicide attempters with major depressive disorder (MDD) during decision-making. Electroencephalography (EEG) was recorded from 79 individuals aged 16–25 with MDD, including 39 with past suicide attempts (SA group) and 40 without (NSA group), as well as from 40 age- and sex- matched healthy controls (HCs) during the Iowa Gambling Task (IGT). All participants completed diagnostic interviews, self-report questionnaires. Our study examined feedback processing by measuring the feedback-related negativity (FRN), ΔFN (FRN-loss minus FRN-gain), and the P300 as electrophysiological indicators of feedback evaluation. The SA group showed poorest IGT performance. SA group and NSA group, compared with HC group, exhibited specific deficits in decision-making (i.e., exhibited smaller (i.e., blunted) ΔFN). Post hoc analysis found that the SA group was the least sensitive to gains and the most sensitive to losses. In addition, we also found that the larger the value of ΔFN, the better the decision-making ability and the lower the impulsivity. Our study highlights the link between suicide attempts and impaired decision-making in individuals with major depressive disorder. These findings constitute an important step in gaining a better understanding of the specific reward-related abnormalities that could contribute to the young MDD patients with suicide attempts.

Tonotopic organization of the auditory cortex has been extensively studied in many mammalian species using various methodologies and physiological preparations. Tonotopy mapping in primates, however, is more limited due to constraints such as cortical folding, use of anesthetized subjects, and mapping methodology. Here we applied a combination of through-skull and through-window intrinsic optical signal imaging, wide-field calcium imaging, and neural probe recording techniques in awake marmosets (Callithrix jacchus), a New World monkey with most of its auditory cortex located on a flat brain surface. Coarse tonotopic gradients, including a recently described rostral-temporal (RT) to parabelt gradient, were revealed by the through-skull imaging of intrinsic optical signals and were subsequently validated by single-unit recording. Furthermore, these tonotopic gradients were observed with more detail through chronically implanted cranial windows with additional verifications on the experimental design. Moreover, the tonotopy mapped by the intrinsic-signal imaging methods was verified by wide-field calcium imaging in an AAV-GCaMP labeled subject. After these validations and with further effort to expand the field of view more rostrally in both windowed and through-skull subjects, an additional putative tonotopic gradient was observed more rostrally to the area RT, which has not been previously described by the standard model of tonotopic organization of the primate auditory cortex. Together, these results provide the most comprehensive data of tonotopy mapping in an awake primate species with unprecedented coverage and details in the rostral proportion and support a caudal-rostrally arranged mesoscale organization of at least three repeats of functional gradients in the primate auditory cortex, similar to the ventral stream of primate visual cortex.

Background. Diffuse large B-cell lymphoma (DLBCL) is one of the largest lymphoma subcategories. Usually, 50%–70% of DLBCL patients can be cured by the standard treatment. But, at least one third have bad prognosis. Based on this situation, the research on DLBCL therapy strategy is still indispensable. Methods. A prognostic signature was built according to the public data and bioinformatics methods, the stability and reliability was assessed and validated. GSEA was performed to explore the difference in different groups. Consensus clustering and immune infiltration analysis were conducted comprehensively. Results. In this work, a signature based on multiple metabolism-associated genes (MTGs) was established, containing 16 MTGs, to predict the prognosis of DLBCL patients. The accuracy and effectiveness of this signature have been verified by three external validation sets. According to the risk formula, DLBCL patients were divided into high- and low-risk groups, and the survival rate of the low-risk group was significantly higher than that of the high-risk group. Furthermore, gene set enrichment analysis (GSEA) demonstrated that beta-alanine metabolism and regulation of actin cytoskeleton signal pathways were enriched in the low-risk group. The actual survival and nomogram-predicted survival matched well both in the training cohort and verification cohorts. Conclusion. In general, our prognostic signature can provide reliable and valuable information for medical workers in predicting the prognosis of DLBCL. A preprint was made available by the research square in the following link: “https://www.researchsquare.com/article/rs-1468741/v2.”

Objective: To analyze the current research status, hotspots, and frontiers in the field of Gastrointestinal (GI) cancer and quality of life (QoL) through the bibliometrics method, and to provide references and guidance for future research. Methods: Literature related to GI cancer and QoL from April 1, 2003 to March 31, 2023 was retrieved from the Web of Science Core Collection database. CiteSpace 6.2.R1 was performed for collaboration analysis, keyword co-occurrence analysis, and document co-citation analysis. Results: A total of 1224 publications were included in this study. There has been a significant increase in the number of publications in this field over the past two decades. The United States, the Karolinska Institute and the University of Amsterdam, and Pernilla Lagergren are the most prolific country, institution, and author, respectively. The links between most of the research constituents were relatively thin (centrality

Abstract Background Addressing persistent and pervasive health inequities is a global moral imperative, which has been highlighted and magnified by the societal and health impacts of the COVID-19 pandemic. Observational studies can aid our understanding of the impact of health and structural oppression based on the intersection of gender, race, ethnicity, age and other factors, as they frequently collect this data. However, the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline, does not provide guidance related to reporting of health equity. The goal of this project is to develop a STROBE-Equity reporting guideline extension. Methods We assembled a diverse team across multiple domains, including gender, age, ethnicity, Indigenous background, disciplines, geographies, lived experience of health inequity and decision-making organizations. Using an inclusive, integrated knowledge translation approach, we will implement a five-phase plan which will include: (1) assessing the reporting of health equity in published observational studies, (2) seeking wide international feedback on items to improve reporting of health equity, (3) establishing consensus amongst knowledge users and researchers, (4) evaluating in partnership with Indigenous contributors the relevance to Indigenous peoples who have globally experienced the oppressive legacy of colonization, and (5) widely disseminating and seeking endorsement from relevant knowledge users. We will seek input from external collaborators using social media, mailing lists and other communication channels. Discussion Achieving global imperatives such as the Sustainable Development Goals (e.g., SDG 10 Reduced inequalities, SDG 3 Good health and wellbeing) requires advancing health equity in research. The implementation of the STROBE-Equity guidelines will enable a better awareness and understanding of health inequities through better reporting. We will broadly disseminate the reporting guideline with tools to enable adoption and use by journal editors, authors, and funding agencies, using diverse strategies tailored to specific audiences.

In the study, natural deep eutectic solvents (NADESs) were used as alternatives to traditional chemical solvents for the extraction of polyphenols from Elaeagnus angustifolia L. Nine NADESs were tested for the first time and compared with ethanol and water (traditional solvents) regarding the extraction of phenolic compounds from E. angustifolia L. These solvents were particularly effective at extracting polyphenols, whose low water solubility usually requires high amounts of organic solvents. The solvent based on choline chloride and malonic acid provided optimal results and was selected for further optimization. The effects of material-to-liquid ratio, ultrasound time, and ultrasound temperature on the extraction efficiency were studied through single-factor experiments. These parameters were optimized by Box–Behnken design using response surface methodology. The optimal conditions identified were 49.86 g/mL of material-to-liquid ratio, 31.10 min of ultrasound time, and 62.35 °C of ultrasound temperature, resulting in a high yield of 140.30 ± 0.19 mg/g. The results indicated that the NADES extraction technique provided a higher yield than the conventional extraction process. The antioxidant activity of the extract of polyphenols from E. angustifolia L. was determined, and UPLC–IMS–QTOF–MS was used to analyze the phenolic compounds in it. The results revealed that the scavenging ability of 1,1-diphenyl-2-picryl-hydrazil and 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulphonate) extracted by NADES was higher than that of polyphenols extracted by water and ethanol. Furthermore, a total of 24 phenolic compounds were identified in the extract. To the best of our knowledge, this is the first study in which a green and efficient NADES extraction method has been used to extract bioactive polyphenols from E. angustifolia L., which could provide potential value in pharmaceuticals, cosmetics, and food additives.

Background: Patient-based real-time quality control (PBRTQC) can be a valuable tool in clinical laboratories due to its cost-effectiveness and constant monitoring. More focus is placed on discovering and improving algorithms that compliment conventional internal control techniques. The practical implementation of PBRTQC with a biochemical instrument comparison is lacking. We aim to evaluate PBRTQC’s efficacy and practicality by comparing low-density lipoprotein cholesterol (LDL-C) test results to ensure consistent real-time monitoring across biochemical instrumentations in clinical laboratories. Method: From 1 September 2021 to 30 August 2022, the First Affiliated Hospital of Xi’an Jiaotong University collected data from 158,259 both healthy and diseased patients, including 84,187 male and 74,072 female patients, and examined their LDL-C results. This dataset encompassed a group comprising 50,556 individuals undergoing health examinations, a group comprising 42,472 inpatients (IP), and a group comprising 75,490 outpatients (OP) for the PBRTQC intelligent monitoring platform to conduct daily tests, parameter configuration, program development, real-time execution, and performance validation of the patients’ data. Moreover 40 patients’ LDL-C levels were assessed using two biochemical analyzers, designated as the reference and comparator instruments. A total of 160 LDL-C results were obtained from 40 both healthy and diseased patients, including 14 OP, 16 IP, and 10 health examination attendees, who were selected to represent LDL-C levels broadly. Two biochemical instruments measured LDL-C measurements from the same individuals to investigate consistency and reproducibility across patient statuses and settings. We employed exponentially weighted moving average (EWMA) and moving median (MM) methods to calculate inter-instrument bias and ensure analytical accuracy. Inter-instrument bias for LDL-C measurements was determined by analyzing fresh serum samples, different concentrations of quality control (QC), and commercialized calibrators, employing both EWMA and MM within two assay systems. The assessment of inter-instrumental bias with five different methods adhered to the external quality assessment standards of the Clinical Laboratory Center of the Health Planning Commission, which mandates a bias within ±15.0%. Result: We calculated inter-instrument comparison bias with each of the five methods based on patient big data. The comparison of fresh serum samples, different concentrations of QC, commercialized calibrators, and EWMA were all in the permissive range, except for MM. MM showed that the bias between two biochemical instruments in the concentration ranges of 1.5 mmoL/L–6.2 mmoL/L exceeded the permissible range. This was mainly due to the small number of specimens, affected by variations among individual patients, leading to increased false alarms and reduced effectiveness in monitoring the consistency of the inter-instrumental results. Moreover, the inter-comparison bias derived from EWMA was less than 3.01%, meeting the 15% range assessment criteria. The bias result for MM was lower than 24.66%, which was much higher than EWMA. Thus, EWMA is better than MM for monitoring inter-instrument comparability. PBRTQC can complement the use of inter-comparison bias between biochemical analyzers. EWMA has comparable inter-instrument comparability monitoring efficacy. Conclusions: The utilization of AI-based PBRTQC enables the automated real-time comparison of test results across different biochemical instruments, leading to a reduction in laboratory operating costs, enhanced work efficiency, and improved QC. This advanced technology facilitates seamless data integration and analysis, ultimately contributing to a more streamlined and efficient laboratory workflow in the biomedical field.

In order to overcome the interface emulsification problem of TBP-FeCl3 systems and the instability of β-diketone systems in high-concentration alkaline medium, it is necessary to design and synthesize some new extractants. By introducing amino groups into a phosphorus extractant, a new 2-ethylhexyl hydrogen {[bis(2-ethylhexyl)amino]methyl} phosphonate acid (HA) extractant was synthesized. In this study, an efficient method of recovering lithium from the effluent of spent lithium-ion batteries (LIBs) is proposed. Experiments were conducted to assess the influential factors in lithium recovery, including the solution pH, saponification degree, extractant concentration, and phase ratio. Over 95% of lithium in the effluent was extracted into the organic phase, and nearly all lithium in the organic phase could be stripped into the aqueous phase using a 3 mol/L HCl solution. There was no significant decrease in extraction capacity after 10 cycles. The experimental results indicated that the extraction mechanism was a cation exchange process, and the extractive complex was proposed as LiA. Importantly, after three months of stable operation, the process demonstrated excellent stability and extraction efficiency, with rapid phase separation and a clear interface. This study offers an efficient, cost-effective, and environmentally friendly method for lithium extraction from the effluent of spent LIBs.

“Cytokine storm” is common in critically ill COVID-19 patients, however, mechanisms remain largely unknown. Here, we reported that overexpression of SARS-CoV-2 N protein in diabetic db/db mice significantly increased tubular death and the release of HMGB1, one of the damage-associated molecular patterns (DAMPs), to trigger M1 proinflammatory macrophage activation and production of IL-6, TNF-α, and MCP-1 via a Mincle-Syk/NF-κB-dependent mechanism. This was further confirmed in vitro that overexpression of SARS-CoV-2 N protein caused the release of HMGB1 from injured tubular cells under high AGE conditions, which resulted in M1 macrophage activation and production of proinflammatory cytokines via a Mincle-Syk/NF-κB-dependent mechanism. This was further evidenced by specifically silencing macrophage Mincle to block HMGB1-induced M1 macrophage activation and production of IL-6, TNF-α, and MCP-1 in vitro. Importantly, we also uncovered that treatment with quercetin largely improved SARS-CoV-2 N protein-induced AKI in db/db mice. Mechanistically, we found that quercetin treatment significantly inhibited the release of a DAMP molecule HMGB1 and inactivated M1 pro-inflammatory macrophage while promoting reparative M2 macrophage responses by suppressing Mincle-Syk/NF-κB signaling in vivo and in vitro. In conclusion, SARS-CoV-2 N protein-induced AKI in db/db mice is associated with Mincle-dependent M1 macrophage activation. Inhibition of this pathway may be a mechanism through which quercetin inhibits COVID-19-associated AKI.

Key Clinical Messase Periungual warts are frequently encountered in the field of dermatology. Here, we describe the case of a 69‐year‐old individual who presented with hand warts. The wart growth extended to the finger stump, resulting in a soft tissue defect on the fingertip of the right thumb. A treatment approach involving superficial x‐ray therapy in combination with tretinoin was employed to address this finding. The warts disappeared after completing 26 days of the treatment regimen. Fingertip soft tissue defects due to periungual warts are a rare occurrence in clinical settings. This report serves as the first documented case of such a problem successfully managed with the treatment approach mentioned above.

IntroductionAutosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder. The PKD1 gene is responsible for the majority of ADPKD cases, and the mutations in this gene exhibit high genetic diversity. This study aimed to investigate the association between genotype and phenotype in ADPKD patients with PKD1 gene mutations through pedigree analysis.MethodsEight Chinese pedigrees affected by ADPKD were analyzed using whole-exome sequencing (WES) on peripheral blood DNA. The identified variants were validated using Sanger sequencing, and clinical data from the patients and their families were collected and analyzed.ResultsNine novel mutation sites in PKD1 were discovered across the pedigrees, including c.4247T > G, c.3298_3301delGAGT, c.4798A > G, c.7567G > A, c.11717G > C, c.7703 + 5G > C, c.3296G > A, c.8515_8516insG, and c.5524C > A. These mutations were found to be associated with a range of clinical phenotypes, including chronic kidney disease, hypertension, and polycystic liver. The age of onset and disease progression displayed significant heterogeneity among the pedigrees, with some individuals exhibiting early onset and rapid disease progression, while others remained asymptomatic or had milder disease symptoms. Inheritance patterns supported autosomal dominant inheritance, as affected individuals inherited the mutations from affected parents. However, there were instances of individuals carrying the mutations who remained asymptomatic or exhibited milder disease phenotypes.ConclusionThis study highlights the importance of comprehensive genotype analysis in understanding the progression and prognosis of ADPKD. The identification of novel mutation sites expands our knowledge of PKD1 gene mutations. These findings contribute to a better understanding of the disease and may have implications for personalized therapeutic strategies.

Background: Major depressive disorder (MDD), a common mental disorder worldwide, frequently coexists with various physical illnesses, and recent studies have shown an increased prevalence of subclinical hypothyroidism (SHypo) among MDD patients. However, the neural mechanisms shared and unique to these disorders and the associated alterations in brain function remain largely unknown. This study investigated the potential brain function mechanisms underlying comorbid MDD and SHypo. Method: Thirty MDD patients (non-comorbid group), 30 MDD patients comorbid with SHypo (comorbid group), 26 patients with SHypo, and 30 healthy controls were recruited for resting-state functional magnetic resonance imaging (rs-fMRI). We used regional homogeneity (ReHo) to examine differences in internal cerebral activity across the four groups. Results: Compared with the non-comorbid group, the comorbid group exhibited significantly higher ReHo values in the right orbital part of the middle frontal gyrus (ORBmid) and bilateral middle frontal gyrus; decreased ReHo values in the right middle temporal gyrus, right thalamus, and right superior temporal gyrus, and right insula. Within the comorbid group, serum TSH levels were negatively associated with the ReHo values of the right insula; the ReHo values of the right Insula were negatively associated with the retardation factor score; the ReHo values of the right ORBmid were positively correlated with the anxiety/somatization factor scores. Conclusions: These findings provide valuable clues for exploring the shared neural mechanisms between MDD and SHypo and have important implications for understanding the pathophysiological mechanisms of the comorbidity of the two disorders.

Abstract Purpose The study was aimed at evaluating the bioequivalence and safety of oseltamivir phosphate for suspension, provided by Shenzhen Beimei Pharmaceutical Co. Ltd. and manufactured by Hetero Labs Limited, and the reference product TAMIFLU® in healthy Chinese subjects. Methods A single-dose, randomized, two-phase, self-crossed model was adopted. Among 80 healthy subjects, 40 subjects in the fasting group and 40 subjects in the fed group. Subjects in the fasting group were randomized into two sequences according to the proportion of 1:1, each given 75 mg/12.5 mL of Oseltamivir Phosphate for Suspension or TAMIFLU®, and cross-administered after 7 days. Postprandial group is the same as fasting group. Results The Tmax of TAMIFLU® and Oseltamivir Phosphate for Suspension in the fasting group were 1.50 h and 1.25 h, which in the fed group were both 1.25 h. Geometrically adjusted mean ratios of the PK parameters of Oseltamivir Phosphate for Suspension along with TAMIFLU® under fasting and postprandial conditions were in the range of 80.00–125.00% at the 90% confidence interval (CI). The 90% CI of Cmax, AUC0-t, AUC0-∞ for fasting group and postprandial group were (92.39,106.50), (94.26,100.67), (94.32,100.89) and (93.61,105.83),(95.64,100.19),(96.06,102.66). Among the subjects on medication, a total of 18 subjects reported 27 adverse events, all of which were treatment-emergent adverse events (TEAEs), six of these TEAEs were rated as grade 2 in severity and the rest were as grade 1. The number of TEAEs in the test product and the reference product were 14,13 respectively. Conclusion Two Oseltamivir phosphate for suspensions are safe and bioequivalent.

Purpose: To conduct an integrated bioinformatics analysis of extant aqueous humor (AH) gene expression datasets in order to identify key genes and the regulatory mechanism governing primary open-angle glaucoma (POAG) progression. Methods: Two datasets (GSE101727 and GSE105269) were downloaded from the Gene Expression Omnibus, and the messenger RNAs (mRNAs), microRNAs (miRNAs), and long noncoding RNAs (lncRNAs) were identified between controls and POAG patients. Differentially expressed (DE) mRNAs and DElncRNAs were then subjected to pathway enrichment analyses, after which a protein–protein interaction (PPI) network was generated. This network was then expanded to establish lncRNA–miRNA–mRNA and miRNA–transcription factor (TF)–mRNA networks. Results: The GSE101727 dataset was used to identify 2746 DElncRNAs and 2208 DEmRNAs, while the GSE105269 dataset was used to identify 45 DEmiRNAs. We ultimately constructed a competing endogenous RNA (ceRNA) network incorporating 47 lncRNAs, six miRNAs, and 17 mRNAs. The proteins encoded by these 17 hub mRNAs were found to be significantly enriched for activities that may be linked to POAG pathogenesis. In addition, we generated a miRNA–TF–mRNA regulatory network containing two miRNAs (miR-135a-5p and miR-139-5p), five TFs (TGIF2, TCF3, FOS, and so on), and five mRNAs (SHISA7, ST6GAL2, TXNIP, and so on). Conclusion: The SHISA7, ST6GAL2, TXNIP, FOS, and DCBLD2 genes may be viable therapeutic targets for the prevention or treatment of POAG and are regulated by the TFs (TGIF2, HNF1A, TCF3, and FOS).

Abstract The pandemic progression is a dynamic process, in which measures yield outcomes, and outcomes in turn influence subsequent measures and outcomes. Due to the dynamics of pandemic progression, it is challenging to analyse the long-term influence of an individual measure in the sequence on pandemic outcomes. To demonstrate the problem and find solutions, in this article, we study the first wave of the pandemic—probably the most dynamic period—in the Nordic countries and analyse the influences of the Swedish measures relative to the measures adopted by its neighbouring countries on COVID-19 mortality, general mortality, COVID-19 incidence, and unemployment. The design is a longitudinal observational study. The linear regressions based on the Poisson distribution or the binomial distribution are employed for the analysis. To show that analysis can be timely conducted, we use table data available during the first wave. We found that the early Swedish measure had a long-term and significant causal effect on public health outcomes and a certain degree of long-term mitigating causal effect on unemployment during the first wave, where the effect was measured by an increase of these outcomes under the Swedish measures relative to the measures adopted by the other Nordic countries. This information from the first wave has not been provided by available analyses but could have played an important role in combating the second wave. In conclusion, analysis based on table data may provide timely information about the dynamic progression of a pandemic and the long-term influence of an individual measure in the sequence on pandemic outcomes.

Objectives The prognosis for adults with relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is poor. Blinatumomab is a CD3/CD19-directed BiTE® (bispecific T-cell engager) molecule approved globally for the treatment of BCP-ALL in adults and children. This multicenter open-label single-arm China registrational study evaluated the safety, efficacy, and pharmacokinetics of blinatumomab in Chinese adults with Philadelphia chromosome-negative (Ph−) R/R BCP-ALL (NCT03476239).Methods Patients aged ≥ 18 years were treated with up to 5 cycles of blinatumomab. The primary objective was to evaluate the hematological response rate (complete remission/complete remission with partial hematological recovery [CR/CRh]) within 2 cycles of blinatumomab.Results At the interim analysis (April 12, 2019), 90 patients (median age 31.5 years [range: 18-74]; 53.3% female; 77.8% with bone marrow blasts ≥ 50% at study entry) were enrolled at 23 study centers in China and had received blinatumomab. As of data cutoff, 43 patients (47.8%) continued the study. The CR/CRh rate within 2 cycles of blinatumomab was 45.6% (41/90 [CR, 37; CRh, 4]; 95% CI: 35.0–56.4). Median overall survival was 9.2 months (95% CI: 6.5–11.7); median relapse-free survival was 4.3 months (95% CI: 3.2–9.4). Mean serum concentration at steady-state and systemic clearance of blinatumomab in Chinese patients were within the range reported in adults from global clinical trials. No new safety risks were identified in Chinese patients.Conclusions The efficacy and safety of blinatumomab in these heavily pre-treated Chinese patients with Ph− R/R BCP-ALL is comparable to that for patients within global clinical trials.

Iron deficiency anemia (IDA) affects more than 1.2 billion individuals globally. In addition to anemia, reactive thrombocytosis is also a common clinical hematological condition in patients with IDA. However, some case reports have described the thrombotic complications in association with IDA-induced thrombocytosis. Patients with a high risk of thrombosis need prompt identification and effective treatment to prevent thrombotic complications. While iron replacement treatment has been shown to decrease platelet count in this context, there is limited published evidence on how iron supplementation affects the thrombocytosis caused by IDA. We retrospectively examined the clinical records of 440 patients with IDA from an RCT completed from 1 January 2016, to 30 December 2017, and data obtained from this study was used for post hoc analysis to examine the effect of iron on platelet count in IDA-induced thrombocytosis. The mean ± standard deviation (SD) platelet counts of the 440 patients with IDA was 310.23 ± 98.72 × 109/L. With baseline platelet counts>450 × 109 /L as the cutoff for thrombocytosis, patients were divided into 2 groups: 36 (8.1%) in the IDA with thrombocytosis group (mean ± SD platelet count, 521.67 ± 73.85 × 109/L) and the remaining 404 in the IDA without thrombocytosis group (mean ± SD platelet count, 291.39 ± 76.11 × 109/L). Differences were found in baseline characteristics including white blood cell (WBC) count, hemoglobin (Hb) level, mean corpuscular volume (MCV), transferrin saturation (TSAT), serum iron (SI) level, and total iron-binding capacity (TIBC) between the two groups (P

Accurate detection of antigen p24 for HIV−1 early diagnosis remains challenging. Here the authors present a click chemistry amplified nanopore (CAN) assay that allows p24 quantification at ultralow concentration range in clinical samples.

Abstract To determine the effectiveness and safety of amino acids in preventing the mortality and morbidity among preterm infants. We conducted a systematic review and network meta-analysis. We searched MEDLINE, EMBASE, Web of Science, CINAHL, Scopus, Cochrane, and Google Scholar, and grey literature, from databases inception to January 2021. We included randomized trials that evaluated any amino acids on preterm or low-birth weight infants. We performed frequentist pairwise and network meta-analyses and used the GRADE methodology to assess the certainty of the evidence and provide a summary of the results.We included 18 trials (3702 infants). Low certainty evidence showed that there seems to be no benefit for arginine, glutamine, or N-acetylcysteine in reducing all-cause mortality. Oral arginine likely results in reduction of necrotizin enterocolitis (NEC) stage ≥ II (OR 0.48; 95% CI 0.26–0.90; moderate certainty). Oral glutamine may reduce the likelihood of developing late-onset sepsis (LOS) compared to placebo (OR 0.62; 95% CI 0.47–0.82; low certainty); and likely reduces time to reach full enteral feeding (MD = − 2.63 days; 95% CI − 4.99 to − 0.27; moderate certainty). Amino acids may have no effect on mortality. Oral arginine may reduce severe NEC, and oral glutamine may reduce LOS and the time to reach full feeding. Systematic review registration: PROSPERO registration number: CRD4201603873.