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Abstract Background Colorectal cancer (CRC) metachronous liver metastasis is a significant clinical challenge, largely attributable to the late detection and the intricate molecular mechanisms that remain poorly understood. This study aims to elucidate the role of Solute Carrier Family 14 Member 1 (SLC14A1) in the pathogenesis and progression of CRC metachronous liver metastasis. Methods We conducted a comprehensive analysis of CRC patient data from The Cancer Genome Atlas and GSE40967 databases, focusing on the differential expression of genes associated with non-metachronous liver metastasis and metachronous liver metastasis. Functional assays, both in vitro and in vivo, were performed to assess the biological impact of SLC14A1 modulation in CRC cells. Gene set enrichment analysis, molecular assays and immunohistochemical analyses on clinical specimens were employed to unravel the underlying mechanisms through which SLC14A1 exerts its effects. Results SLC14A1 was identified as a differentially expressed gene, with its overexpression significantly correlating with poor relapse-free and overall survival. Mechanistically, elevated SLC14A1 levels enhanced CRC cell invasiveness and migratory abilities, corroborated by upregulated TGF-β/Smad signaling and Epithelial-Mesenchymal Transition. SLC14A1 interacted with TβRII and stabilized TβRII protein, impeding its Smurf1-mediated K48-linked ubiquitination and degradation, amplifying TGF-β/Smad signaling. Furthermore, TGF-β1 reciprocally elevated SLC14A1 mRNA expression, with Snail identified as a transcriptional regulator, binding downstream of SLC14A1’s transcription start site, establishing a positive feedback loop. Clinically, SLC14A1, phosphorylated Smad2, and Snail were markedly upregulated in CRC patients with metachronous liver metastasis, underscoring their potential as prognostic markers. Conclusions Our findings unveil SLC14A1 as a critical regulator in CRC metachronous liver metastasis, providing novel insights into the molecular crosstalk between SLC14A1 and TGF-β/Smad signaling. These discoveries not only enhance our understanding of CRC metachronous liver metastasis pathogenesis, but also highlight SLC14A1 as a promising target for therapeutic intervention and predictive marker.

High-speed railway tunnels in various countries have continuously reported accidents of vault falling concrete blocks. Once the concrete block falling occurs, serious consequences follow, and traffic safety may be endangered. The aerodynamic shockwave evolves from the initial compression wave may be an important inducement causing the tunnel lining cracks to grow and form falling concrete blocks. A joint calculation framework is established based on ANSYS Fluent, ABAQUS, and FRANC3D for calculating the crack tip field under the aerodynamic shockwave. The intensification effect of aerodynamic shockwaves in the crack is revealed, and the evolution characteristics of the crack tip field and the influence factors of stress intensity factor (SIF) are analyzed. Results show that (1) the aerodynamic shockwave intensifies after entering the crack, resulting in more significant pressure in the crack than the input pressure. The maximum pressure of the inclined and longitudinal cracks is higher than the corresponding values of the circumferential crack, respectively. (2) The maximum SIF of the circumferential, inclined, and longitudinal crack appears at 0.5, 0.68, and 0.78 times the crack front length. The maximum SIF of the circumferential crack is higher than that of the inclined and longitudinal crack. The possibility of crack growth of the circumferential crack is the highest under aerodynamic shockwaves. (3) The influence of train speed on the SIF of the circumferential crack is more than 40%. When the train speed, crack depth, and crack length change, the change of pressure in the crack is the direct cause of the change of SIF.

Abstract Background Ovarian carcinoma (OC) is a fatal malignancy, with most patients experiencing recurrence and resistance to chemotherapy. In contrast to hematogenous metastasizing tumors, ovarian cancer cells disseminate within the peritoneal cavity, especially the omentum. Previously, we reported omental crown-like structure (CLS) number is associated with poor prognosis of advanced-stage OC. CLS that have pathologic features of a dead or dying adipocyte was surrounded by several macrophages is well known a histologic hallmark for inflammatory adipose tissue. In this study, we attempted to clarify the interaction between metastatic ovarian cancer cells and omental CLS, and to formulate a therapeutic strategy for advanced-stage ovarian cancer. Methods A three-cell (including OC cells, adipocytes and macrophages) coculture model was established to mimic the omental tumor microenvironment (TME) of ovarian cancer. Caspase-1 activity, ATP and free fatty acids (FFA) levels were detected by commercial kits. An adipocyte organoid model was established to assess macrophages migration and infiltration. In vitro and in vivo experiments were performed for functional assays and therapeutic effect evaluations. Clinical OC tissue samples were collected for immunochemistry stain and statistics analysis. Results In three-cell coculture model, OC cells-derived IL-6 and IL-8 could induce the occurrence of pyroptosis in omental adipocytes. The pyroptotic adipocytes release ATP to increase macrophage infiltration, release FFA into TME, uptake by OC cells to increase chemoresistance. From OC tumor samples study, we demonstrated patients with high gasdermin D (GSDMD) expression in omental adipocytes is highly correlated with chemoresistance and poor outcome in advanced-stage OC. In animal model, by pyroptosis inhibitor, DSF, effectively retarded tumor growth and prolonged mice survival. Conclusions Omental adipocyte pyroptosis may contribute the chemoresistance in advanced stage OC. Omental adipocytes could release FFA and ATP through the GSDMD-mediate pyroptosis to induce chemoresistance and macrophages infiltration resulting the poor prognosis in advanced-stage OC. Inhibition of adipocyte pyroptosis may be a potential therapeutic modality in advanced-stage OC with omentum metastasis.

Abstract Objective The study aimed to investigate the predictive value of dynamic contrast-enhanced ultrasound (DCE-US) in differentiating small-duct (SD) and large-duct (LD) types of intrahepatic cholangiocarcinoma (ICC). Methods This study retrospectively enrolled 110 patients with pathologically confirmed ICC lesions who were subject to preoperative contrast-enhanced ultrasound (CEUS) examinations between January 2022 and February 2023. Patients were further classified according to the subtype: SD-type and LD-type, and an optimal predictive model was established and validated using the above pilot cohort. The test cohort, consisting of 48 patients prospectively enrolled from March 2023 to September 2023, was evaluated. Results In the pilot cohort, compared with SD-type ICCs, more LD-type ICCs showed elevated carcinoembryonic antigen (p

Abstract Background In order to ensure adequate radiation protection of critical groups such as staff, caregivers and the general public coming into proximity of nuclear medicine (NM) patients, it is necessary to consider the impact of the radiation emitted by the patients during their stay at the hospital or after leaving the hospital. Current risk assessments are based on ambient dose rate measurements in a single position at a specified distance from the patient and carried out at several time points after administration of the radiopharmaceutical to estimate the whole-body retention. The limitations of such an approach are addressed in this study by developing and validating a more advanced computational dosimetry approach using Monte Carlo (MC) simulations in combination with flexible and realistic computational phantoms and time activity distribution curves from reference biokinetic models. Results Measurements of the ambient dose rate equivalent Ḣ * (10) at 1 m from the NM patient have been successfully compared against MC simulations with 5 different codes using the ICRP adult reference computational voxel phantoms, for typical clinical procedures with 99mTc-HDP/MDP, 18FDG and Na131I. All measurement data fall in the 95% confidence intervals, determined for the average simulated results. Moreover, the different MC codes (MCNP-X, PHITS, GATE, GEANT4, TRIPOLI-4®) have been compared for a more realistic scenario where the effective dose rate Ė of an exposed individual was determined in positions facing and aside the patient model at 30 cm, 50 cm and 100 cm. The variation between codes was lower than 8% for all the radiopharmaceuticals at 1 m, and varied from 5 to 16% for the face-to face and side-by-side configuration at 30 cm and 50 cm. A sensitivity study on the influence of patient model morphology demonstrated that the relative standard deviation of Ḣ * (10) at 1 m for the range of included patient models remained under 16% for time points up to 120 min post administration. Conclusions The validated computational approach will be further used for the evaluation of effective dose rates per unit administered activity for a variety of close-contact configurations and a range of radiopharmaceuticals as part of risk assessment studies. Together with the choice of appropriate dose constraints this would facilitate the setting of release criteria and patient restrictions.

Abstract Background The family Rhabdiasidae (Nematoda: Rhabditida) is a globally distributed group of nematode parasites, with over 110 species parasitic mainly in amphibians and reptiles. However, the systematic position of the family Rhabdiasidae in the order Rhabditida remains unsolved, and the evolutionary relationships among its genera are still unclear. Moreover, the present knowledge of the mitochondrial genomes of rhabdiasids remains limited. Methods Two rhabdiasid species: Rhabdias kafunata Sata, Takeuchi & Nakano, 2020 and R. bufonis (Schrank, 1788) collected from the Asiatic toad Bufo gargarizans Cantor (Amphibia: Anura) in China, were identified based on morphology (light and scanning electron microscopy) and molecular characterization (sequencing of the nuclear 28S and ITS regions and mitochondrial cox1 and 12S genes). The complete mitochondrial genomes of R. kafunata and R. bufonis were also sequenced and annotated for the first time. Moreover, phylogenetic analyses based on the amino acid sequences of 12 protein-coding genes (PCGs) of the mitochondrial genomes were performed to clarify the systematic position of the family Rhabdiasidae in the order Rhabditida using maximum likelihood (ML) and Bayesian inference (BI). The phylogenetic analyses based on the 28S + ITS sequences, were also inferred to assess the evolutionary relationships among the genera within Rhabdiasidae. Results The detailed morphology of the cephalic structures, vulva and eggs in R. kafunata and R. bufonis was revealed using scanning electron microscopy (SEM) for the first time. The characterization of 28S and ITS regions of R. kafunata was reported for the first time. The mitogenomes of R. kafunata and R. bufonis are 15,437 bp and 15,128 bp long, respectively, and both contain 36 genes, including 12 PCGs (missing atp8). Comparative mitogenomics revealed that the gene arrangement of R. kafunata and R. bufonis is different from all of the currently available mitogenomes of nematodes. Phylogenetic analyses based on the ITS + 28S data showed Neoentomelas and Kurilonema as sister lineages, and supported the monophyly of Entomelas, Pneumonema, Serpentirhabdias and Rhabdias. Mitochondrial phylogenomic results supported Rhabdiasidae as a member of the superfamily Rhabditoidea in the suborder Rhabditina, and its occurrance as sister to the family Rhabditidae. Conclusions The complete mitochondrial genome of R. kafunata and R. bufonis were reported for the first time, and two new gene arrangements of mitogenomes in Nematoda were revealed. Mitogenomic phylogenetic results indicated that the family Rhabdiasidae is a member of Rhabditoidea in Rhabditina, and is closely related to Rhabditidae. Molecular phylogenies based on the ITS + 28S sequence data supported the validity of Kurilonema, and showed that Kurilonema is sister to Neoentomelas. The present phylogenetic results also indicated that the ancestors of rhabdiasids seem to have initially infected reptiles, then spreading to amphibians. Graphical Abstract

Distributed energy systems relying on renewable energy sources such as wind and solar energies are faced with challenges, including excessive frequency fluctuations and the complexity of hybrid energy storage control. To address these issues, the paper proposes a frequency control method based on Nash equilibrium quantum particle swarm optimization (NEQPSO) for distributed energy systems. Initially, a model is established to simulate distributed energy systems containing renewable energy sources and featuring hybrid energy storage. Subsequently, the outputs from both the slide mode controller (SMC) and the linear active disturbance rejection controller (LADRC) observer are integrated into the proportional derivative (PD) controller of the LADRC, leading to an improved slide mode-linear active disturbance rejection controller (SM-LADRC). Following this, NEQPSO is utilized to optimize the controller parameters to secure optimal configurations. Finally, comparative validation experiments are conducted under different settings, demonstrating that the optimized controller significantly outperformed conventional proportional integral derivative (PID) and proportional integral (PI) controllers. The optimization capability of NEQPSO proved clearly superior to that of particle swarm algorithm (PSO) and genetic algorithm (GA). Moreover, in subsequent on-load experiments and sensitivity validation experiments, distributed energy systems employing SM-LADRC based on NEQPSO exhibited swift responsiveness, strong disturbance rejection, improved frequency stability, and enhanced steady-state performance.

High-speed trains (HSTs) transiting subgrade-cutting transition sections in crosswinds have become a common operating scenario. This paper utilizes the Improved Delayed Detached Eddy Simulation (IDDES) turbulence model, considers air compressibility, and establishes a three-dimensional coupled train-subgrade-wind dynamics model. The aerodynamic load (AL) variation rules of trains and discrepancies in the flow field mechanisms when HSTs transit various types of subgrade-cutting transition sections [half cutting and half flat (HCHF), double side cutting (DC), and half cutting and half embankment (HCHE)] under crosswind conditions are revealed using this model. The results indicate the following. (1) The aerodynamic performance deteriorates when trains transit three subgrade-cutting transition sections under crosswinds. (2) As trains enter the transition section from a flat approach, the head car’s AL power spectrum density (PSD) is the largest when operating in the DC case. (3) After the train drives into the subsequent operating scenario, the average of the AL in the DC case is the lowest. (4) In the DC case, a slope of 1:0.75 should be taken as the basis for the design of the corresponding cutting parameters. (5) After the train enters the cutting, the winding flow speed and number of vortex structures surrounding the trains increase significantly.

Spinal cord injury (SCI) is a severe event that occurs in the central nervous system (CNS). Long noncoding RNAs (lncRNAs) have already been proven to play key roles in different diseases of the CNS. Nevertheless, the roles of messenger RNAs (mRNAs) and lncRNAs one week after SCI remain to be elucidated. We established a rat model of SCI and examined the differential levels of mRNAs and lncRNAs, and then, the differentially expressed mRNAs (DE mRNAs) and lncRNAs (DE lncRNAs) were investigated. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DE lncRNAs and mRNAs were subsequently carried out to explore crucial biological processes and signaling pathways. Moreover, we constructed protein–protein interaction (PPI) networks, the STRING database, and identified the 10 high degree core nodes. We also established a co-expression network by calculating the correlation between lncRNA expression profile and mRNA expression profile. The identified DE lncRNAs and DE mRNAs may potentially be critical targets for the diagnosis and treatment of SCI in the future. Abbreviations: SCI: spinal cord injury; CNS: central nervous system; YLDs: years of life lived with disability; lncRNAs: long noncoding RNAs; mRNAs: messenger RNAs; DE: differentially expressed; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; GSEA: gene set enrichment analysis; RIN: Renewable Identification Number; PCA: principal component analysis; PPI: protein–protein interaction; MF, molecular function; BP: biological process; CC: cellular component; MCODE: molecular complex detection

While the topic of attracting and maintaining inbound international students has received much scholarly attention in higher education, attracting female international students has rarely been discussed. This study addresses the issue of attracting degree-seeking female international students. Based on the notion of situational factors and total quality management (TQM), we assumed both institutional design and students’ satisfaction are core concepts for attracting and retaining female international students that will make a difference in higher education. A total of 215 survey responses were analyzed, and a covariance-based structural equation modeling (CB-SEM) approach was developed. The results confirm female international students’ perception of 14 observed variables in the three first-order components and suggest that they can create a second-order construct of push factors, institutional situations, and satisfaction (latent variables). This study demonstrates that higher-order modeling leads to theoretical parsimony and reduces model complexity in the proposed CB-SEM. The findings suggest that the casual relationship works well and both institutional leadership and international strategy can play crucial roles in the process of transforming female international students’ learning satisfaction.

Introduction Spinal cord injury (SCI) is a catastrophic event with devastating physical, social and occupational consequences for patients and their families. The number of patients with acute SCI in China continues to grow rapidly, but there have been no large prospective cohort studies of patients with acute SCI. This proposed study aims to establish a multicentre, extensive sample cohort of clinical data and biological samples of patients in China, which would aid the systematisation and standardisation of clinical research and treatment of acute SCI, thus reducing the heavy burden of acute SCI on patients and society.Methods and analysis The Chinese Real-World Evidence for Acute Spinal Cord Injury (ChiRES) study is an observational, multicentre cohort study of patients with acute SCI admitted to the Qilu Hospital of Shandong University and other participating centres with prospective collection of their clinical data and biological samples. We aim to recruit 2097 patients in this study. Demographics, disease history, emergency intervention information, motor and sensory examinations, surgical information, medication information and rehabilitation evaluation will be recorded. This will facilitate the development of a prediction model for complications and prognosis of patients with acute SCI and an evaluation of the current management of acute SCI. Among these variables, detailed information on surgical treatment will also be used to assess procedures for acute SCI treatment. Outcome measurements, including the International Standard for Neurological Classification of Spinal Cord Injury examinations, the occurrence of complications and death, will be performed repeatedly during follow-up. We will analyse imaging data and blood samples to develop SCI imaging markers and biomarkers.Ethics and dissemination This study protocol has been approved by the Medical Ethics Committee of the Qilu Hospital of Shandong University and all other participating centres. The findings will be disseminated in peer-reviewed journals and academic conferences.

Objective: Molidustat is a novel agent investigated for the treatment of anemia in both dialysisdependent (DD) and non-dialysis-dependent (NDD) patients. Its efficacy and safety are still unclear. Methods: We searched five databases to identify randomized controlled trials comparing molidustat to erythropoiesis-stimulating agents (ESAs) or placebo in patients with anemia. Results: Six studies containing 2025 eligible participants were identified. For NDD patients, the change in Hb levels from baseline (ΔHb) was significantly higher for molidustat than for placebo [mean difference (MD) = 1.47 (95 % CI: 1.18 to 1.75), P

Potential toxic element (PTE) pollution has emerged as a significant environmental and social concern in global agriculture. Chromium (Cr) occurs in different oxidation states naturally, among them Cr(VI), which is highly toxic. This study carried out biochemical and molecular tests to elucidate the accumulation of total soluble phenolics (TSPs) in rice plants exposed to Cr(VI) at 2.0, 8.0, and 16.0 mg Cr/L, emphasizing the interaction between polyamines (PAs) and abscisic acid (ABA). The results revealed significant Cr accumulation in different tissues of rice plants, which hindered their growth. Cr(VI) exposure increased the ABA concentration, with higher levels detected in the shoots than in the roots. The TSP concentration in rice tissues showed a positive relationship with the supplied concentrations of Cr(VI). The measured PAs, including spermine (Spm), putrescine (Put), and spermidine (Spd), exhibited varied responses to Cr(VI) stress, with only Spm concentration increasing with Cr(VI) concentrations. Real-time qRT-PCR showed PAs and ABA synthesis-associated genes such as OsADC1, OsAIH, OsCPA1, and OsCPA4 were significantly up-regulated in shoot of rice plants treated with Cr(VI). These genes are associated with the second pathway of Put synthesis, originating from Arg. Almost all genes activated in the Met pathway were significantly up-regulated as well. Moreover, the genes involved in the interconversion among the three species of PAs exhibited completely different responses to Cr(VI) exposure. Overall, the biochemical analysis and gene expression data indicate that the interaction between ABA and Spm is likely to enhance the TSP levels in rice plants subjected to Cr(VI) toxicity.

Summary: Background: Clinical appearance and high-frequency ultrasound (HFUS) are indispensable for diagnosing skin diseases by providing internal and external information. However, their complex combination brings challenges for primary care physicians and dermatologists. Thus, we developed a deep multimodal fusion network (DMFN) model combining analysis of clinical close-up and HFUS images for binary and multiclass classification in skin diseases. Methods: Between Jan 10, 2017, and Dec 31, 2020, the DMFN model was trained and validated using 1269 close-ups and 11,852 HFUS images from 1351 skin lesions. The monomodal convolutional neural network (CNN) model was trained and validated with the same close-up images for comparison. Subsequently, we did a prospective and multicenter study in China. Both CNN models were tested prospectively on 422 cases from 4 hospitals and compared with the results from human raters (general practitioners, general dermatologists, and dermatologists specialized in HFUS). The performance of binary classification (benign vs. malignant) and multiclass classification (the specific diagnoses of 17 types of skin diseases) measured by the area under the receiver operating characteristic curve (AUC) were evaluated. This study is registered with www.chictr.org.cn (ChiCTR2300074765). Findings: The performance of the DMFN model (AUC, 0.876) was superior to that of the monomodal CNN model (AUC, 0.697) in the binary classification (P = 0.0063), which was also better than that of the general practitioner (AUC, 0.651, P = 0.0025) and general dermatologists (AUC, 0.838; P = 0.0038). By integrating close-up and HFUS images, the DMFN model attained an almost identical performance in comparison to dermatologists (AUC, 0.876 vs. AUC, 0.891; P = 0.0080). For the multiclass classification, the DMFN model (AUC, 0.707) exhibited superior prediction performance compared with general dermatologists (AUC, 0.514; P = 0.0043) and dermatologists specialized in HFUS (AUC, 0.640; P = 0.0083), respectively. Compared to dermatologists specialized in HFUS, the DMFN model showed better or comparable performance in diagnosing 9 of the 17 skin diseases. Interpretation: The DMFN model combining analysis of clinical close-up and HFUS images exhibited satisfactory performance in the binary and multiclass classification compared with the dermatologists. It may be a valuable tool for general dermatologists and primary care providers. Funding: This work was supported in part by the National Natural Science Foundation of China and the Clinical research project of Shanghai Skin Disease Hospital.

Tenuazonic acid (TeA) and patulin (PAT), as the naturally occurring mycotoxins with various toxic effects, are often detected in environment and food chain, has attracted more and more attention due to their widespread and high contaminations as well as the coexistence, which leads to potential human and animals’ risks. However, their combined toxicity has not been reported yet. In our study, C. elegans was used to evaluate the type of combined toxicity caused by TeA+PAT and its related mechanisms. The results showed that TeA and PAT can induce synergistic toxic effects based on Combination Index (CI) evaluation model (Chou-Talalay method), that is, the body length, brood size as well as the levels of ROS, CAT and ATP were significantly affected in TeA+PAT-treated group compared with those in TeA- or PAT-treated group. Besides, the expressions of oxidative (daf-2, daf-16, cyp-35a2, ctl-1, ctl-3, pmk-1, jnk-1, skn-1) and intestinal (fat-5, pod-2, egl-8, pkc-3, ajm-1, nhx-2) stress-related genes were disrupted, among which daf-16 displayed the most significant alternation. Further study on daf-16 gene defective C. elegans showed that the damages to the mutant nematodes were significantly attenuated. Since daf-2, daf-16, jnk-1 and pmk-1 are evolutionarily conserved, our findings could hint synergistic toxic effects of TeA+PAT on higher organisms.

Objectives: The prevalence of G6PD deficiency has not been reported in Yangjiang, a western city in Guangdong province. This study aims to investigate the molecular characteristics of G6PD deficiency in this region.Methods: Blood samples were collected from adults at a local hospital to screen for G6PD deficiency. The deficient samples were subjected to further analysis using PCR and reverse dot blot to determine the specific G6PD variants.Results: Among the 3314 male subjects, 250 cases of G6PD deficiency were found using the G6PD enzyme quantitative assay, resulting in a prevalence of 7.54% (250/3314) in the Yangjiang region. The prevalence of G6PD deficiency in females was 3.42% (176/5145). Out of the 268 cases of G6PD deficiency tested for G6PD mutations, reverse dot blot identified 20 different G6PD variants. The most common G6PD variant was c.1388G>A (81/268), followed by c.1376G>T (48/268), c.95A>G (32/268), c.1024C>T (9/268), c.392G>T (7/268), and c.871G>A/c.1311C>T (6/268). It was observed that c.871G>A was always linked to the polymorphism of c.1311C>T in this population.Conclusion: This investigation into G6PD deficiency in this area is expected to significantly improve our understanding of the prevalence and molecular characterization of this condition.

Objective: Peroxiredoxin-3 (Prx-3) is widely acknowledged as an antioxidant that protects against mitochondrialreactive oxygen species. Nonetheless, its role in cardiac fibrosis has not been elucidated. We aim to explore the roleand mechanism of Prx-3 in cardiac fibrosis.Materials and Methods: In this experimental study, mice received subcutaneous injections of isoproterenol (ISO) for 14consecutive days (10 mg/kg/d for three days, followed by 5 mg/kg/d for 11 days) to establish a cardiac fibrosis model. Themice were subsequently injected with adenovirus-Prx-3 (ad-Prx-3) to enable Prx-3 overexpression. Echocardiographywas used to evaluate cardiac function. Mice heart fibroblasts were isolated and stimulated with transforming growthfactor β1 (TGFβ1) to induce fibrosis in vitro. Cells were also transfected with ad-Prx-3 for overexpression of Prx-3.Results: Echocardiographic diameters and fibrosis markers indicated that Prx-3 could inhibit ISO-induced cardiacdysfunction and fibrosis. Fibroblasts with Prx-3 overexpression exhibited reduced activation, proliferation, and collagentranscription. We found that Prx-3 reduced the expression of NADPH oxidase 4 (NOX4) and reduced P38 levels. Aftertreatment with a P38 inhibitor, the Prx-3 overexpression-induced anti-fibrosis effect was mitigated.Conclusion: Prx-3 could protect against ISO-induced cardiac fibrosis by inhibiting the NOX4-P38 pathway.

Abstract N1-Methyladenosine (m1A) is an abundant modification of transcripts, plays important roles in regulating mRNA structure and translation efficiency, and is dynamically regulated under stress. However, the characteristics and functions of mRNA m1A modification in primary neurons and oxygen glucose deprivation/reoxygenation (OGD/R) induced remain unclear. We first constructed a mouse cortical neuron OGD/R model and then used methylated RNA immunoprecipitation (MeRIP) and sequencing technology to demonstrate that m1A modification is abundant in neuron mRNAs and dynamically regulated during OGD/R induction. Our study suggests that Trmt10c, Alkbh3, and Ythdf3 may be m1A-regulating enzymes in neurons during OGD/R induction. The level and pattern of m1A modification change significantly during OGD/R induction, and differential methylation is closely associated with the nervous system. Our findings show that m1A peaks in cortical neurons aggregate at both the 5’ and 3’ untranslated regions. m1A modification can regulate gene expression, and peaks in different regions have different effects on gene expression. By analysing m1A-seq and RNA-seq data, we show a positive correlation between differentially methylated m1A peaks and gene expression. The correlation was verified by using qRT-PCR and MeRIP-RT-PCR. Moreover, we selected human tissue samples from Parkinson’s disease (PD) and Alzheimer’s disease (AD) patients from the Gene Expression Comprehensive (GEO) database to analyse the selected differentially expressed genes (DEGs) and differential methylation modification regulatory enzymes, respectively, and found similar differential expression results. We highlight the potential relationship between m1A modification and neuronal apoptosis following OGD/R induction. Furthermore, by mapping mouse cortical neurons and OGD/R-induced modification characteristics, we reveal the important role of m1A modification in OGD/R and gene expression regulation, providing new ideas for research on neurological damage.

We demonstrate CW optical waveguiding in a silica MNF with power up to 13 W, making it possible for high-speed optomechanical driving of microparticles, and efficient second/third harmonic generation.

Cerebral ischaemiareperfusion injury is an important pathological process in nervous system diseases during which neurons undergo oxygenglucose deprivation and reoxygenation (OGD/R) injury. No study has used epitranscriptomics to explore the characteristics and mechanism of injury. N6methyladenosine (m6A) is the most abundant epitranscriptomic RNA modification. However, little is known about m6A modifications in neurons, especially during OGD/R. m6A RNA immunoprecipitation sequencing (MeRIPseq) and RNA-sequencing data for normal and OGD/R-treated neurons were analysed by bioinformatics. MeRIP quantitative real-time polymerase chain reaction was used to determine the m6A modification levels on specific RNAs. We report the m6A modification profiles of the mRNA and circRNA transcriptomes of normal and OGD/R-treated neurons. Expression analysis revealed that the m6A levels did not affect m6A mRNA or m6A circRNA expression. We found crosstalk between m6A mRNAs and m6A circRNAs and identified three patterns of m6A circRNA production in neurons; thus, distinct OGD/R treatments induced the same genes to generate different m6A circRNAs. Additionally, m6A circRNA biogenesis during distinct OGD/R processes was found to be time specific. These results expand our understanding of m6A modifications in normal and OGD/R-treated neurons, providing a reference to explore epigenetic mechanisms and potential treatments for OGD/R-related diseases.

The purpose of this study was to explore transrectal ultrasound (TRUS) findings of prostate cancer (PCa) guided by multiparametric magnetic resonance imaging (mpMRI) and to improve the Prostate Imaging Reporting and Data System (PI-RADS) system for avoiding unnecessary mpMRI-guided targeted biopsy (TB). From January 2018 to October 2019, fusion mpMRI and TRUS-guided biopsies were performed in 162 consecutive patients. The study included 188 suspicious lesions on mpMRI in 156 patients, all of whom underwent mpMRI-TRUS fusion imaging-guided TB and 12-core transperineal systematic biopsy (SB). Univariate analyses were performed to investigate the relationship between TRUS features and PCa. Then, logistic regression analysis with generalized estimating equations was performed to determine the independent predictors of PCa and obtain the fitted probability of PCa. The detection rates of PCa based on TB alone, SB alone, and combined SB and TB were 55.9% (105 of 188), 52.6% (82 of 156), and 62.8% (98 of 156), respectively. The significant predictors of PCa on TRUS were hypoechogenicity (odds ratio [OR]: 9.595, P = 0.002), taller-than-wide shape (OR: 3.539, P = 0.022), asymmetric vascular structures (OR: 3.728, P = 0.031), close proximity to capsule (OR: 3.473, P = 0.040), and irregular margins (OR: 3.843, P = 0.041). We propose subgrouping PI-RADS score 3 into categories 3a, 3b, 3c, and 3d based on different numbers of TRUS predictors, as the creation of PI-RADS 3a (no suspicious ultrasound features) could avoid 16.7% of mpMRI-guided TBs. Risk stratification of PCa with mpMRI-TRUS fusion imaging-directed ultrasound features could avoid unnecessary mpMRI-TBs.

The purpose of this study was to analyze the value of transrectal shear-wave elastography (SWE) in combination with multivariable tools for predicting adverse pathological features before radical prostatectomy (RP). Preoperative clinicopathological variables, multiparametric magnetic resonance imaging (mp-MRI) manifestations, and the maximum elastic value of the prostate (Emax) on SWE were retrospectively collected. The accuracy of SWE for predicting adverse pathological features was evaluated based on postoperative pathology, and parameters with statistical significance were selected. The diagnostic performance of various models, including preoperative clinicopathological variables (model 1), preoperative clinicopathological variables + mp-MRI (model 2), and preoperative clinicopathological variables + mp-MRI + SWE (model 3), was evaluated with area under the receiver operator characteristic curve (AUC) analysis. Emax was significantly higher in prostate cancer with extracapsular extension (ECE) or seminal vesicle invasion (SVI) with both P < 0.001. The optimal cutoff Emax values for ECE and SVI were 60.45 kPa and 81.55 kPa, respectively. Inclusion of mp-MRI and SWE improved discrimination by clinical models for ECE (model 2 vs model 1, P = 0.031; model 3 vs model 1, P = 0.002; model 3 vs model 2, P = 0.018) and SVI (model 2 vs model 1, P = 0.147; model 3 vs model 1, P = 0.037; model 3 vs model 2, P = 0.134). SWE is valuable for identifying patients at high risk of adverse pathology.

ObjectiveThe objective of this study was to analyze the clinical characteristics of pregnant women infected with the COVID-19 omicron variant and their neonates during the outbreak in Guangdong province, China.MethodsThe clinical data of pregnant women infected with the COVID-19 omicron variant and their neonates were retrospectively collected from two hospitals in Guangdong province. Information recorded included age of mother, date of birth, sex, weight at birth, mode of delivery, gestational age, feeding mode, Apgar score, signs, medical records, underlying comorbidities and laboratory results. The presence of SARS-CoV-2 viral RNA was tested using an real-time PCR assay.ResultsSeventy-nine pregnant women infected with COVID-19 omicron variant and their 68 neonates were included in this study. The vast majority (86.1%) of pregnant women was in their third trimester of pregnancy, and only 11 cases (15%) were in the first or second trimester. Of 79 pregnant women, 39 cases were asymptomatic at the time of infection, and 40 mothers presented with mild manifestations of COVID-19. The most common symptoms were fever (92.5%, 37/40) and cough (57.5%, 21/40). All of pregnant women did not receive chest computed tomography (CT) scan or X-ray. No pregnant woman developed severe pneumonia. A total of 68 neonates (3 set of twins) from 65 mothers with COVID-19 were reviewed. Among women who delivered, 34 cases underwent cesarean section, 31 cases underwent vaginal delivery. According to the timing of birth, there were 10 (14.7%) preterm neonates. Two babies were born dead (intrauterine fetal death after 22 weeks of gestation). Of the live babies born (66 cases) from mothers with COVID-19, 9 newborns were lower weight, and one preterm case was born with respiratory distress and intubated, he recovered and developed normally. SARS-CoV-2 nucleic acid testing was conducted on 41 neonates daily after birth, with only one neonate testing positive for SARS-CoV-2 infection on the third day after birth. The infected neonate exhibited typical fever and acute respiratory tract syndrome but ultimately had a good prognosis, recovering after 5 days of treatment.ConclusionAlthough preliminary data suggests the risk of severe maternal and fetal complications from Omicron variant infection during pregnancy is lower than previous variants and Delta variant. Our study, which was conducted on a limited population sample, indicates that there is a possibility of severe complications, such as stillbirth, occurring in some fetal cases. These findings emphasize the need for continued attention from obstetricians.

ObjectiveGender differences are prevalent in major depressive disorder (MDD), but the gender differences in the relationship between comorbid anxiety and thyroid hormones in young first-episode and drug-naive (FEND) MDD patients are unknown.MethodsA total of 1,289 young outpatients with FEDN MDD were recruited. Demographic and clinical data were collected for each patient. The patient’s blood glucose, blood pressure, thyroid hormone, and thyroid antibody levels were measured. The Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA), and Positive and Negative Syndrome Scale (PANSS) were used to assess patients’ depression, anxiety, and positive symptoms, respectively.ResultsThe prevalence of comorbid anxiety disorders was 80.4 and 79.4% in male and female MDD patients, respectively. Patients with anxiety had higher HAMD and PANSS scores, higher serum thyroid stimulating hormone (TSH), anti-thyroglobulin antibody (A-TG), and thyroid peroxidase antibody (A-TPO) levels, higher blood glucose and blood pressure levels, and more patients with psychotic symptoms and suicide attempts. Male patients were younger and had a younger age of onset. Logistic regression analysis showed that HAMD score and comorbid suicide attempts were significant predictors of anxiety symptoms in both males and females, whereas A-TG predicted anxiety symptoms in female patients only. Limitations: No causal relationship could be drawn due to the cross-sectional design.ConclusionThis study showed gender differences in factors associated with anxiety symptoms in patients with MDD. Some factors were associated with anxiety symptoms in both male and female patients, while A-TG was only associated with anxiety symptoms in female patients.

ObjectiveGlucose 6-phosphate dehydrogenase (G6PD) deficiency increases the risk of neonatal hyperbilirubinemia. The aim of this study is to evaluate the risk factors associated with hyperbilirubinemia in infants from the western part of Guangdong Province, and to assess the contribution of G6PD deficiency to neonatal jaundice.MethodsThe term infants with neonatal hyperbilirubinemia in People's Hospital of Yangjiang from June 2018 to July 2022 were recruited for the retrospective analysis. All the infants underwent quantitative detection of the G6PD enzyme. The etiology was determined through laboratory tests and clinical manifestations.ResultsOut of 1,119 term infants, 435 cases presented with jaundice. For the etiology analysis, infection was responsible for 16.09% (70/435), G6PD deficiency accounted for 9.66% (42/435), of which 3 were complicated with acute bilirubin encephalopathy), bleeding accounted for 8.05% (35/435), hemolytic diseases accounted for 3.45% (15/435), and breast milk jaundice accounted for 2.53% (11/435). One case (0.23%) was attributed to congenital hypothyroidism, multiple etiologies accounted for 22.3% (97/435), and 35.63% (155/435) were of unknown etiology. Of the jaundiced infants, 19.54% (85/435) had G6PD deficiency, while only 10.23% (70/684) of non-jaundiced infants had G6PD deficiency; this difference was found to be statistically significant (P G, c.392G > T, c.1024C > T, c.1311C > T, c.1376G > T, c.1388G > A, c.871G > A/c.1311C > T, c.392G > T/c.1388G > A, and c.1376G > T/c.1311C > T.65iciencyConclusionIn newborns in Yangjiang, G6PD deficiency, infection, and neonatal hemolytic disease were identified as the main causes of hyperbilirubinemia and acute bilirubin encephalopathy. Specifically, Hemolytic factors in infants with G6PD deficiency may lead to reduced hemoglobin and increased bilirubin levels in jaundiced infants.

In this study, copper nanoparticles (Cu NPs) were synthesized in an eco-friendly pathway applying Mentha piperita extract as reducing/stabilizing agent. The morphological and physicochemical features of the prepared nanoparticles were determined using several advanced techniques like FE-SEM, EDX, and UV–Vis studies. The as synthesized Cu NPs was explored in the antioxidant and anti-human esophageal cancer tests. The in vitro cytotoxic and anti-esophageal cancer effects of biologically synthesized Cu NPs against human esophageal squamous cell carcinoma (KYSE-270), human caucasian esophageal carcinoma (OE33), and adenocarcinoma of the gastroesophageal junction (ESO26) cancer cell lines were assessed. The anti-esophageal cancer properties of the Cu NPs could significantly remove KYSE-270, OE33, and ESO26 cancer cell lines in a time and concentration-dependent manner by MTT assay. The IC50 of the Cu NPs were 241, 278, and 240 µg/mL against KYSE-270, OE33, and ESO26 cancer cell lines. The antioxidant activity of Cu NPs was determined by DPPH method. The Cu NPs showed the high antioxidant activity according to the IC50 value. It seems that the anti-human esophageal cancer effect of recent nanoparticles is due to their antioxidant effects.

Liver fibrosis is a common pathologic stage of the development of liver failure. It has showed that exosomes loaded with therapeutic circRNAs can be manufactured in bulk by exosome secreted cells in vitro, thus enabling personalized treatment. This study aimed to investigate the role of exosome-based delivery of circDIDO1 in liver fibrosis. Levels of genes and proteins were examined by qRT-PCR and Western blot. Cell proliferation, apoptosis, and cell cycle were analyzed by using cell counting kit-8 (CCK-8) assay, EdU assay, and flow cytometry, respectively. The binding between circDIDO1 and miR-141-3p was confirmed by dual-luciferase reporter, RNA pull-down and RIP assays. Exosomes were isolated by ultracentrifugation, and qualified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and Western blot. CircDIDO1 overexpression or miR-141-3p inhibition suppressed the proliferation, reduced pro-fibrotic markers, and induced apoptosis as well as cell cycle arrest in hepatic stellate cells (HSCs) by blocking PTEN/AKT pathway. Mechanistically, circDIDO1 acted as an endogenous sponge for miR-141-3p, further rescue experiments showed that circDIDO1 suppressed HSC activation by targeting miR-141-3p. Extracellular circDIDO1 could be incorporated into exosomes isolated from mesenchymal stem cells (MSCs), and transmitted to HSCs to restrain HSC activation. Clinically, low levels of serum circDIDO1 in exosome were correlated with liver failure, and serum exosomal circDIDO1 had a well diagnostic value for liver fibrosis in liver failure patients. Transfer of circDIDO1 mediated by MSC-isolated exosomes suppressed HSC activation through the miR-141-3p/PTEN/AKT pathway, gaining a new insight into the prevention of liver fibrosis in liver failure patients.

Smaller communities, such as those on islands, under ecological network simplification reduce interactions between specialist organisms.

The comparison of sn-2 palmitate content in human milk and animal milk in China, Europe and the United States, as well as the research reports on the physiological function of infants and young children were reviewed. The application and potential prospect of sn-2 palmitate in infant food were also prospected.

Purpose This study investigated the value of synchronous tele-ultrasonography (TUS) for naive operators in thyroid ultrasonography (US) examinations. Methods Ninety-seven patients were included in this prospective, parallel-controlled trial. Thyroid scanning and diagnosis were completed by resident A independently, resident B with guidance from a US expert through synchronous TUS, and an on-site US expert. The on-site expert’s findings constituted the reference standard. Two other off-site US experts analyzed all data in a blind manner. Inter-operator consistency between the two residents and the on-site US expert for thyroid size measurements, nodule measurements, nodule features, American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) categories, and image quality was compared. Two questionnaires were completed to evaluate the clinical benefit. Results Resident B detected more nodules consistent with the on-site expert than resident A did (89.4% vs. 56.5%, P0.75), while resident A achieved lower consistency in ACR TI-RADS categories, composition, echogenicity, margin, echogenic foci, and vascularity (all ICCs 0.40-0.75). Residents A and B had excellent consistency in target nodule measurements (all ICCs >0.75). Resident B achieved better performance than resident A for gray values, time gain compensation, depth, color Doppler adjustment, and the visibility of key information (all P

ObjectiveTo analyze the clinical characteristics of neonatal infection during the outbreak of COVID-19 omicron variant in Guangdong province of China.MethodThe clinical data of neonates infected with COVID-19 omicron variant were collected from three hospitals of Guangdong province, their epidemiological history, clinical manifestation and prognosis were summarized.ResultsFrom December 12, 2022 to January 15, 2023, a total of 52 neonates with COVID-19 infection were identified across three hospitals in Guangdong Province, including 34 males and 18 females. The age of diagnosis was 18.42 ± 6.32 days. 24 cases had clear contact history with adults who were suspected to be infected with COVID-19. The most common clinical manifestation was fever (43/52, 82.7%), the duration of fever was 1–8 days. The other clinical manifestations were cough (27/52, 51.9%), rales (21/52, 40.4%), nasal congestion (10/52, 19.2%), shortness of breath (2/52, 3.8%), and vomiting (4/52, 7.7%). C-reactive protein was only increased in 3 cases. Chest radiological examination was performed in 42 neonates, twenty-three cases showed abnormal chest radiographic findings, including ground-glass opacity and consolidation. Fifty cases were admitted with COVID-19 presentation, two cases were admitted for jaundice. The hospital stay was 6.59 ± 2.77 days. The clinical classification included 3 cases of severe COVID-19 and one critical case. Fifty-one cases were cured and discharged after general treatment, and one critical case with respiratory failure was intubated and transferred to another hospital.ConclusionThe COVID-19 omicron variant infection in neonates is usually mild. The clinical manifestation and laboratory results are not specific, and the short-term prognosis is good.

Summary: Background: Identifying patients with clinically significant prostate cancer (csPCa) before biopsy helps reduce unnecessary biopsies and improve patient prognosis. The diagnostic performance of traditional transrectal ultrasound (TRUS) for csPCa is relatively limited. This study was aimed to develop a high-performance convolutional neural network (CNN) model (P-Net) based on a TRUS video of the entire prostate and investigate its efficacy in identifying csPCa. Methods: Between January 2021 and December 2022, this study prospectively evaluated 832 patients from four centres who underwent prostate biopsy and/or radical prostatectomy. All patients had a standardised TRUS video of the whole prostate. A two-dimensional CNN (2D P-Net) and three-dimensional CNN (3D P-Net) were constructed using the training cohort (559 patients) and tested on the internal validation cohort (140 patients) as well as on the external validation cohort (133 patients). The performance of 2D P-Net and 3D P-Net in predicting csPCa was assessed in terms of the area under the receiver operating characteristic curve (AUC), biopsy rate, and unnecessary biopsy rate, and compared with the TRUS 5-point Likert score system as well as multiparametric magnetic resonance imaging (mp-MRI) prostate imaging reporting and data system (PI-RADS) v2.1. Decision curve analyses (DCAs) were used to determine the net benefits associated with their use. The study is registered at https://www.chictr.org.cn with the unique identifier ChiCTR2200064545. Findings: The diagnostic performance of 3D P-Net (AUC: 0.85–0.89) was superior to TRUS 5-point Likert score system (AUC: 0.71–0.78, P = 0.003–0.040), and similar to mp-MRI PI-RADS v2.1 score system interpreted by experienced radiologists (AUC: 0.83–0.86, P = 0.460–0.732) and 2D P-Net (AUC: 0.79–0.86, P = 0.066–0.678) in the internal and external validation cohorts. The biopsy rate decreased from 40.3% (TRUS 5-point Likert score system) and 47.6% (mp-MRI PI-RADS v2.1 score system) to 35.5% (2D P-Net) and 34.0% (3D P-Net). The unnecessary biopsy rate decreased from 38.1% (TRUS 5-point Likert score system) and 35.2% (mp-MRI PI-RADS v2.1 score system) to 32.0% (2D P-Net) and 25.8% (3D P-Net). 3D P-Net yielded the highest net benefit according to the DCAs. Interpretation: 3D P-Net based on a prostate grayscale TRUS video achieved satisfactory performance in identifying csPCa and potentially reducing unnecessary biopsies. More studies to determine how AI models better integrate into routine practice and randomized controlled trials to show the values of these models in real clinical applications are warranted. Funding: The National Natural Science Foundation of China (Grants 82202174 and 82202153), the Science and Technology Commission of Shanghai Municipality (Grants 18441905500 and 19DZ2251100), Shanghai Municipal Health Commission (Grants 2019LJ21 and SHSLCZDZK03502), Shanghai Science and Technology Innovation Action Plan (21Y11911200), and Fundamental Research Funds for the Central Universities (ZD-11-202151), Scientific Research and Development Fund of Zhongshan Hospital of Fudan University (Grant 2022ZSQD07).

Aims: This study aimed to evaluate the effects of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) on iron metabolism and inflammation in dialysis-dependent chronic kidney disease (DD-CKD) patients. Methods: PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov websites were searched for randomized controlled trials (RCTs) investigating HIF-PHIs versus ESAs for DD-CKD patients. Key findings: Twenty studies with 14,737 participants were included in the meta-analysis, which demonstrated no significant difference in the effect of transferrin saturation and ferritin between HIF-PHIs and the ESAs group (MD, 0.65; 95%CI, −0.45 to 1.75; very low certainty; SMD, −0.03; 95% CI, −0.13 to 0.07; low certainty). However, HIF-PHIs significantly increased the iron (MD, 2.30; 95% CI, 1.40 to 3.20; low certainty), total iron-binding capacity (SMD, 0.82; 95% CI, 0.66 to 0.98; low certainty), and transferrin (SMD, 0.90; 95%CI, 0.74 to 1.05; moderate certainty) levels when compared with the ESAs group. In contrast, the hepcidin level and dosage of intravenous iron were significantly decreased in the HIF-PHIs group compared with the ESAs group (MD, −15.06, 95%CI, −21.96 to −8.16; low certainty; MD, −18.07; 95% CI, −30.05 to −6.09; low certainty). The maintenance dose requirements of roxadustat were independent of baseline CRP or hsCRP levels with respect to the effect on inflammation. Significance: HIF-PHIs promote iron utilization and reduce the use of intravenous iron therapy. Furthermore, HIF-PHIs, such as roxadustat, maintain the erythropoietic response independent of the inflammatory state. Thus, HIF-PHIs may be an alternative treatment strategy for anemia in DD-CKD patients, where ESA is hyporesponsive due to iron deficiency and inflammation.

Summary: Pancreatic progenitor cell differentiation and proliferation factor (PPDPF) has been reported to play a role in tumorigenesis. However, its function in hepatocellular carcinoma (HCC) remains poorly understood. In this study, we report that PPDPF is significantly downregulated in HCC and the decreased PPDPF expression indicates poor prognosis. In the dimethylnitrosamine (DEN)-induced HCC mouse model, hepatocyte-specific depletion of Ppdpf promotes hepatocarcinogenesis, and reintroduction of PPDPF into liver-specific Ppdpf knockout (LKO) mice inhibits the accelerated HCC development. Mechanistic study shows that PPDPF regulates nuclear factor κB (NF-κB) signaling through modulation of RIPK1 ubiquitination. PPDPF interacts with RIPK1 and facilitates K63-linked ubiquitination of RIPK1 via recruiting the E3 ligase TRIM21, which catalyzes K63-linked ubiquitination of RIPK1 at K140. In addition, liver-specific overexpression of PPDPF activates NF-κB signaling and attenuates apoptosis and compensatory proliferation in mice, which significantly suppresses HCC development. This work identifies PPDPF as a regulator of NF-κB signaling and provides a potential therapeutic candidate for HCC.

The blood-brain barrier (BBB) is an important barrier separating the central nervous system from the periphery. The composition includes endothelial cells, pericytes, astrocytes, synapses and tight junction proteins. During the perioperative period, anesthesia and surgical operations are also a kind of stress to the body, which may be accompanied by blood-brain barrier damage and brain metabolism dysfunction. Perioperative blood-brain barrier destruction is closely associated with cognitive impairment and may increase the risk of postoperative mortality, which is not conducive to enhanced recovery after surgery. However, the potential pathophysiological process and specific mechanism of blood-brain barrier damage during the perioperative period have not been fully elucidated. Changes in blood-brain barrier permeability, inflammation and neuroinflammation, oxidative stress, ferroptosis, and intestinal dysbiosis may be involved in blood-brain barrier damage. We aim to review the research progress of perioperative blood-brain barrier damage and its potential adverse effects and potential molecular mechanisms, and provide ideas for the study of homeostasis maintenance of brain function and precision anesthesia.

Shaobei injection is a softening and shrinking agent, which is applied to treat axillary osmidrosis and rarely causes adverse reactions. Panniculitis is a skin disease that involves the subcutaneous fat layer. In this article, one case of panniculitis secondary to Shaobei injection was reported. The 37-year-old female patient developed left-sided subcutaneous nodules complicated with pain at 8 d after Shaobei injection. Subsequently, subcutaneous fat liquefaction and necrosis occurred, which were recovered after incision and drainage. Pathological examination of subcutaneous tissues of the lesions displayed degeneration and necrosis of fibrous adipose tissues. The patient was diagnosed with panniculitis. This case prompts that although Shaobei injection rarely yields adverse reactions, it might lead to panniculitis. For patients developing panniculitis post-Shaobei injection, incision and drainage should be performed to promptly eliminate the lesions.

Abstract Tibial cortex transverse transport (TTT) surgery is an extension of the Ilizarov technique. Based on the law of tension‐stress, its primary function is to rebuild microcirculation which can relieve ischemic symptoms and promote wound healing. It has received more and more scholars' attention and has experienced a series of changes for 20 years since it entered PR China. The mechanisms involved have gradually become clear, such as the reconstruction of the polarization balance of macrophages, the promotion of vascular tissue regeneration, and the mobilization and regulation of bone marrow‐derived stem cells. TTT technique is mainly used in the treatment of chronic ischemic diseases of the lower extremities. It has recently been successfully used in the treatment of primary lymphedema of the lower extremities. A series of improvements have been made in the external fixator's style, the size of skin incision and osteotomy, and distraction method. For example, the annular external fixator has been redesigned as a unilateral external fixator, and accordion technology has been introduced. For distraction methods after surgery, there was no uniform standard in the past. The technique can also be used in combination with other treatments to achieve better effects, such as interventional therapy, negative pressure sealed drainage, 3D printing technology, traditional Chinese medicine. Nevertheless, the surgery may bring some complications, such as secondary fracture, nail infection, skin necrosis at the surgical site, etc. Reports of complications and doubts about the technique have made the TTT technique controversial. In 2020, the relevant expert consensus was published with treatment and management principles, which might guide the better application and development of this technique.

Purpose This prospective study explored the value of synchronous tele-ultrasound (US) to aid doctors inexperienced in US with breast US examinations. Methods In total, 99 patients were enrolled. Two trainee doctors who were inexperienced in US (trainee A [TA] and trainee B [TB]) and one doctor who was an expert in US completed the US examinations sequentially. TA completed the US examinations independently, while TB was instructed by the expert using synchronous tele-US. Subsequently, the expert performed on-site US examinations in person. Separately, they selected the most clinically significant nodule as the target nodule. Consistency with the expert and image quality were compared between TA and TB to evaluate tele-US. Furthermore, TB and the patients evaluated tele-US through questionnaires. Results TB demonstrated higher consistency with the expert in terms of target nodule selection than TA (93.3% vs. 63.3%, P0.75) with the expert on five US features (5/9, 55.6%), while TA only did so for one (1/9, 11.1%) (P=0.046). TB’s image quality was higher than TA’s in gray value, time gain compensation, depth, color Doppler adjustment, and the visibility of key information (P=0.018, P

Plain Language Summary In the context of pregnancy preparation, attention has recently shifted from the period just before pregnancy to the early years, or even throughout one’s life. The World Health Organization identifies adolescents as requiring specific attention. Adolescents’ health behaviors can impact their adulthood years and have significant repercussions on the health of the future generation. In addition, recent studies consistently report that the preparedness of both men and women is essential to pregnancy preparation. Therefore, it is now time to present a new strategy by identifying and grasping the different factors that influence the two genders. This study can raise awareness of healthy pregnancy preparation behavior from adolescence onwards of both genders. There were differences in factors affecting HPPB by gender. For healthy pregnancy preparation, interventions based on HBM constructs and smoking should be presented for both male and female adolescents. Imparting education to females on the importance of HPPB (β = 0.19, p = 0.005) and males on confidence in HPPB (β = 0.12, p = 0.401), gender equality related to pregnancy and childbirth (β = − 0.20, p = 0.001 for women’s responsibility variable, β = 0.14, p = 0.018 for men’s responsibility variable), and alcohol consumption (β = − 0.10, p = 0.022) should be emphasized; and effective healthy pregnancy preventive strategies should be developed based on these findings. Interventions to prepare for a healthy pregnancy from an early age can ensure the health of both mother and child.

Plain English summary Starting in early adulthood, such as college students in the preconception stage, it is necessary to take care of one’s mental health (including depression) in order to have a healthy pregnancy in the future. The early identification of adults needing depression management is also a major challenge. In this study, an online survey was conducted to investigate levels of depression among Korean college students and their intention to manage depression for a healthy future pregnancy, as well as to identify the influencing factors. Convenience recruitment was conducted by e-mail at one university in Korea, and 828 male and female college students responded to the survey. An analysis of the factors affecting the intention to manage depression for a healthy future pregnancy identified the components of the Theory of Planned Behavior as influencing factors in both men and women. In particular, self-efficacy had the greatest influence. However, the current level of depression was only a significant factor among women. These findings could help nurses recognize differences in gender characteristics for the intention of preventive depression management for a healthy pregnancy, and provide evidence to develop and implement the intervention. These efforts will ultimately reduce high-risk pregnancies due to poor mental health.

Abstract Although arboreal camera trapping is a growing field, it has rarely been used for monitoring plant‐frugivore interactions in the trees. Frugivore foraging behavior generally occurs in trees, hence arboreal camera trapping can be a potentially useful tool for frugivory research. We developed a camera trap sampling method to monitor plant‐frugivore interactions during mature fruiting periods. We used this method to monitor 318 individuals (camera sites) of 18 fleshy‐fruit plant species on 22 subtropical land‐bridge islands in the Thousand Island Lake, China. We recorded a total of at least 52 frugivorous animals, including a ground‐foraging bird species (Lophura nycthemera) and several mammals with foraging behaviors in the trees. We also recorded 4399 independent interaction events, including 275 unique plant‐bird interactions. We proposed a framework to classify interaction types and performed a sampling completeness test. We found that a sampling strategy that covered approximately a third of the fruit maturation period when most fruits were ripe was sufficient to sample plant‐frugivore interactions. Our results demonstrated that our sampling method with camera transects is reliable to monitor plant‐frugivore interactions in a fragmented landscape. This study helps to lay the methodological foundation for building networks of plant‐frugivore interactions with arboreal camera trapping on large spatial/temporal scales. As a non‐invasive, labor‐saving, and largely unbiased sampling method, the field application of arboreal camera trapping in different regions can advance the technology of biodiversity monitoring and lead to more accurate biodiversity inventories in arboreal environments.

Background & Aims: Hepatocellular carcinoma (HCC) is a highly heterogeneous solid tumor with high morbidity and mortality. AT-rich interaction domain 1A (ARID1A) accounts for up to 10% of mutations in liver cancer, however, its role in HCC remains controversial, and no targeted therapy has been established. Methods: The expression of ARID1A in clinical samples was examined by Western blot and immunohistochemical staining. ARID1A was knocked out by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) in HCC cell lines, and the effects of glucose deprivation on cell viability, proliferation, and apoptosis were measured. Mass spectrometry analysis was used to find ARID1A-interacting proteins, and the result was verified by co-immunoprecipitation and Glutathione S Transferase (GST) pull-down. The regulation of ARID1A target gene USP9X was investigated by chromatin immunoprecipitation, Glutathione S Transferase (GST) pull-down, luciferase reporter assay, and so forth. Finally, drug treatments were performed to explore the therapeutic potential of the agents targeting ARID1A-deficient HCC in vitro and in vivo. Results: Our study has shown that ARID1A loss protected cells from glucose deprivation–induced cell death. A mechanism study disclosed that AIRD1A recruited histone deacetylase 1 via its C-terminal region DUF3518 to the promoter of USP9X, resulting in down-regulation of USP9X and its target protein kinase AMP-activated catalytic subunit α2 (PRKAA2). ARID1A knockout and a 1989∗ truncation mutant in HCC abolished this effect, increased the levels of H3K9 and H3K27 acetylation at the USP9X promoter, and up-regulated the expression of USP9X and protein kinase AMP-activated catalytic subunit α2 (PRKAA2), which mediated the adaptation of tumor cells to glucose starvation. Compound C dramatically inhibited the growth of ARID1A-deficient tumors and prolongs the survival of tumor-bearing mice. Conclusions: HCC patients with ARID1A mutation may benefit from synthetic lethal therapy targeting the ubiquitin-specific peptidase 9 X-linked (USP9X)–adenosine 5‘-monophosphate–activated protein kinase (AMPK) axis.

This study presents new geochronological and geochemical data for Early Cretaceous volcanic rocks in the southern margin of the North China Craton (NCC), to discuss the crust–mantle interaction. The studied rocks include pyroxene andesites from Daying Formation, hornblende andesites and andesites from Jiudian Formation, and rhyolites from a hitherto unnamed Formation. These rocks formed in Early Cretaceous (138–120 Ma), with enrichment in light rare earth elements (REE), depletion in heavy REE and arc-like trace elements characteristics. Pyroxene andesites show low SiO2 contents and enriched Sr–Nd–Pb–Hf isotopic compositions, with orthopyroxene phenocryst and Paleoproterozoic (2320–1829 Ma) inherited zircons, suggesting that they originated from lithospheric mantle after metasomatism with NCC lower crustal materials. Hornblende andesites have low SiO2 contents and high Mg# (Mg# = 100 Mg/(Mg + Fe2+)) values, indicating a lithospheric-mantle origin. Considering the distinct whole-rock Sr isotopic compositions we divide them into two groups. Among them, the low (87Sr/86Sr)i andesites possess amount inherited Neoarchean to Neoproterozoic (2548–845 Ma) zircons, indicating the origin of lithospheric mantle with addition of Yangtze Craton (YC) and NCC materials. In comparison, the high (87Sr/86Sr)i andesites, with abundant Neoarchean–Paleozoic inherited zircons (3499–261 Ma), are formed by partial melting of lithospheric mantle with incorporation of NCC supracrustal rocks and YC materials. Rhyolites have extremely high SiO2 (77.63–82.52 wt.%) and low total Fe2O3, Cr, Ni contents and Mg# values, combined with ancient inherited zircon ages (2316 and 2251 Ma), suggesting an origin of NCC lower continental crust. Considering the presence of resorption texture of quartz phenocryst, we propose a petrogenetic model of ‘crystal mushes’ for rhyolites prior to their eruption. These constraints record the intense crust–mantle interaction in the southern margin of the NCC. Given the regional data and spatial distribution of Early Cretaceous rocks within NCC, we believe that the formation of these rocks is related to the contemporaneous far-field effect of the Paleo-Pacific Plate.

Cross-sector collaboration is widely considered beneficial for the sustainable development of social enterprises (SEs). This study provides a nuanced assessment of the impacts of cross-sector collaboration in supporting SE development (cross-sector support; CSS) by highlighting legitimacy building as the crucial goal for SEs in achieving sustainability. Studying Hong Kong, we examine the institutional pressures confronting SEs in their legitimacy building, their efforts to respond, and the role of CSS therein. Data from surveys and in-depth interviews show that the three key types of CSS—venture capital, operational, and promotional—have mixed effects on the efforts of SEs to cope with the various institutional pressures. Our findings suggest the necessity of an integrated blend of governance styles—a metagovernance approach—in shaping and guiding CSS of SEs and an approach that is sensitive to the plural, changing pressures in SE entrepreneurial processes to achieve financial sustainability as well as social legitimacy.

ObjectivesTo investigate the clinical and radiographic outcomes of EXP-IFC in single-level MIS-TLIF.MethodsThis study included patients aged ≥18 years who received a single-level MIS-TLIF procedure with at least 1 year of follow-up. Outcome measures: clinical features, preoperative and neurological complications. Imaging analysis included disc height (DH) restoration, surgical and contralateral side foraminal height (FH), lumbar lordosis angle (LL), segmental lordosis (SL). Visual analog scale (VAS) score for low back pain (VAS-LBP) and leg pain (VAS-LP), Oswestry Disability Index (ODI) and Japanese Orthopaedic Association (JOA) score were used to evaluate clinical outcomes. Statistical analysis was performed using independent sample t-test and sample t-test. The significance was set to p

BackgroundAging is an influential risk factor for progression of both degenerative and oncological diseases of the bone. Osteosarcoma, considered the most common primary mesenchymal tumor of the bone, is a worldwide disease with poor 5-year survival. This study investigated the role of aging-/senescence-induced genes (ASIGs) in contributing to osteosarcoma diagnosis, prognosis, and therapeutic agent prediction.MethodsTherapeutically Applicable Research to Generate Effective Treatments (TARGET), Gene Expression Omnibus (GEO), and The Cancer Genome Atlas (TCGA) were used to collect relevant gene expression and clinical data of osteosarcoma and paracancerous tissues. Patients were clustered by consensus using prognosis-related ASIGs. ssGSEA, ESTIMATE, and TIMER were used to determine the tumor immune microenvironment (TIME) of subgroups. Functional analysis of differentially expressed genes between subgroups, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set variation analyses (GSVAs), was performed to clarify functional status. Prognostic risk models were constructed by univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression. SCISSOR was used to identify relevant cells in osteosarcoma single-cell data for different risk groups. The effect of immunotherapy was predicted based on TIDE scores and chemotherapy drug sensitivity using CTRP and PRISM.ResultsThree molecular subgroups were identified based on prognostic differentially expressed ASIGs. Immunological infiltration levels of the three groups differed significantly. Based on GO and KEGG analyses, differentially expressed genes between the three subgroups mainly relate to immune and aging regulation pathways; GSVA showed substantial variations in multiple Hallmark pathways among the subgroups. The ASIG risk score built based on differentially expressed genes can predict patient survival and immune status. We also developed a nomogram graph to accurately predict prognosis in combination with clinical characteristics. The correlation between the immune activation profile of patients and the risk score is discussed. Through single-cell analysis of the tumor microenvironment, we identified distinct risk-group-associated cells with significant differences in immune signaling pathways. Immunotherapeutic efficacy and chemotherapeutic agent screening were evaluated based on risk score.ConclusionAging-related prognostic genes can distinguish osteosarcoma molecular subgroups. Our novel aging-associated gene signature risk score can be used to predict the osteosarcoma immune landscape and prognosis. Moreover, the risk score correlates with the TIME and provides a reference for immunotherapy and chemotherapy in terms of osteosarcoma.

Zinc ash is a serious defect of hot-dip galvanized process and has great impact on products with high surface level requirements. During galvanizing process, the zinc ash formed by the oxidation of zinc vapor in a furnace snout was easy to adhere to the surface of strip steel, influencing the surface quality of the coating. At present, the effective control measures were to control the dew point by humidifying the furnace snout. If the dew point of the furnace snout was too high or too low, it would produce defects. In this paper, the control methods of selecting the appropriate dew point by controlling the process parameters such as pressure and flow were expounded according to the existing working conditions.

Background ET-26 hydrochloride (ET-26HCl) is a novel analogue of etomidate approved for clinical trials. However, all results from recent studies were accomplished in young adult animals. The objective of this study was to evaluate the efficacy and safety of ET-26HCl in aged rats. Methods Aged Sprague-Dawley rats were randomly divided into three groups (three males and three females in each group) were given dose of two-fold of median effective dose (ED50) of ET-26HCl, etomidate and propofol: the measurements of loss of the righting reflex (LORR) and cardiovascular and respiratory function after injection at the two-fold dose of the median effective dose were used for evaluation of effectiveness and safety, and the modified adrenocorticotropic hormone-stimulation experiment was used to evaluate the inhibition effect of the drugs on the synthesis of adrenal cortical hormones. Results There was no significant difference in the onset time among propofol, etomidate and ET-26HCl. The duration of propofol (850.5 ± 77.4 s) was significantly longer than that caused by etomidate (489.8 ± 77.0 s, p = 0.007) and ET-26HCl (347.3 ± 49.0 s, p = 0.0004). No significant difference was observed in the time to stand and normal activity among drugs. A total of 66.7% of rats in the ET-26HCl group were evaluated to have mild hematuria. Then, etomidate and ET-26HCl had a milder blood pressure inhibition effect than propofol. Apnea was observed in all rats administered propofol and the duration for this side effect was 45.0 ± 9.0 s. For etomidate and ET-26HCl, no apnea was observed. No other clinical signs of side-effect were observed, and no rats died. No significant difference was observed in corticosterone concentrations between ET-26HCl and solvent group. However, rats administered etomidate had lower corticosterone concentrations than those administered ET-26HCl at 15, 30, and 60 min. Conclusions Our results indicate ET-26HCl in aged rats is an effective sedative-hypnotic with stable myocardial and respiratory performance and also have mild adrenocortical suppression. Thus, these findings increase the potential for the clinical use of ET-26HCl in the elderly population.

Abstract Background Rhodococcus kroppenstedtii is an aerobic, gram-positive bacterium firstly identified in the environment, which has not been reported in human-related infection. Herein, we reported the first case of peritoneal dialysis (PD)-associated peritonitis caused by R. kroppenstedtii which was identified by whole genome sequencing. Case presentation A 69-year-old man was admitted to hospital with abdominal pain and fever. Over the last 2 years, he had been undergoing continuous ambulatory peritoneal dialysis (CAPD) due to end-stage renal disease. Clinical symptom and sign in combination with laboratory examinations supported the clinical diagnosis of PD-associated peritonitis. Thus, ceftizoxime and teicoplanin were empirically used after PD effluent was collected for bacterial culture. A gram-positive bacterium was found from the PD effluent culture, which could not be identified by either Vitek 2 Compact ANC card or matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The strain was finally confirmed to be R. kroppenstedtii by whole genome sequencing (WGS) through the average nucleotide identity (ANI) analysis. With a continuous treatment with teicoplanin and imipenem for 15 days and intraperitoneal catheter removed, the infection symptom was improved evidenced by a normal body temperature, also with white blood cell count (WBC), procalcitonin (PCT) and C-reactive protein (CRP) dropped to normal levels. Peritoneal dialysis effluent culture showed a negative result. Then, hemodialysis and arteriovenous fistula angioplasty were performed, but the patient developed a progressive blood pressure loss, accompanied by multiple organ disorder, and died on Feb 25, 2020. Conclusions To the best of our knowledge, this is the first time to report a peritoneal dialysis-associated peritonitis caused by R. kroppenstedtii which was identified by average nucleotide identity analysis based on WGS.