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Abstract Background Gastric intramural hematoma is a rare disease. Here we report a case of spontaneous isolated gastric intramural hematoma combined with spontaneous superior mesenteric artery intermural hematoma. Case presentation A 75-years-old man was admitted to our department with complaints of abdominal pain. He underwent a whole abdominal computed tomography (CT) scan in the emergency department, which showed extensive thickening of the gastric wall in the gastric body and sinus region with enlarged surrounding lymph nodes, localized thickening of the intestinal wall in the transverse colon, localized indistinct demarcation between the stomach and transverse colon, and a small amount of fluid accumulation in the abdominal cavity. Immediately afterwards, he was admitted to our department, and then we arranged a computed tomography with intravenously administered contrast agent showed a spontaneous isolated gastric intramural hematoma combined with spontaneous superior mesenteric artery intermural hematoma. Therefore, we treated him with anticoagulation and conservative observation. During his stay in the hospital, he was given low-molecular heparin by subcutaneous injection for anticoagulation therapy, and after discharge, he was given oral anticoagulation therapy with rivaroxaban. At the follow-up of more than 4 months, most of the intramural hematoma was absorbed and became significantly smaller, and the intermural hematoma of the superior mesenteric artery was basically absorbed, which also confirmed that the intramural mass was an intramural hematoma. Conclusion A gastric intramural hematoma should be considered, when an intra-abdominal mass was found to be attached to the gastric wall. Proper recognition of gastric intramural hematoma can reduce the misdiagnosis rate of confusion with gastric cancer.

Abstract Age-related cataract and hearing difficulties are major sensory disorders that often co-exist in the global-wide elderly and have a tangible influence on the quality of life. However, the epidemiologic association between cataract and hearing difficulties remains unexplored, while little is known about whether the two share their genetic etiology. We first investigated the clinical association between cataract and hearing difficulties using the UK Biobank covering 502,543 individuals. Both unmatched analysis (adjusted for confounders) and a matched analysis (one control matched for each patient with cataract according to confounding factors) were undertaken and confirmed that cataract was associated with hearing difficulties (OR, 2.12; 95% CI, 1.98–2.27; OR, 2.03; 95% CI, 1.86–2.23, respectively). Furthermore, we explored and quantified the shared genetic architecture of these two complex sensory disorders at the common variant level using the bivariate causal mixture model (MiXeR) and conditional/conjunctional false discovery rate method based on the largest available genome-wide association studies of cataract (N = 585,243) and hearing difficulties (N = 323,978). Despite detecting only a negligible genetic correlation, we observe polygenic overlap between cataract and hearing difficulties and identify 6 shared loci with mixed directions of effects. Follow-up analysis of the shared loci implicates candidate genes QKI, STK17A, TYR, NSF, and TCF4 likely contribute to the pathophysiology of cataracts and hearing difficulties. In conclusion, this study demonstrates the presence of epidemiologic association between cataract and hearing difficulties and provides new insights into the shared genetic architecture of these two disorders at the common variant level.

We studied a class of a stochastic hybrid SIQRS model with nonlinear incidence and vertical transmission and obtained a threshold $ \Delta $ to distinguish behaviors of the model. Concretely, the disease was extinct exponentially when $ \Delta < 0 $. If $ \Delta > 0 $, the model we discussed admitted an invariant measure. A new class of the Lyapunov function was constructed in proving the latter conclusion. Some remarks were presented to shed light on the major results. Finally, several numerical simulations were provided to test the reached results.

Abstract Background Chemoresistance is associated with tumor relapse and unfavorable prognosis. Multiple mechanisms underlying chemoresistance have been elucidated, including stemness and DNA damage repair. Here, the involvement of the WNT receptor, FZD5, in ovarian cancer (OC) chemoresistance was investigated. Methods OC cells were analyzed using in vitro techniques including cell transfection, western blot, immunofluorescence and phalloidin staining, CCK8 assay, colony formation, flowcytometry, real-time PCR, and tumorisphere formation. Pearson correlation analysis of the expression levels of relevant genes was conducted using data from the CCLE database. Further, the behavior of OC cells in vivo was assessed by generation of a mouse xenograft model. Results Functional studies in OC cells showed that FZD5 contributes to epithelial phenotype maintenance, growth, stemness, HR repair, and chemoresistance. Mechanistically, FZD5 modulates the expression of ALDH1A1, a functional marker for cancer stem-like cells, in a β-catenin-dependent manner. ALDH1A1 activates Akt signaling, further upregulating RAD51 and BRCA1, to promote HR repair. Conclusions Taken together, these findings demonstrate that the FZD5-ALDH1A1-Akt pathway is responsible for OC cell survival, and targeting this pathway can sensitize OC cells to DNA damage-based therapy.

Abstract The development of facile tailoring approach to adjust the intrinsic activity and stability of atomically-precise metal nanoclusters catalysts is of great interest but remians challenging. Herein, the well-defined Au8 nanoclusters modified by single-atom sites are rationally synthesized via a co-eletropolymerization strategy, in which uniformly dispersed metal nanocluster and single-atom co-entrenched on the poly-carbazole matrix. Systematic characterization and theoretical modeling reveal that functionalizing single-atoms enable altering the electronic structures of Au8 clusters, which amplifies their electrocatalytic reduction of CO2 to CO activity by ~18.07 fold compared to isolated Au8 metal clusters. The rearrangements of the electronic structure not only strengthen the adsorption of the key intermediates *COOH, but also establish a favorable reaction pathway for the CO2 reduction reaction. Moreover, this strategy fixing nanoclusters and single-atoms on cross-linked polymer networks efficiently deduce the performance deactivation caused by agglomeration during the catalytic process. This work contribute to explore the intrinsic activity and stability improvement of metal clusters.

Abstract While genome-wide studies have identified genomic loci in hosts associated with life-threatening Covid-19 (critical Covid-19), the challenge of resolving these loci hinders further identification of clinically actionable targets and drugs. Building upon our previous success, we here present a priority index solution designed to address this challenge, generating the target and drug resource that consists of two indexes: the target index and the drug index. The primary purpose of the target index is to identify clinically actionable targets by prioritising genes associated with Covid-19. We illustrate the validity of the target index by demonstrating its ability to identify pre-existing Covid-19 phase-III drug targets, with the majority of these targets being found at the leading prioritisation (leading targets). These leading targets have their evolutionary origins in Amniota (‘four-leg vertebrates’) and are predominantly involved in cytokine-cytokine receptor interactions and JAK-STAT signaling. The drug index highlights opportunities for repurposing clinically approved JAK-STAT inhibitors, either individually or in combination. This proposed strategic focus on the JAK-STAT pathway is supported by the active pursuit of therapeutic agents targeting this pathway in ongoing phase-II/III clinical trials for Covid-19.

As the wide application of power electronics devices, supply containing low-order harmonic becomes more and more common in industry. It may cause the significant vibration of induction motors (IMs). This study firstly analyzed the time-space distribution characteristics of the additional electromagnetic force caused by the low-order harmonics in supply. Then, an improved concentric and unequal-turn windings is designed and its impact on unconventional vibration of IMs is also analyzed. The increase ratio of force amplitude between the force in different cases is defined, by which the force characteristics of IMs with supply containing low-order harmonics and concentric and unequal-turn windings can be revealed under different load conditions. With a 32-kW IM, harmonic response analysis and experimental validation are also carried out, the results show that, with concentric unequal-turn winding, the vibration in different frequency bands can be reduced effectively, the average vibration can be suppressed from 89.7dB to 86.9dB.

Abstract Background A previously trained deep learning-based smartphone app provides an artificial intelligence solution to help diagnose biliary atresia from sonographic gallbladder images, but it might be impractical to launch it in real clinical settings. This study aimed to redevelop a new model using original sonographic images and their derived smartphone photos and then test the new model’s performance in assisting radiologists with different experiences to detect biliary atresia in real-world mimic settings. Methods A new model was first trained retrospectively using 3659 original sonographic gallbladder images and their derived 51,226 smartphone photos and tested on 11,410 external validation smartphone photos. Afterward, the new model was tested in 333 prospectively collected sonographic gallbladder videos from 207 infants by 14 inexperienced radiologists (9 juniors and 5 seniors) and 4 experienced pediatric radiologists in real-world mimic settings. Diagnostic performance was expressed as the area under the receiver operating characteristic curve (AUC). Results The new model outperformed the previously published model in diagnosing BA on the external validation set (AUC 0.924 vs 0.908, P = 0.004) with higher consistency (kappa value 0.708 vs 0.609). When tested in real-world mimic settings using 333 sonographic gallbladder videos, the new model performed comparable to experienced pediatric radiologists (average AUC 0.860 vs 0.876) and outperformed junior radiologists (average AUC 0.838 vs 0.773) and senior radiologists (average AUC 0.829 vs 0.749). Furthermore, the new model could aid both junior and senior radiologists to improve their diagnostic performances, with the average AUC increasing from 0.773 to 0.835 for junior radiologists and from 0.749 to 0.805 for senior radiologists. Conclusions The interpretable app-based model showed robust and satisfactory performance in diagnosing biliary atresia, and it could aid radiologists with limited experiences to improve their diagnostic performances in real-world mimic settings.

Arbuscular mycorrhizal fungi (AMF) play a key role in regulating the carbon cycle in terrestrial ecosystems. However, there is little information on how AMF inoculation affects the carbon fluxes of paddy fields, which are major sources of global carbon emissions. We, therefore, designed an experiment to study the effects of AMF inoculation on methane and carbon dioxide emissions from a paddy field. Results showed that: (1) Among the tested factors, the C/N ratio was the main environmental determinant of microbial community structure in the investigated soil; (2) compared with traditional fertilisation (control), the soil C/N ratio increased by 2.1~15.2% and 1.4~10.5% as a result of AMF application alone (M) or in combination with mineral fertiliser (FM) throughout the growing season, respectively. This change shifted microbial community composition to higher G+/G- bacterial and fungal/bacterial ratios; (3) the microbial community change favoured soil carbon retention. Methane (CH4) emission peaks were reduced by 59.4% and 76.0% versus control in the M treatment and by 52.5% and 29.4% in the FM treatment in the midseason and end-of-season drainage periods, and CO2 emission peaks were reduced by 70.1% and 52.3% in the M plots and by 55.4% and 66.4% in the FM plots.

Abstract The study of jets in the Earth’s magnetosheath has been a subject of extensive investigation for over a decade due to their profound impact on the geomagnetic environment and their close connection with shock dynamics. While the variability of the solar wind and its interaction with Earth’s magnetosphere provide valuable insights into jets across a range of parameters, a broader parameter space can be explored by examining the magnetosheath of other planets. Here we report the existence of anti-sunward and sunward jets in the Jovian magnetosheath and show their close association with magnetic discontinuities. The anti-sunward jets are possibly generated by a shock–discontinuity interaction. Finally, through a comparative analysis of jets observed at Earth, Mars, and Jupiter, we show that the size of jets scales with the size of bow shock.

Introduction: Antibiotic-resistant bacterial infections, such as Pseudomonas aeruginosa and Staphylococcus aureus, are prevalent in lung cancer patients, resulting in poor clinical outcomes and high mortality. Etoposide (ETO) is an FDA-approved chemotherapy drug that kills cancer cells by damaging DNA through oxidative stress. However, it is unclear if ETO can cause unintentional side effects on tumor-associated microbial pathogens, such as inducing antibiotic resistance. Objectives: We aimed to show that prolonged ETO treatment could unintendedly confer fluoroquinolone antibiotic resistance to P. aeruginosa, and evaluate the effect of tumor-associated P. aeruginosa on tumor progression. Methods: We employed experimental evolution assay to treat P. aeruginosa with prolonged ETO exposure, evaluated the ciprofloxacin resistance, and elucidated the gene mutations by DNA sequencing. We also established a lung tumor-P. aeruginosa bacterial model to study the role of ETO-evolved intra-tumoral bacteria in tumor progression using immunostaining and confocal microscopy. Results: ETO could generate oxidative stress and lead to gene mutations in P. aeruginosa, especially the gyrase (gyrA) gene, resulting in acquired fluoroquinolone resistance. We further demonstrated using a microfluidic-based lung tumor-P. aeruginosa coculture model that bacteria can evolve ciprofloxacin (CIP) resistance in a tumor microenvironment. Moreover, ETO-induced CIP-resistant (EICR) mutants could form multicellular biofilms which protected tumor cells from ETO killing and enabled tumor progression. Conclusion: Overall, our preclinical proof-of-concept provides insights into how anti-cancer chemotherapy could inadvertently allow tumor-associated bacteria to acquire antibiotic resistance mutations and shed new light on the development of novel anti-cancer treatments based on anti-bacterial strategies.

Shrimp (Penaeus vannamei) proteins have been shown an allergenic potential; however, little information is available on the sensitizing and eliciting capacity of shrimp protein digestion products. In this study, a BALB/c mice model was used to explore the allergenicity of shrimp protein sample (SPS) and their gastric and gastrointestinal digestion products (GDS/GIDS). As compared with the SPS groups, the GDS/GIDS groups caused lower specific immunoglobulins (IgE/IgG1) levels (P < 0.05), but higher than the control groups, indicating that the digestion products sensitized the mice. Meanwhile, spleen index, mouse mast cell protease-1 (mMCP-1) concentration and proportion of degranulated mast cells were significantly reduced in the GDS/GIDS groups (P < 0.05); simultaneously, allergic symptoms, vascular permeability and histopathological changes of tissues were alleviated. Nevertheless, the allergenicity of digestion products cannot be eliminated and still cause systemic allergic reactions in mice. The study showed that the digestion products of shrimp still had high sensitizing and eliciting capacity.

Abstract Background Neural tube defects (NTDs) are one of the most severe congenital abnormalities characterized by failures of the neural tube to close during early embryogenesis. Maternal folate deficiency could impact the occurrence of NTDs, however, the mechanisms involved in the cause of NTDs are poorly defined. Results Here, we report that histone H3 methyltransferase disruptor of telomeric silencing 1-like (DOT1L) expression was significantly downregulated, and low levels of H3K79me2 were found in the corresponding NTDs samples with their maternal serum folate under low levels. Using ChIP-seq assays, we found that a decrease of H3K79me2 downregulates the expression of Shh and Sufu in mouse embryonic stem cells (mESC) under folate deficiency. Interestingly, folate antagonist methotrexate treatment led to attenuation of H3K79me2 due to Dot1l, affecting Shh and Sufu genes regulation. Upon further analysis, we find that the genes Shh and Sufu are both downregulated in the brain tissues of mice and humans with NTDs. There was a positive correlation between the transcription levels of Shh, Sufu and the protein levels of DOT1L by Pearson correlation analysis. Conclusion Our results indicate that abnormal Shh and Sufu genes expression reduced by aberrant Dot1l-mediated H3K79me2 levels could be the cause of NTDs occurrence.

Abstract Endometriosis (EMT) is an aggressive disease of the reproductive system, also called “benign cancer”. However, effective treatments for EMT are still lacking in clinical practice. Interestingly, immune infiltration is significantly involved in EMT pathogenesis. Currently, no studies have shown the involvement of cuproptosis-related genes (CRGs) in regulating immune infiltration in EMT. This study identified three CRGs such as GLS, NFE2L2, and PDHA1, associated with EMT using machine learning algorithms. These three CRGs were upregulated in the endometrium of patients with moderate/severe EMT and downregulated in patients with infertility. Single sample genomic enrichment analysis (ssGSEA) revealed that these CRGs were closely correlated with autoimmune diseases such as systemic lupus erythematosus. Furthermore, these CRGs were correlated with immune cells such as eosinophils, natural killer cells, and macrophages. Therefore, profiling patients based on these genes aid in a more accurate diagnosis of EMT progression. The mRNA and protein expression levels of GLS, NFE2L2 and PDHA1 were validated by qRT-PCR and WB studies in EMT samples. These findings provide a new idea for the pathology and treatment of endometriosis, suggesting that CRGs such as GLS, NFE2L2 and PDHA1 may play a key role in the occurrence and development of endometriosis.

Tumor vascular normalization profoundly affects the advancement of cancer therapy. Currently, with the rapid increase in research on tumor vascular normalization, few analytical and descriptive studies have investigated the trends in its development, key research power, present research hotspots, and future outlooks. In this study, articles and reviews published between January 1, 2003, and October 29, 2022 were retrieved from Web of Science database. Subsequently, published research trends, countries/regions, institutions, authors, journals, references, and keywords were analyzed based on traditional bibliometric laws (such as Price's exponential growth, Bradford's, Lotka's, and Zipf's). Our results showed that the last two decades have seen an increase in tumor vascular normalization research. USA emerged as the preeminent contributor to the field, boasting the highest H-index and accruing the greatest quantity of publications and citations. Among institutions, Massachusetts General Hospital and Harvard University made significant contributions, and Professor RK Jain was identified as a key leader in this field. Out of 583 academic journals, Cancer Research and Clinical Cancer Research published the most articles on vascular normalization. The research focal points in the field primarily include immunotherapy, tumor microenvironments, nanomedicine, and emerging frontier themes such as metabolism and mechanomedicine. Concurrently, the challenges of vascular normalization in cancer are discussed as well. In conclusion, the study presented a thorough analysis of the literature covering the past 20 years on vascular normalization in cancer, highlighting leading countries, institutions, authors, journals, and the emerging research focal points in this field. Future studies will advance the ongoing efforts in the field of tumor vascular normalization, aiming to enhance our ability to effectively manage and treat cancer.

Summary: Mesenchymal stem cell (MSC)-mediated coupling of osteogenesis and angiogenesis is a critical phenomenon in bone formation. Herein, we investigated the role and mechanism of SGMS1 in the osteogenic differentiation of MSCs and, in combination with osteogenesis and angiogenesis, to discover new therapeutic targets for skeletal dysplasia and bone defects. SGMS1 addition accelerated MSC osteogenic differentiation, whereas SGMS1 silencing suppressed this process. Moreover, SGMS1 overexpression inhibited ceramide (Cer) and promoted sphingomyelin (SM) levels. SM treatment neutralized the suppressive effect of shSGMS1 on osteogenesis. SGMS1 restrained PP2A activity by regulating Cer/SM metabolism and thus enhanced the levels of phosphorylated Akt, Runx2, and vascular endothelial growth factor (VEGF). Furthermore, SGMS1 transcription was regulated by Runx2. SGMS1 increased MSC-mediated angiogenesis by promoting VEGF expression. SGMS1 addition promoted rat bone regeneration in vivo. In conclusion, SGMS1 induces osteogenic differentiation of MSCs and osteogenic-angiogenic coupling through the regulation of the Cer/PP2A/Akt signaling pathway.

Background: The higher prevalence of anemia in females and elderly may be attributed to its association with worsened outcomes in ST-elevation myocardial infarction (STEMI) patients. We aimed to evaluate the precise effects of age and gender on the association between anemia and 30-day outcomes. Method: We identified 4350 STEMI patients and divided into anemia and non-anemia. Effects were analyzed as categories using Cox proportional-hazards regression and as continuous using restricted cubic splines. Propensity score matching (PSM) and mediation analysis were applied to identify intermediate effects. Results: Anemic patients were older, more likely to be female, and experienced doubled all-cause death (7.3 % versus 15.0 %), main adverse cardiovascular and cerebrovascular events (MACCE, 11.1 % versus 20.2 %), heart failure (HF, 5.1 % versus 8.6 %), and bleeding events (2.7 % versus 5.4 %). After adjustment, the association between anemia and all-cause death (Hazard ratio (HR) 1.15, 95 % confidence interval (95 %CI) 0.93–1.14), MACCE (HR 1.14, 95 %CI 0.95–1.36) and HF (HR 1.19, 95 %CI 0.92–1.55) were insignificant, the effects persisted nullified across age classes (P-interaction > 0.05) and PSM (P > 0.05). Ulteriorly, age mediated 77.6 %, 66.2 %, 48.0 %, gender mediated 38.1 %, 15.0 %, 3.2 %, age and gender together mediated 99.8 % 72.9 %, 48.1 % of the relationship. Anemia was independently associated with bleeding events (HR 2.02, 95 %CI 1.42–2.88), the effects consisted significant regardless of PSM (P 0.05), and no mediating role of age and gender were observed. Conclusions: In STEMI patients, age and gender largely mediated the relationship between anemia and all-cause death, MACCE, and HF, anemia was independently associated with bleeding complications.

Periodontitis drives irreversible destruction of periodontal tissue and is prone to exacerbating inflammatory disorders. Systemic immunomodulatory management continues to be an attractive approach in periodontal care, particularly within the context of ‘predictive, preventive, and personalized’ periodontics. The present study incorporated genetic proxies identified through genome-wide association studies for circulating immune cells and periodontitis into a comprehensive Mendelian randomization (MR) framework. Univariable MR, multivariable MR, subgroup analysis, reverse MR, and Bayesian model averaging (MR-BMA) were utilized to investigate the causal relationships. Furthermore, transcriptome-wide association study and colocalization analysis were deployed to pinpoint the underlying genes. Consequently, the MR study indicated a causal association between circulating neutrophils, natural killer T cells, plasmacytoid dendritic cells, and an elevated risk of periodontitis. MR-BMA analysis revealed that neutrophils were the primary contributors to periodontitis. The high-confidence genes S100A9 and S100A12, located on 1q21.3, could potentially serve as immunomodulatory targets for neutrophil-mediated periodontitis. These findings hold promise for early diagnosis, risk assessment, targeted prevention, and personalized treatment of periodontitis. Considering the marginal association observed in our study, further research is required to comprehend the biological underpinnings and ascertain the clinical relevance thoroughly.

To address the challenges related to lengthy construction period, complex maintenance requirement, and the elevated risk of shrinkage cracking associated with cast-in-place UHPC reinforcement of orthotropic steel bridge decks. This paper proposes a novel solution that prefabricated ultra-high-performance concrete (UHPC) slab with epoxy bond connection is used as a reinforcement layer for orthotropic steel bridge decks. Four sets of bending tests on composite bridge deck were carried out to compare the flexural performance of composite bridge decks under different joint forms and loading patterns. The results indicate that the precast UHPC decks delaminated from the epoxy bonding layer without failure of the epoxy layer itself in all cases. The positive bending capacity of the jointless composite bridge deck is approximately 27.67 kN, while the negative bending capacity is around 16.58 kN. For the composite bridge deckwith epoxy adhesive joints (EA-J-Ln), the negative bending capacity is 2.54 kN, and the negative bending capacity of the joint area reinforced with carbon fiber cloth (EA-JC-Ln) is increased to 4.17 kN. Therefore, the use of carbon fiber cloth can significantly improve the bending resistance of the joints. Finally, numerical model of the composite deck based on Cohesive Zone Model (CZM) was established, validating the applicability of this simulation method in the novel composite bridge deck.

When we complete sequential movements with different intentions, we plan our movements and adjust ahead. Such a phenomenon is called anticipatory planning for prior intentions and is known to decline with age. In daily life activities, we often need to consider and plan for multiple demands in one movement sequence. However, previous studies only considered one dimension of prior intentions, either different types of onward actions or different precisions of fit or placement. Therefore, in this study, we investigated anticipatory planning for both extrinsic (movement direction) and intrinsic (fit precision) target-related properties in a computer-based movement task and analyzed the computer cursor movement kinematics of both young and older adults. We found that older people consider and adjust for different properties step-by-step, with movement direction being considered as a prior intention during reach movement and fit precision as a motor constraint during drop movement. The age-related changes in the completion of onward actions are constrained by one’s general cognitive ability, sensorimotor performance and effective motor planning for prior intentions. Age-related decline in motor planning can manifest as counterproductive movement profiles, resulting in suboptimal performance of intended actions.

Introduction: In the early stage of embryonic development, the neural tube (NT) cannot be closed properly due to some complex factors, including environmental factors, genetic factors, and the relationship between various factors, leading to the occurrence of neural tube defects (NTDs).Methods: In this study, we induced a mouse model of NTDs by feeding mice with a low-folate diet and intraperitoneally injecting them with 1.5 mg/kg methotrexate on E7.5. Fetal mice were achieved at E13.5, and we extracted proteins from brain tissues with trypsin digestion. After enzymatic digestion, peptides were labeled with TMT/iTRAQ and separated in high-performance liquid chromatography (HPLC) for subsequent liquid chromatography tandem mass spectroscopy (LC-MS/MS) analysis. We used gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation to analyze proteomic changes and analyze the functional enrichment of differentially expressed proteins (DEPs) in the NTD mice tissues.Results: A low-folate-induced mouse model was successfully constructed. Folate was used as a sensitizing agent, and the teratogenicity rate of the NTD fetal mice increased to 36.5% when the concentration of methotrexate was at 1.5 mg/kg. Mass spectrometry was used to identify 6,614 proteins, and among them, 5,656 proteins were quantified. In the following proteomic analysis, GO classification and KEGG pathway enrichment analysis were conducted, and heatmaps were drawn for differentially expressed proteins (DEPs). The main pathways associated with NTDs, such as the Hedgehog, Wnt, p53, and Hippo signaling pathways and the one-carbon pool mediated by folate, can be identified through a protein–protein interaction (PPI) network. It was also found that the regulation of ribosomal proteins, such as RPL13 and RPL14, which are upregulated in NTDs, has a certain impact on neural tube development.Discussion: Our results revealed proteomic changes in the tissues of low-folate-induced NTD mice. Validation showed that ribosomal proteins play a regulatory role during the development of NTDs and provides new ideas for the pathogenesis and preventive measures of NTDs.

Power transformer plays a very important role in power system, its long-term operation will cause various kinds of faults. Accurate identification and timely elimination of transformer faults are the basis of safe operation of power grid. As one of the most commonly used fault diagnosis methods, dissolved gas analysis (DGA) technology is used to identify fault types through dissolved gas in transformer oil, and its reliability has been proved. In order to analyze these gases and diagnose transformer fault types with the results, many methods have been developed, such as Key Gas Method, Method of Duval, IEC 60599 Method, Method of Dornenburg and Method of Rogers, etc. In some cases, the accuracy of these traditional methods is reduced and cannot be applied for diagnosis, since they have fixed input features and is not flexible for input combination. In order to achieve the propose of solving this defect, this paper introduces a deep belief network-based DGA method to diagnose the faults and states of power transformers with customized input features. For this work, six fault classifications were considered based on the nine characteristics extracted from the gases precipitated from the insulating oil of power transformers. The deep belief network was tested using oil samples collected from power transformers. Experiments have shown that the performance of the network has obtained relatively good accuracy results.

Abstract The aim of this phase I study is to evaluate, for the first time, the safety and efficacy of sintilimab in pediatric patients diagnosed with advanced or recurrent malignancies. During the dose escalation phase, patients received a single intravenous infusion of sintilimab at varying doses of 1, 3, and 10 mg/kg. The primary endpoints included the identification of dose-limiting toxicities (DLTs) as well as the evaluation of safety and tolerance. Secondary endpoints focused on assessing objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). A total of 29 patients were enrolled, including 10 individuals diagnosed with Hodgkin lymphoma (HL) and 19 patients with various other tumor categories. Notably, diverse pathological types such as thymoma, choroid plexus carcinoma, and NK/T-cell lymphoma were also included in the study cohort. By the safety data cutoff, most adverse events were grade 1 or 2, with grade 3 or higher treatment-related adverse events (TRAE) occurring in 10% of patients. Among the 27 evaluated subjects, four achieved confirmed complete response (CR) while seven patients exhibited confirmed partial response (PR). Additionally, seven patients maintained disease (SD) during the study period. Notably, sintilimab demonstrated remarkable tolerability without DLTs and exhibited promising anti-tumor effects in pediatric HL. Whole-exome sequencing (WES) was conducted in 15 patients to assess the mutational landscape and copy number variation (CNV) status. The completion of this phase I study establishes the foundation for potential combination regimens involving sintilimab in childhood cancer treatment. The trial is registered on ClinicalTrials.gov with the identifier NCT04400851.

Abstract The interleukin-17 (IL-17) family comprises six members (IL-17A–17F), and recently, all of its related receptors have been discovered. IL-17 was first discovered approximately 30 years ago. Members of this family have various biological functions, including driving an inflammatory cascade during infections and autoimmune diseases, as well as boosting protective immunity against various pathogens. IL-17 is a highly versatile proinflammatory cytokine necessary for vital processes including host immune defenses, tissue repair, inflammatory disease pathogenesis, and cancer progression. However, how IL-17 performs these functions remains controversial. The multifunctional properties of IL-17 have attracted research interest, and emerging data have gradually improved our understanding of the IL-17 signaling pathway. However, a comprehensive review is required to understand its role in both host defense functions and pathogenesis in the body. This review can aid researchers in better understanding the mechanisms underlying IL-17’s roles in vivo and provide a theoretical basis for future studies aiming to regulate IL-17 expression and function. This review discusses recent progress in understanding the IL-17 signaling pathway and its physiological roles. In addition, we present the mechanism underlying IL-17’s role in various pathologies, particularly, in IL-17-induced systemic lupus erythematosus and IL-17-related tumor cell transformation and metastasis. In addition, we have briefly discussed promising developments in the diagnosis and treatment of autoimmune diseases and tumors.

Abstract Background The advent of clinical trial data sharing platforms has created opportunities for making new discoveries and answering important questions using already collected data. However, existing methods for meta-analyzing these data require the presence of shared control groups across studies, significantly limiting the number of questions that can be confidently addressed. We sought to develop a method for meta-analyzing potentially heterogeneous clinical trials even in the absence of a common control group. Methods This work was conducted within the context of a broader effort to study comparative efficacy in Crohn’s disease. Following a search of clnicaltrials.gov we obtained access to the individual participant data from nine trials of FDA-approved treatments in Crohn’s Disease (N = 3392). We developed a method involving sequences of regression and simulation to separately model the placebo- and drug-attributable effects, and to simulate head-to-head trials against an appropriately normalized background. We validated this method by comparing the outcome of a simulated trial comparing the efficacies of adalimumab and ustekinumab against the recently published results of SEAVUE, an actual head-to-head trial of these drugs. This study was pre-registered on PROSPERO (#157,827) prior to the completion of SEAVUE. Results Using our method of sequential regression and simulation, we compared the week eight outcomes of two virtual cohorts subject to the same patient selection criteria as SEAVUE and treated with adalimumab or ustekinumab. Our primary analysis replicated the corresponding published results from SEAVUE (p = 0.9). This finding proved stable under multiple sensitivity analyses. Conclusions This new method may help reduce the bias of individual participant data meta-analyses, expand the scope of what can be learned from these already-collected data, and reduce the costs of obtaining high-quality evidence to guide patient care.

Abstract Salmonella is an important foodborne pathogen, which can cause serious public health problems. Rapid and accurate detection of Salmonella infection and drug resistance mutations in patients will provide timely guidance for clinical treatment and avoid disease progression and other related clinical problems. Here, we established a highly sensitive and quick method for Salmonella and drug resistance mutation detection based on polymerase chain reaction (PCR) and CRISPR-lbCas12a system and evaluated its practicability with clinical samples. Specific CRISPR RNAs (crRNAs) and primers are designed for Salmonella DNA and parC gene S80I mutation diagnosis. CrRNAs with and without phosphorylated modification and different crRNA preparation methods are used to assess the effect on the detection system. After optimization, we detected as low as one copy of Salmonella DNA and drug resistance mutation parC S80I with the Salmonella DNA standard. For 94 clinical samples, this method also showed high sensitivity (100%, 95% CI: 84.98–100%) and specificity (98.48%, 95% CI: 90.73–99.92%) with less time (3 h) than plate culture (16 h) and conventional antimicrobial susceptibility testing (over 16 h). Besides, one parC S80I mutant strain was detected, which is consistent with the result of DNA sequencing. Taken together, we established a highly sensitive and specific method for Salmonella infection and parC S80I drug resistance mutation detection with fewer reagents and ordinary instruments. This assay has wide application prospects for fast detection of pathogen (bacterium and virus) infection, drug resistance determination, and proper treatment guidance.

ABSTRACT Importance Preserving skin health is crucial for atopic dermatitis control as well as for the thriving of children. However, a well‐developed and validated tool that measures the knowledge, attitude, and practice of skin care is lacking. Objective To develop and validate the atopic dermatitis and infant skincare knowledge, attitude, and practice (ADISKAP 1.0) scale that measures parental health literacy on atopic dermatitis and skin care. Methods We conducted a review of the literature, a focus group (two dermatologists and 12 parents), and a panel discussion in order to generate the ADISKAP prototype. Two samples of parents with knowingly superior (dermatologists, n = 59) and inferior (general population, n = 395) knowledge traits participated in the validation of ADISKAP. Cronbach's alpha was reported as a measure of internal consistency, and the intraclass correlation coefficient (ICC) was calculated to assess the test‐retest validity. The known‐groups technique was used to evaluate construct validity. Results The ADISKAP scale contained 17 items after content and face validity validation. After removing items that displayed poor test‐retest reliability (n = 4) and construct validity (n = 3), 12 items were retained in the ADISKAP 1.0. Interpretation ADISKAP 1.0 is a reliable and valid tool for assessing parental knowledge, attitude, and practice on infantile atopic dermatitis and skin care.

ABSTRACT Importance Nagashima‐type palmoplantar keratosis (NPPK) is a hereditary dermatosis mostly caused by a nonsense mutation in SERPINB7. Despite the increasing interest in readthrough gentamicin treatment of NPPK, clinical evidence for this treatment is limited. Objective This study aimed to provide further evidence for the use of topical gentamicin in the treatment of NPPK in children with nonsense mutations. Methods We designed a bilaterally controlled study of topical gentamicin ointment. Children diagnosed with NPPK carrying nonsense mutations were enrolled in this study. A 0.1% gentamicin ointment was applied to one hand and an emollient to the other for 3 months. A bilateral comparison of the visual analog scale scores for clinical manifestations and safety was performed. Results Ten children with NPPK were included in this study. In comparison with the emollient side, the topical gentamicin side showed significant improvements in hyperkeratosis, erythema, maceration, and desquamation after 1 and 3 months of treatment (P < 0.05). However, hyperhidrosis and odor did not improve significantly. No adverse events were observed during the systemic safety monitoring examinations. Interpretation Topical gentamicin ointment showed good safety in the treatment of NPPK with nonsense mutations, indicating that it is a promising therapeutic choice in children with NPPK.

Abstract. Background:. Limited data are available on the changes in the quality of care for ST elevation myocardial infarction (STEMI) during China's health system reform from 2009 to 2020. This study aimed to assess the changes in care processes and outcome for STEMI patients in Henan province of central China between 2011 and 2018. Methods:. We compared the data from the Henan STEMI survey conducted in 2011-2012 (n = 1548, a cross-sectional study) and the Henan STEMI registry in 2016-2018 (n = 4748, a multicenter, prospective observational study). Changes in care processes and in-hospital mortality were determined. Process of care measures included reperfusion therapies, aspirin, P2Y12 antagonists, β-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins. Therapy use was analyzed among patients who were considered ideal candidates for treatment. Results:. STEMI patients in 2016-2018 were younger (median age: 63.1 vs. 63.8 years) with a lower proportion of women (24.4% [1156/4748] vs. 28.2% [437/1548]) than in 2011-2012. The composite use rate for guideline-recommended treatments increased significantly from 2011 to 2018 (60.9% [5424/8901] vs. 82.7% [22,439/27,129], P

Abstract Six-membered N-containing heterocycles, such as 2-piperidinone derivatives, with diverse substitution patterns are widespread in natural products, drug molecules and serve as key precursors for piperidines. Thus, the development of stereoselective synthesis of multi-substituted 2-piperidinones are attractive. However, existing methods heavily rely on modification of pre-synthesized backbones which require tedious multi-step procedure and suffer from limited substitution patterns. Herein, an organophotocatalysed [1 + 2 + 3] strategy was developed to enable the one-step access to diverse substituted 2-piperidinones from easily available inorganic ammonium salts, alkenes, and unsaturated carbonyl compounds. This mild protocol exhibits exclusive chemoselectivity over two alkenes, tolerating both terminal and internal alkenes with a wide range of functional groups.

The missing and abnormal data in power transformer operation and monitoring greatly affect the accuracy of fault diagnosis and thus threaten the stable operation of power systems. To conduct outlier detection and improve data quality for safety warning, this paper proposes a transformer operation data preprocessing method based on KNN (K-nearest neighbor) and LOF (local outlier factor) for power transformer operation data classification. Firstly, this paper analyzes the characteristics of transformer operation data. Secondly, the local reachable density of the input data is calculated by LOF algorithm. The local outlier factor score of the data is derived according to the local reachable density, and the abnormal data is output according to the abnormal score. Then, KNN algorithm is utilized to classify the relevant data around the abnormal value and missing value of the transformer. The data are filled or corrected according to the classification results. Thirdly, the elbow method is used to determine the optimal K value and cluster operation data by K-Means algorithm. Finally, the proposed method is applied and verified with real transformer operation data in case study. The results show the method can effectively detect and correct the abnormal and missing data, conduct transformer data cleaning and preprocessing and provide accurate and effective data samples for transformer fault diagnosis.

IntroductionChronic intermittent hypoxia (CIH) can negatively affect hippocampal function through various molecular mechanisms. Protein acetylation, a frequently occurring modification, plays crucial roles in synaptic plasticity and cognitive processes. However, the global protein acetylation induced by CIH in the hippocampus and its specific effects on hippocampal function and behavior remain poorly understood.MethodsTo address this gap, we conducted a study using liquid chromatography-tandem mass spectrometry to analyze the lysine acetylome and proteome of the hippocampus in healthy adult mice exposed to intermittent hypoxia for 4 weeks (as a CIH model) compared to normoxic mice (as a control).ResultsWe identified and quantified a total of 2,184 lysine acetylation sites in 1,007 proteins. Analysis of these acetylated proteins revealed disturbances primarily in oxidative phosphorylation, the tricarboxylic acid (TCA) cycle, and glycolysis, all of which are localized exclusively to mitochondria. Additionally, we observed significant changes in the abundance of 21 proteins, some of which are known to be associated with cognitive impairments.DiscussionThis study helps to elucidate the molecular mechanisms underlying CIH-induced changes in protein acetylation in the hippocampus. By providing valuable insights into the pathophysiological processes associated with CIH and their impacts on hippocampal function, our findings contribute to a better understanding of the consequences of CIH-induced changes in protein acetylation in the hippocampus and the potential role of CIH in cognitive impairment.

Jieyu Anshen Granules (JY) is a traditional Chinese medicine formula commonly used as an adjuvant treatment for Alzheimer's disease (AD) complicated with depression. However, the specific underlying mechanisms and therapeutic targets of JY remain unclear. We used the TCMSP, TCMID, BATMAN-TCM, and other databases to screen the components and assumed targets of JY. Next, the GEO and DisGeNET databases were used to identify the related targets of both AD and Major Depressive Disorder (MDD). Enrichment analyses of core targets were performed, and the main components and core targets of JY for the comorbidity of AD and MDD were identified via protein–protein interaction (PPI) network construction and machine learning algorithms. Lastly, we verified binding affinity using the AutoDock software and molecular docking was performed. A total of 171 components were identified from JY, and 979 targets were obtained from the screening process. Bioinformatics analysis displayed 397 differentially expressed genes (DEGs) were shared by AD and MDD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis revealed significant enrichment of genes associated with neurotransmitter receptor activity, G protein-coupled amine receptor activity, as well as signaling pathways such as the cAMP signaling pathway, PI3K-Akt signaling pathway, and cholinergic synapses. Through the PPI network and machine learning, we identified three hub genes (Ataxia telangiectasia-mutated gene [ATM], Colony stimulating factor 1 receptor [CSF1R], EPH receptor B2 [EPHB2]) as potential therapeutic targets. Molecular docking confirmed that the components of JY (Mairin, Hederagenin, 3-Epioleanolic Acid) could effectively bind to multiple key targets. This study revealed the effective components and potential mechanisms associated with JY treatment regarding AD and MDD comorbidities, offering valuable insights into promising therapeutic targets for subsequent studies.

Background. Here, we report a case of a male patient with bilateral focal choroidal excavation (FCE) and central serous chorioretinopathy (CSC). A 33-year-old man complained of mild blurring of vision in the right eye. Optical coherence tomography (OCT) revealed FCE in both eyes, with subretinal fluid in both eyes and serous pigment epithelial detachment in the right eye. Standard laser fluence (50 J/cm2) was used in the right eye, and a subthreshold micropulse laser (SML) was simultaneously used in the left eye. Follow-up visits were recommended. At his last visit (5 months after treatment), the visual acuity was 16/20 in the right eye and 20/20 in the left eye and OCT showed a completed resolution of SRF. Conclusion. FCE is defined as a localized depression of the choroid detected by OCT. It may be congenital or acquired secondarily. We present a case of uncommon focal choroidal excavation and central serous chorioretinopathy (CSC) coexisting in both eyes at a relatively young age in which visual acuity was improved and subretinal fluid (SRF) completely resolved with laser treatment. Timely treatment can promote SRF absorption and improve vision.

The wide-scale expansion of renewable energy sources has triggered the demand for advanced energy storage technologies. Aqueous zinc ion batteries (AZIBs) have been widely noticed in recent years because of their intrinsic safety, abundant raw materials, and environmental friendliness. Among the reported cathode materials for ZIBs, Mn-oxide materials stand out as one of the most promising candidates with their diverse structures, high capacity, and cost-effectiveness. However, the complex energy storage mechanism and unstable electrochemical properties persistently obstruct the practical application of this technology. It has been realized that these disturbances are related to the structural evolution of Mn-oxide materials during the charge/discharge process, and considerable relevant research was carried out. In this review, we present an up-to-date review of the most recent advancements and challenges concerning Mn-oxide cathode materials for aqueous zinc ion batteries. Firstly, we offer a concise summary and categorization of several widely recognized energy storage mechanisms and crystal structures. Then, we focused on sorting out the structural evolution path of Mn-oxide materials, and explored the relevant influencing factors and the relationship between phase evolution and property fluctuations. Finally, we distill key optimization strategies and provide a forward-looking perspective on future research.

Fibromyalgia syndrome (FMS) is a recurrent pain condition that can be challenging to treat. Transcranial direct current stimulation (tDCS) has become a promising non-invasive therapeutic option in alleviating FMS pain, but the mechanisms underlying its effectiveness are not yet fully understood. In this article, we discuss the most current research investigating the analgesic effects of tDCS on FMS and discuss the potential mechanisms. TDCS may exert its analgesic effects by influencing neuronal activity in the brain, altering cortical excitability, changing regional cerebral blood flow, modulating neurotransmission and neuroinflammation, and inducing neuroplasticity. Overall, evidence points to tDCS as a potentially safe and efficient pain relief choice for FMS by multiple underlying mechanisms. This article provides a thorough overview of our ongoing knowledge regarding the mechanisms underlying tDCS and emphasizes the possibility of further studies to improve the clinical utility of tDCS as a pain management tool.

ObjectivesWe aim to investigate the functional profiles of perilesional gray matter (GM) in epileptic patients with focal cortical dysplasia (FCD) and to correlate these profiles with FCD II subtypes, surgical outcomes, and different antiseizure medications (ASMs) treatment response patterns.MethodsNine patients with drug-responsive epilepsy and 30 patients with drug-resistant epilepsy (11 were histologically confirmed FCD type IIa, 19 were FCD type IIb) were included. Individual-specific perilesional GM and contralateral homotopic GM layer masks were generated. These masks underwent a two-voxel (2 mm) dilation from the FCD lesion and contralateral homotopic region, resulting in 10 GM layers (20 mm). Layer 1, the innermost, progressed to Layer 10, the outermost. Amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) analyses were conducted to assess the functional characteristics of ipsilateral perilesional GM and contralateral homotopic GM.ResultsCompared to the contralateral homotopic GM, a significant reduction of ALFF was detected at ipsilateral perilesional GM layer 1 to 6 in FCD type IIa (after Bonferroni correction p

To study the adverse effects of butyl benzyl phthalate (BBP) on Brachionus plicatilis, rotifers were exposed to different BBP concentrations (0 [control], 0.001, 0.01, 0.1, and 1 mg/L). We measured the activities of the antioxidant enzymes superoxide dismutase, catalase, and reduced glutathione, which play a key role in detoxification, and the malondialdehyde content, which represents the level of lipid peroxidation. In addition, we investigated the effect of BBP on the submicroscopic structure and transcriptome of rotifer ovary cells. Our results showed that B. plicatilis exhibited a rapid oxidative stress response accompanied by a significant increase in superoxide dismutase enzyme activity. High BBP concentrations resulted in a significant decrease in malondialdehyde content, which indicated that BBP interferes with the lipid metabolism of rotifer cells. Our observations showed that the endoplasmic reticulum structure of rotifer ovary cells was severely damaged by BBP exposure. Transcriptomic data further demonstrated that oxidative stress and cellular sub-microstructural damage were associated with altered expression of functional genes related to rotifer redox regulation, biosynthetic processes, and cellular damage components. In conclusion, our study demonstrates that BBP triggers changes in antioxidant-related indicators in rotifers; this leads to activation of related genes and subsequent changes in intracellular signaling, which in turn triggers endoplasmic reticulum stress and ultimately leads to disruption of cell function and structure. These findings highlight the potential risks associated with BBP exposure and provide fundamental insights into its toxicological effects on marine invertebrates.

Abstract Improving health and delaying aging is the focus of medical research. Previous studies have shown that mesenchymal stem cell (MSC) senescence is closely related to organic aging and the development of aging-related diseases such as osteoarthritis (OA). m6A is a common RNA modification that plays an important role in regulating cell biological functions, and ALKBH5 is one of the key m6A demethylases. However, the role of m6A and ALKBH5 in MSC senescence is still unclear. Here, we found that the m6A level was enhanced and ALKBH5 expression was decreased in aging MSCs induced by multiple replications, H2O2 stimulation or UV irradiation. Downregulation of ALKBH5 expression facilitated MSC senescence by enhancing the stability of CYP1B1 mRNA and inducing mitochondrial dysfunction. In addition, IGF2BP1 was identified as the m6A reader restraining the degradation of m6A-modified CYP1B1 mRNA. Furthermore, Alkbh5 knockout in MSCs aggravated spontaneous OA in mice, and overexpression of Alkbh5 improved the efficacy of MSCs in OA. Overall, this study revealed a novel mechanism of m6A in MSC senescence and identified promising targets to protect against aging and OA.

Because plant mechanical strength influences plant growth and development, the regulatory mechanisms underlying cell-wall synthesis deserve investigation. Rice mutants are useful for such research. We have identified a novel brittle culm 25 (bc25) mutant with reduced growth and partial sterility. BC25 encodes an UDP-glucuronic acid decarboxylase involved in cellulose synthesis and belongs to the UXS family. A single-nucleotide mutation in BC25 accounts for its altered cell morphology and cell-wall composition. Transmission electron microscopy analysis showed that the thickness of the secondary cell wall was reduced in bc25. Monosaccharide analysis revealed significant increases in content of rhamnose and arabinose but not of other monosaccharides, indicating that BC25 was involved in xylose synthesis with some level of functional redundancy. Enzymatic assays suggested that BC25 functions with high activity to interconvert UDP-glucuronic acid (UDP-GlcA) and UDP-xylose. GUS staining showed that BC25 was ubiquitously expressed with higher expression in culm, root and sheath, in agreement with that shown by quantitative real-time (qRT)-PCR. RNA-seq further suggested that BC25 is involved in sugar metabolism. We conclude that BC25 strongly influences rice cell wall formation.

Abstract Background The triglyceride–glucose (TyG) index has been proposed as a potential predictor of adverse prognosis of cardiovascular diseases (CVDs). However, its prognostic value in patients with coronary heart disease (CHD) and hypertension remains unclear. Methods A total of 1467 hospitalized patients with CHD and hypertension from January 2021 to December 2021 were included in this prospective and observational clinical study. The TyG index was calculated as Ln [fasting triglyceride level (mg/dL) × fasting plasma glucose level (mg/dL)/2]. Patients were divided into tertiles according to TyG index values. The primary endpoint was a compound endpoint, defined as the first occurrence of all-cause mortality or total nonfatal CVDs events within one-year follow up. The secondary endpoint was atherosclerotic CVD (ASCVD) events, including non-fatal stroke/transient ischemic attack (TIA) and recurrent CHD events. We used restricted cubic spline analysis and multivariate adjusted Cox proportional hazard models to investigate the associations of the TyG index with primary endpoint events. Results During the one-year follow-up period, 154 (10.5%) primary endpoint events were recorded, including 129 (8.8%) ASCVD events. After adjusting for confounding variables, for per standard deviation (SD) increase in the TyG index, the risk of incident primary endpoint events increased by 28% [hazard ratio (HR) = 1.28, 95% confidence interval (CI) 1.04–1.59]. Compared with subjects in the lowest tertile (T1), the fully adjusted HR for primary endpoint events was 1.43 (95% CI 0.90–2.26) in the middle (T2) and 1.73 (95% CI 1.06–2.82) in highest tertile (T3) (P for trend = 0.018). Similar results were observed in ASCVD events. Restricted cubic spline analysis also showed that the cumulative risk of primary endpoint events increased as TyG index increased. Conclusions The elevated TyG index was a potential marker of adverse prognosis in patients with CHD and hypertension.

Abstract Hepatoma-derived growth factor (HDGF) expression is associated with poor prognosis in non-small cell lung cancer (NSCLC); however, whether HDGF affects gefitinib resistance in NSCLC remains unknown. This study aimed to explore the role of HDGF in gefitinib resistance in NSCLC and to discover the underlying mechanisms. Stable HDGF knockout or overexpression cell lines were generated to perform experiments in vitro and in vivo. HDGF concentrations were determined using an ELISA kit. HDGF overexpression exacerbated the malignant phenotype of NSCLC cells, while HDGF knockdown exerted the opposite effects. Furthermore, PC-9 cells, which were initially gefitinib-sensitive, became resistant to gefitinib treatment after HDGF overexpression, whereas HDGF knockdown enhanced gefitinib sensitivity in H1975 cells, which were initially gefitinib-resistant. Higher levels of HDGF in plasma or tumor tissue also indicated gefitinib resistance. The effects of HDGF on promoting the gefitinib resistance were largely attenuated by MK2206 (Akt inhibitor) or U0126 (ERK inhibitor). Mechanistically, gefitinib treatment provoked HDGF expression and activated the Akt and ERK pathways, which were independent of EGFR phosphorylation. In summary, HDGF contributes to gefitinib resistance by activating the Akt and ERK signaling pathways. The higher HDGF levels may predict poor efficacy for TKI treatment, thus it has the potential to serve as a new target for overcoming tyrosine kinase inhibitor resistance in combating NSCLC.

Laser trackers are instruments used to measure the three-dimensional coordinates of objects with high precision. It is necessary to study calibration methods to identify geometric errors of laser trackers so as to compensate for errors and improve measurement accuracy. Among the offsets, tilts, and eccentricity errors in the system, the transit tilt and offset errors play important roles and have an essential effect on the measurement accuracy, which need to be calibrated and compensated for. Current methods for detecting geometric errors between the transit and standing axes are complex and time-consuming. In this paper, a fast and novel calibration method is proposed, which can be easily operated with high precision. Two test rods are coaxially mounted on the ends of the transit axis to extend the hidden transit axis. Then, a telecentric measurement system is used to record the projection images of the test rods and identify the position of the transit axis. The transit offset and tilt errors were thus obtained by comparing the central axis positions of the two test rods before and after the standing axis rotated 180 degrees. Moreover, a numerical analysis method was proposed based on the least square circle fitting method to calibrate the installation eccentricity errors of the test rods. Experimental results verify that the measurement accuracy of the laser tracker can be improved after error compensation using the calibrated transit offset and tilt errors. The measurement error of the laser tracker can be reduced from 161 µm to about 73 µm after compensation at a distance of 5 m, while the error can be decreased from 143 µm to about 108 µm at a distance of 10 m.

The relatively low export innovation capacity is not conductive to the steady transformation and upgrading of China’s manufacturing industry, and it is necessary to implement suitable policies to enhance export innovation capacity. This study empirically analyzes the data of 827,471 manufacturing enterprises from 2000 till 2013 to investigate the impact of subsidy policy on export innovation. The overall results show that China’s subsidy policy has a significant crowding-out effect on export innovation, and subsidy for relatively small enterprises is more conducive to promoting export innovation; however, enterprises’ independent investment does not own much impact on export innovation. The econometric results made from perspectives of the sub-region and the industry reveal that subsidy policy is not conducive to export innovation, independent investment is not beneficial to export innovation, and export innovation ability is positively correlated with enterprise scale, but the influence coefficient shows obvious differences.

Bone cystic echinococcosis (CE) is one of the most complex and dangerous of all echinococcoses. The lack of typical imaging features and clinical manifestations makes diagnosis and treatment of this disease difficult. X-ray and computed tomography (CT) images of bone CE are similar to those of bone cysts, giant-cell bone tumors, and bone metastases, but magnetic resonance imaging (MRI) shows good diagnostic value due to excellent soft-tissue imaging features. Serological tests cannot be used as a definitive diagnostic method for bone CE due to cross-reactivity, which can lead to false-positive or false-negative results. The development of novel antigens can open new frontiers in the diagnosis of the disease. Currently, views conflict on how to diagnose and treat bone CE. Both surgical and pharmacological treatments can be used, but determining which is appropriate is difficult due to the different sites and clinical manifestations of bone CE. Radical resection is not indicated for large-bone injuries, and Pharmacotherapy becomes important. This article reviews the progress of research into the pathogenesis and clinical manifestations of, and diagnostic strategies and treatment options for, bone CE. We aimed to provide a reference for clinical diagnosis and -treatment options.

BackgroundTumor microenvironment (TME) status is closely related to breast cancer (BC) prognosis and systemic therapeutic effects. However, to date studies have not considered the interactions of immune and stromal cells at the gene expression level in BC as a whole. Herein, we constructed a predictive model, for adjuvant decision-making, by mining TME molecular expression information related to BC patient prognosis and drug treatment sensitivity.MethodsClinical information and gene expression profiles were extracted from The Cancer Genome Atlas (TCGA), with patients divided into high- and low-score groups according to immune/stromal scores. TME-related prognostic genes were identified using Kaplan-Meier analysis, functional enrichment analysis, and protein-protein interaction (PPI) networks, and validated in the Gene Expression Omnibus (GEO) database. Least absolute shrinkage and selection operator (LASSO) Cox regression analysis was used to construct and verify a prognostic model based on TME-related genes. In addition, the patients’ response to chemotherapy and immunotherapy was assessed by survival outcome and immunohistochemistry (IPS). Immunohistochemistry (IHC) staining laid a solid foundation for exploring the value of novel therapeutic target genes.ResultsBy dividing patients into low- and high-risk groups, a significant distinction in overall survival was found (p < 0.05). The risk model was independent of multiple clinicopathological parameters and accurately predicted prognosis in BC patients (p < 0.05). The nomogram-integrated risk score had high prediction accuracy and applicability, when compared with simple clinicopathological features. As predicted by the risk model, regardless of the chemotherapy regimen, the survival advantage of the low-risk group was evident in those patients receiving chemotherapy (p < 0.05). However, in patients receiving anthracycline (A) therapy, outcomes were not significantly different when compared with those receiving no-A therapy (p = 0.24), suggesting these patients may omit from A-containing adjuvant chemotherapy. Our risk model also effectively predicted tumor mutation burden (TMB) and immunotherapy efficacy in BC patients (p < 0.05).ConclusionThe prognostic score model based on TME-related genes effectively predicted prognosis and chemotherapy effects in BC patients. The model provides a theoretical basis for novel driver-gene discover in BC and guides the decision-making for the adjuvant treatment of early breast cancer (eBC).