Altered landscape of total RNA, tRNA and sncRNA modifications in the liver and spleen of mice infected by Toxoplasma gondii.

BACKGROUND: Pathogens can impact host RNA modification machinery to establish a favorable cellular environment for their replication. In the present study, we investigated the effect of Toxoplasma gondii infection on host RNA modification profiles and explored how these modifications may influence the host-parasite interaction. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the modification levels of ∼ 80 nt tRNA and 17-50 nt sncRNAs in mouse liver, spleen, and serum using liquid chromatography and tandem mass spectrometry analysis. The results revealed alterations in RNA modification profiles, particularly during acute infection. The liver exhibited more differentially abundant RNA modifications than the spleen. RNA modification levels in serum were mostly downregulated during acute infection compared to control mice. Correlations were detected between different RNA modifications in the liver and spleen during infection and between several RNA modifications and many cytokines. Alterations in RNA modifications affected tRNA stability and protein translation. CONCLUSIONS/SIGNIFICANCE: These findings provide new insight into the role of RNA modifications in mediating the murine host response to T. gondii infection.

Association between early-life mosquito repellents exposure and ADHD-like behaviours.

BACKGROUND: Limited research has explored the impact of mosquito repellents exposure during early life on ADHD symptoms. This study aimed to explore the associations of exposure to mosquito repellents from pregnancy to 3 years old and the prevalence of ADHD-like behaviours among children aged 3-9 years, and further identify the sensitive exposure period. METHODS: A cross-sectional study was conducted, including 12 275 children in Hefei City, China. Exposure was self-reported via primary caregivers. ADHD-like behaviours were measured by the Swanson, Nolan and Pelham, version IV scale (SNAP-IV), and Conners' Parent Rating Scale (CPRS). Cross-over analysis, binary logistic regression and linear regression were employed. RESULTS: After adjusting for confounding variables, early-life exposure to mosquito repellents was associated with a higher risk of ADHD-like behaviours (OR = 1.81, 95% CI = 1.49-2.19). By comparing the strength of the association for each subgroup, we found exposure during 1-3 years old was a sensitive period (OR = 1.89, 95% CI = 1.25-2.87) by the cross-over analysis. Furthermore, we found a dose-response relationship in which the likelihood of ADHD-like behaviours increased with children's early-life mosquito repellents exposure dose. CONCLUSIONS: Early-life exposure to mosquito repellents is linked with an elevated risk of ADHD-like behaviours in children, with a sensitive period identified during 1-3 years old.

Effects of component ratios on the properties of sweet potato-oat composite dough and the quality of its steamed cake.

To enhance the value proposition of sweet potato and oat while broadening their applicability in further processing, this study systematically investigated the impact of oat flour incorporation ratios (5%-25% of sweet potato dry weight) on the quality attributes of sweet potato-oat composite dough and its resulting steamed cake products. The results showed that the addition of oat flour could promote the rheological, water retention, and thermomechanical properties of the composite dough and improve the internal microstructure, specific volume, texture, and other processing properties of the steamed cake products. The rheology, water retention, and protein stability of the dough were maximized when the proportion of oat flour was 25%. The textural properties of steamed cakes, hardness, elasticity, cohesion, adhesion, chewiness, and recovery significantly increased (p < 0.05) and viscosity significantly decreased (p < 0.05) with the addition of oat flour. It is noteworthy that thermodynamic properties, internal structure of the dough, and air holding capacity, which are critical for processing, showed the best results at 20% oat flour addition. Therefore, the addition of 20%-25% oats is recommended to produce composite doughs with optimal quality and processing characteristics. PRACTICAL APPLICATION: As living standards improve, traditional cereals may no longer able to meet people's health needs. Therefore, there is an urgent consumer demand for nutritious, tasty alternatives to staple foods. In this study, oat flour and sweet potato mash were mixed to make sweet potato-oat cake, and the effect of ingredient ratio on the performance and quality of composite dough containing sweet potato-oat flour was analyzed, thus proposing an innovative approach to the research, development, and industrial production of sweet potato and oat food products.

The Efficiency and Toxicity Of Anlotinib in Combination With Docetaxel Followed by Epirubicin and Cyclophosphamide Regimen as Neoadjuvant Treatment in IIB to IIIA Triple Negative Breast Cancer: A Single-Arm, Multicenter, Open-Label, Phase II Study.

BACKGROUND: The combination of neoadjuvant chemotherapy and anti-angiogenesis therapy for patients with triple-negative breast cancer (TNBC) remains inadequately supported by evidence. We conducted a single-arm, open-label, multicenter, phase II trial to evaluate the efficacy and toxicity of anlotinib plus epirubicin and cyclophosphamide followed by paclitaxel in patients with IIB to IIIA stage TNBC. METHODS: Newly diagnosed patients received epirubicin at 90 mg/m2 and cyclophosphamide at 600 mg/m2 followed by docetaxel at 100 mg/m2 (21 days per cycle; total of 4 cycles), along with oral anlotinib (12 mg qd, d1-14; 21 days per cycle; total of 4 cycles). Subsequently, patients underwent surgery. The primary endpoint of this study was pathologic complete response (pCR). RESULTS: Among the 34 included patients, the median age was 46.5 years (range: 27-72); all were female. Pathological assessment revealed that 17 patients achieved RCB 0 response, which is currently defined as pathologic complete response; 3 patients achieved RCB 1; 12 patients achieved RCB 2; and 1 patient achieved RCB 3. The probability of a grade 3 adverse reaction was 17.6%, and no grade 4 adverse reactions occurred. The most common hematological adverse reaction was leukopenia (13/34, 38.2%), of which 5.9% (2/34) were grade 3. The most common non-hematological adverse reactions were oral mucositis (16/34, 58.8%), fatigue (50.0%), hand-foot syndrome (50.0%), hypertension (44.1%), bleeding (44.1%), and alopecia (32.4%). CONCLUSION: The combination of anlotinib and EC-T chemotherapy demonstrated tolerable side effects in the neoadjuvant treatment of early TNBC. pCR was higher than what has been reported in previous clinical studies of chemotherapy alone. This study provides additional rationale for using anlotinib plus docetaxel-epirubicin-based chemotherapy regimen in patients with early-stage TNBCs.

Multi-omics analysis elucidates the relationship between intratumor microbiome and host immune heterogeneity in breast cancer.

Research has indicated that intratumor microbiomes affect the occurrence, progression, and therapeutic response in many cancer types by influencing the immune system. We aim to evaluate the characteristics of immune-related intratumor microbiomes (IRIMs) in breast cancer (BC) and search for potential prognosis prediction factors and treatment targets. The clinical information, microbiome data, transcriptomics data of The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) patients were obtained from Kraken-TCGA-Raw-Data and TCGA portal. The core tumor-infiltrating immune cell was identified using univariate Cox regression analysis. Based on consensus clustering analysis, BC patients were categorized into two immune subtypes, referred to as immune-enriched and immune-deficient subtypes. The immune-enriched subtype, characterized by higher levels of immune infiltration of CD8+ T and macrophage M1 cells, demonstrated a more favorable prognosis. Furthermore, significant differences in alpha-diversity and beta-diversity were observed between the two immune subtypes, and the least discriminant analysis effect size method identified 33 types of IRIMs. An intratumor microbiome-based prognostic signature consisting of four prognostic IRIMs (Acidibacillus, Succinimonas, Lachnoclostridium, and Pseudogulbenkiania) was constructed using the Cox proportional-hazard model, and it had great prognostic value. The prognostic IRIMs were correlated with immune gene expression and the sensitivity of chemotherapy drugs, specifically tamoxifen and docetaxel. In conclusion, our research has successfully identified two distinct immune subtypes in BC, which exhibit contrasting prognoses and possess unique epigenetic and intratumor microbiomes. The critical IRIMs were correlated with prognosis, tumor-infiltrating immune cell abundance, and immunotherapeutic efficacy in BC. Consequently, this study has identified potential IRIMs as biomarkers, providing a novel therapeutic approach for treating BC.IMPORTANCERecent research has substantiated the presence of the intratumor microbiome in tumor immune microenvironment, which could influence tumor occurrence and progression, as well as provide new opportunities for cancer diagnosis and treatment. This study identified the critical immune-related intratumor microbiome (Acidibacillus, Succinimonas, Lachnoclostridium, and Pseudogulbenkiania), which were correlated with prognosis, tumor-infiltrating immune cell abundance, and immunotherapeutic efficacy in breast cancer and might be the novel target to regulate immunotherapy in BC.

A meta-analysis of technology acceptance in healthcare from the consumer's perspective.

Consumer-oriented health care technologies are increasingly available and transforming global health delivery systems. However, there is a paucity of research that systematically investigates health care technology acceptance from the consumer's perspective. This study conducts a literature review and meta-analysis to examine consumers' adoption intentions toward health care technologies. The findings suggest that technology acceptance models are transferable to health care technology with modifications, and factors such as perceived risks, technology performance expectancy, consumer trust, and habit significantly correlate with consumers' adoption intentions. This study provides valuable insights into health care technology management and practical implications for health care service designers, providers, and regulatory authorities.

Machine learning predicts the risk of osteoporosis in patients with breast cancer and healthy women.

OBJECTIVE: In this study, we investigated the effects of endocrine therapy and related drugs on the body composition and bone metabolism of patients with breast cancer. Additionally, using body composition-related indicators in machine learning algorithms, the risks of osteoporosis in patients with breast cancer and healthy women were predicted. METHODS: We enrolled postmenopausal patients with breast cancer who were hospitalized in a tertiary hospital and postmenopausal women undergoing health checkups in our hospital between 2019 and 2021. The basic information, body composition, bone density-related indicators, and bone metabolism-related indicators of all the study subjects were recorded. Machine learning models were constructed using cross-validation. RESULTS: Compared with a healthy population, the body composition of patients with breast cancer was low in bone mass, protein, body fat percentage, muscle, and basal metabolism, whereas total water, intracellular fluid, extracellular fluid, and waist-to-hip ratio were high. In patients with breast cancer, the bone mineral density (BMD), Z value, and T value were low and the proportion of bone loss and osteoporosis was high. BMD in patients with breast cancer was negatively correlated with age, endocrine therapy status, duration of medication, and duration of menopause, and it was positively correlated with body mass index (BMI) and basal metabolism. The parameters including body composition, age, hormone receptor status, and medication type were used for developing the machine learning model to predict osteoporosis risk in patients with breast cancer and healthy populations. The model showed a high accuracy in predicting osteoporosis, reflecting the predictive value of the model. CONCLUSIONS: Patients with breast cancer may have changed body composition and BMD. Compared with the healthy population, the main indicators of osteoporosis in patients with breast cancer were reduced nonadipose tissue, increased risk of edema, altered fat distribution, and reduced BMD. In addition to age, duration of treatment, and duration of menopause, body composition-related indicators such as BMI and basal metabolism may be considerably associated with BMD of patients with breast cancer, suggesting that BMD status can be monitored in clinical practice by focusing on changes in the aforementioned indexes, which may provide a way to prevent preclinical osteoporosis.

Transcriptomic profiling of long non-coding RNAs and messenger RNAs in the liver of mice during Toxoplasma gondii infection.

BACKGROUND: Toxoplasma gondii is an intracellular protozoan parasite that can infect a wide range of warm-blooded animals, including humans. It poses significant health risks, particularly in immunocompromised individuals and during pregnancy, leading to severe disease manifestations. The liver, being a crucial organ involved in immune response and metabolic regulation, plays a critical role in the host's defense against T. gondii infection. METHODS: In this study, we utilized RNA sequencing to investigate the expression profiles of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in the liver of mice infected with T. gondii. By employing this method, we obtained a comprehensive overview of the alterations in gene expression occurring in the liver during infection. RESULTS: By comparing the infected groups to the control groups, we identified numerous differentially expressed lncRNAs DElncRNAs and DEmRNAs at two stages of infection. Specifically, at the acute infection stage, we found 628 DElncRNAs, and 6346 DEmRNAs. At the chronic infection stage, we identified 385 DElncRNAs and 2513 DEmRNAs. Furthermore, we identified 1959 commonly expressed DEmRNAs, including IL27, Nos2, and Cxcr2, across two infection stages. Enrichment and co-location analyses revealed pathways linked to immune and inflammatory responses during T. gondii infection. Notably, through co-location analysis, our analysis revealed several DElncRNAs, including Gm29156, Gm29157, and Gm28644, which are potentially implicated in the progression of liver inflammation induced by T. gondii. Additionally, functional enrichment analysis disclosed stage-specific characteristics of liver inflammation and immune response, alongside changes in metabolic regulation and immunosuppression pathways. CONCLUSIONS: Our findings provide valuable insights into the expression patterns of lncRNAs and mRNAs in the liver at different stages of T. gondii infection. We identified potential regulatory factors and pathways implicated in liver inflammation, thereby enhancing our understanding of the molecular mechanisms underlying liver inflammation and immune responses during T. gondii infection. These findings could contribute to the development of targeted therapeutic strategies for liver inflammation in the context of T. gondii infection.

Integrated evaluation of biomechanical and biological properties of the biomimetic structural bone scaffold: Biomechanics, simulation analysis, and osteogenesis.

A porous structure is essential for bone implants because it increases the bone ingrowth space and improves mechanical and biological properties. The biomimetically designed porous Voronoi scaffold can reconstruct the structure and function of cancellous bone; however, its comprehensive properties need to be investigated further. In this study, algorithms based on scaling factors were used to design the Voronoi scaffolds. Classic approaches, such as computer-aided design and the implicit surface method, have been used to design Diamond, Gyroid, and I-WP scaffolds as controls. All scaffolds were prepared by selective laser melting of titanium alloys and three-dimensional printing. Mechanical tests, finite element analysis, and in vitro and in vivo experiments were performed to investigate the biomechanical, cytologic, and osteogenic performance of the scaffolds, while computational fluid dynamics simulations were used to explore the underlying mechanisms. Diamond scaffolds have a better loading capacity, and the mechanical behaviors and fluid flow of Voronoi scaffolds are similar to those of the human trabecular bone. Cells showed more proliferation and distribution on the Diamond and Voronoi scaffolds and exhibited evident differentiation on Gyroid and Voronoi scaffolds. Bone formation was apparent on the inner part of the Gyroid, the outer part of the I-WP, and the entire Diamond and Voronoi scaffolds. The hydrodynamic properties and stimulus response of cells influenced by the porous structure account for the varied biological performance of the scaffolds. The Voronoi scaffolds with bionic mechanical behavior and an appropriate hydrodynamic response exhibit evident cell growth and osteogenesis, making them preferable for porous structural bone implants.

Effects of freezing and drying programs on IgY aggregation and activity during microwave freeze-drying: Protective effects and interactions of trehalose and mannitol.

The acquisition of high quality lyophilized IgY products, characterized by an aesthetically pleasing visage, heightened stability, and a marked preservation of activity, constitutes an indispensable pursuit in augmenting the safety and pragmatic utility of IgY. Within this context, an exploration was undertaken to investigate an innovative modality encompassing microwave freeze-drying (MFD) as a preparatory methodology of IgY. Morphological assessments revealed that both cryogenic freezing and subsequent MFD procedures resulted in aggregation of IgY, with the deleterious influence posed by the MFD phase transcending that of the freezing phase. The composite protective agent comprised of trehalose and mannitol engendered a safeguarding effect on the structural integrity of IgY, thereby attenuating reducing aggregation between IgY during the freeze-drying process. Enzyme-linked immunosorbent assay (ELISA) outcomes demonstrated a discernible correlation between IgY aggregation and a notable reduction in its binding affinity towards the pertinent antigen. Comparative analysis vis-à-vis the control sample delineated that when the trehalose-to-mannitol ratio was upheld at 1:3, a two-fold outcome was achieved: a mitigation of the collapse susceptibility within the final product as well as a deterrence of IgY agglomeration, concomitant with an elevated preservation rate of active antibodies (78.57 %).

Effect of gum arabic and thermal modification of whey protein isolate on the characteristics of Cornus officinalis flavonoid microcapsules.

Whey protein isolates (WPIs) were treated at 50, 60, 70, and 80°C to obtain thermally modified WPI. Gum arabic (GA) and thermal modification of WPI were used as novel wall materials to improve the quality of Cornus officinalis flavonoid (COF) microcapsules using microwave freeze-drying technique in this study. Results showed that all the thermal modification treatment decreased emulsifying activity index of WPI, whereas the solubility and emulsifying stability index (ESI) of WPI gradually increased with the increase of heating temperature. Compared to the untreated protein, the thermal modification treatment at 70°C increased the solubility and ESI of WPI by 14.91% ± 0.71% and 26.70% ± 0.94%, respectively. The microcapsules prepared with the modified protein at 60°C had the highest encapsulation efficiency (95.13% ± 2.36%), the lowest moisture content (1.42% ± 0.34%), and the highest solubility (84.41% ± 0.91). Scanning electron microscopy images showed that COF microcapsules were uniformly spherical, and the sizes of the microcapsules were in the following order: 12.42 ± 0.37 µm (80°C) > 11.7 ± 0.23 µm (untreated group) > 9.44 ± 0.33 µm (60°C) > 9.24 ± 0.14 µm (50°C) > 7.69 ± 0.29 µm (70°C). In the simulated in vitro digestion experiments, the release rate of COF microcapsules in the gastric digestion phase was less than that in the intestinal digestion phase, and it reached 66.46% at intestinal digestion phase. These results suggested that heated WPI and GA could be an effective nanocarrier to enhance the stability of COF.

Potato virus Y viral protein 6K1 inhibits the interaction between defense proteins during virus infection.

14-3-3 proteins play vital roles in plant defense against various pathogen invasions. To date, how 14-3-3 affects virus infections in plants remains largely unclear. In this study, we found that Nicotiana benthamiana 14-3-3h interacts with TRANSLATIONALLY CONTROLLED TUMOR PROTEIN (TCTP), a susceptibility factor of potato virus Y (PVY). Silencing of Nb14-3-3h facilitates PVY accumulation, whereas overexpression of Nb14-3-3h inhibits PVY replication. The antiviral activities of 3 Nb14-3-3h dimerization defective mutants are significantly decreased, indicating that dimerization of Nb14-3-3h is indispensable for restricting PVY infection. Our results also showed that the mutant Nb14-3-3hE16A, which is capable of dimerizing but not interacting with NbTCTP, has reduced anti-PVY activity; the mutant NbTCTPI65A, which is unable to interact with Nb14-3-3h, facilitates PVY replication compared with the wild-type NbTCTP, indicating that dimeric Nb14-3-3h restricts PVY infection by interacting with NbTCTP and preventing its proviral function. As a counter-defense, PVY 6K1 interferes with the interaction between Nb14-3-3h and NbTCTP by competitively binding to Nb14-3-3h and rescues NbTCTP to promote PVY infection. Our results provide insights into the arms race between plants and potyviruses.

Rotational gland dissection for refractory granulomatous mastitis: A single-center retrospective study.

BACKGROUND: Refractory granulomatous mastitis (RGM) is a chronic benign breast disease that commonly occurred in women of childbearing age and is usually treated with surgery, with numerous cases suffering from unsatisfied postoperative recovery of breast shape, high rates of surgical complications, and even high recurrence. This study tries to evaluate the efficacy of an innovative surgical procedure, the rotational gland dissection for the treatment of RGM. METHODS: 129 patients with RGM who underwent surgical treatment at the Second Affiliated Hospital of Xi'an Jiaotong University between Apr. 2017 and May. 2021 were retrospectively included in this study. The article analyzed the age, local symptoms, lesion location, and size, days in hospital, recurrence rate, and satisfaction rate of the patients. RESULTS: Patients ranged in age from 19 to 58 years, with a median age of onset of 32 years. In 63 patients (48.84%), their lesions coverage exceeded two quadrants, and 52.71% of patients had lesions larger than 10 cm2. The average days in hospital of patients was 7.5 days, and 85.27% of them were satisfied with their post-surgery breast appearance. Within the median follow-up of 56 months, only 3.10% of patients experienced a recurrence of mastitis on the operation side. CONCLUSION: This novel surgical procedure we created is an effective treatment for RGM with a high success rate, high patient satisfaction, and low recurrence rate, and is significantly superior to other studies for it has the largest sample size and longest follow-up in this field.

Advances in Atomically Dispersed Metal and Nitrogen Co-Doped Carbon Catalysts for Advanced Oxidation Technologies and Water Remediation: From Microenvironment Modulation to Non-Radical Mechanisms.

Atomically dispersed metal and nitrogen co-doped carbon catalysts (M-N-C) have been attracting tremendous attentions thanks to their unique MNx active sites and fantastic catalytic activities in advanced oxidation technologies (AOTs) for water remediation. However, precisely tailoring the microenvironment of active sites at atomic level is still an intricate challenge so far, and understanding of the non-radical mechanisms in persulfate activation exists many uncertainties. In this review, latest developments on the microenvironment modulation strategies of atomically dispersed M-N-C catalysts including regulation of central metal atoms, regulation of coordination numbers, regulation of coordination heteroatoms, and synergy between single-atom catalysts (SACs) with metal species are systematically highlighted and discussed. Afterwards, progress and underlying limitations about the typical non-radical pathways from production of singlet oxygen, electron transfer mechanism to generation of high-valent metal species are well demonstrated to inspire intrinsic insights about the mechanisms of M-N-C/persulfate systems. Lastly, perspectives for the remaining challenges and opportunities about the further development of carbon-based SACs in environment remediation are also pointed out. It is believed that this review will be much valuable for the further design of active sites in M-N-C/persulfate catalytic systems and promote the wide application of SACs in various fields.

Aptamer-Assisted Blockade of the Immune Suppressor Sialic Acid-Binding Immunoglobulin-Like Lectin-15 for Cancer Immunotherapy.

The percentage of low response and adaptive resistance to current antibody-based immune checkpoint blockade (ICB) therapy requires the development of novel immunotherapy strategies. Here, we developed an aptamer-assisted immune checkpoint blockade (Ap-ICB) against sialic acid-binding immunoglobulin-like lectin-15 (Siglec-15), a novel immune suppressor broadly upregulated on cancer cells and tumor infiltrating myeloid cells, which is mutually exclusive of programmed cell death ligand 1 (PD-L1). Using protein aptamer selection, we identified WXY3 aptamer with high affinity against Siglec-15 protein/Siglec-15 positive cells. We demonstrated that WXY3 aptamer rescued antigen-specific T cell responses in vitro and in vivo. Importantly, the WXY3 Ap-ICB against Siglec-15 amplified anti-tumor immunity in the tumor microenvironment and inhibited tumor growth/metastasis in syngeneic mouse model, which may result from enhanced macrophage and T cell functionality. In addition, by using aptamer-based spherical nucleic acids, we developed a synergetic ICB strategy of multivalent binding and steric hindrance, which further improves the in vivo anti-tumor effect. Taken together, our results support Ap-ICB targeted Siglec-15 as a potential strategy for normalization cancer immunotherapy.

BCLAF1-induced HIF-1α accumulation under normoxia enhances PD-L1 treatment resistances via BCLAF1-CUL3 complex.

Bcl-2-associated transcription factor-1 (BCLAF1), an apoptosis-regulating protein of paramount significance, orchestrates the progression of various malignancies. This study reveals increased BCLAF1 expression in hepatocellular carcinoma (HCC) patients, in whom elevated BCLAF1 levels are linked to escalated tumor grades and diminished survival rates. Moreover, novel BCLAF1 expression is particularly increased in HCC patients who were not sensitive to the combined treatment of atezolizumab and bevacizumab, but not in patients who had tumors that responded to the combined regimen. Notably, overexpression of BCLAF1 increases HCC cell proliferation in vitro and in vivo, while the conditioned medium derived from cells overexpressing BCLAF1 strikingly enhances the tube-formation capacity of human umbilical vein endothelial cells. Furthermore, compelling evidence demonstrates that BCLAF1 attenuates the expression of prolyl hydroxylase domain protein 2 (PHD2) and governs the stability of hypoxia-inducible factor-1α (HIF-1α) under normoxic conditions without exerting any influence on transcription, as determined by Western blot and RT‒qPCR analyses. Subsequently, employing coimmunoprecipitation and immunofluorescence, we validated the reciprocal interaction between BCLAF1 and Cullin 3 (CUL3), through which BCLAF1 actively upregulates the ubiquitination and degradation of PHD2. The Western blot and RT‒qPCR results suggests that programmed death ligand-1 (PD-L1) is one of the downstream responders to HIF-1α in HCC. Thus, we reveal the pivotal role of BCLAF1 in promoting PD-L1 transcription and, through binding to CUL3, in promoting the accumulation of HIF-1α under normoxic conditions, thereby facilitating the ubiquitination and degradation of PHD2.

Lymph node and bone metastasis of pulmonary intestinal adenocarcinoma: A case report.

Pulmonary enteric adenocarcinoma (PEAC) is a rare pathological type of lung adenocarcinoma, accounting for ~0.6% of primary lung adenocarcinoma, which has similar morphological and immunohistochemical characteristics to colorectal adenocarcinoma. Making a certain differential diagnosis of PEAC based on morphological and immunohistochemical results is difficult. It is known that PEAC may metastasize to the pancreas, skin, soleus muscle and intestine, but no bone metastasis has been reported. At our department, a rare case of PEAC with bone and lymph node metastasis was previously diagnosed. The present case study reports on a 58-year-old male patient encountered at our hospital with pain in the lumbar, back and right iliac with no obvious cause. Chest CT indicated a space-occupying lesion in the left upper lung lobe, enlarged lymph nodes in the mediastinum and left lung, and partial vertebral bone destruction. Enhanced CT results indicated multiple foci of active bone metabolism in the body, while rectal colonoscopy showed no obvious abnormalities. Histopathological and immunohistochemical results after right iliac bone puncture suggested stage IV PEAC with secondary malignancies in bones, mediastinal lymph node, hilar lymph node and left supraclavicular lymph node.

Harnessing the power of optical microscopy for visualization and analysis of histopathological images.

Histopathology is the foundation and gold standard for identifying diseases, and precise quantification of histopathological images can provide the pathologist with objective clues to make a more convincing diagnosis. Optical microscopy (OM), an important branch of optical imaging technology that provides high-resolution images of tissue cytology and structural morphology, has been used in the diagnosis of histopathology and evolved into a new disciplinary direction of optical microscopic histopathology (OMH). There are a number of ex-vivo studies providing applicability of different OMH approaches, and a transfer of these techniques toward in vivo diagnosis is currently in progress. Furthermore, combined with advanced artificial intelligence algorithms, OMH allows for improved diagnostic reliability and convenience due to the complementarity of retrieval information. In this review, we cover recent advances in OMH, including the exploration of new techniques in OMH as well as their applications, and look ahead to new challenges in OMH. These typical application examples well demonstrate the application potential and clinical value of OMH techniques in histopathological diagnosis.

A high-efficiency primary-side regulation control strategy for half-bridge LLC resonant converter with wide input voltage range.

The requirement of the half-bridge LLC resonant converter with a wide input voltage range is becoming higher in photovoltaic applications because of its simple structure and low switching loss. Conventional frequency modulation (FM) requires a wide switching frequency range and a high-quality factor circuit design, leading to reduced efficiency and large component volumes at light loads. To solve the problems, a high-efficiency control strategy using adaptive pulse-width and frequency modulation (APWFM) is proposed. APWFM adjusts the gain by changing the switching frequency and duty cycle simultaneously. When the output power is below the reference value, the switching frequency decreases linearly as the output power decreases, and the duty cycle is simultaneously modulated to achieve constant output voltage, so the switching frequency variation range is smaller than FM. This results in improved light or medium load efficiency in a limited frequency range while keeping a small volume of magnetic components. Also, the proposed control strategy is realized with primary-side regulation (PSR) to eliminate the optocoupler and simplify the control circuit. Experimental results demonstrate a significant improvement in efficiency at medium and light loads compared to FM, and the average efficiency is improved by 5% based on low cost and simple operation.

Causal associations of Sjögren's syndrome with cancers: a two-sample Mendelian randomization study.

BACKGROUND: Several observational studies have explored the associations between Sjögren's syndrome (SS) and certain cancers. Nevertheless, the causal relationships remain unclear. Mendelian randomization (MR) method was used to investigate the causality between SS and different types of cancers. METHODS: We conducted the two-sample Mendelian randomization with the public genome-wide association studies (GWASs) summary statistics in European population to evaluate the causality between SS and nine types of cancers. The sample size varies from 1080 to 372,373. The inverse variance weighted (IVW) method was used to estimate the causal effects. A Bonferroni-corrected threshold of P < 0.0031 was considered significant, and P value between 0.0031 and 0.05 was considered to be suggestive of an association. Sensitivity analysis was performed to validate the causality. Moreover, additional analysis was used to assess the associations between SS and well-accepted risk factors of cancers. RESULTS: After correcting the heterogeneity and horizontal pleiotropy, the results indicated that patients with SS were significantly associated with an increased risk of lymphomas (odds ratio [OR] = 1.0010, 95% confidence interval [CI]: 1.0005-1.0015, P = 0.0002) and reduced risks of prostate cancer (OR = 0.9972, 95% CI: 0.9960-0.9985, P = 2.45 × 10-5) and endometrial cancer (OR = 0.9414, 95% CI: 0.9158-0.9676, P = 1.65 × 10-5). Suggestive associations were found in liver and bile duct cancer (OR = 0.9999, 95% CI: 0.9997-1.0000, P = 0.0291) and cancer of urinary tract (OR = 0.9996, 95% CI: 0.9992-1.0000, P = 0.0281). No causal effect of SS on other cancer types was detected. Additional MR analysis indicated that causal effects between SS and cancers were not mediated by the well-accepted risk factors of cancers. No evidence of the causal relationship was observed for cancers on SS. CONCLUSIONS: SS had significant causal relationships with lymphomas, prostate cancer, and endometrial cancer, and suggestive evidence of association was found in liver and bile duct cancer and cancer of urinary tract, indicating that SS may play a vital role in the incidence of these malignancies.