Targeting Nuclear Receptor Coactivator SRC-1 Prevents Colorectal Cancer Immune Escape by Reducing Transcription and Protein Stability of PD-L1.

Programmed death-ligand 1 (PD-L1) is overexpressed in multiple cancers and critical for their immune escape. It has previously shown that the nuclear coactivator SRC-1 promoted colorectal cancer (CRC) progression by enhancing CRC cell viability, yet its role in CRC immune escape is unclear. Here, we demonstrate that SRC-1 is positively correlated with PD-L1 in human CRC specimens. SRC-1 deficiency significantly inhibits PD-L1 expression in CRC cells and retards murine CRC growth in subcutaneous grafts by enhancing CRC immune escape via increasing tumor infiltration of CD8+ T cells. Genetic ablation of SRC-1 in mice also decreases PD-L1 expression in AOM/DSS-induced murine CRC. These results suggest that tumor-derived SRC-1 promotes CRC immune escape by enhancing PD-L1 expression. Mechanistically, SRC-1 activated JAK-STAT signaling by inhibiting SOCS1 expression and coactivated STAT3 and IRF1 to enhance PD-L1 transcription as well as stabilized PD-L1 protein by inhibiting proteasome-dependent degradation mediated by speckle type POZ protein (SPOP). Pharmacological inhibition of SRC-1 improved the antitumor effect of PD-L1 antibody in both subcutaneous graft and AOM/DSS-induced murine CRC models. Taken together, these findings highlight a crucial role of SRC-1 in regulating PD-L1 expression and targeting SRC-1 in combination with PD-L1 antibody immunotherapy may be an attractive strategy for CRC treatment.

Combined transcriptomic and metabolomic analysis revealed that pH changes affected the expression of carbohydrate and ribosome biogenesis-related genes in Aspergillus niger SICU-33.

The process of carbohydrate metabolism and genetic information transfer is an important part of the study on the effects of the external environment on microbial growth and development. As one of the most significant environmental parameters, pH has an important effect on mycelial growth. In this study, the effects of environmental pH on the growth and nutrient composition of Aspergillus niger (A. niger) filaments were determined. The pH values of the medium were 5, 7, and 9, respectively, and the molecular mechanism was further investigated by transcriptomics and metabolomics methods. The results showed that pH 5 and 9 significantly inhibited filament growth and polysaccharide accumulation of A. niger. Further, the mycelium biomass of A. niger and the crude polysaccharide content was higher when the medium's pH was 7. The DEGs related to ribosome biogenesis were the most abundant, and the downregulated expression of genes encoding XRN1, RRM, and RIO1 affected protein translation, modification, and carbohydrate metabolism in fungi. The dynamic changes of pargyline and choline were in response to the oxidative metabolism of A. niger SICU-33. The ribophorin_I enzymes and DL-lactate may be important substances related to pH changes during carbohydrate metabolism of A.niger SICU-33. The results of this study provide useful transcriptomic and metabolomic information for further analyzing the bioinformatic characteristics of A. niger and improving the application in ecological agricultural fermentation.

Effects of different post-harvest processing methods on changes in the active ingredients of licorice based on LC-MS and plant metabolomics.

INTRODUCTION: Licorice, the dried roots and rhizomes of the Glycyrrhiza uralensis Fisch., holds a prominent status in various formulations within the realm of Chinese medicinal practices. The traditional processing methods of licorice hinder quality assurance, thus prompting Chinese medicine researchers to focus on the fresh processing methods to enhancing processing efficiency and quality. OBJECTIVE: This study aimed to identify the differential compounds of licorice between traditional and fresh processing methods and provide a scientific basis for the fresh processing of licorice and for further research on the processing mechanism. METHODOLOGY: A methodology integrating ultra-performance liquid chromatography with quadrupole-time-of-flight tandem mass spectrometry combined with multivariate statistical analysis was employed to characterize the differential compounds present in licorice between traditional processing and fresh processing. RESULTS: The results derived from principal component analysis and heat map analyses underscored significant differences in the content of bioactive compounds between the two processing methods. By applying conditions of VIP > 1.5 and p < 0.05, a total of 38 differential compounds were identified through t tests, and the transformation mechanisms of select compounds were illustrated. CONCLUSION: The adoption of fresh processing techniques not only improved processing efficiency but also significantly enhanced the preservation of bioactive compounds within licorice. This research has established a rapid and efficient analytical method for the identification of differential compounds present in differently processed licorice products.

Effects of warming at embryonic and larval stages on tadpole fitness in high-altitude Rana kukunoris.

Global warming may affect the early developmental stages of high-altitude amphibians, thereby influencing their later fitness. Yet, this has been largely unexplored. To investigate whether and how the temperatures experienced by embryonic and larval stages affect their fitness at later developmental stages, we designed two experiments in which the embryos and larvae were treated with three temperatures (24, 18 and 12 °C), respectively. Then, the life history traits of the tadpoles during the metamorphotic climax in all treatments were evaluated, including growth rate, survival rate, morphology, thermal physiology, swimming performance, standard metabolic rate (SMR), oxidative and antioxidative system, and metabolic enzyme activities. The results revealed that elevated temperature accelerated metamorphosis but decreased body size at metamorphosis. Additionally, warming during the embryonic and larval stages decreased the thermal tolerance range and induced increased oxidative stress. Furthermore, high embryonic temperature significantly decreased the hatching success, but had no significant effect on swimming performance and SMR. Warming during larval periods was harmful to the survival and swimming performance of tadpoles. The effect size analysis revealed that the negative impacts of embryonic temperature on certain physiological traits, such as growth and development, survival and swimming performance, were more pronounced than those of larval temperature. Our results highlight the necessity for particular attention to be paid to the early stages of amphibians, notably the embryonic stages when evaluating the impact of global warming on their survival.

Sarcopenia adversely impacts clinical outcomes in patients undergoing pancreaticoduodenectomy: A systematic review and meta-analysis.

BACKGROUND: Sarcopenia is a syndrome marked by a gradual and widespread reduction in skeletal muscle mass and strength, as well as a decline in functional ability, which is associated with malnutrition, hormonal changes, chronic inflammation, disturbance of intestinal flora, and exercise quality. Pancreatoduodenectomy is a commonly employed clinical intervention for conditions such as pancreatic head cancer, ampulla of Vater cancer, and cholangiocarcinoma, among others, with a notably high rate of postoperative complications. Sarcopenia is frequent in patients undergoing pancreatoduodenectomy. However, data regarding the effects of sarcopenia in patients undergoing pancreaticoduodenectomy (PD) are both limited and inconsistent. AIM: To assess the influence of sarcopenia on outcomes in patients undergoing PD. METHODS: The PubMed, Cochrane Library, Web of Science, and Embase databases were screened for studies published from the time of database inception to June 2023 that described the effects of sarcopenia on the outcomes and complications of PD. Two researchers independently assessed the quality of the data extracted from the studies that met the inclusion criteria. Meta-analysis using RevMan 5.3.5 and Stata 14.0 software was conducted. Forest and funnel plots were used, respectively, to demonstrate the outcomes of the sarcopenia group vs the non-sarcopenia group after PD and to evaluate potential publication bias. RESULTS: Sixteen studies encompassing 2381 patients were included in the meta-analysis. The patients in the sarcopenia group (n = 833) had higher overall postoperative complication rates [odds ratio (OR) = 3.42, 95% confidence interval (CI): 1.95-5.99, P < 0.0001], higher Clavien-Dindo class ≥ III major complication rates (OR = 1.41, 95%CI: 1.04-1.90, P = 0.03), higher bacteremia rates (OR = 4.46, 95%CI: 1.42-13.98, P = 0.01), higher pneumonia rates (OR = 2.10, 95%CI: 1.34-3.27, P = 0.001), higher pancreatic fistula rates (OR = 1.42, 95%CI: 1.12-1.79, P = 0.003), longer hospital stays (OR = 2.86, 95%CI: 0.44-5.28, P = 0.02), higher mortality rates (OR = 3.17, 95%CI: 1.55-6.50, P = 0.002), and worse overall survival (hazard ratio = 2.81, 95%CI: 1.45-5.45, P = 0.002) than those in the non-sarcopenia group (n = 1548). However, no significant inter-group differences were observed regarding wound infections, urinary tract infections, biliary fistulas, or postoperative digestive bleeding. CONCLUSION: Sarcopenia is a common comorbidity in patients undergoing PD. Patients with preoperative sarcopenia have increased rates of complications and mortality, in addition to a poorer overall survival rate and longer hospital stays after PD.

Molybdenum disulphide nanoparticles accelerate the transformation of levofloxacin in planting soil upon exposure.

The use of nanocatalytic particles for the removal of refractory organics from wastewater is a rapidly growing area of environmental purification. However, little has been done to investigate the effects of nanoparticles on soil-plant systems with antibiotic contamination. This work assessed the effect of molybdenum disulfide (MoS2) on the soil-Phragmites communis system containing levofloxacin (LVX). The results showed that the addition of MoS2 had restoration potential for stressed plant. The MoS2 with catalytic activity promoted the transformation of LVX in rhizosphere soils. The transformation pathways of LVX in the different exposure groups were proposed. The continuous output of radicals in the high MoS2 dosage group facilitated the transformation of LVX to small molecule compounds, which were eventually mineralized. Moreover, the electron-density-difference analysis revealed the easier flow of electrons from the MoS2 surface towards the LVX molecules. This finding provides theoretical support for the application of nanocatalytic particles in ecological environments.

Resilience mechanisms of Trichopria drosophilae (Hymenoptera: Diapriinae) under global extreme cooling: insights into parasitic response and physiological adaptation.

Global climate warming and frequent extreme low-temperature events have made it essential to investigate the impact of low temperatures on parasitic wasps to protect and strengthen farmland biodiversity, which in turn enhances the biological control potential of natural enemies such as parasitic wasps. We systematically examined how low-temperature stress affects the parasitic functional response of Trichopria drosophilae to Drosophila suzukii (Diptera: Drosophilidae) pupae. Our findings indicate that the parasitic behavior of T. drosophilae towards D. suzukii pupae aligns with the Holling II functional response model following exposure to different temperatures. Within the temperature range of 8 °C to -8 °C, lower temperatures correlated decreased instantaneous attack rate of T. drosophilae and an increase in processing time. The search constant Q initially increased and then decreased with declining temperatures. Short-term low-temperature stress negatively impacted the parasitic and searching abilities of T. drosophilae but did not alter its parasitic functional response model. Notably, short-term low-temperature stress had minimal effects on the water content, protein content, and total sugar content of male and female T. drosophilae adults. However, as temperatures decreased, the activities of key enzymes, including GAPDH, SOD, T-AOC, and malondialdehyde (MDA), exhibited an initial increase followed by a decrease. Conversely, the activities of LDH and HOAD decreased, while the activities of CAT and POD increased. Further study on the effect of short-term low temperature on T. drosophilae can provide a research basis for the large-scale production and low-temperature refrigeration technology of T. drosophilae, and provide a scientific basis for its efficient use in the field.

Paradoxical cognitive and language function recovery by zolpidem in a patient with traumatic brain injury: A case report.

BACKGROUND: Traumatic brain injury (TBI) is a significant public health issue, often resulting from traffic accidents and falls, leading to a wide spectrum of outcomes from mild concussions to severe brain damage. The neurorehabilitation of TBI focuses on enhancing recovery and improving quality of life. Zolpidem, traditionally used for short-term management of insomnia, has shown potential in improving cognitive functions and language in TBI patients. Advances in neuroimaging techniques, such as functional near-infrared spectroscopy (fNIRS), have facilitated the exploration of the effects of therapeutic interventions on brain activity and functional connectivity in TBI patients. CASE SUMMARY: We present the case of a 34-year-old male who sustained a TBI from a traffic collision. Despite severe impairments in cognitive and language functions, administration of 10 mg of zolpidem resulted in temporary but significant improvements in these areas, as evidenced by increased Mini-Mental State Examination scores and observed behavioral changes. fNIRS assessments before and after zolpidem administration revealed notable changes in cerebral cortex activity, including increased left hemisphere activation and a shift in functional connectivity to the bilateral frontal lobes, corresponding with the patient's improvement. CONCLUSION: This case study highlights the potential of zolpidem, a medication traditionally used for insomnia, in enhancing cognitive and verbal functions in a patient with TBI, suggesting a potential therapeutic role for zolpidem in neurorehabilitation, supported by changes in brain activity and connectivity observed through fNIRS. However, further investigation is warranted to validate these findings and elucidate zolpidem's long-term effects on cognitive and functional outcomes in TBI patients.

Integrative analysis of bulk and single-cell RNA sequencing reveals the gene expression profile and the critical signaling pathways of type II CPAM.

BACKGROUD: Type II congenital pulmonary airway malformation (CPAM) is a rare pulmonary microcystic developmental malformation. Surgical excision is the primary treatment for CPAM, although maternal steroids and betamethasone have proven effective in reducing microcystic CPAM. Disturbed intercellular communication may contribute to the development of CPAM. This study aims to investigate the expression profile and analyze intercellular communication networks to identify genes potentially associated with type II CPAM pathogenesis and therapeutic targets. METHODS: RNA sequencing (RNA-seq) was performed on samples extracted from both the cystic area and the adjacent normal tissue post-surgery in CPAM patients. Iterative weighted gene correlation network analysis (iWGCNA) was used to identify genes specifically expressed in type II CPAM. Single-cell RNA-seq (scRNA-seq) was integrated to unveil the heterogeneity in cell populations and analyze the communication and interaction within epithelial cell sub-populations. RESULTS: A total of 2,618 differentially expressed genes were identified, primarily enriched in cilium-related biological process and inflammatory response process. Key genes such as EDN1, GPR17, FPR2, and CHRM1, involved in the G protein-coupled receptor (GPCR) signaling pathway and playing roles in cell differentiation, apoptosis, calcium homeostasis, and the immune response, were highlighted based on the protein-protein interaction network. Type II CPAM-associated modules, including ciliary function-related genes, were identified using iWGCNA. By integrating scRNA-seq data, AGR3 (related to calcium homeostasis) and SLC11A1 (immune related) were identified as the only two differently expressed genes in epithelial cells of CPAM. Cell communication analysis revealed that alveolar type 1 (AT1) and alveolar type 2 (AT2) cells were the predominant communication cells for outgoing and incoming signals in epithelial cells. The ligands and receptors between epithelial cell subtypes included COLLAGEN genes enriched in PI3K-AKT singaling and involved in epithelial to mesenchymal transition. CONCLUSIONS: In summary, by integrating bulk RNA-seq data of type II CPAM with scRNA-seq data, the gene expression profile and critical signaling pathways such as GPCR signaling and PI3K-AKT signaling pathways were revealed. Abnormally expressed genes in these pathways may disrupt epithelial-mesenchymal transition and contribute to the development of CPAM. Given the effectiveness of prenatal treatments of microcystic CPAM using maternal steroids and maternal betamethasone administration, targeting the genes and signaling pathways involved in the development of CPAM presents a promising therapeutic strategy.

A 52-week follow-up, multi-center, randomized, double-blinded comparison of efficacy and safety of two hyaluronic acid fillers for the treatment of moderate-to-severe nasolabial folds in Chinese population.

INTRODUCTION: To investigate the efficacy and safety of Cutegel® MAX (Cutegel) in the correction of moderate-to-severe nasolabial folds (NLFS) compared to Restylane® (Restylane, control). METHODS: This study was a 52-week, multicenter, randomized, double-blinded, active-controlled clinical trial. Qualified participants with moderate-to-severe NLFs were randomly assigned in a 1:1 ratio to receive Cutegel or Restylane. For the primary efficacy endpoint, the response rate was defined as the percentage of subjects exhibiting an improvement of at least one-point based on blinded evaluation of Wrinkle Severity Rating Scale (WSRS) at 24 weeks after injection. Other secondary efficacy endpoints and treatment-emergent adverse events (TEAEs) were assessed. RESULTS: Of 340 subjects randomized, 317 completed the week 52 visit. In the per protocol set (PPS), the blinded evaluator-assessed response rates at week 24 were 81.17% for Cutegel versus 77.56% for Restylane (p = 0.327). The between-group treatment differences in response rates were 3.60% [95% confidence interval (CI) = (-5.39%, 12.60%)], which demonstrated the noninferiority of Cutegel. Other secondary efficacy endpoints supported this. No significant differences were observed in the occurrence of adverse events between the two groups. CONCLUSION: Similar to Restylane, Cutegel was effective and well tolerated in correcting moderate-to-severe NLFs among the Chinese population.

Nasolabial folds (NLFs) are among the early indicators of facial aging process. In the past, rhytidectomy has been considered a safe procedure, yet it continues to carry risks such as hematoma, skin necrosis, nerve injury, and infection. With the ongoing development of biomaterials including hyaluronic acid (HA), minimally invasive injection procedures for the aesthetic correction of NLFs have become the preferred choice in recent years. The widespread use of HA has resulted in the development of various types of commercial HA fillers, such as Cutegel and Restylane. It is well known that HA filler products produce varying effects, attributable to differences in their components and physical properties. Previous studies have established that Restylane is a safe and effective HA dermal filler for the correction of NLFs. However, there is a lack of studies on both the cosmetic results and safety data for Cutegel in the published literature. Therefore, a randomized, double-blinded, active-controlled clinical trial was conducted at seven Chinese hospitals to evaluate the efficacy and safety of Cutegel for the correction of moderate-to-severe NLFs, compared to the approved Restylane in China. Among the 340 randomized subjects, 170 subjects received Cutegel, and 169 subjects received Restylane. Both groups reported similar improvements in WSRS (the between-group treatment differences in response rates exceeded the prespecified noninferiority margins), and also in other efficacy evaluations. Additionally, the two treatment groups showed similar safety profiles. In summary, Cutegel proved to be well tolerated and effective in this randomized, active-controlled clinical study, demonstrating its noninferiority to Restylane and validating its use as an alternative treatment for Chinese subjects with moderate-to-severe NLFs.

A simple projection method to correlate the principal mechanical direction with the principal microstructural direction of human osteoporotic femoral heads.

The mechanics of the trabecular bone is related to its structure; this work aimed to propose a simple projection method to clarify the correlation between the principal mechanical direction (PMD) and the principal microstructural direction (PMSD) of trabecular bones from osteoporotic femoral heads. A total of 529 trabecular cubes were cropped from five osteoporotic femoral heads. The micro computed tomography (µCT) sequential images of each cube were first projected onto the three Cartesian coordinate planes to have three overlapped images, and the trabecular orientation distribution in the three images was analyzed. The PMSD corresponding to the greatest distribution frequency of the trabecular orientation in the three images was defined. Then, the voxel finite element (FE) models of the cubes were reconstructed and simulated to obtain their compliance matrices, and the matrices were subjected to transversal rotation to find their maximum elastic constants. The PMD corresponding to the maximum elastic constant was defined. Subsequently, the correlation of the defined PMSD and PMD was analyzed. The results showed that PMSD and PMD of the trabecular cubes did not show a significant difference at the xy- and yz-planes except that at the zx-plane. Despite this, the mean PMSD-PMD deviations at the three coordinate planes were close to 0°, and the PMSD-PMD fitting to the line PMSD = PMD demonstrated their high correlation. This study might be helpful to identify the loading direction of anisotropic trabecular bones in experiments by examining the PMSD and also to guide bone scaffold design for bone tissue repair.

Bacterial community in the buckwheat rhizosphere responds more sensitively to single microplastics in lead-contaminated soil compared to the arbuscular mycorrhizal fungi community.

Soil pollution by microplastics (MPs), defined as plastic particles <5 mm, and heavy metals is a significant environmental issue. However, studies on the co-contamination effects of MPs and heavy metals on buckwheat rhizosphere microorganisms, especially on the arbuscular mycorrhizal fungi (AMF) community, are limited. We introduced low (0.01 g kg-1) and high doses of lead (Pb) (2 g kg-1) along with polyethylene (PE) and polylactic acid (PLA) MPs, both individually and in combination, into soil and assessed soil properties, buckwheat growth, and rhizosphere bacterial and AMF communities in a 40-day pot experiment. Notable alterations were observed in soil properties such as pH, alkaline hydrolyzable nitrogen (AN), and the available Pb (APb). High-dose Pb combined with PLA-MPs hindered buckwheat growth. Compared to the control, bacterial Chao1 richness and Shannon diversity were lower in the high dose Pb with PLA treatment, and differentially abundant bacteria were mainly detected in the high Pb dose treatments. Variations in bacterial communities correlated with APb, pH and AN. Overall, the AMF community composition remained largely consistent across all treatments. This phenomenon may be due to fungi having lower nutritional demands than bacteria. Stochastic processes played a relatively important role in the assembly of both bacterial and AMF communities. In summary, MPs appeared to amplify both the positive and negative effects of high Pb doses on the buckwheat rhizosphere bacteria.

Survival outcome and prognostic factors of remnant gastric cancer: a propensity score-matched analysis.

Background: Studies on survival and prognostic factors in individuals with remnant gastric cancer (RGC) after gastric cancer (GC) are rare. It is debatable whether prognosis of RGC after GC is worse than that of only primary GC (OPGC). The objective of this study is to compare the survival outcomes between post-GC RGC and OPGC undergoing surgical resection and to identify the prognostic factors of disease-specific survival (DSS) for RGC. Methods: We retrospectively collected data from the Surveillance, Epidemiology, and End Results (SEER) database among patients who underwent GC surgery in 1988-2020. Propensity score matching (PSM) was conducted to balance baseline characteristics. Kaplan-Meier (KM) survival analysis was performed to compare their overall survival (OS) and DSS. Multivariable Cox analyses were performed to identify the independent prognostic factors of DSS for post-GC RGC by estimating hazard ratios (HRs) with 95% confidence intervals (CIs). Results: There were 76 patients with RGC and 32,763 patients with OPGC included and analyzed. After balancing the baseline characteristics by PSM, no significant difference existed between OPGC and RGC groups in both OS (P=0.65) and DSS (P=0.28). Fixed-time analyses also showed no difference between the two groups for the 5-year (60.0%, RGC vs. 53.3%, OPGC, P=0.38) and 10-year DSS (56.7%, RGC vs. 48.3%, OPGC, P=0.34). Multivariable analysis revealed that area of lower income ($75,000+ vs. <$55,000, HR =0.21, 95% CI: 0.05-0.89, P=0.03), cardiac tumor [middle vs. cardia, HR =0.16, 95% CI: 0.03-0.77, P=0.02; distal vs. cardia, HR =0.10, 95% CI: 0.02-0.58, P=0.01; not otherwise specified (NOS) vs. cardia, HR =0.11, 95% CI: 0.03-0.51, P=0.004], deeper invasion (T3-4 vs. Tis-2, HR =5.19, 95% CI: 1.21-22.15, P=0.03), higher grade (G3 vs. G1-2, HR =7.35, 95% CI: 1.41-38.48, P=0.02) and not receiving chemotherapy (yes vs. no/unknown, HR =0.16, 95% CI: 0.04-0.60, P=0.007) were independent risk factors for postsurgical DSS in patients with post-GC RGC. Conclusions: The prognosis of post-GC RGC was comparable to that of OPGC following surgical resection. The independent prognostic factors for RGC are similar to those established for OPGC. Our findings suggest that RGC following first GC might be the same entity to OPGC and curative resection should be considered in selected patients.

Impact of different categories of intermediate risk factors on the recurrence of papillary thyroid carcinoma: a retrospective cohort study.

BACKGROUND: Data regarding the long-term recurrence in patients with intermediate-risk papillary thyroid carcinoma (PTC) are limited. The aim of this study was to assess the impact of primary tumor-related risk factors and lymph node (LN)-only risk factors on recurrence-free survival (RFS) in patients with intermediate-risk PTC. MATERIALS AND METHODS: Patients with PTC who received initial treatment at our institution between 2010 and 2016 were retrospectively reviewed. A total of 799 intermediate-risk PTC patients were included and further categorized into subgroups according to the different categories of intermediate risk factors. The RFS rates of these subgroups were investigated and compared. RESULTS: Structural recurrence developed in 11 patients (1.4%) of the whole cohort during a median follow-up duration of 96 months. There were no significant differences in RFS between the primary tumor-only risk group and the LN-only risk group, while the combined group of primary tumor risk factors and LN risk factor (metastatic LNs >5) was associated with a worse RFS rate. In the matched-pair analysis, no significant difference in RFS was found between patients who underwent thyroid lobectomy (TL) and those who underwent total thyroidectomy (TT) (6-year RFS: 99.6% vs. 98.8%, P = 0.316) during a median follow-up duration of 100 months. CONCLUSIONS: Intermediate-risk PTC patients who underwent TL had a comparable RFS to those who underwent TT. The combination of primary tumor risk factors and LN risk factor (metastatic LNs >5) may be a useful tool for predicting the risk of long-term structural recurrence in patients with intermediate-risk PTC.

Viral shedding pattern of severe fever with thrombocytopenia syndrome virus in severely ill patients: A prospective, Multicenter cohort study.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is spreading rapidly in Asia. The pathway of SFTS virus shedding from patient and specific use of personal protective equipments (PPEs) against viral transmission have rarely been reported. The study was to determine SFTS virus (SFTSV) shedding pattern from the respiratory, digestive and urinary tract to outside in patients. Methods: Patients were divided into mild and severe groups in three sentinel hospitals for SFTS in Anhui province from April 2020 to October 2022. SFTSV level from blood, throat swabs, fecal/anal swabs, urine and bedside environment swabs of SFTS patients were detected by qRT-PCR. Specific PPEs were applied in healthcare workers contacting with the patients who had oropharyngeal virus shedding and hemorrhagic signs. Results: A total of 189 SFTSV-confirmed patients were included in the study, 54 patients died (case fatality rate, 28.57 %). Positive SFTSV in throat swabs (T-SFTSV), fecal/anal swabs (F-SFTSV) and urine (U-SFTSV) were detected in 121 (64.02 %), 91 (48.15 %) and 65 (34.4 %) severely ill patients, respectively. The levels of T-SFTSV, F-SFTSV and U-SFTSV were positively correlated with the load of SFTSV in blood. We firstly revealed that SFTSV positive rate of throat swabs were correlated with occurrence of pneumonia and case fatality rate of patients (P < 0.0001). Specific precaution measures were applied by healthcare workers in participating cardiopulmonary resuscitation and orotracheal intubation for severely ill patients with positive T-SFTSV, no event of SFTSV human-to-human transmission occurred after application of effective PPEs. Conclusions: Our research demonstrated SFTSV could shed out from blood, oropharynx, feces and urine in severely ill patients. The excretion of SFTSV from these parts was positively correlated with viral load in the blood. Effective prevention measures against SFTSV human-to-human transmission are needed.

Dynamically changing antineutrophil cytoplasmic antibodies in granulomatosis with polyangiitis: A case report.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is one of the most prevalent forms of the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. GPA is characterized histologically by necrotizing granulomatous inflammation in addition to vasculitis. The diagnosis of GPA depends on clinical presentation, serological evidence of a positive ANCA, and/or histological evidence of necrotizing vasculitis or granulomatous destructive parenchymal inflammation. Cytoplasmic ANCA (c-ANCA) is positive in 65%-75% of GPA patients, accompanied by proteinase 3 (PR3), the main target antigen of c-ANCA, another 5% of GPA patients had negative ANCA. CASE SUMMARY: The patient, a 52-year-old male, presented with unexplained nasal congestion, tinnitus, and hearing loss. After a duration of 4 months experiencing these symptoms, the patient subsequently developed fever and headache. The imaging examination revealed the presence of bilateral auricular mastoiditis and partial paranasal sinusitis, and the ANCA results were negative. The anti-infective therapy proved to be ineffective, but the patient's symptoms and fever were quickly relieved after 1 wk of treatment with methylprednisolone 40 mg once a day. However, after continuous use of methylprednisolone tablets for 3 months, the patient experienced a recurrence of fever accompanied by right-sided migraine, positive c-ANCA and PR3, and increased total protein in cerebrospinal fluid. The patient was diagnosed with GPA. After receiving a treatment regimen of intravenous methylprednisolone 40 mg/d and cyclophosphamide 0.8 g monthly, the patient experienced alleviation of fever and headache. Additionally, the ANCA levels became negative and there has been no recurrence. CONCLUSION: For GPA patients with negative ANCA, there is a potential for early missed diagnosis. The integration of histopathological results and multidisciplinary communication plays a crucial role in facilitating ANCA-negative GPA.

CENPF May Act as a Novel Marker and Highlight the Influence of Pericyte in Infantile Hemangioma.

Infantile hemangioma (IH), a benign microvascular tumor, is marked by early and extensive proliferation of immature hemangioma endothelial cells (Hem-ECs) that naturally regress through differentiation into fibroblasts or adipocytes. However, a challenge persists, as the unique biological behavior of IH remains elusive, despite its general sensitivity to propranolol treatment. Recent evidence suggests that abnormal volume proliferation in IH is primarily attributed to the accumulation of hemangioma pericytes (Hem-Pericytes), in addition to Hem-ECs. Centromere protein F (CENPF) is involved in regulating mitotic processes and has been associated with malignant tumor cell proliferation. It is a key player in maintaining genomic stability during cell division. Our findings revealed specific expression of CENPF in Hem-Pericytes, with a proliferation index (PI) approximately half that of Ki67 (3.28 vs 6.97%) during the proliferative phase of IH. This index decreased rapidly in the involuting phase (P < .05), suggesting that the contribution of pericytes to IH development was comparable to that of Hem-ECs. Tumor expansion and shrinkage may be due to the proliferation, reduction, and differentiation of Hem-Pericytes. In conclusion, we speculate CENPF as a novel marker for clinical pathological diagnosis and a potential therapeutic target, fostering advancements in drug development.

Wideband Circularly Polarization and High-Gain of a Slot Patch Array Antenna Realized by a Hybrid Metasurface.

In this paper, a patch array antenna with wideband circular polarization and high gain is proposed by utilizing a hybrid metasurface (MS). A corner-cut slotted patch antenna was chosen as the source due to the possible generation of CP mode. The hybrid MS (HMS), consisting of a receiver MS (RMS) arranged in a 2 × 2 array of squared patches and a linear-to-circular polarization conversion (LCPC) MS surrounding it was then utilized as the superstrate driven by the source. The LCPC MS cell is a squared-corner-cut patch with a 45° oblique slot etched, which has the capability for wideband LCPC. The LCPC unit cell possesses wideband PC capabilities, as demonstrated by the surface current analysis and S-parameter simulations conducted using a Floquet-port setup. The LP EM wave radiated by the source antenna was initially received by the RMS, then converted to a CP wave as it passed through the LCPC MS, and ultimately propagated into space. To further enhance the LCPC properties, an improved HMS (IHMS) was then proposed with four cells cut at the corners, based on the original HMS design. To verify this design, both CMA and E-field were utilized to analyze the three MSs, indicating that the IHMS possessed a wideband LCPC capability compared to the other two MSs. The proposed antenna was then arranged in a 2 × 2 array with sequential rotation to further enhance its properties. As demonstrated by the measurements, the array antenna achieved an S11 bandwidth of 60.5%, a 3 dB AR bandwidth of 2.85 GHz, and a peak gain of 15.1 dBic, all while maintaining a low profile of only 0.09λ0.

A Novel Continuous Sleep State Artificial Neural Network Model Based on Multi-Feature Fusion of Polysomnographic Data.

Purpose: Sleep structure is crucial in sleep research, characterized by its dynamic nature and temporal progression. Traditional 30-second epochs falter in capturing the intricate subtleties of various micro-sleep states. This paper introduces an innovative artificial neural network model to generate continuous sleep depth value (SDV), utilizing a novel multi-feature fusion approach with EEG data, seamlessly integrating temporal consistency. Methods: The study involved 50 normal and 100 obstructive sleep apnea-hypopnea syndrome (OSAHS) participants. After segmenting the sleep data into 3-second intervals, a diverse array of 38 feature values were meticulously extracted, including power, spectrum entropy, frequency band duration and so on. The ensemble random forest model calculated the timing fitness value for all the features, from which the top 7 time-correlated features were selected to create detailed sleep sample values ranging from 0 to 1. Subsequently, an artificial neural network (ANN) model was trained to delineate sleep continuity details, unravel concealed patterns, and far surpassed the traditional 5-stage categorization (W, N1, N2, N3, and REM). Results: The SDV changes from wakeful stage (mean 0.7021, standard deviation 0.2702) to stage N3 (mean 0.0396, standard deviation 0.0969). During the arousal epochs, the SDV increases from the range (0.1 to 0.3) to the range around 0.7, and decreases below 0.3. When in the deep sleep (≤0.1), the probability of arousal of normal individuals is less than 10%, while the average arousal probability of OSA patients is close to 30%. Conclusion: A sleep continuity model is proposed based on multi-feature fusion, which generates SDV ranging from 0 to 1 (representing deep sleep to wakefulness). It can capture the nuances of the traditional five stages and subtle differences in microstates of sleep, considered as a complement or even an alternative to traditional sleep analysis.

Biomechanical impact of labiolingual diameter on endodontically treated anterior teeth with crown restoration under occlusal loading.

OBJECTIVE: To evaluate the effect of the labiolingual diameter and construction of an endodontically treated (ET) anterior tooth with crown restoration on stress distribution and biomechanical safety under occlusal loading. METHODOLOGY: Three-dimensional finite element models were generated for maxillary central incisors with all-ceramic crown restorations. The labiolingual diameters of the tooth, defined as the horizontal distance between the protrusion of the labial and lingual surfaces, were changed as follows: (D1) 6.85 mm, (D2) 6.35 mm, and (D3) 5.85 mm. The model was constructed as follows: (S0) vital pulp tooth; (S1) ET tooth; (S2) ET tooth with a 2 mm ferrule, restored with a fiber post and composite resin core; (S3) ET tooth without a ferrule, restored with a fiber post and composite resin core. A total of 12 models were developed. In total, two force loads (100 N) were applied to the crown's incisal edge and palatal surface at a 45° oblique angle to the longitudinal axis of the teeth. The Von Mises stress distribution and maximum stress of the models were analyzed. RESULTS: Regardless of the loading location, stress concentration and maximum stress (34.07~66.78MPa) in all models occurred in the labial cervical 1/3 of each root. Both labiolingual diameter and construction influenced the maximum stress of the residual tooth tissue, with the impact of the labiolingual diameter being greater. A reduction in labiolingual diameter led to increased maximum stress throughout the tooth. The ferrule reduced the maximum stress of the core of S2 models (7.15~10.69 MPa), which is lower compared with that of S3 models (19.45~43.67 MPa). CONCLUSION: The labiolingual diameter exerts a greater impact on the biomechanical characteristics of ET anterior teeth with crown restoration, surpassing the influence of the construction. The ferrule can reduce the maximum stress of the core and maintain the uniformity of stress distribution.