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This retrospective study assessed the diagnostic accuracy of targeted biopsy (TB) and unilateral systematic biopsy in detecting clinically significant prostate cancer (csPCa) in 222 men with single magnetic resonance imaging (MRI) lesions (Prostate Imaging Reporting and Data System [PI-RADS] ≥ 3).

Abstract In a multicenter case–control investigation, we assessed the efficacy of the Electrooculogram Signal Analysis (EOG-SA) method, which integrates attention-related visual evocation, electrooculography, and nonlinear analysis, for distinguishing between intellectual and developmental disabilities (IDD) and typical development (TD) in children. Analyzing 127 participants (63 IDD, 64 TD), we applied nonlinear dynamics for feature extraction. Results indicated EOG-SA’s capability to distinguish IDD, with higher template thresholds and Correlation Dimension values correlating with clinical severity. The template threshold proved a robust indicator, with higher values denoting severe IDD. Discriminative metrics showed areas under the curve of 0.91 (template threshold) and 0.85/0.91 (D2), with sensitivities and specificities of 77.6%/95.9% and 93.5%/71.0%, respectively. EOG-SA emerges as a promising tool, offering interpretable neural biomarkers for early and nuanced diagnosis of IDD.

In this study, adlay rice bran-zinc chelate (ABP-Zn) was prepared as a novel and effective zinc supplement to mitigate environmental pollution and reduce the wastage of protein resources during adlay rice production. Under optimal conditions, i.e. time = 60 min, peptide-to-zinc mass ratio = 3:1, pH = 6.0, temperature = 60°C, the Zn content of the ABP-Zn chelate reached 53.52 ± 3.32 mg/g. The ABP-Zn chelate was formed as a result of the bonding of the carbonyl, amino, and carboxyl groups with Zn2+. This was demonstrated by fluorescence spectra, X-ray diffraction, ultra-violet spectroscopy, Fourier transform infrared spectroscopy, surface elemental composition, amino acid composition, multiangle analyses, and physical attributes, such as microstructure and particle size. Compared to zinc gluconate and zinc sulfate, the ABP-Zn chelate exhibited increased stability under various temperatures, pH, and simulated digestive digestion conditions. Furthermore, ABP-Zn significantly promoted the transport of zinc in the Caco-2 cell model. These findings suggest that zinc-binding peptide derived from adlay rice protein has great potential to be used as an ingredient in zinc supplements.

Abstract Esophageal cancer is common worldwide, with ESCC being the most frequent tumor in East Asia. Tumor-associated macrophages are an important component of the ESCC microenvironment. SUMOylation is a post-translational modification of proteins, and SUMO-specific proteases (SENPs) play an important role in de-SUMOylation. In human patients, we discovered that the levels of SENP3 were upregulated in the tumor-associated macrophages. Furthermore, the loss of SENP3 enhanced the alternative activation of macrophages in the 4-NQO-induced ESCC mice model. This is the first study to identify SENP3-mediated macrophage polarization via the de-SUMOylation of interferon regulatory factor 4 (IRF4) at the K349 site. Alternative activation of macrophages increases the migration and invasion potential of ESCC cells and promotes their progression in vivo. Moreover, patients with relatively low SENP3 expression in macrophages exhibit higher primary PET SUVmax value and lymph node metastasis rates. In summary, this study revealed that SENP3-mediated IRF4 de-SUMOylation is crucial for the alternative activation of macrophages and influences the progression of ESCC. Graphical Abstract

Periodontitis is one of the most prevalent inflammatory disease worldwide, which affects 11% of the global population and is a major cause of tooth loss. Recently, oxidative stress (OS) has been found to be the pivital pathophysiological mechanism of periodontitis, and overactivated OS will lead to inflammation, apoptosis, pyroptosis and alveolar bone resorption. Interestingly, heme oxygenase-1 (HO-1), a rate-limiting enzyme in heme degradation, can exert antioxidant activites through its products—carbon monoxide (CO), Fe2+, biliverdin and bilirubin in the inflammatory microenvironment, thus exhibiting anti-inflammatory, anti-apoptotic, anti-pyroptosis and bone homeostasis-regulating properties. In this review, particular focus is given to the role of HO-1 in periodontitis, including the spatial-temporal expression in periodental tissues and pathophysiological mechanisms of HO-1 in periodontitis, as well as the current therapeutic applications of HO-1 targeted drugs for periodontitis. This review aims to elucidate the potential applications of various HO-1 targeted drug therapy in the management of periodontitis, investigate the influence of diverse functional groups on HO-1 and periodontitis, and pave the way for the development of a new generation of therapeutics that will benefit patients suffering from periodontitis.

Abstract Subauroral red (SAR) arcs are commonly observed ionospheric red line emissions. They are usually attributed to subauroral electron heating by inner magnetospheric heat flux (IMHF). However, the role of IMHF in changing the ionosphere‐thermosphere (IT) still remains elusive. We conduct controlled numerical experiments with the Thermosphere‐Ionosphere Electrodynamic General Circulation Model (TIEGCM). Coulomb collisional heat flux derived with the Comprehensive Inner Magnetosphere Ionosphere (CIMI) model and empirical subauroral polarization streams (SAPS) are implemented in TIEGCM. The heat flux causes electron temperature enhancement, electron density depletion, and consequently SAR arcs formed in the dusk‐to‐midnight subauroral ionosphere region. SAPS cause more substantial plasma and neutral heating and plasma density variations in a broader region. The maximum enhancement of subauroral red line emission rate is comparable to that caused by the heat flux. However, the visibility of SAR arcs also depends on the relative enhancement to the background brightness.

Abstract Background Overerupted maxillary molars is common in adults, which can lead to insufficient intermaxillary vertical space ,great difficulty in prosthetic reconstruction ,and cause occlusal interference in movements.To reconstruct occlusal function, it is necessary to prepare enough space for prostheses. The aim of the present study was to evaluate the effect of space-adjustment occlusal splint on overerupted maxillary molars by clinical and electromyographic signals analysis. Methods Eighteen patients with overerupted maxillary molars were selected to wear space-adjustment occlusal splint suppressing overerupted maxillary molars for three months. Satisfaction was assessed by 5-point Likert; intermaxillary vertical space and the teeth transportation distance were measured in models; clinical periodontal status were evaluated by periodontal probing depth (PPT) and bleeding index (BI); electromyographic recordings of the masseter and anterior temporal muscles were monitored by Cranio-Mandibular K7 Evaluation System. Results All the patients were satisfied with the treatment effect (Likert scale ≧ 4). The intermaxillary space in edentulous areas after treatment showed statistically significant increasing when compared with those before treatment. PPT and BI showed no significant difference. No statistically significant differences were found in electromyographic activity of anterior temporal muscles, while a reduction of muscle activity in masseter in the contralateral side were detected in post-treatment evaluations compared with pre-treatment at mandibular rest position. Conclusions Space-adjustment occlusal splint is an efficient treatment option on overerupted maxillary molars by intruding the maxillary molar to obtain adequate intermaxillary space for prostheses.

ABSTRACTThis study employed laser directed energy deposition (DED) with in-situ ultrasonic vibration to obtain AA7075 deposits. The results showed that with ultrasonic treatment, the grain morphology of DED produced AA7075 was changed from columnar grains with an average area of 1751 µm2 to equiaxed grains of 118.2 µm2, representing a reduction of about 93%. Also, the application of ultrasonic treatment led to the increase of average hardness from 93.1 HV to 110.2 HV, and the increase of average ultimate tensile strength from 226.8 MPa to 314.7 MPa, representing relative increases of 18.36% and 38%, respectively. However, it did not result in a significant reduction of ductility. It is believed that ultrasonic vibration promotes the formation of additional nucleation sites due to cavitation and acoustic streaming, as well as the formation of secondary phase particles at grain boundaries. Both mechanisms effectively augment the mechanical properties of DED produced AA7075.

The durability of concrete roads in mountainous regions may be reduced due to underground water infiltration and surface water erosion within highway tunnels. A promising solution is the use of pervious concrete as a drainage subgrade layer to drain away the water, and then to prevent water-induced pavement damage of pavement. For pervious concrete to be an ideal drainage layer for high-traffic loads, it must have compressive strength and permeability coefficient exceeding 25 MPa and 15 mm/s, simultaneously. However, traditional pervious concrete tends to emphasize either in high-strength or high-permeability, depending on its porosity. This study introduces an innovative proportion design method of pervious concrete, which enables higher compressive strength and permeability coefficient by adjusting its skeleton structure, and thus catering to high-traffic load applications. In addition, the workability and setting time of pervious concrete were optimized according to the local environmental conditions, facilitating large-scale and efficient paving of the drainage subgrade. As a result, a drainage subgrade layer with a 28-day compressive strength of 26.43 MPa and permeability coefficient of 18.86 mm/s was successfully applied in a highway tunnel. This study provides a theoretical framework and technical support for widespread application of pervious concrete in drainage subgrade of high-traffic load road.

Cancer is one of the top 10 fatal diseases worldwide, among which advanced metastatic carcinoma has the highest mortality rate. Sunitinib and immune checkpoint blockers are commonly used to treat metastatic renal carcinoma with limited efficacy. Therefore, there is an urgent need to develop novel targeted therapies for metastatic renal cancer. In this study, we designed an antibody fusion protein, 57103, that simultaneously targeted the cluster of differentiation 24 (CD24), interleukin 4 receptor (IL-4R), and integrin receptors αvβ3 and α5β1. In vitro assays showed that 57103 significantly suppressed the proliferation, migration, invasion, colony formation, and adhesion abilities of renal cancer cells, resulting in a comprehensive and significant antitumor effect. Furthermore, 57103 inhibited angiogenesis, promoted THP1-derived M0-type macrophage phagocytosis, and enhanced the antibody-dependent cellular cytotoxicity of peripheral blood mononuclear and NK92MI-CD16a cells. In vivo experiments revealed significant inhibition of tumor growth in ACHN cell xenograft nude mice and an MC38-hCD24 tumor-bearing mouse model. Immunohistochemical analysis showed that 57103 decreased the proliferation and induced the apoptosis of renal cancer cells, while inhibiting angiogenesis. The MC38-hPDL1 and MC38-hCD24-hPDL1 tumor-bearing mouse models further offer the possibility of combining 57103 with the PDL1 antagonist atezolizumab. In conclusion, 57103 is a potential candidate drug for the treatment of metastatic renal carcinoma or PDL1-overexpressing cancer.

Abstract Deep water and shallow layers mostly feature weakly cemented formations, with complex geological structures, geological looseness, susceptibility to collapse. In order to obtain information on weakly cemented formation materials, weakly cemented argillaceous siltstone is simulated as the research object and the focus is on analysing the influence of ultrasonic frequency, density, particle size (porosity), and compressive strength on P-wave velocity and establishing the correlation relationship between longitudinal wave velocity and each parameter through indoor simulation experiments. The results showed that there is a linear relationship between P-wave velocity and ultrasonic frequency in terms of positive correlation as well as compressive strength. The nonlinear relationship between P-wave velocity and particle size (porosity) is a negative correlation, while the nonlinear relationship between sound velocity and density is a positive correlation. In addition, the influence of core height on P-wave velocity is analysed; it is found that as the core height increases, the velocity slightly decreases, and each ultrasonic frequency has an ultimate height for sound wave penetration. Through the response relationship between ultrasound and the physical properties of weakly cemented formations, indirect acquisition can be achieved, which is of great significance for the development of oil and gas in weakly cemented formations.

Rosa roxburghii (R. roxburghii), native to the southwest provinces of China, is a fruit crop of important economic value in Guizhou Province. However, the changes in fruit quality and flavor during R. roxburghii fruit ripening have remained unknown. Here, this study investigated the changes of seven active components and volatile organic compounds (VOCs) during the ripening of the R. roxburghii fruit at five different ripening stages including 45, 65, 75, 90, and 105 days after anthesis. The results indicated that during the ripening process, the levels of total acid, vitamin C, and soluble sugar significantly increased (p < 0.05), while the levels of total flavonoids, superoxide dismutase (SOD), and soluble tannin significantly decreased (p < 0.05). Additionally, the content of total phenol exhibited a trend of first decreasing significantly and then increasing significantly (p < 0.05). A total of 145 VOCs were detected by HS-SPME-GC-MS at five mature stages, primarily consisting of aldehydes, alcohols, esters, and alkenes. As R. roxburghii matured, both the diversity and total quantity of VOCs in the fruit increased, with a notable rise in the contents of acids, ketones, and alkenes. By calculating the ROAV values of these VOCs, 53 key substances were identified, which included aromas such as fruit, citrus, green, caramel, grass, flower, sweet, soap, wood, and fat notes. The aromas of citrus, caramel, sweet, and wood were predominantly concentrated in the later stages of R. roxburghii fruit ripening. Cluster heatmap analysis revealed distinct distribution patterns of VOCs across five different maturity stages, serving as characteristic chemical fingerprints for each stage. Notably, stages IV and V were primarily characterized by a dominance of alkenes. OPLS-DA analysis categorized the ripening process of R. roxburghii fruit into three segments: the first segment encompassed the initial three stages (I, II, and III), the second segment corresponded to the fourth stage (IV), and the third segment pertained to the fifth stage (V). Following the variable importance in projection (VIP) > 1 criterion, a total of 30 key differential VOCs were identified across the five stages, predominantly comprising ester compounds, which significantly influenced the aroma profiles of R. roxburghii fruit. By integrating the VIP > 1 and ROAV > 1 criteria, 21 differential VOCs were further identified as key contributors to the aroma changes in R. roxburghii fruit during the ripening process. This study provided data on the changes in quality and aroma of R. roxburghii fruit during ripening and laid the foundation for the investigation of the mechanism of compound accumulation during ripening.

Acute myeloid leukemia (AML) with t(16;21)(p11;q22)/FUS::ERG is a rare AML subtype associated with poor prognosis. However, its clinical and molecular features remain poorly defined. We determined the clinicopathological, genomic, and transcriptomic characteristics and outcomes of patients with AML harboring FUS::ERG at our center. Thirty-six AML patients harboring FUS::ERG were identified, with an incidence rate of 0.3%. These patients were characterized by high lactate dehydrogenase levels (median: 838.5 U/L), elevated bone marrow blast counts (median: 71.5%), and a CD56-positive immunophenotype (94.3%). Notably, we found that RTK–RAS GTPase (RAS) pathway genes, including NRAS (33%) and PTPN11 (24%), were frequently mutated in this subtype. Transcriptome analysis revealed enrichment of the phosphatidylinositol-3-kinase-Akt (PI3K-Akt), mitogen-activated protein kinase (MAPK), and RAS signaling pathways and upregulation of BCL2, the target of venetoclax, in FUS::ERG AML compared to RUNX1::RUNX1T1 AML, a more common AML subtype with good prognosis. The median event-free survival in patients with FUS::ERG AML was 11.9 (95% confidence interval [CI]: 9.0–not available [NA]) months and the median overall survival was 18.2 (95% CI: 12.4–NA) months. Allogeneic hematopoietic stem cell transplantation failed to improve outcomes. Overall, the high incidence of RTK–RAS pathway mutations and high expression of BCL2 may indicate promising therapeutic targets in this high-risk AML subset.

Abstract The ionospheric convection electric field is often assumed to be a potential field. This assumption is not always valid, especially when the ionosphere changes on short time scales T≲5 min. We present a technique for estimating the induction electric field using ground magnetometer measurements. The technique is demonstrated on real and simulated data for sudden increases in solar wind dynamic pressure of ∼1 and 10 nPa, respectively. For the real data, the ionospheric induction electric field is 0.15 ± 0.015 mV/m, and the corresponding compressional flow is 2.5 ± 0.3 m/s. For the simulated data, the induction electric field and compressional flow reach 3 mV/m and 50 m/s, respectively. The induction electric field can locally constitute tens of percent of the total electric field. Inclusion of the induction electric field increased the total Joule heating by 2.4%. Locally the Joule heating changed by tens of percent. This corresponds to energy dissipation that is not accounted for in existing models.

Grasslands are among the most widespread environments on Earth, yet we still have poor knowledge of their microbial-mediated carbon cycling in the context of human activity and climate change. We conducted a systematic bibliometric analysis of 1,660 literature focusing on microbial-mediated grassland carbon cycling in the Scopus database from 1990 to 2022. We observed a steep increase in the number of multidisciplinary and interdisciplinary studies since the 2000s, with focus areas on the top 10 subject categories, especially in Agricultural and Biological Sciences. Additionally, the USA, Australia, Germany, the United Kingdom, China, and Austria exhibited high levels of productivity. We revealed that the eight papers have been pivotal in shaping future research in this field, and the main research topics concentrate on microbial respiration, interaction relationships, microbial biomass carbon, methane oxidation, and high-throughput sequencing. We further highlight that the new research hotspots in microbial-mediated grassland carbon cycling are mainly focused on the keywords “carbon use efficiency,” “enzyme activity,” “microbial community,” and “high throughput sequencing.” Our bibliometric analysis in the past three decades has provided insights into a multidisciplinary and evolving field of microbial-mediated grassland carbon cycling, not merely summarizing the literature but also critically identifying research hotspots and trends, the intellectual base, and interconnections within the existing body of collective knowledge and signposting the path for future research directions.

The magnetospheric systems of ice giants, as the ideal and the unique template of a typical class of exoplanets, have not been sufficiently studied in the past decade. The complexity of these asymmetric and extremely dynamic magnetospheres provides us a great chance to systematically investigate the general mechanism of driving the magnetospheres of such common exoplanets in the Universe, and the key factors of influencing the global and local magnetospheric structures of this type of planets. In this paper, we discuss the science return of probing magnetospheric systems of ice giants for the future missions, throughout different magnetospheric regions, across from the interaction with upstream solar wind to the downstream region of the magnetotail. We emphasize the importance of detecting the magnetospheric systems of ice giants in the next decades, which enables us to deeply understand the space enviroNMent and habitability of not only the ice giants themselves but also the analogous exoplanets which are widely distributed in the Universe.

Abstract Geomagnetic storms of G1-class were observed on 3 and 4 February 2022, which caused the loss of 38 out of 49 SpaceX satellites during their launch due to enhanced neutral density. The effects of storm-time neutral dynamics and electrodynamics over the American sector during this minor storm have been investigated using Global Positioning System—total electron content (TEC) and Global‐scale Observations of the Limb and Disk (GOLD) mission measured thermospheric composition and temperature. Results revealed an unexpected feature in terms of increase in O/N2 and depletion in TEC over the American low-latitudes. This feature is in addition to the classic storm time ionospheric variations of enhancement in ionospheric electron density in presence of enhanced O/N2 and an intense equatorial electrojet (EEJ). Further, significant morning-noon electron density reductions were observed over the southern mid-high latitudes along the American longitudes. Results from Multiscale Atmosphere-Geospace Environment (MAGE) model simulations elucidated storm-induced equatorward thermospheric wind which caused the strong morning counter electrojet by generating the disturbance dynamo electric field. This further explains the morning TEC depletion at low-latitudes despite an increase in O/N2. Sub-storm related magnetospheric convection resulted in significant noon-time peak in EEJ on 4 February. Observation and modelling approaches together suggested that combined effects of storm-time neutral dynamic and electrodynamic forcing resulted in significant ionospheric variations over the American sector during minor geomagnetic storms.

Luminescent solar concentrators (LSCs) are attractive for the easy operation and high compatibility with building integrated photovoltaics due to their low cost, large-scale and applicability. However, underutilized sunlight in visible wavelengths often impedes the advance of LSCs. Here, we demonstrate an orange-emitting carbon nanodots-based LSC (O-CDs) with excitation concentrated in the visible wavelengths. The orange-emitting carbon nanodots (O-CDs) with highly localized excitonic emission are prepared via atomic condensation of doped pyrrolic nitrogen, delivering a high photoluminescence quantum yield of 80 % and a suitable Stokes shift with absorption spectrum situated in the visible region. The O-CDs are embedded in polyvinylpyrrolidone to obtain a highly transparent, stable and environmentally friendly O-CDs-based LSC. Thanks to efficient utilization of solar radiation in visible areas and well match between the emission of O-CDs and the response bands of photovoltaic cells, the O-CDs-based LSC reveals an optical conversion efficiency of 5.17 %, superior to that of most carbon nanodots-based LSCs. These results provide an effective strategy to develop carbon-based luminescent concentrated materials for architectural integrated photovoltaic technology.

Brain imaging methods have effectively revealed drivers' underlying psychological and neural processes when they perform driving tasks and promote driving behavior research in a more scientific direction. With research no longer limited to indirect inferences about external behavior, some researchers combine behavior and driver brain activity to understand the human factors in driving essentially. However, most researchers in the field of driving behavior still have little understanding of how brain imaging methods are used. This paper aims to review and analyze the application of brain imaging methods in driving behavior research, including bibliometric analysis and an individual critical literature review. Regarding bibliometric analysis, this field's knowledge structure and development trend are described macroscopically, using data such as annual distribution of publications, country/region statistics and partnerships, publication sources, literature co-citation analysis, and keyword co-occurrence analysis. In a review of the individual critical literature, eight research themes were identified that examined driving behavior using brain imaging methods: substance consumption, fatigue or sleep deprivation, workload, distraction, aging brains, brain impairment and other diseases, automated/semi-automated environments, emotions influence and risk-taking, and general driving process. In addition, the study reports on six brain imaging methods and their advantages and disadvantages, involving electroencephalography (EEG), functional magnetic resonance imaging (fMRI), functional near-infrared spectroscopy (fNIRS), magnetoencephalography (MEG), positron emission tomography (PET), and transcranial magnetic stimulation (TMS). The contribution of this study is twofold. The first part relates to providing the researchers with a comprehensive understanding of the field's knowledge structure and development trends. The second part goes beyond reviewing and analyzing previous studies, and the discussion section points out the directions and challenges for future research.

Castanopsis hystrix Hook. f. & Thomson ex A. DC. 1863 (Fagaceae) is an evergreen broad-leaved tree with high economic and ecological value. In this study, the complete chloroplast genome of C. hystrix was sequenced, assembled and annotated. The plastome (plastid genome) of C. hystrix was 160,624 bp in size, consisting of a pair of inverted repeats (IRs, 25,699 bp), a large-single-copy (LSC, 90,276 bp) region, and a small-single-copy (SSC, 18,950 bp). The overall GC content of C. hystrix was 36.8%. A total of 133 genes were annotated, including 88 protein-coding genes (PCG), 37 transfer RNA genes (tRNA), and eight ribosomal RNA genes (rRNA). A maximum likelihood analysis showed that the Castanopsis species form a monophyletic clade. C. hystrix is most closely related to C. tibetana with 100% bootstrap support value. The result enriches the genomic data for the genus Castanopsis, which will contribute to future studies in phylogenetics and evolution.

BackgroundDelirium significantly contributes to both mortality and morbidity among hospitalized older adults. Furthermore, delirium leads to escalated healthcare expenditures, extended hospital stays, and enduring cognitive deterioration, all of which are acknowledged detrimental outcomes. Nonetheless, the current strategies for predicting and managing delirium remain constrained. Our aim was to employ Mendelian randomization (MR) to investigate the potential causal relationship between metabolites and delirium, as well as to identify potential therapeutic targets.MethodsWe identified 129 distinct blood metabolites from three genome-wide association studies (GWASs) conducted on the metabolome, involving a total of 147,827 participants of European descent. Genetic information pertaining to delirium was sourced from the ninth iteration of the Finngen Biobank, encompassing 359,699 individuals of Finnish ancestry. We conducted MR analyses to evaluate the connections between blood metabolites and delirium. Additionally, we extended our analysis to encompass the entire phenome using MR, aiming to uncover potential on-target consequences resulting from metabolite interventions.ResultsIn our investigation, we discovered three metabolites serving as causal mediators in the context of delirium: clinical low density lipoprotein cholesterol (LDL-C) (odds ratio [OR]: 1.47, 95% confidence interval [CI]: 1.25-1.73, p = 3.92 x 10-6), sphingomyelin (OR: 1.47, 95% CI: 1.25-1.74, p = 5.97 x 10-6), and X-11593–O-methylascorbate (OR: 0.21, 95% CI: 0.10-0.43, p = 1.86 x 10-5). Furthermore, utilizing phenome-wide MR analysis, we discerned that clinical LDL-C, sphingomyelin, and O-methylascorbate not only mediate delirium susceptibility but also impact the risk of diverse ailments.Limitations(1) Limited representation of the complete blood metabolome, (2) reliance on the PheCode system based on hospital diagnoses may underrepresent conditions with infrequent hospital admissions, and (3) limited to European ancestry.ConclusionThe genetic prediction of heightened O-methylascorbate levels seems to correspond to a diminished risk of delirium, in contrast to the association of elevated clinical LDL-C and sphingomyelin levels with an amplified risk. A comprehensive analysis of side-effect profiles has been undertaken to facilitate the prioritization of drug targets. Notably, O-methylascorbate emerges as a potentially auspicious target for mitigating and treating delirium, offering the advantage of lacking predicted adverse side effects.

Several international centers have used and reported pediatric-inspired regimens for adolescent and adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL). However, there is a lack of prospective data on the Chinese population. Herein, we performed a prospective study with a pediatric-inspired regimen (IH-2014 regimen) in treating adolescent and adult Ph- ALL patients in our center. From 2014 to 2021, a total of 415 patients aged between 14 and 65 years (median age, 27) were included in this study. After a median follow-up of 40.8 months, the 5-year overall survival, disease-free survival, and event-free survival rates were 53.8%, 51.1% and 45.0%, respectively. The regimen was generally well tolerated and safe, and the overall chemotherapy-related mortality was 3.6%. Age ≥ 40 years and persistent detectable minimal residual disease (MRD) post-induction were independent prognostic factors. Traditional risk factors for adult patients combined with MRD post-induction exhibit predictive significance for survival and relapse, which is helpful in the selection of subsequent treatment. Patients with high risk factors who can achieve deep MRD response after induction do not derive benefit from allogeneic hematopoietic stem cell transplantation.

ABSTRACTPneumocystis pneumonia (PCP) is a serious fungal lung infection caused by Pneumocystis jirovecii in immunosuppressed individuals. The lack of viable in vitro/ex vivo PCP models has greatly hindered the progress in studying the biology of these fungi, the host/pathogen interactions, as well as antifungal susceptibility testing. In this study, we show the utility of precision-cut lung slices (PCLS) to support the survival of Pneumocystis murina in vitro. We cultured PCLS tissue derived from wild type and immunocompromised mice with a P. murina inoculum in submerged or air-liquid interface models for up to 14 days. We isolated total RNA from the cultured lung tissues at days 0, 3, 7, 10, and 14 and analyzed for the expression of host lung genes and P. murina genes (Gsc1 for asci and Sp for trophs) by real-time quantitative PCR. When cultured in media alone, P. murina died gradually within a few days. However, when cultured on PCLS, both the troph and ascus forms survived throughout the incubation period of 2 weeks. Moreover, immunohistochemistry staining of P. murina inoculated PCLS sections using polyclonal anti-Pneumocystis sera and showed evidence of fungal aggregation and possible biofilm formation. Additionally, in vitro (PCLS) antibiotic susceptibility testing using commonly used antifungal drugs confirmed successful targeting of the troph and ascus forms by trimethoprim sulfamethoxazole and the ascus form by echinocandins.IMPORTANCEOur study reveals the potential of precision-cut lung slices as an ex vivo platform to study the growth/survival of Pneumocystis spp. that can facilitate the development of new anti-fungal drugs.

Abstract Objective Occlusal splints are always applied on individuals with bruxism to reduce tooth wear and relieve orofacial symptoms such as myofascial pain. The stomatognathic system is mainly composed of tooth, occlusion, masticatory muscles, and temporomandibular joint. The occlusion and masticatory muscles function are regarded as the important parameters for evaluating the stomatognathic system state objectively. However, the effects of occlusal splints on individuals with bruxism is rarely elucidated from accurate neuromuscular analysis and occlusion evaluation. The aim of the present study was to estimate the effects of three different splints (two clinically common full coverage occlusal splint and an modified anterior splint) on subjects with bruxism using K7-J5 neuromuscular analysis system and Dental Prescale II (DP2) to evaluate occlusion. Methods Sixteen subjects claimed to be suffering from nocturnal bruxism,with complete dentition and stable occlusal relationship, were selected for study.The intermaxillary space and the baselines of EMG-activity of the anterior temporalis and masseter were recorded for all the subjects. The participants was treated with three different splints, and outcomes were estimated by comfort index, occlusion and surface electromyography of anterior temporalis and masseter. Results At teeth clenched position, EMG data were significantly lower in the participants with use of modified anterior splint than with hard, soft occlusal splint or without splint (p

Abstract Background Chronic hepatitis C virus (HCV) infection causes hepatocellular carcinoma (HCC). The HCC risk, while decreased compared with active HCV infection, persists in HCV-cured patients by direct-acting antiviral agents (DAA). We previously demonstrated that Wnt/β-catenin signaling remained activated after DAA-mediated HCV eradication. Developing therapeutic strategies to both eradicate HCV and reverse Wnt/β-catenin signaling is needed. Methods Cell-based HCV long term infection was established. Chronically HCV infected cells were treated with DAA, protein kinase A (PKA) inhibitor H89 and endoplasmic reticulum (ER) stress inhibitor tauroursodeoxycholic acid (TUDCA). Western blotting analysis and fluorescence microscopy were performed to determine HCV levels and component levels involved in ER stress/PKA/glycogen synthase kinase-3β (GSK-3β)/β-catenin pathway. Meanwhile, the effects of H89 and TUDCA were determined on HCV infection. Results Both chronic HCV infection and replicon-induced Wnt/β-catenin signaling remained activated after HCV and replicon eradication by DAA. HCV infection activated PKA activity and PKA/GSK-3β-mediated Wnt/β-catenin signaling. Inhibition of PKA with H89 both repressed HCV and replicon replication and reversed PKA/GSK-3β-mediated Wnt/β-catenin signaling in both chronic HCV infection and replicon. Both chronic HCV infection and replicon induced ER stress. Inhibition of ER stress with TUDCA both repressed HCV and replicon replication and reversed ER stress/PKA/GSK-3β-dependent Wnt/β-catenin signaling. Inhibition of either PKA or ER stress both inhibited extracellular HCV infection. Conclusion Targeting ER stress/PKA/GSK-3β-dependent Wnt/β-catenin signaling with PKA inhibitor could be a novel therapeutic strategy for HCV-infected patients to overcomes the issue of remaining activated Wnt/β-catenin signaling by DAA treatment. Video Abstract

Abstract Background Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer. We performed a systematic review and meta‐analysis to evaluate the prevalence of genomic alterations in NEPC and better understand its molecular features to potentially inform precision medicine. Methods EMBASE, PubMed, and Cochrane Central Register of Controlled Trials databases were searched for eligible studies until March 2022. Study qualities were assessed using the Q‐genie tool. The prevalence of gene mutations and copy number alterations (CNAs) were extracted, and meta‐analysis was performed using R Studio with meta package. Results A total of 14 studies with 449 NEPC patients were included in this meta‐analysis. The most frequently mutated gene in NEPC was TP53 (49.8%), and the prevalence of deleterious mutations in ATM/BRCA was 16.8%. Common CNAs in NEPC included RB1 loss (58.3%), TP53 loss (42.8%), PTEN loss (37.0%), AURKA amplification (28.2%), and MYCN amplification (22.9%). RB1/TP53 alterations and concurrent RB1 and TP53 alterations were remarkably common in NEPC, with a prevalence of 83.8% and 43.9%, respectively. Comparative analyses indicated that the prevalence of (concurrent) RB1/TP53 alterations was significantly higher in de novo NEPC than in treatment‐emergent NEPC (t‐NEPC). Conclusions This study presents the comprehensive prevalence of common genomic alterations and potentially actionable targets in NEPC and reveals the genomic differences between de novo NEPC and t‐NEPC. Our findings highlight the importance of genomic testing in patients for precision medicine and provide insights into future studies exploring different NEPC subtypes.

Dictyophora rubrovolvata volva, an agricultural by-product, is often directly discarded resulting in environmental pollution and waste of the proteins’ resources. In this study, D. rubrovolvata volva proteins (DRVPs) were recovered using the ultrasound-assisted extraction (UAE) method. Based on one-way tests, orthogonal tests were conducted to identify the effects of the material–liquid ratio, pH, extraction time, and ultrasonic power on the extraction rate of DRVPs. Moreover, the impact of UAE on the physicochemical properties, structure characteristics, intermolecular forces, and functional attributes of DRVPs were also examined. The maximum protein extraction rate was achieved at 43.34% under the best extraction conditions of UAE (1:20 g/mL, pH 11, 25 min, and 550 W). UAE significantly altered proteins’ morphology and molecular size compared to the conventional alkaline method. Furthermore, while UAE did not affect the primary structure, it dramatically changed the secondary and tertiary structure of DRVPs. Approximately 13.42% of the compact secondary structures (α-helices and β-sheets) underwent a transition to looser structures (β-turns and random coils), resulting in the exposure of hydrophobic groups previously concealed within the molecule’s core. In addition, the driving forces maintaining and stabilizing the sonicated protein aggregates mainly involved hydrophobic forces, disulfide bonding, and hydrogen bonding interactions. Under specific pH and temperature conditions, the water holding capacity, oil holding capacity, foaming capacity and stability, emulsion activity, and stability of UAE increased significantly from 2.01 g/g to 2.52 g/g, 3.90 g/g to 5.53 g/g, 92.56% to 111.90%, 58.97% to 89.36%, 13.85% to 15.37%, and 100.22% to 136.53%, respectively, compared to conventional alkali extraction. The findings contributed to a new approach for the high-value utilization of agricultural waste from D. rubrovolvata.

A three-layer terahertz dual-function absorber with broadband absorption and narrowband absorption switching is proposed based on the special electrically tunable non-equilibrium optical response of graphene. Instead of using phase change materials, the structure uses patterned graphene in the top layer to achieve the switching effect. Patterned graphene consists of a cross and an external square frame. The relaxation time is adjusted by applying an electric field to the graphene to achieve broadband and narrowband switching. The structure can achieve broadband absorption when the relaxation time of graphene is 0.2 ps. From 1.27 to 2.16 THz, the absorbance of the structure can exceed 90%, and the average absorption rate can reach 96.88%. At 1.68–1.96 THz, the absorbance of the structure can even exceed 99%. When the relaxation time of graphene is 3 ps, the structure achieves narrowband absorption at 1.72 THz with a maximum absorption rate of 99%, achieving “perfect” absorption. Simultaneously, the proposed structure is highly symmetric, both modes are stable in the incidence angle range of 0–60°, and polarization insensitive. Once the absorber achieves broadband absorption, we control the chemical potential of graphene by adjusting the applied voltage to switch the absorption rate from 0% to 99%. Once the absorber achieves narrow-band absorption, we verify that the structure can be used as a sensor by changing the refractive index of the surrounding environment. Accordingly, we demonstrate that the absorber proposed in this study has potential applications in the fields of photoelectric switches, terahertz energy harvesting, and refractive index sensing.

In the process of shale gas extraction, fracturing technology is often used, and the extracted gas contains large amounts of sand, resulting in the risk of blockage and erosion of surface gathering equipment, which seriously affects safe production. To address this problem, this paper presents a numerical study of the sand removal performance and erosion characteristics of the filter desander used in Sichuan shale gas fields under different operating conditions (flow velocity, sand mass flow rate, operating pressure, and sand particle size) using CFD method. The results show that the increase of shale gas velocity is not conducive to the efficient operation of the filter desander. So the flow velocity should be controlled within 10 m/s as much as possible to avoid the rapid drawdown of separation efficiency and overly high erosion rate. When the sand size increases from 10μm to 100μm, the erosion area of the filter desander changes to sheet-like distribution, and the separation efficiency increases to 85%, a 2.3-fold increase. In addition, the change in operating pressure has a relatively small impact on the erosion wear of the desander.

Objective To understand the effect of long-term high-frequency platelet donation on the health, safety and platelet quality of blood donors. Methods From August 2020 to July 2022, blood donors who donated platelets for single collection in the station were selected as two groups: those who donated for 20-29 times and those who donated for 30-44 times. Such 14 test indexes as red blood cell count (RBC), hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), platelet count (Plt), white blood cell count (WBC), large platelet ratio (P-LCR), lymphocyte (LYM) , neutrophil (NE), mean hemoglobin content (MCH), mean hemoglobin concentration (MCHC), platelet specific volume (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) were grouped and statistically analyzed for 5 times in each group. In addition, blood donors who have donated platelets more than 100 times in the station were chosen; the changes of their 5 parameters as RBC, Hb, Hct, PLT and WBC, as well as the correlation with the total number of platelet donations were analyzed through statistical analysis of the first 100 donations(10 donations/group). Results During 2 years, the hematological parameters were similar between 20-29 donation group(n=30) and 30-44 donation group(n=11) (P>0.05). For donors with donations≥100 occasions, RBC, Hb, Hct and WBC were negatively correlated with the number of blood donations, while Plt was positively correlated. There were significant differences in Hb, Hct, WBC and Plt among groups (P

Creep characterization of different diameter silica bar core during directional solidification of the single crystal superalloy was investigated by suspension method. The scanning electron microscope (SEM) was employed to observe the microstructure of the surface and transversal section of crept silica bar. The energy dispersive spectroscopy (EDS) and X-ray diffraction technology were used to analyse and determine the composition of the reaction product. The experimental results show that the crept deformation amount increases with prolonging of creep time and decreasing of the diameter of the silica bar. When the creep time is 60 min, the diameter 0.5 mm silica bar has the largest creep deformation, and the average deformation is 30 mm, while the 2 mm silica bar is 24 mm. The interfacial reaction of SiO2 with C and Al, which are deposited on the silica bar surface due to the elevated temperature and low vacuum, induces the formation of porous layer. The volume fraction of the porous reaction products leads to the different crept deformation amount of different diameter silica bars. The creep deformation amount of silica bars has a linear relationship with the volume fraction of surface reaction products.

Background Resembling acute promyelocytic leukemia (APL) is a unique subtype of APL who sharing clinical, morphological, and immunophenotypic features with typical APL, but lacking evidence of PML-RARA fusion gene and usually insensitive to arsenic trioxide (ATO) and all-trans retinoic acid (ATRA). For years, RARA, RARB and RARG rearrangement were found in resembling APL continually. The confirmed partner genes of RARG rearrangement included CPSF6, NUP98, NPM1, PML, and HNRNPC. These patients were a group of resembling APL with rare molecular genetic abnormality and unfavorable prognosis. They usually were resistant to ATO and ATRA but partially sensitive to anthracycline-based chemotherapy.Case presentation We reported a 25-year-old female patient with a novel fusion gene RARG-HNRNPM (RARG chr12:53606869: –; HNRNPM chr19: 8527413: + based on GRCh37/hg19 Assembly) through RNA-seq as resembling APL. The patient with RARG-HNRNPM was benefited from a combined chemotherapy homoharringtonine, cytarabine, and aclacinomycin (HAA) regimen with no relapse.Discussion and conclusions RARG rearrangement resembling APL are various. The treatment should be switched from ATRA/ATO to AML combined chemotherapy regimen early.

Abstract Background The diagnosis of mixed phenotype acute leukemia (MPAL) with T/megakaryocyte or T/myeloid lineages accompanied by t(3;3) is always a challenge. Therefore, multiple experimental methods are usually required to avoid misdiagnosis. In this report, we presented a rare case of MPAL with T/myeloid lineages accompanied by t(3;3) and discussed the experience of differential diagnosis and our appreciation of the MPAL with T/megakaryocyte and T/myeloid lineages accompanied by t(3;3). Case presentation: A 31-year-old woman was admitted to our hospital due to recurrent fever for 20 days. Two distinct blast populations were detected by flow cytometry analysis: one population fulfills the immunophenotypic criteria for T-lymphoblastic leukemia, while the other population is highly suggestive of megakaryoblasts. These immunophenotypic features support the diagnosis of MPAL (T/megakaryocyte), which is rarely reported​. Interestingly, a complex karyotype was detected afterward by cytogenetics with t(3;3)(q21;q26.2), indicating a diagnosis of AML with t(3;3), a subset of which is also characterized by megakaryocytic markers such as CD41 and CD61. It seems that the second blast population detected by flow cytometry could not be classified into either diagnosis based on the morphology, immunophenotyping, and even cytogenetic findings, posing a real diagnostic problem because of the lack of clear-cut cytogenetic morphological defined criteria to distinguish between acute megakaryocytic leukemia and AML with t(3;3). Combining all of the examination data, this case was ultimately diagnosed as MPAL (T + My)-NOS with t(3;3) through differential diagnosis. Before the cytogenetic results were available, the patient received an acute lymphoblastic leukemia (ALL) regimen for MPAL treatment, but the effect was unsatisfactory. After the diagnosis was clear, she received an AML-like regimen with azacitidine for 7 days and venetoclax for 14 days, and achieved complete morphological remission. Conclusion MPAL with either T/megakaryocyte or T/myeloid lineages accompanied by t(3;3) is rare, and it is difficult to make a clear diagnosis. Thus, comprehensive examinations, including bone marrow cell morphology, flow cytometry analysis, cytogenetics, and molecular analysis are recommended to avoid misdiagnosis. AML-like regimen including azacitidine and venetoclax may be effective for treating MPAL (T + My)-NOS with t(3;3).

Thermospheric wind observations from high to mid latitudes are compared with the newly developed Multiscale Atmosphere Geospace Environment (MAGE) model for the Nov 3–4 geomagnetic storm. The observation and simulation comparison shows a very good agreement and is better at high latitudes in general. We were able to identify a thermospheric poleward wind reduction possibly linked to a northward turning of the Interplanetary Magnetic Field (IMF) at ~22 UT on Nov 3 and an enhancement of the poleward wind to a southward turning near 10 UT on Nov 4 at high latitudes. An IMF southward turning may have led to an enhancement of equatorward winds at Boulder, Colorado near midnight. Simultaneous occurrence of aurora may be associated with an IMF By turning negative. The MAGE model wind simulations are consistent with observations in these cases. The results show the model can be a very useful tool to further study the magnetosphere and ionosphere coupling on short time scales.

CXCR7 is an atypical chemokine receptor that recruits β-arrestin (ARRB2) and internalizes into clathrin-coated intracellular vesicles where the complex acts as a scaffold for cytoplasmic kinase assembly and signal transduction. Here, we report that CXCR7 was elevated in the majority of prostate cancer (PCa) cases with neuroendocrine features (NEPC). CXCR7 markedly induced mitotic spindle and cell cycle gene expression. Mechanistically, we identified Aurora Kinase A (AURKA), a key regulator of mitosis, as a novel target that was bound and activated by the CXCR7-ARRB2 complex. CXCR7 interacted with proteins associated with microtubules and golgi, and, as such, the CXCR7-ARRB2-containing vesicles trafficked along the microtubules to the pericentrosomal golgi apparatus, where the complex interacted with AURKA. Accordingly, CXCR7 promoted PCa cell proliferation and tumor growth, which was mitigated by AURKA inhibition. In summary, our study reveals a critical role of CXCR7-ARRB2 in interacting and activating AURKA, which can be targeted by AURKA inhibitors to benefit a subset of patients with NEPC.

With the continuing advancement in China’s exploration and development technologies of shale gas resources, there was a significant increase in shale gas oil-based drilling cuttings. In this paper, oil-based drilling cutting pyrolysis residues (ODCPRs) was used as the main raw material for preparing lightweight and high-strength building ceramsites to eliminate the environmental risks and recycle industrial waste. Firstly, orthogonal experiments were used to study the influences of raw material composition, preheating temperature, preheating time, sintering temperature, and sintering time on the properties of building ceramsites. From the results, the sintering temperature and the content of ODCPRs were discovered to be the key factors affecting the sintering process of ceramsites. Secondly, the influences of sintering temperature and heating rate on the properties of building ceramists were further explored to find the optimum sintering conditions. When the content of ODCPRs in the ceramsite was set to be 50%, the obtained building ceramsites presented excellent properties with particle compressive strength of 6.31 MPa, bulk density of 575.11 kg/m3, apparent density of 1097.24 kg/m3, and the water absorption of 1.89%. Finally, XRD, SEM, TG-DSC, and heavy metal leaching experiments were comprehensively conducted to analyze the composition structure variation and sintering mechanism of the building ceramsite. This paper presents an approach for the recycling, utilization, and disposal of oil-based drilling cuttings in the oil field waste management.

Grassland, as a key component of the carbon cycle in terrestrial ecosystems, is vital in confronting global climate change. Characterising the carbon density of grassland ecosystems in the Longzhong Loess Plateau is important for accurately assessing the contribution of grasslands to global climate change and achieving the goal of “peak carbon” and “carbon neutral”. In this study, the Longzhong Loess Plateau was used as the research object to explore changes in the plant–soil system carbon density in two grassland types by analysing the aboveground vegetation biomass carbon density, belowground vegetation biomass carbon density, 0–100 cm soil carbon density, and ecosystem carbon density of temperate steppe and temperate desert. The results showed that the vegetation biomass (standing and living, litter, and belowground biomass), soil, and ecosystem carbon densities of the temperate steppe were significantly higher than those of the temperate desert (p < 0.05). Their carbon densities were 700.51, 7612.95, and 8313.45 g·m−2, respectively. The vertical distribution of belowground biomass and soil carbon density in the temperate steppe was significantly higher than that in the temperate desert. The overall trend of belowground biomass carbon density in the temperate steppe and temperate desert showed a gradual decrease, whereas soil carbon density showed a steady increase. More than 91% and 96% of the carbon was stored in soil in the temperate steppe and temperate desert, respectively, and the belowground biomass carbon stock accounted for more than 84% of the total biomass carbon pools in both temperate steppe and temperate desert. Temperate steppe has a significant effect in improving the carbon stock of grassland ecosystems, so ecological protection and restoration of grassland should be strengthened in the future to enhance the capacity of grassland to sequester carbon and increase sinks.

Background: Diabetic liver disease is one of the main complications that leads to the aggravation of diabetes, but it has not received sufficient attention. This study aimed to provide a better understanding of the altered molecular networks in in diabetic rats with liver damage after stem cell therapy. To a certain extent, our research would be instructive, since almost no studies of this kind have been performed on patients with diabetic liver disease after stem cell therapy. Methods: Streptozotocin-induced diabetic rats were treated with adipose-derived stem cells. RNA-Seq analysis was performed on the liver tissues of these animals, and key pathway factors were further identified and validated. Results: RNA-Seq analysis revealed numerous affected signaling pathways and functional categories. The results showed that the network of dual specificity phosphatase 1 (DUSP1), an oxidative stress-related gene, was prominently activated in the liver after stem cell therapy, and the enrichment of genes associated with liver damage, steatosis and fibrosis was also detected. The extracellular regulated protein kinase (ERK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway may be involved in this process by regulating the nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. Conclusions: These data provide novel insights into liver biology, suggest common alterations in the molecular networks during diabetic liver damage, and show the advantages of stem cell therapy, indicating its further application potential for early treatment of diabetic liver damage and delaying the progression of liver fibrosis in the later stage.

Abstract We show the possible existence of a significant axial asymmetry in the reconnection separator at the Jovian magnetopause using first‐principle, physics‐based global simulations. Under eastward interplanetary magnetic field (IMF) conditions near Jupiter's orbit, reconnection occurs at the southern‐dusk and northern magnetopause with large shear angles between the magnetospheric and magnetosheath magnetic fields. When driven by the westward IMF, the reconnection position switches to the northern‐dusk and southern magnetopause. Component reconnection at the southern‐dusk/northern‐dusk magnetopause is associated with the interaction of the IMF with the nearly‐dipolar background fields. Nearly‐antiparallel reconnection near the noon‐midnight plane at the northern/southern magnetopause is related to the dawn‐dusk asymmetric, helical, closed lobe magnetic fields, which is a consequence of significant planetary corotation effects and not expected at Earth. Such configuration is testable as Juno has proceeded its orbit to the high‐altitude cusps and provides new insight into the interpretation of measurements from other rotationally‐driven systems.

ObjectiveContrast-induced encephalopathy (CIE) is a rare neurological complication that can occur in the context of various endovascular procedures. Although many potential risk factors for CIE have been reported, it is still unclear whether anesthesia is a risk factor for the occurrence of CIE. The goal of this study was to investigate the incidence of CIE in patients who underwent endovascular treatment under different anesthesia methods and anesthetics administration and to explore whether general anesthesia was a potential risk factor for CIE.MethodsWe retrospectively reviewed available clinical data from 1,043 patients with neurovascular diseases undergoing endovascular treatment between June 2018 and June 2021 in our hospital. A propensity score-based matching strategy and logistic regression were used to analyze the association between anesthesia and the occurrence of CIE.ResultsIn this study, we implemented the embolization of intracranial aneurysm in 412 patients, stent implantation of extracranial artery stenosis in 346, stent implantation of intracranial artery stenosis in 187, embolization of cerebral arteriovenous malformation or dural arteriovenous fistula in 54, endovascular thrombectomy in 20, and other endovascular treatments in 24. A total of 370 patients (35.5%) received treatment under local anesthesia, while the remaining 673 (64.5%) underwent treatment under general anesthesia. In total, 14 patients were identified as CIE, resulting in a total incidence rate of 1.34%. After propensity score-based matching of anesthesia methods, the occurrence of CIE was significantly different between the general anesthesia and local anesthesia group (P = 0.007). After propensity score-based matching of CIE, the anesthesia methods were significantly different between the two groups. Pearson contingency coefficients and logistic regression showed a significant correlation between general anesthesia and the risk of CIE.ConclusionGeneral anesthesia might be a risk factor for CIE, and propofol might be associated with the increased occurrence of CIE.

OBJECTIVES The aim of this study was to evaluate the disease burden of prostate cancer (PC) and assess key influencing factors associated with the disease expenditures of PC in the United States. METHODS The total deaths, incidence, prevalence, and disability-adjusted life-years of PC were obtained from the Global Burden of Disease Study 2019. The Medical Expenditure Panel Survey was used to estimate healthcare expenditures and productivity loss and to investigate patterns of payment and use of healthcare resources in the United States. A multivariable logistic regression model was conducted to identify key factors influencing expenditures. RESULTS For patients aged 50 and older, the burden for all age groups showed a modest increase over the 6-year period. Annual medical expenditures were estimated to range from US$24.8 billion to US$39.2 billion from 2014 to 2019. The annual loss in productivity for patients was approximately US$1,200. The top 3 major components of medical costs were hospital inpatient stays, prescription medicines, and office-based visits. Medicare was the largest source of payments for survivors. In terms of drug consumption, genitourinary tract agents (57.0%) and antineoplastics (18.6%) were the main therapeutic drugs. High medical expenditures were positively associated with age (p=0.005), having private health insurance (p=0.016), more comorbidities, not currently smoking (p=0.001), and patient self-perception of fair/poor health status (p

Objective Rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone, once every 3 weeks (R-CHOP21) is commonly used in non-Hodgkin’s lymphoma (NHL), but accompanied by Pneumocystis carinii pneumonia (PCP) as a fatal treatment complication. This study aims to estimate the specific effectiveness and cost-effectiveness of PCP prophylaxis in NHL undergoing R-CHOP21.Design A two-part decision analytical model was developed. Prevention effects were determined by systemic review of PubMed, Embase, Cochrane Library and Web of Science from inception to December 2022. Studies reporting results of PCP prophylaxis were included. Enrolled studies were quality assessed with Newcastle-Ottawa Scale. Costs were derived from the Chinese official websites, and clinical outcomes and utilities were obtained from published literature. Uncertainty was evaluated through deterministic and probabilistic sensitivity analyses (DSA and PSA). Willingness-to-pay (WTP) threshold was set as US$31 315.23/quality-adjusted life year (QALY) (threefold the 2021 per capita Chinese gross domestic product).Setting Chinese healthcare system perspective.Participants NHL receiving R-CHOP21.Interventions PCP prophylaxis versus no prophylaxis.Main outcome measures Prevention effects were pooled as relative risk (RR) with 95% CI. QALYs and incremental cost-effectiveness ratio (ICER) were calculated.Results A total of four retrospective cohort studies with 1796 participants were included. PCP risk was inversely associated with prophylaxis in NHL receiving R-CHOP21 (RR 0.17; 95% CI 0.04 to 0.67; p=0.01). Compared with no prophylaxis, PCP prophylaxis would incur an additional cost of US$527.61, and 0.57 QALYs gained, which yielded an ICER of US$929.25/QALY. DSA indicated that model results were most sensitive to the risk of PCP and preventive effectiveness. In PSA, the probability that prophylaxis was cost-effective at the WTP threshold was 100%.Conclusion Prophylaxis for PCP in NHL receiving R-CHOP21 is highly effective from retrospective studies, and routine chemoprophylaxis against PCP is overwhelmingly cost-effective from Chinese healthcare system perspective. Large sample size and prospective controlled studies are warranted.

Abstract Background Low-density lipoprotein receptor-related protein 4 (LRP4) plays a critical role in the central nervous system (CNS), including hippocampal synaptic plasticity, maintenance of excitatory synaptic transmission, fear regulation, as well as long-term potentiation (LTP). Results In this study, we found that Lrp4 was highly expressed in layer II of the piriform cortex. Both body weight and brain weight decreased in Lrp4 ECD/ECD mice without TMD (Transmembrane domain) and ICD (intracellular domain) of LRP4. However, in the piriform cortical neurons of Lrp4 ECD/ECD mice, the spine density increased, and the frequency of both mEPSC (miniature excitatory postsynaptic current) and sEPSC (spontaneous excitatory postsynaptic current) was enhanced. Intriguingly, finding food in the buried food-seeking test was prolonged in both Lrp4 ECD/ECD mice and Lrp4 cKO (conditional knockout of Lrp4 in the piriform cortex) mice. Conclusions This study indicated that the full length of LRP4 in the piriform cortex was necessary for maintaining synaptic plasticity and the integrity of olfactory function.

Abstract Nitrocellulose (NC) membranes, as porous paper-like substrates with high protein-binding capabilities, are very popular in the field of point-of-care immunoassays. However, generating robust hydrophobic structures in NC membranes to fabricate microfluidic paper-based analytical devices (μPADs) remains a great challenge. At present, the main method relies on an expensive wax printer. In addition, NC membranes very easy to adhere during the printing process due to electrostatic adsorption. Herein, we developed a facile, fast and low-cost strategy to fabricate μPADs in NC membranes by screen-printing polyurethane acrylate (PUA) as a barrier material for defining flow channels and reaction zones. Moreover, hydrophobic barriers based on UV-curable PUA can resist various surfactant solutions and organic solvents that are generally used in immunoassays and biochemical reactions. To validate the feasibility of this PUA-based NC membrane for immunoassays in point-of-care testing (POCT), we further designed and assembled a rotational paper-based analytical device for implementing a multiplexed enzyme-linked immunosorbent assay (ELISA) in a simple manner. Using the proposed device under the optimal conditions, alpha fetoprotein (AFP) and carcinoembryonic antigen (CEA) could be identified, with limits of detection of 136 pg/mL and 174 pg/mL, respectively, which are below the threshold values of these two cancer biomarkers for clinical diagnosis. We believe that this reliable device provides a promising platform for the diagnosis of disease based on ELISA or other related bioassays in limited settings or remote regions.

The decomposition of hydrates can cause serious sand production and collapse problems, hindering the long-term effective production of hydrates. This study proposes a theory for framework reconstruction and reinforcement for deep-water hydrate layers based on grouting fracturing technology and chemical sand control principles. The setting liquid was injected via fracturing and grouting to form several cracks with a certain depth and width. The setting liquid remains in the fracture and solidifies to form a “reconstruction body.” Simultaneously, the setting liquid permeates and diffuses from the cracks to the surrounding hydrate layer, bonding with the sediment and forming a gradient solidification zone to achieve solidification and reinforcement of the hydrate layer. To achieve effective production of hydrates, the reconstruction body must consider internal reinforcement, sand control, and good permeability. The parameters of the reconstruction body were designed based on the geological characteristics of hydrate formation in a certain area. In order to effectively support the hydrate layer, the reconstruction body was designed with a 24 h compressive strength of at least 3.20 MPa and a long-term compressive strength of at least 17.70 MPa. To ensure that the permeability characteristics of the reconstructed body meet production needs, the permeability of the reconstructed body must be greater than that of the hydrate layer. The maximum concentrated pore size of the skeleton reconstruction body is designed to be 9 μm based on the particle characteristics of shale sand in hydrate reservoirs. This study provides a new approach to solving sand production and collapse.

The rapid development of deep learning technology provides powerful tools for the research of deepfake.Forged videos and images are more and more difficult for human eyes to distinguish between real and fake.Videos and images on the internet may have a huge negative impact on social life,such as financial fraud,the spread of fake news,and personal bullying.At present,the fake face detection technology based on deep learning has reached a high accuracy on multiple benchmark databases such as FaceForensics++,but the detection accuracy on cross-databases is much lower than accuracy on the source database,that is,it is difficult for many detection methods to generalize to different types of forgeries,or unknown types of forgeries,which also motivates more scholars to focus on generalization methods.The generalization research of face forgery detection focuses on methods based on deep learning.Firstly,the commonly used datasets including real-world datasets and multi-task datasets for forgery detection are discussed and compared.Secondly,it classifies and summarizes the generalization of video and image tampering detection from three aspects:data,features,and learning strategies.The data refers to data augmentation in deepfake detection.The features include single-domain features such as frequency domain features and multi-domain features.The learning strategies consist of transfer learning,multi-task learning,meta-learning,and incremental learning.And the advantages and shortcomings of three different types are analyzed.Finally,the future development direction and challenges of face tampering detection generalization are discussed.

Prenatal depression and preeclampsia (PE) are well-known risk factors of maternal and fetal mortality and morbidity. In recent years, there are emerging evidence suggesting that prenatal depression and PE could be environmental risk factors for several neurodevelopment disorders of offspring. Prenatal depression and PE were also found to be risk factors of each other. At present, the mechanism (s) of how prenatal depression and PE affect one another and their roles in the development of maternal and fetal adverse outcomes are uncertain. In this review, we outline the most recent clinical studies on the effects of prenatal depression and PE on the neurodevelopmental outcomes of offspring, as well as the plausible mechanism(s) of how these two maternal conditions affect each other and their roles in the neurodevelopment of offspring, including inflammation, oxidative stress, and maternal immune activation. We postulate that the overproduction of pro-inflammatory cytokines and increased cortisol levels in maternal depression can alter fetal neurodevelopment, and the autonomic nervous system dysfunction caused by maternal depression may accelerate heart rate and elevate blood pressure in mothers. Similarly, in PE, the elevated inflammation and exaggerated oxidative stress in the mothers, placenta, and fetus could negatively affect maternal depression on and impair the neurodevelopment of offspring. Further studies are needed to examine the combined effects of prenatal depression and PE on the health outcomes of mothers and offspring, to explore the mechanism of maternal depression in the development of PE and to investigate their roles in the neurodevelopment of offspring.

LY01005 is an investigational new drug product of goserelin acetate which is formulated as extended-release microspheres for intramuscular injection. To support the proposed clinical trials and marketing application of LY01005, pharmacodynamics, pharmacokinetics and toxicity studies were performed in rats. In the pharmacological study in rats, LY01005 induced an initial supra-physiological level increase of testosterone at 24 h post-dosing which then rapidly fell to castration level. The potency of LY01005 was comparable to the comparator Zoladex® but its effect lasted longer and more stable. A single-dose pharmacokinetics study in rats demonstrated that the Cmax and AUClast of LY01005 increased in a dose-proportional manner in the range of 0.45–1.80 mg/kg and the relative bioavailability was 101.0% between LY01005 and Zoladex®. In the toxicity study, almost all of the positive findings of LY01005 in rats including the changes in hormones (follicle-stimulating hormone, luteinizing hormone, testosterone, progestin) and in reproductive system (uterus, ovary, vagina, cervix uteri, mammary gland, testis, epididymis and prostate) were related to the direct pharmacological effects of goserelin. Mild histopathological changes in foreign body removal reaction induced by excipient were also observed. In conclusion, LY01005 displayed a sustained-release profile of goserelin, and exerted a continuous efficacy in vivo in animal models, which had a comparable potency but with a more sustained effect than that of Zoladex®. The safety profile of LY01005 was largely the same with Zoladex®. These results strongly support the planned LY01005 clinical trials.

Abstract Kinase fusions represent an important type of somatic alterations that promote oncogenesis and serve as diagnostic markers in lung cancer. We aimed to identify the landscape of clinically relevant kinase fusions in Chinese lung cancer and to explore rare kinase rearrangements; thus, providing valuable evidence for therapeutic decision making. We performed genomic profiling of 425 cancer-relevant genes from tumor/plasma biopsies from a total of 17,442 Chinese lung cancer patients using next generation sequencing (NGS). Patients’ clinical characteristics and treatment histories were retrospectively studied. A total of 1162 patients (6.66%; 1162/17,442) were identified as having kinase fusions, including 906 adenocarcinomas (ADCs) and 35 squamous cell carcinomas (SCCs). In ADC, 170 unique gene fusion pairs were observed, including rare kinase fusions, SLC12A2-ROS1, NCOA4-RET, and ANK3-RET. As for SCC, 15 unique gene fusions were identified, among which the most frequent were EML4-ALK and FGFR3-TACC3. Analyses of oncogenic mutations revealed a dual role for the gene fusions, CCDC6-RET and FGFR3-TACC3, in driving oncogenesis or serving as acquired resistance mechanisms to kinase inhibitors. In addition, our real-world evidence showed that patients with recurrent kinase fusions with low frequency (two occurrences) could benefit from treatment with kinase inhibitors’ off-label use. Notably, patients with stage IV ADC who had novel RORB-ALK or AFF2-RET fusions, but no other known oncogenic driver mutations, demonstrated favorable clinical outcomes on tyrosine kinase inhibitors. Our data provide a comprehensive overview of the landscape of oncogenic kinase fusions in lung cancer, which assist in recognizing potentially druggable fusions that can be translated into therapeutic applications.