Characteristics and phytotoxicity of hydrochar-derived dissolved organic matter: Effects of feedstock type and hydrothermal temperature.

The dissolved organic matter (DOM) with high mobility and reactivity plays a crucial role in soil. In this study, the characteristics and phytotoxicity of DOM released from the hydrochars prepared from different feedstocks (cow manure, corn stalk and Myriophyllum aquaticum) under three hydrothermal carbonization (HTC) temperatures (180, 200 and 220°C) were evaluated. The results showed that the hydrochars had high dissolved organic carbon content (20.15 to 37.65 mg/g) and its content showed a gradual reduction as HTC temperature increased. Three fluorescent components including mixed substance of fulvic acid-like and humic acid-like substances (C1, 30.92%-58.32%), UVA humic acid-like substance (C2, 25.27%-29.94%) and protein-like substance (C3, 11.74%-41.92%) were identified in hydrochar DOM by excitation emission matrix spectra coupled with parallel factor analysis. High HTC temperature increased the relative proportion of aromatic substances (C1+C2) and humification degree of hydrochar DOM from cow manure, while it presented adverse effects on the hydrochar DOM from corn stalk and Myriophyllum. aquaticum. The principal component analysis suggested that feedstock type and HTC temperature posed significant effects on the characteristics of hydrochar DOM. Additionally, seed germination test of all hydrochar DOM demonstrated that the root length was reduced by 8.88%-26.43% in contrast with control, and the germination index values were 73.57%-91.12%. These findings provided new insights into the potential environmental effects for hydrochar application in soil.

Nutrition literacy level of medical personnel in tertiary hospitals: evidence from a cross-sectional study.

BACKGROUND: Nutrition literacy (NL), stemming from health literacy, profoundly influences dietary habits and chronic diseases. Despite their pivotal societal role, scant research exists on NL levels among medical personnel. This study examined NL levels among tertiary hospital medical staff in Bengbu and identified influencing factors. METHODS: Using cluster sampling, all Bengbu tertiary hospitals were selected, with 4-5 departments randomly chosen. A structured questionnaire assessed demographic characteristics, while the NL short-form scale (NL-SF12) evaluated NL. SPSS 26.0 and AMOS conducted statistical analysis, including confirmatory factor analysis and Cronbach's α for reliability. Chi-square tests and logistic regression analyzed group differences and influencing factors. RESULTS: The NL-SF12 demonstrated robust reliability and validity. Of participants, 34.22% were male and 65.78% female; 41.03% were doctors and 42.16% nurses. Overall, 45.68% exhibited high NL. Females showed higher total NL (OR = 1.47, 95% CI: 1.08-1.98), cognition (OR = 1.66, 95% CI: 1.22-2.24), skills (OR = 1.48, 95% CI: 1.09-2.00), and interactive NL (OR = 2.21, 95% CI: 1.53-3.19) than males. Those with a master's or higher had higher total NL (OR = 2.20, 95% CI: 1.33-3.65) and cognition (OR = 3.23, 95% CI: 1.94-5.37) than those with an associate degree or less. Pharmacists, inspectors, and technicians had higher total NL (OR = 1.55, 95% CI: 1.06-2.26) and functional NL (OR = 1.49, 95% CI: 1.02-2.17). Gender, education level, and career were the influencing factors of nutrition literacy among medical personnel. CONCLUSIONS: Female medical staff and those with a master's degree or higher showed higher nutrition literacy (NL), particularly in cognition and skills. Pharmacists, inspectors, and other technicians exhibited higher levels of total NL and functional NL. Gender, education level, and career were identified as significant influencing factors of nutrition literacy among medical personnel. Understanding and considering these factors are crucial for developing targeted strategies to enhance nutrition literacy among healthcare professionals. Future efforts to improve nutrition literacy through training and interventions should be tailored to the characteristics of different groups to effectively enhance the capabilities and proficiency of healthcare professionals in nutrition knowledge and practice.

On-Demand Picoliter-Level-Droplet Inkjet Printing for Micro Fabrication and Functional Applications.

With the advent of Internet of Things (IoTs) and wearable devices, manufacturing requirements have shifted toward miniaturization, flexibility, environmentalization, and customization. Inkjet printing, as a non-contact picoliter-level droplet printing technology, can achieve material deposition at the microscopic level, helping to achieve high resolution and high precision patterned design. Meanwhile, inkjet printing has the advantages of simple process, high printing efficiency, mask-free digital printing, and direct pattern deposition, and is gradually emerging as a promising technology to meet such new requirements. However, there is a long way to go in constructing functional materials and emerging devices due to the uncommercialized ink materials, complicated film-forming process, and geometrically/functionally mismatched interface, limiting film quality and device applications. Herein, recent developments in working mechanisms, functional ink systems, droplet ejection and flight process, droplet drying process, as well as emerging multifunctional and intelligence applications including optics, electronics, sensors, and energy storage and conversion devices is reviewed. Finally, it is also highlight some of the critical challenges and research opportunities. The review is anticipated to provide a systematic comprehension and valuable insights for inkjet printing, thereby facilitating the advancement of their emerging applications.

Proteomic stable isotope probing with an upgraded Sipros algorithm for improved identification and quantification of isotopically labeled proteins.

BACKGROUND: Proteomic stable isotope probing (SIP) is used in microbial ecology to trace a non-radioactive isotope from a labeled substrate into de novo synthesized proteins in specific populations that are actively assimilating and metabolizing the substrate in a complex microbial community. The Sipros algorithm is used in proteomic SIP to identify variably labeled proteins and quantify their isotopic enrichment levels (atom%) by performing enrichment-resolved database searching. RESULTS: In this study, Sipros was upgraded to improve the labeled protein identification, isotopic enrichment quantification, and database searching speed. The new Sipros 4 was compared with the existing Sipros 3, Calisp, and MetaProSIP in terms of the number of identifications and the accuracy and precision of atom% quantification on both the peptide and protein levels using standard E. coli cultures with 1.07 atom%, 2 atom%, 5 atom%, 25 atom%, 50 atom%, and 99 atom% 13C enrichment. Sipros 4 outperformed Calisp and MetaProSIP across all samples, especially in samples with ≥ 5 atom% 13C labeling. The computational speed on Sipros 4 was > 20 times higher than Sipros 3 and was on par with the overall speed of Calisp- and MetaProSIP-based pipelines. Sipros 4 also demonstrated higher sensitivity for the detection of labeled proteins in two 13C-SIP experiments on a real-world soil community. The labeled proteins were used to trace 13C from 13C-methanol and 13C-labeled plant exudates to the consuming soil microorganisms and their newly synthesized proteins. CONCLUSION: Overall, Sipros 4 improved the quality of the proteomic SIP results and reduced the computational cost of SIP database searching, which will make proteomic SIP more useful and accessible to the border community. Video Abstract.

Green transformation of oily sludge through geopolymer: Material properties and hydration mechanisms.

Oily sludge (OS) is a kind of hazardous waste generated from the petrochemical industry. Currently, pyrolysis has been widely applied for OS disposal, while low-oil content (<5 wt%) OS still lacks novel technology to achieve efficient resource utilization and harmful substances immobilization. In this study, a kind of OS-based geopolymer was developed by OS and ground granulated blast furnace slag (GGBS). The results showed that in geopolymer with 30 wt% OS, the content of total petroleum hydrocarbons (TPHs) decreased by 82%, Zn achieved 100% stabilization, and the 28 d compressive strength could still reach 32.8 MPa. The appropriate oil content filled the pores and cracks in geopolymer matrix. The constructed model compounds further elucidated the hydration mechanisms of OS-geopolymer. The nucleation effect of crude oil and micro-aggregate effect of minerals jointly improved the polymerization degree of C-(A)-S-H gels. OS promoted the transformation of [SiO4]4- monomers into C-(A)-S-H unbranched middle groups and three-dimensional networks, thereby efficiently stabilizing harmful substances. Sustainability analysis showed that OS-based geopolymer had good environmental and economic benefits. Overall, this work provides theoretical guidance for the green transformation of OS in the construction field.

Infection and chronic disease activate a systemic brain-muscle signaling axis.

Infections and neurodegenerative diseases induce neuroinflammation, but affected individuals often show nonneural symptoms including muscle pain and muscle fatigue. The molecular pathways by which neuroinflammation causes pathologies outside the central nervous system (CNS) are poorly understood. We developed multiple models to investigate the impact of CNS stressors on motor function and found that Escherichia coli infections and SARS-CoV-2 protein expression caused reactive oxygen species (ROS) to accumulate in the brain. ROS induced expression of the cytokine Unpaired 3 (Upd3) in Drosophila and its ortholog, IL-6, in mice. CNS-derived Upd3/IL-6 activated the JAK-STAT pathway in skeletal muscle, which caused muscle mitochondrial dysfunction and impaired motor function. We observed similar phenotypes after expressing toxic amyloid-ß (Aß42) in the CNS. Infection and chronic disease therefore activate a systemic brain-muscle signaling axis in which CNS-derived cytokines bypass the connectome and directly regulate muscle physiology, highlighting IL-6 as a therapeutic target to treat disease-associated muscle dysfunction.

A novel phosphotriesterase hybrid nanoflower-hydrogel sensor equipped with a smartphone detector for real-time on-site monitoring of organophosphorus pesticides.

Designing efficient and rapid methods for the detection of organophosphorus pesticides (OPs) residue is a prerequisite to mitigate their negative health impacts. In this study, we propose the concept of an enzyme catalysis system-based hydrogel kit integrated with a smartphone detector for in-field screening of OPs. Here, we rapidly prepared phosphotriesterase hybrid nanoflowers (PTE-HNFs) using a self-assembly strategy by adding external energy and embedded the nanocomposite in sodium alginate (SA) hydrogel to construct a target-responsive hydrogel kit. The color response of the kit is induced by catalyzing methyl parathion (MP) to produce p-nitrophenol. For on-site quantification, the color variations of the portable kit are converted into digital information through a smartphone, which exhibits an applicable linear range towards OPs. The hydrogel sensing platform demonstrates a wide linear range (1-150 µM) and low detection limit (0.15 µM) for MP while maintaining high reliability, excellent long-term stability, and ease of operation. Overall, the PTE-HNFs-based SA hydrogel kit provides a useful strategy for simple and sensitive detection of MP and holds great potential for applications in detecting OPs in food and environmental water.

Lack of signal peptide in insect prophenoloxidase to avoid glycosylation to damage the zymogen activity.

Insect prophenoloxidases (PPOs) are important immunity proteins for defending against the invading pathogens and parasites. As a Type-Ⅲ copper-containing proteins, unlike Homo sapiens tyrosinases, the insect PPOs and most bacterial tyrosinases contain no signal peptides for unknown reason, however they can still be released. To this end, we fused different signal peptides to Drosophila melanogaster PPOs for in vitro and in vivo expression, respectively. We demonstrate that an artificial signal peptide can help PPO secretion in vitro. The secreted PPO appeared larger than wild-type PPO on molecular weight sizes due to glycosylation when expressed in S2 cells. Two asparagine residues for potential glycosylation in PPO1 were identified when a signal peptide was fused. After purification, the glycosylated PPO1 lost zymogen activity. When PPO1 containing a signal peptide was over-expressed in Drosophila larvae, the glycosylation and secretion of PPO1 was detected in vivo. Unlike insect PPO, human tyrosinase needs a signal peptide for protein expression and maintaining enzyme activity. An artificial signal peptide fused to bacterial tyrosinase had no influence on the protein expression and enzyme activity. These Type-Ⅲ copper-containing proteins from different organisms may evolve to perform their specific functions. Intriguingly, our study revealed that the addition of calcium inhibits PPO secretion from the transiently cultured larval hindguts in vitro, indicating that the calcium concentration may regulate PPO secretion. Taken together, insect PPOs can maintain enzyme activities without any signal peptide.

Dietary Amino Acids Promote Glucagon-like Hormone Release to Generate Novel Calcium Waves in Adipose Tissues.

Nutrient sensing and the subsequent metabolic responses are fundamental functions of animals, closely linked to diseases such as type 2 diabetes and various obesity-related morbidities. Among different metabolic regulatory signals, cytosolic Ca2+ plays pivotal roles in metabolic regulation, including glycolysis, gluconeogenesis, and lipolysis. Recently, intercellular calcium waves (ICWs), the propagation of Ca2+ signaling through tissues, have been found in different systems to coordinate multicellular responses. Nevertheless, our understanding of how ICWs are modulated and operate within living organisms remains limited. In this study, we explore the real-time dynamics, both in organ culture and free-behaving animals, of ICWs in Drosophila larval and adult adipose tissues. We identified Adipokinetic hormone (AKH), the fly functional homolog of mammalian glucagon, as the key factor driving Ca2+ activities in adipose tissue. Interestingly, we found that AKH, which is released in a pulsatile manner into the circulating hemolymph from the AKH-producing neurosecretory cells (APCs) in the brain, stimulates ICWs in the larval fat by a previously unrecognized gap-junction-independent mechanism to promote lipolysis. In the adult fat body, however, gap-junction-dependent random ICWs are triggered by a presumably uniformly diffused AKH. This highlights the stage-specific interplay of hormone secretion, extracellular diffusion, and intercellular communication in the regulation of Ca2+ dynamics. Additionally, we discovered that specific dietary amino acids activate the APCs, leading to increased intracellular Ca2+ and subsequent AKH secretion. Altogether, our findings identify that dietary amino acids regulate the release of AKH peptides from the APCs, which subsequently stimulates novel gap-junction-independent ICWs in adipose tissues, thereby enhancing lipid metabolism.

A Unified Adsorption Kinetic Model Inspired by Epidemiological Model: Based on Adsorbates "Infect" Adsorbents.

Adsorption is a unit operation used in various fields, including the environmental, chemical, and pharmaceutical industries. Understanding the adsorption kinetics is crucial to designing efficient adsorption systems. However, existing empirical adsorption models are limited in providing insights into the mass transfer mechanisms. Additionally, the absence of a unified adsorption kinetic model hampers the effective comparison of different adsorption systems. Here, we viewed the adsorption as an "infectious process of adsorbates by adsorbents" akin to epidemiology. In epidemiology, individuals can be divided into susceptible, infected, and recovered compartments, ignoring the complexities of movement among individuals. Analogously, we have categorized the adsorbates as adsorbable, adsorbed, and removed compartments. Thus, we proposed a unified adsorption kinetic model (the monolayer-multilayer-adsorbable-adsorbed-removed model) that accommodates monolayer/multilayer adsorption. The model was designed to encompass diverse adsorption setups, including continuous and batch processes with fixed/dispersed adsorbents. The versatility and applicability of the model were demonstrated through validation using a diverse set of experimental data. This validation underscored its effectiveness in water/wastewater treatment, salt reduction, metal recovery, and drug purification. A MATLAB-based program for solving this model was made available to researchers for their utilization and further investigations. Overall, this study developed a versatile adsorption kinetic model that offers a comprehensive and unified understanding of adsorption kinetics across various applications.

Buck technique supplemented by temporary intersegmental pedicle screw fixation to repair lumbar spondylolysis in youth.

BACKGROUND: Lumbar spondylolysis is a bone defect in the pars interarticularis of the lumbar vertebral, which is a common cause of low back pain in youth. Although non-surgical treatment is a mainstream option, surgery is necessary for patients with persistent symptoms. Buck technique is widely used as a classical direct repair technique, but it cannot achieve reduction of low-grade spondylolisthesis and reconstruction of lumbosacral sagittal balance. We have described a novel surgical procedure based on Buck technique with temporary intersegmental pedicle screw fixation, and report a series of clinical outcomes in 5 patients to provide a reference for the clinical treatment of young lumbar spondylolysis. METHODS: Five young patients with symptomatic lumbar spondylolysis with a mean age of 19.20 ± 5.41 years underwent surgical treatment after an average of 7.60 ± 1.52 months of failure to respond to conservative treatment, using a new surgical procedure based on Buck technique combined with temporary intersegmental pedicle screw fixation. RESULTS: Five patients were successfully operated without serious complications such as nerve and vascular injury. The average operation time was 109.00 ± 7.42 min, the interpretative average blood loss was 148.00 ± 31.14 ml, and the average fusion time was 11.20 ± 1.64 months. All patients were followed up for 2 years after surgery, and the visual analogue score (VAS) of low back pain and Oswestry disability index (ODI) scores were significantly improved compared with those before surgery, and the Henderson's evaluation were rated excellent or good. After the removal of the internal fixation, it was observed that temporary intersegmental fixation could repair the isthmus, reduce lumbar spondylolisthesis, and reconstruct the sagittal balance of the lumbosacral vertebrae while preserving lumbar motion and preventing intervertebral disc degeneration. Postoperative MRI indicated the Pfirrmann classification of the affected discs: 1 case from grade III to grade II, 3 cases from grade II to grade I, and 1 case remained grade II. CONCLUSIONS: Buck technique supplemented by temporary intersegmental pedicle screw fixation is a highly applicable and effective method for the treatment of adolescent lumbar spondylolysis. The isthmic fusion is accurate, and temporary intersegmental fixation can effectively prevent disc degeneration and reconstruct the sagittal balance of lumbosacral vertebra.

Automatic Electrochemiluminescence Method for the Detection of Cancerous Exosomes Incorporating Specific Aptamer-Magnetic Beads and Signal Nanoprobes.

Exosomes, as an emerging biomarker, have exhibited remarkable promise in early cancer diagnosis. Here, a highly sensitive, selective, and automatic electrochemiluminescence (ECL) method for the detection of cancerous exosomes was developed. Specific aptamer-(EK)4 peptide-tagged magnetic beads (MBs-(EK)4-aptamer) were designed as a magnetic capture probe in which the (EK)4 peptide was used to reduce the steric binding hindrance of cancerous exosomes with a specific aptamer. One new universal ECL signal nanoprobe (CD9 Ab-PEG@SiO2ϵRu(bpy)32+) was designed and synthesized by using microporous SiO2 nanoparticles as the carrier for loading ECL reagent Ru(bpy)32+, polyethylene glycol (PEG) layer, and anticluster of differentiation 9 antibody (CD9 Ab). A "sandwich" biocomplex was formed on the surface of the magnetic capture probe after mixing the capture probe, target exosomes, and ECL signal nanoprobe, and then it was introduced into an automated ECL analyzer for rapid and automatic ECL measurement. It was found that the designed signal nanoprobe shows a 270-fold improvement in the signal-to-noise ratio than that of the ruthenium complex-labeled CD9 antibody signal probe. The relative ECL intensity was proportional to MCF-7 exosomes as a model in the range of 102 to 104 particle/µL, with a detection limit of 11 particle/µL. Furthermore, the ECL method was employed to discriminate cancerous exosomes based on fingerprint responses using the designed multiple magnetic capture probes and the universal ECL signal nanoprobe. This work demonstrates that the utilization of a designed automated ECL tactic using the MBs-(EK)4-aptamer capture probe and the CD9 Ab-PEG@SiO2ϵRu(bpy)32+ signal nanoprobe will provide a unique and robust method for the detection and discrimination of cancerous exosomes.

Improvement of gram staining effect by ethanol pretreatment and quantization of staining image by unsupervised machine learning.

In this study, we propose an Ethanol Pretreatment Gram staining method that significantly enhances the color contrast of the stain, thereby improving the accuracy of judgement, and demonstrated the effectiveness of the modification by eliminating unaided-eye observational errors with unsupervised machine learning image analysis. By comparing the traditional Gram staining method with the improved method on various bacterial samples, results showed that the improved method offers distinct color contrast. Using multimodal assessment strategies, including unaided-eye observation, manual image segmentation, and advanced unsupervised machine learning automatic image segmentation, the practicality of ethanol pretreatment on Gram staining was comprehensively validated. In our quantitative analysis, the application of the CIEDE2000, and CMC color difference standards confirmed the significant effect of the method in enhancing the discrimination of Gram staining.This study not only improved the efficacy of Gram staining, but also provided a more accurate and standardized strategy for analyzing Gram staining results, which might provide an useful analytical tool in microbiological diagnostics.

A bibliometric analysis of interstitial cells of Cajal research.

Objective: The significance of interstitial cells of Cajal (ICC) in the gastrointestinal tract has garnered increasing attention. In recent years, approximately 80 articles on ICC have been published annually in various journals. However, no bibliometric study has specifically focused on the literature related to ICC. Therefore, we conducted a comprehensive bibliometric analysis of ICC to reveal dynamic scientific developments, assisting researchers in exploring hotspots and emerging trends while gaining a global perspective. Methods: We conducted a literature search in the Web of Science Core Collection (WoSCC) from January 1, 2013, to December 31, 2023, to identify relevant literature on ICC. We employed bibliometric software, namely VOSviewer and CiteSpace, to analyze various aspects including annual publication output, collaborations, research hotspots, current status, and development trends in this domain. Results: A total of 891 English papers were published in 359 journals by 928 institutions from 57 countries/regions. According to the keyword analysis of the literature, researchers mainly focused on "c-Kit," "expression," "smooth muscle," and "nitric oxide" related to ICC over the past 11 years. However, with "SIP syncytium," "ANO1," "enteric neurons," "gastrointestinal stromal tumors (GIST)," and "functional dyspepsia (FD)," there has been a growing interest in the relationship between ANO1, SIP syncytium, and ICC, as well as the role of ICC in the treatment of GIST and FD. Conclusion: Bibliometric analysis has revealed the current status of ICC research. The association between ANO1, SIP syncytium, enteric neurons and ICC, as well as the role of ICC in the treatment of GIST versus FD has become the focus of current research. However, further research and collaboration on a global scale are still needed. Our analysis is particularly valuable to researchers in gastroenterology, oncology, and cell biology, providing insights that can guide future research directions.

USV Trajectory Tracking Control Based on Receding Horizon Reinforcement Learning.

We present a novel approach for achieving high-precision trajectory tracking control in an unmanned surface vehicle (USV) through utilization of receding horizon reinforcement learning (RHRL). The control architecture for the USV involves a composite of feedforward and feedback components. The feedforward control component is derived directly from the curvature of the reference path and the dynamic model. Feedback control is acquired through application of the RHRL algorithm, effectively addressing the problem of achieving optimal tracking control. The methodology introduced in this paper synergizes with the rolling time domain optimization mechanism, converting the perpetual time domain optimal control predicament into a succession of finite time domain control problems amenable to resolution. In contrast to Lyapunov model predictive control (LMPC) and sliding mode control (SMC), our proposed method employs the RHRL controller, which yields an explicit state feedback control law. This characteristic endows the controller with the dual capabilities of direct offline and online learning deployment. Within each prediction time domain, we employ a time-independent executive-evaluator network structure to glean insights into the optimal value function and control strategy. Furthermore, we substantiate the convergence of the RHRL algorithm in each prediction time domain through rigorous theoretical proof, with concurrent analysis to verify the stability of the closed-loop system. To conclude, USV trajectory control tests are carried out within a simulated environment.

Enhancing Escherichia coli Inactivation: Synergistic Mechanism of Ultraviolet Light and High-Voltage Electric Field.

This study investigated the bactericidal effects of ultraviolet (UV) radiation, a high-voltage electric field (HVEF), and their combination on Escherichia coli. The results indicated that UV and combined disinfection were more effective with longer exposure, leading to significant reductions in microbial activity. Specifically, the single UV disinfection alone reduced activity by 3.3 log after 5 min, while combined disinfection achieved a 4.2 log reduction. In contrast, short-term HVEF treatment did not exhibit significant bactericidal effects, only achieving a reduction of 0.17 log in 5 min. Furthermore, prolonged exposure to both UV disinfection and an HVEF was found to damage cell membranes, ultimately causing cell death, while shorter durations did not. Despite rapid cell count decreases, flow cytometry did not detect apoptotic or necrotic cells, likely due to rapid cell rupture. This study suggests that combining UV radiation and an HVEF could be a promising approach for inhibiting bacterial reproduction, with HVEF enhancing UV effects. These findings provide insights for using combined HVEF and UV disinfection in food safety and preservation.

Cholesterol neutralized vemurafenib treatment by promoting melanoma stem-like cells via its metabolite 27-hydroxycholesterol.

Vemurafenib has been used as first-line therapy for unresectable or metastatic melanoma with BRAFV600E mutation. However, overall survival is still limited due to treatment resistance after about one year. Therefore, identifying new therapeutic targets for melanoma is crucial for improving clinical outcomes. In the present study, we found that lowering intracellular cholesterol by knocking down DHCR24, the limiting synthetase, impaired tumor cell proliferation and migration and abrogated the ability to xenotransplant tumors. More importantly, administration of DHCR24 or cholesterol mediated resistance to vemurafenib and promoted the growth of melanoma spheroids. Mechanistically, we identified that 27-hydroxycholesterol (27HC), a primary metabolite of cholesterol synthesized by the enzyme cytochrome P450 27A1 (CYP27A1), reproduces the phenotypes induced by DHCR24 or cholesterol administration and activates Rap1-PI3K/AKT signaling. Accordingly, CYP27A1 is highly expressed in melanoma patients and upregulated by DHCR24 induction. Dafadine-A, a CYP27A1 inhibitor, attenuates cholesterol-induced growth of melanoma spheroids and abrogates the resistance property of vemurafenib-resistant melanoma cells. Finally, we confirmed that the effects of cholesterol on melanoma resistance require its metabolite 27HC through CYP27A1 catalysis, and that 27HC further upregulates Rap1A/Rap1B expression and increases AKT phosphorylation. Thus, our results suggest that targeting 27HC may be a useful strategy to overcome treatment resistance in metastatic melanoma.

[Identification of a novel variant in a patient with Calsequestrin 1 related myopathy].

OBJECTIVE: To explore the genetic basis of a myopathic patient with pathological characteristics including tubular aggregates and vacuoles. METHODS: Next generation sequencing was carried out for the patient, and candidate variant was verified by Sanger sequencing. RESULTS: Genetic testing revealed that the patient has harbored a heterozygous c.730G>C (p.D244H) variant of Calsequestrin 1 (CASQ1) gene. The same variant was not found in his unaffected parents. Based on guidelines from the American College of Medical Genetics and Genomics, the variant was rated as pathogenic (PS1+PM2+PP3). CONCLUSION: The novel c.730G>C (p.D244H) variant of the CASQ1 gene probably underlay the myopathy in this patient. Above finding has enriched the mutational spectrum of the CASQ1 gene.

Long-term co-circulation of multiple influenza A viruses in pigs, Guangxi, China.

Influenza A viruses (IAVs) pose a persistent potential threat to human health because of the spillover from avian and swine infections. Extensive surveillance was performed in 12 cities of Guangxi, China, during 2018 and 2023. A total of 2540 samples (including 2353 nasal swabs and 187 lung tissues) were collected from 18 pig farms with outbreaks of respiratory disease. From these, 192 IAV-positive samples and 19 genomic sequences were obtained. We found that the H1 and H3 swine influenza A viruses (swIAVs) of multiple lineages and genotypes have continued to co-circulate during that time in this region. Genomic analysis revealed the Eurasian avian-like H1N1 swIAVs (G4) still remained predominant in pig populations. Strikingly, the novel multiple H3N2 genotypes were found to have been generated through the repeated introduction of the early H3N2 North American triple reassortant viruses (TR H3N2 lineage) that emerged in USA and Canada in 1998 and 2005, respectively. Notably, when the matrix gene segment derived from the H9N2 avian influenza virus was introduced into endemic swIAVs, this produced a novel quadruple reassortant H1N2 swIAV that could pose a potential risk for zoonotic infection.

Transformer-based de novo peptide sequencing for data-independent acquisition mass spectrometry.

Tandem mass spectrometry (MS/MS) stands as the predominant high-throughput technique for comprehensively analyzing protein content within biological samples. This methodology is a cornerstone driving the advancement of proteomics. In recent years, substantial strides have been made in Data-Independent Acquisition (DIA) strategies, facilitating impartial and non-targeted fragmentation of precursor ions. The DIA-generated MS/MS spectra present a formidable obstacle due to their inherent high multiplexing nature. Each spectrum encapsulates fragmented product ions originating from multiple precursor peptides. This intricacy poses a particularly acute challenge in de novo peptide/protein sequencing, where current methods are ill-equipped to address the multiplexing conundrum. In this paper, we introduce Transformer-DIA, a deep-learning model based on transformer architecture. It deciphers peptide sequences from DIA mass spectrometry data. Our results show significant improvements over existing STOA methods, including DeepNovo-DIA and PepNet. Transformer-DIA enhances precision by 15.14% to 34.8%, recall by 11.62% to 31.94% at the amino acid level, and boosts precision by 59% to 81.36% at the peptide level. Integrating DIA data and our Transformer-DIA model holds considerable promise to uncover novel peptides and more comprehensive profiling of biological samples. Transformer-DIA is freely available under the GNU GPL license at https://github.com/Biocomputing-Research-Group/Transformer-DIA.