Refining the targeted population and achieving better for colorectal cancer screening.

This editorial comments on the article entitled "Stage at diagnosis of colorectal cancer through diagnostic route: Who should be screened?" by Agatsuma et al, who conducted a retrospective study aiming at clarifying the stage at colorectal cancer (CRC) diagnosis based on different diagnostic routes. We share our opinion about CRC screening programs. The current situation suggests the need for a more specific and targeted population for CRC screening.

Scale offers the possibility of identifying adherence to lifestyle interventions in patients with non-alcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder, and dietary and lifestyle interventions remain the mainstays of NAFLD therapy. Zeng et al established a prediction system to evaluate adherence to lifestyle interventions in patients with NAFLD and choose optimal management. Here, we discuss the application scenarios of the scale and the areas warranting further attention, aiming to provide a possible reference for clinical recommendations.

In vitro colon fermentation behaviors of Ca2+ cross-linked guluronic acid block from sodium alginate.

The degradation of sodium alginate by human gut microbiota was found to be retarded via calcium cross-linking in our previous study. We hypothesized that the guluronic acid block (GB) on the alginate molecule might be the key structural region affecting alginate degradation by the gut microbiota when cross-linked with calcium. This study aims to prove this hypothesis by studying the structural features of the cross-linked GB on its in vitro fecal fermentation behaviors concerning the aspects of total carbohydrate contents, monosaccharide contents, short-chain fatty acids production, calcium state variations, and structural variations. Herein, GB isolated from sodium alginate was cross-linked under ranges of molar ratios of [Ca2+]/[-COOH] that further restricted the degradation by gut microbiota similar to the cross-linked alginates. First, total carbohydrate contents, short-chain fatty acids production, monosaccharides contents, and calcium state analyses confirmed that the degradation of GB by gut microbiota was restricted by calcium cross-linking. Furthermore, the tracking analysis of structural variations during in vitro fermentation revealed that the "granules" structure could further restrict degradation by the gut microbiota, leaving more cross-linked GB fragments surviving in comparison to the "networks" structure. In addition, Bacteroides xylanisolvens showed a significant positive correlation to the "cross-linking porosity (R = 0.825, p < 0.001), which supported our previous findings on fermentation behaviors of cross-linked alginate. Together, guluronic acid blocks are the key structural regions that retard the degradation of sodium alginate by the gut microbiota when cross-linked with calcium.

Enhancement of Thermal Management Performance of Copper Foil Using Additive-Free Graphene Coating.

Advanced thermal interface materials with high thermal conductivity are crucial for addressing the heat dissipation issue in high-power, highly integrated electronic devices. One great potential way in this field is to take advantage of cooling copper foil (Cu) materials based on graphene (G). However, the current manufacturing of these cooling copper foil materials is accompanied by high cost, process complexity, and environmental problems, which limit their development and application. In this work, a simple, low-cost, environmentally friendly graphene-copper foil composite film (rGO/G-Cu) with high thermal conductivity was successfully prepared using graphene oxide directly as a dispersant and binder of graphene coating. The microstructure characterization, thermal conductivity and thermal management performance tests were carried out on the composite films. The results demonstrate that compared to pure copper foil (342.47 W·m-1·K-1) and 10% PVA/G-Cu (367.98 W·m-1·K-1) with polyvinyl alcohol as a binder, 10% rGO/G-Cu exhibits better thermal conductivity (414.56 W·m-1·K-1). The introduction of two-dimensional graphene oxide effectively enhances the adhesion between the coating and the copper foil while greatly improving its thermal conductivity. Furthermore, experimental results indicate that rGO/G-Cu exhibits excellent heat transfer performance and flexibility. This work is highly relevant to the development of economical and environmentally friendly materials with high thermal conductivity to meet the increasing demand for heat dissipation.

Inactivated cGAS-STING Signaling Facilitates Endocrine Resistance by Forming a Positive Feedback Loop with AKT Kinase in ER+HER2- Breast Cancer.

Endocrine-resistant ER+HER2- breast cancer (BC) is particularly aggressive and leads to poor clinical outcomes. Effective therapeutic strategies against endocrine-resistant BC remain elusive. Here, analysis of the RNA-sequencing data from ER+HER2- BC patients receiving neoadjuvant endocrine therapy and spatial transcriptomics analysis both show the downregulation of innate immune signaling sensing cytosolic DNA, which primarily occurs in endocrine-resistant BC cells, not immune cells. Indeed, compared with endocrine-sensitive BC cells, the activity of sensing cytosolic DNA through the cGAS-STING pathway is attenuated in endocrine-resistant BC cells. Screening of kinase inhibitor library show that this effect is mainly mediated by hyperactivation of AKT1 kinase, which binds to kinase domain of TBK1, preventing the formation of a trimeric complex TBK1/STING/IRF3. Notably, inactivation of cGAS-STING signaling forms a positive feedback loop with hyperactivated AKT1 to promote endocrine resistance, which is physiologically important and clinically relevant in patients with ER+HER2- BC. Blocking the positive feedback loop using the combination of an AKT1 inhibitor with a STING agonist results in the engagement of innate and adaptive immune signaling and impairs the growth of endocrine-resistant tumors in humanized mice models, providing a potential strategy for treating patients with endocrine-resistant BC.

Mathematical derivation and mechanism analysis of beta oscillations in a cortex-pallidum model.

In this paper, we develop a new cortex-pallidum model to study the origin mechanism of Parkinson's oscillations in the cortex. In contrast to many previous models, the globus pallidus internal (GPi) and externa (GPe) both exert direct inhibitory feedback to the cortex. Using Hopf bifurcation analysis, two new critical conditions for oscillations, which can include the self-feedback projection of GPe, are obtained. In this paper, we find that the average discharge rate (ADR) is an important marker of oscillations, which can divide Hopf bifurcations into two types that can uniformly be used to explain the oscillation mechanism. Interestingly, the ADR of the cortex first increases and then decreases with increasing coupling weights that are projected to the GPe. Regarding the Hopf bifurcation critical conditions, the quantitative relationship between the inhibitory projection and excitatory projection to the GPe is monotonically increasing; in contrast, the relationship between different coupling weights in the cortex is monotonically decreasing. In general, the oscillation amplitude is the lowest near the bifurcation points and reaches the maximum value with the evolution of oscillations. The GPe is an effective target for deep brain stimulation to alleviate oscillations in the cortex.

Group A Streptococcal meningitis in children: a short case series and systematic review.

BACKGROUND: Group A streptococcal(GAS) meningitis is a severe disease with a high case fatality rate. In the era of increasing GAS meningitis, our understanding about this disease is limited. PURPOSE: To gain a better understanding about GAS meningitis. METHODS: Five new cases with GAS meningitis were reported. GAS meningitis related literatures were searched for systematic review in PUBMED and EMBASE. Case reports and case series on paediatric cases were included. Information on demographics, risk factors, symptoms, treatments, outcomes, and emm types of GAS was summarized. RESULTS: Totally 263 cases were included. Among 100 individuals, 9.9% (8/81) had prior varicella, 11.1% (9/81) had anatomical factors, and 53.2% (42/79) had extracranial infections. Soft tissue infections were common among infants (10/29, 34.5%), while ear/sinus infections were more prevalent in children ≥ 3 years (21/42, 50.0%). The overall case fatality rate (CFR) was 16.2% (12/74). High risk of death was found in patients with shock or systemic complications, young children(< 3 years) and cases related to hematogenic spread. The predominate cause of death was shock(6/8). Among the 163 patients included in case series studies, ear/sinus infections ranged from 21.4 to 62.5%, while STSS/shock ranged from 12.5 to 35.7%, and the CFR ranged from 5.9 to 42.9%. CONCLUSIONS: A history of varicella, soft tissue infections, parameningeal infections and CSF leaks are important clinical clues to GAS in children with meningitis. Young children and hematogenic spread related cases need to be closely monitored for shock due to the high risk of death.

Fabrication and functional application of zein-based core-shell structures: A review.

Core-shell structures exhibit a number of distinct absorptive properties that make them attractive tools for use in a range of industrial contexts including pharmaceuticals, biotechnology, cosmetics, and food/agriculture. Several recent studies have focused on the development and fabrication of zein-based core-shell structures for a range of functional material deliveries. However, no recent review article has evaluated the fabrication of such core-shell structures for food-based applications. In this paper, we therefore survey current approaches to fabricating different zein-based platforms including particles, fibers, films, and hydrogels that have appeared in a variety of functionally relevant applications. In addition, we highlight certain challenges and future research directions in this field, thereby providing a novel perspective on zein-based core-shell structures.

A Double Network Composite Hydrogel with Self-Regulating Cu2+/Luteolin Release and Mechanical Modulation for Enhanced Wound Healing.

Designing adaptive and smart hydrogel wound dressings to meet specific needs across different stages of wound healing is crucial. Here, we present a composite hydrogel, GSC/PBE@Lut, that offers self-regulating release of cupric ions and luteolin and modulates mechanical properties to promote chronic wound healing. The double network hydrogel, GSC, is fabricated through photo-cross-linking of gelatin methacrylate, followed by Cu2+-alginate coordination cross-linking. On one hand, GSC allows for rapid Cu2+ release to eliminate bacteria in the acidic pH environment during inflammation and reduces the hydrogel's mechanical strength to minimize tissue trauma during early dressing changes. On the other hand, GSC enables slow Cu2+ release during the proliferation stage, promoting angiogenesis and biocompatibility. Furthermore, the inclusion of pH- and reactive oxygen species (ROS)-responsive luteolin nanoparticles (PBE@Lut) in the hydrogel matrix allows for controlled release of luteolin, offering antioxidant and anti-inflammatory effects and promoting anti-inflammatory macrophage polarization. In a murine model of Staphylococcus aureus infected wounds, GSC/PBE@Lut demonstrates exceptional therapeutic benefits in antibacterial, anti-inflammatory, angiogenic, and tissue regeneration. Overall, our results suggest that smart hydrogels with controlled bioactive agent release and mechanical modulation present a promising solution for treating chronic wounds.

Intercalating Organic Hybrid Cadmium Antimony Sulfide Nanoparticles into Graphene Oxide Nanosheets for Electrochemical Lithium Storage.

Inorganic metal sulfides have received extensive investigation as anode materials in lithium-ion batteries (LIBs). However, applications of crystalline organic hybrid metal sulfides as anode materials in LIBs are quite rare. In addition, combining the nanoparticles of crystalline organic hybrid metal sulfides with conductive materials is expected to enhance the electrochemical lithium storage performance. Nevertheless, due to the difficulty of harvesting the nanoparticles of crystalline organic hybrid metal sulfides, this approach has never been tried to date. Herein, nanoparticles of a crystalline organic hybrid cadmium antimony sulfide (1,4-DABH2)Cd2Sb2S6 (DCAS) were prepared by a top-down method, including the procedures of solvothermal synthesis, ball milling, and ultrasonic pulverization. Thereafter, the nanoparticles of DCAS with sizes of ∼500 nm were intercalated into graphene oxide nanosheets through a freeze-drying treatment and a DCAS@GO composite was obtained. Compared with the reported Sb2S3- and CdS-based composites, the DCAS@GO composite exhibited superior electrochemical Li+ ion storage performance, including a high capacity of 1075.6 mAh g-1 at 100 mA g-1 and exceptional rate tolerances (646.8 mAh g-1 at 5000 mA g-1). In addition, DCAS@GO can provide a high capacity of 705.6 mAh g-1 after 500 cycles at 1000 mA g-1. Our research offers a viable approach for preparing the nanoparticles of crystalline organic hybrid metal sulfides and proves that intercalating organic hybrid metal sulfide nanoparticles into GO nanosheets can efficiently boost the electrochemical Li+ ion storage performance.

Bile metabolic fingerprints distinguish biliary tract cancer from benign biliary diseases.

BACKGROUND AND AIMS: Biliary tract cancers are aggressive gastrointestinal malignancies characterized by a dismal 5-year overall survival rate <20%. Current diagnostic modalities suffer from limitations regarding sensitivity and specificity. This study aimed to develop a bile metabolite-based platform for precise discrimination between malignant and benign biliary diseases. APPROACH AND RESULTS: Samples were collected from 336 patients with biliary tract cancer or benign biliary diseases across 3 independent cohorts. Untargeted metabolic fingerprinting was performed on 300 bile samples using novel nanoparticle-enhanced laser desorption/ionization mass spectrometry. Subsequently, a diagnostic assay was developed based on the exploratory cohort using a selected bile metabolic biomarker panel, with performance evaluated in the validation cohort. Further external validation of disease-specific metabolites from bile samples was conducted in a prospective cohort (n = 36) using quantitative analysis. As a result, we established a novel bile-based assay, BileMet, for the rapid and precise detection of malignancies in the biliary tract system with an AUC of 0.891. We identified 6-metabolite biomarker candidates and discovered the critical role of the chenodeoxycholic acid glycine conjugate as a protective metabolite associated with biliary tract cancer. CONCLUSIONS: Our findings confirmed the improved diagnostic capabilities of BileMet assay in a clinical setting. If applied, the BileMet assay enables intraoperative testing and fast medical decision-making for cases with suspected malignancy where brush cytology detection fails to support malignancy, ultimately reducing the economic burden by over 90%.

A Dual-Functional Integration of Photodetectors and Artificial Optoelectronic Synapses on a VO2/WO3 Heterojunction Device.

Bionic visual systems require multimodal integration of eye-like photodetectors and brain-like image memory. However, the integration of photodetectors (PDs) and artificial optoelectronic synapses devices (OESDs) by one device remains a giant challenge due to their photoresponse discrepancy. Herein, a dual-functional integration of PDs and OESDs based on VO2/WO3 heterojunctions is presented. The device can be able to realize a dual-mode conversion between PDs and OESDs through tuning the bias voltage. Under zero bias voltage, the device exhibiting excellent photodetecting behaviors based on the photovoltaic effect, showing a high self-powered photoresponsivity of 18.5 mA W-1 and high detectivity of 7.5 × 1010 Jones with fast photoresponse. When the external bias voltages are applied, it can be acted as an OESD and exhibit versatile electrical and photonic synaptic characteristics based on the trapping and detrapping effects, including synaptic plasticity and learning-experience behaviors. More importantly, benefiting from the excellent photosensing ability and transporting properties, the device shows ultralow-power consumption of 39.0 pJ and a 4 × 4 OESDs array is developed to realize the visual perception and memory. This work not only supplies a novel route to realize complex functional integration just in one device, but also offers effective strategies for developing neuromorphic visual system.

Discovery and characterization of novel jeilongviruses in wild rodents from Hubei, China.

The genus Jeilongvirus comprises non-segmented negative-stranded RNA viruses that are classified within the Paramyxoviridae family by phylogeny. Jeilongviruses are found in various reservoirs, including rodents and bats. Rodents are typical viral reservoirs with diverse spectra and zoonotic potential. Little is currently known about jeilongviruses in rodents from central China. The study utilized high-throughput and Sanger sequencing to obtain jeilongvirus genomes, including those of two novel strains (HBJZ120/CHN/2021 (17,468 nt) and HBJZ157/CHN/2021 (19,143 nt)) and three known viruses (HBXN18/CHN/2021 (19,212 nt), HBJZ10/CHN/2021 (19,700 nt), HBJM106/CHN/2021 (18,871 nt)), which were characterized by genome structure, identity matrix, and phylogenetic analysis. Jeilongviruses were classified into three subclades based on their topology, phylogeny, and hosts. Based on the amino acid sequence identities and phylogenetic analysis of the L protein, HBJZ120/CHN/2021 and HBJZ157/CHN/2021 were found to be strains rather than novel species. Additionally, according to specific polymerase chain reaction screening, the positive percentage of Beilong virus in Hubei was 6.38%, suggesting that Beilong virus, belonging to the Jeilongvirus genus, is likely to be widespread in wild rodents. The identification of novel strains further elucidated the genomic diversity of jeilongviruses. Additionally, the prevalence of jeilongviruses in Hubei, China, was profiled, establishing a foundation for the surveillance and early warning of emerging paramyxoviruses.

Enhancement of Calcium Chelating Activity in Peptides from Sea Cucumber Ovum through Phosphorylation Modification.

Recently, phosphorylation has been applied to peptides to enhance their physiological activity, taking advantage of its modification benefits and the extensive study of functional peptides. In this study, water-soluble peptides (WSPs) of sea cucumber ovum were phosphorylated in order to improve the latter's calcium binding capacity and calcium absorption. Enzymatic hydrolysis methods were screened via ultraviolet-visible absorption spectroscopy (UV-Vis), the fluorescence spectrum, and calcium chelating ability. Phosphorylated water-soluble peptides (P-WSPs) were characterized via high-performance liquid chromatography, the circular dichroism spectrum, Fourier transform infrared spectroscopy (FTIR), UV-Vis spectroscopy, surface hydrophobicity, and fluorescence spectroscopy. The phosphorus content, calcium chelation rate and absorption rate were investigated. The results demonstrated that phosphorylation enhanced the calcium chelating capacity of WSPs, with the highest capacity reaching 0.96 mmol/L. Phosphate ions caused esterification events, and the carboxyl, amino, and phosphate groups of WSPs and P-WSPs interacted with calcium ions to form these bonds. Calcium-chelated phosphorylated water-soluble peptides (P-WSPs-Ca) demonstrated outstanding stability (calcium retention rates > 80%) in gastrointestinal processes. Our study indicates that these chelates have significant potential to develop into calcium supplements with superior efficacy, bioactivity, and stability.

Oxylipins and metabolites from pyroptotic cells act as promoters of tissue repair.

Pyroptosis is a lytic cell death mode that helps limit the spread of infections and is also linked to pathology in sterile inflammatory diseases and autoimmune diseases1-4. During pyroptosis, inflammasome activation and the engagement of caspase-1 lead to cell death, along with the maturation and secretion of the inflammatory cytokine interleukin-1ß (IL-1ß). The dominant effect of IL-1ß in promoting tissue inflammation has clouded the potential influence of other factors released from pyroptotic cells. Here, using a system in which macrophages are induced to undergo pyroptosis without IL-1ß or IL-1α release (denoted Pyro-1), we identify unexpected beneficial effects of the Pyro-1 secretome. First, we noted that the Pyro-1 supernatants upregulated gene signatures linked to migration, cellular proliferation and wound healing. Consistent with this gene signature, Pyro-1 supernatants boosted migration of primary fibroblasts and macrophages, and promoted faster wound closure in vitro and improved tissue repair in vivo. In mechanistic studies, lipidomics and metabolomics of the Pyro-1 supernatants identified the presence of both oxylipins and metabolites, linking them to pro-wound-healing effects. Focusing specifically on the oxylipin prostaglandin E2 (PGE2), we find that its synthesis is induced de novo during pyroptosis, downstream of caspase-1 activation and cyclooxygenase-2 activity; further, PGE2 synthesis occurs late in pyroptosis, with its release dependent on gasdermin D pores opened during pyroptosis. As for the pyroptotic metabolites, they link to immune cell infiltration into the wounds, and polarization to CD301+ macrophages. Collectively, these data advance the concept that the pyroptotic secretome possesses oxylipins and metabolites with tissue repair properties that may be harnessed therapeutically.

Cistanche deserticola polysaccharide- functionalized dendritic fibrous nano-silica -based adjuvant for H9N2 oral vaccine enhance systemic and mucosal immunity in chickens.

Avian influenza virus subtype H9N2 has the ability to infect birds and humans, further causing significant losses to the poultry industry and even posing a great threat to human health. Oral vaccine received particular interest for preventing majority infection due to its ability to elicit both mucosal and systemic immune responses, but their development is limited by the bad gastrointestinal (GI) environment, compact epithelium and mucus barrier, and the lack of effective mucosal adjuvants. Herein, we developed the dendritic fibrous nano-silica (DFNS) grafted with Cistanche deserticola polysaccharide (CDP) nanoparticles (CDP-DFNS) as an adjuvant for H9N2 vaccine. Encouragingly, CDP-DFNS facilitated the proliferation of T and B cells, and further induced the activation of T lymphocytes in vitro. Moreover, CDP-DFNS/H9N2 significantly promoted the antigen-specific antibodies levels in serum and intestinal mucosal of chickens, indicating the good ability to elicit both systemic and mucosal immunity. Additional, CDP-DFNS facilitate the activation of CD4 + and CD8 + T cells both in spleen and intestinal mucosal, and the indexes of immune organs. This study suggested that CDP-DFNS may be a new avenue for development of oral vaccine against pathogens that are transmitted via mucosal route.

TRPML1 triggers ferroptosis defense and is a potential therapeutic target in AKT-hyperactivated cancer.

Targeting ferroptosis for cancer therapy has slowed because of an incomplete understanding of ferroptosis mechanisms under specific pathological contexts such as tumorigenesis and cancer treatment. Here, we identify TRPML1-mediated lysosomal exocytosis as a potential anti-ferroptotic process through genome-wide CRISPR-Cas9 activation and kinase inhibitor library screening. AKT directly phosphorylated TRPML1 at Ser343 and inhibited K552 ubiquitination and proteasome degradation of TRPML1, thereby promoting TRPML1 binding to ARL8B to trigger lysosomal exocytosis. This boosted ferroptosis defense of AKT-hyperactivated cancer cells by reducing intracellular ferrous iron and enhancing membrane repair. Correlation analysis and functional analysis revealed that TRPML1-mediated ferroptosis resistance is a previously unrecognized feature of AKT-hyperactivated cancers and is necessary for AKT-driven tumorigenesis and cancer therapeutic resistance. TRPML1 inactivation or blockade of the interaction between TRPML1 and ARL8B inhibited AKT-driven tumorigenesis and cancer therapeutic resistance in vitro and in vivo by promoting ferroptosis. A synthetic peptide targeting TRPML1 inhibited AKT-driven tumorigenesis and enhanced the sensitivity of AKT-hyperactivated tumors to ferroptosis inducers, radiotherapy, and immunotherapy by boosting ferroptosis in vivo. Together, our findings identified TRPML1 as a therapeutic target in AKT-hyperactivated cancer.

Interfacial Protein Fibril Polymorphisms Regulate In Vivo Adipose Expansion for Control of Obesity.

Obesity is becoming a worldwide pandemic. Interfacial engineering of food lipid is expected to inhibit diet-induced obesity without damage to the eating enjoyment brought by high-fat diets. Unfortunately, this strategy has not been achieved yet. After screening different plant proteins, bromelain and papain were found to form wormlike and long-straight protein fibrils, respectively. The conversion of long-straight amyloid-like fibrils to wormlike fibrils was demonstrated in the fibrillation of bromelain. Using oil-in-water high internal phase emulsions (HIPEs) as a proof of concept, bromelain fibrils showed dramatically stronger interfacial stabilization capabilities than papain fibrils with high application potentials in the real-world formulation of high-fat food products such as mayonnaise. Compared with papain fibrils, oral administration of HIPEs stabilized by bromelain fibrils resulted in substantially higher fecal lipid contents and significantly decreased expression levels of the genes related to lipid absorption and transport in the intestine, including CD36, FATP-2, FATP-4, and APOA-4, without a difference in intervening gut microbiota. Consequently, dramatically less lipid absorption in the small intestine, markedly smaller chylomicron particles in the plasma, lower serum triglycerides, and controlled energy and lipid metabolism, as well as the inhibition of adipose expansion and overweight, were observed in the group with gavage of HIPEs stabilized by the bromelain fibrils rather than the papain fibrils. Furthermore, with the same calorie, substitution of all the fat in the standard high-fat feed of mice with the HIPEs emulsified by the bromelain fibrils showed a significantly stronger effect than the ones prepared by the papain fibrils on preventing high-fat-diet (HFD)-induced obesity including alleviation of adipose expansion and inflammation as well as fatty liver, also via inhibiting the absorption and transport of lipid in the intestine. The effect is ascribed to the suppressed lipolysis caused by a more compact and elastic interfacial layer formed by the wormlike fibrils than that of the long-straight fibrils, which are resistant to gastric environments and replacement by bile acids in digestion. Therefore, we provide an appealing and general strategy for controlling obesity by reducing the supply of free fatty acids (FAs) for absorption in the enteric lumen through protein fibril polymorphisms at the interface.