Retracted by the authors because the author list is incorrect. Mixed-charge polyurethane (MCPU) copolymers with tunable alkyl side chains (C1, C6, C18) and ionic-block ratios (60%, 70%) are synthesized and assembled into single-network (SN) physical hydrogels. Three different nanostructures were identified by small-angle X-ray scattering (SAXS): weakly segregated domains (C1), periodic microphase separation (C6), and microphase separation with interdigitated lamellar ordering (C18). Rheology studies provide a macroscopic relaxation timescale (τrelax) that quantifies the rate of noncovalent network rearrangement. The SN hydrogels with relatively short τrelax values (C1 and C6) exhibit thermo-optical switching, whereas C18 remains opaque. Blending the MCPU with a covalently crosslinked poly(2-hydroxyethyl methacrylate) (PHEMA) network generates double-network (DN) hydrogels that preserve the thermo-optical switching performance. Monotonic tensile toughness peaks at the intermediate side chain (C6), whereas C18 maximizes modulus, strength, and per-cycle energy dissipation. However, the cyclic durability test shows that C1 survives 50,000 cycles, and C18, which dissipates the most energy per cycle, fails after only ~637 cycles. τrelax therefore tracks both the thermo-optical switchability and the cyclic durability, providing a single kinetic parameter that links them.

Abstract Improving the quality of female Chinese mitten crabs ( Eriocheir sinensis ) has long been a core concern in aquaculture, and carotenoid-supplemented diets are commonly applied during the fattening stage. To mitigate degradation during high-temperature feed processing, β -carotene was supplemented via post-spraying at four graded levels of 0, 40, 80 and 120 mg/kg (Diet 1-Diet 4). A 60-day feeding trial was conducted on fattening female crabs to evaluate the regulatory effects of β -carotene on tissue colouration, carotenoid accumulation, antioxidant capacity and immune defence, followed by correlation analysis. The results showed that dietary β -carotene supplementation had no significant effects on crab growth performance, hepatosomatic index (HSI), and gonadosomatic index (GSI). Crabs in Diet 4 group exhibited significantly lower hepatopancreatic malondialdehyde (MDA) content and glutathione peroxidase (GSH-Px) activity, effectively improving the body antioxidant status. Increasing dietary β -carotene level significantly elevated the redness value ( ) of the carapace and ovary, as well as β -carotene content in the carapace, hepatopancreas, and ovary, with the maximum values observed in Diet 4 group. Correlation analysis revealed that hepatopancreatic total antioxidant capacity (T-AOC) was significantly positively correlated with β -carotene content, yellowness value ( ) was negatively correlated with total carotenoid content, and was negatively correlated with acid phosphatase (ACP) activity. In conclusion, post-spraying β -carotene supplementation effectively improved tissue colouration, carotenoid deposition, antioxidant and immune capability in female E. sinensis , with a supplemental β -carotene level of approximately 120 mg/kg being optimal for maintaining product quality and physiological health. These findings provide a theoretical basis and practical guidance for precise nutritional regulation and feed development for fattening female E. sinensis .

Abstract Persistent bacterial infection, oxidative stress imbalance, and cellular dysfunction within diabetic wound microenvironments represent key clinical challenges that hinder wound healing. To address these challenges, we developed a smart reactive oxygen species (ROS)-responsive bilayer thermoregulatory hydrogel, PP@PZC&SAg. The system was based on a dynamically cross-linked phenylboronate ester network. The in situ green synthesis of Ag nanoparticles endowed the hydrogel with highly efficient photothermal bactericidal capabilities, whereas the incorporated Zn/Ce layered double oxide nanozyme (PZC) mimicked catalase activity to scavenge excess ROS in the microenvironment. The top layer comprised a thermosensitive hydrogel that utilized its phase-change properties to precisely regulate photothermal temperatures, thereby effectively destroying bacterial biofilms while preventing thermal damage to surrounding tissues. The PP@PZC&SAg hydrogel system exhibited considerable photothermal activity, rapidly reaching and maintaining a stable operating temperature while simultaneously eliminating bacteria and disrupting biofilms. Furthermore, through synergistic ROS scavenging and the release of active Zn and Ce ions, this system restored endothelial cell proliferation, migration, and tubulogenic capacity, which are typically impaired under high-glucose conditions, ultimately promoting rapid diabetic wound healing. This approach simultaneously combats bacterial infections, alleviates oxidative stress, and restores cellular function, thereby offering a novel, multifaceted, and targeted therapeutic strategy for treating diabetic wounds.

Chronic infectious wounds in diabetic patients remain a significant clinical challenge due to persistent inflammation, oxidative stress, and bacterial resistance issues. This problem is particularly acute in the area of postoperative surgical incisions, where impaired healing can lead to serious complications. This study aimed to develop a self-healing cascade-catalyzed hydrogel, CS-PBA/ODex@NRGe-Mn (CPONM), featuring borate and Schiff base bonds. This hydrogel exhibits a dual dynamic network structure and incorporates naringenin-Mn nanoparticles (NM NPs) with SOD/POD-like activity. The hydrogel was synthesized by mixing CS-PBA solution with ODex solution containing NM NPs. CPONM exhibits high porosity, swelling capacity, adhesion strength (13.43 kPa), and pH-responsive release properties. In vitro studies demonstrated that CPONM effectively inhibited the growth of Escherichia coli (E.coli, 93.15%) and methicillin-resistant Staphylococcus aureus (MRSA, 94.74%), disrupted bacterial biofilms by up to 92%, and reduced iNOS and IL-6 expression in macrophages. In a diabetic mouse wound model infected with MRSA, CPONM accelerated wound healing (reaching 97.47% by day 18), reduced bacterial infection risk, inhibited NF-κB, and activated Nrf2. Histopathological staining revealed the hydrogel's ability to promote wound epithelialization, collagen deposition, and vascular growth (VEGF, α-SMA). Therefore, CPONM represents a promising approach for treating infected postoperative wounds in diabetic patients.

The undesired adhesion between the dura mater and surrounding tissues is a great challenge in the clinical treatment of spinal stenosis and disc herniation, and this condition can typically lead to failed back surgery syndrome (FBSS) and persistent or recurrent lumbosacral pain or sciatica. Here, a protein-based supramolecular adhesive featured with wet adhesion and on-demand anti-adhesion via non-covalent interactions between anionic glycyrrhizic acid (GA) nanofibers and N-alpha-lauroyl-arginine ethyl ester hydrochloride (LAE) dispersed zein colloid (zein-LAE). By controlling the crosslinking density of the zein-LAE/GA supramolecular polymers, the adhesion and anti-adhesion could be conveniently regulated. In detail, suitable amount of GA improved the adhesion strength of the zein-LAE/GA supramolecular adhesives, whereas excessive GA caused the surface curing and anti-adhesion. It was proposed that the anti-adhesion outcome was attributed to the enhanced cross-linking density and Young's modulus of the supramolecular polymers, and the declined freedom of the binding groups. The excellent biocompatibility and biodegradation enabled the zein-LAE/GA supramolecular polymers to function as easy-to-implement Janus implants for the in vivo prevention of postoperative epidural adhesion in a rat model. In conclusion, the physical barrier of the Janus implant together with the anti-oxidation and antiinflammatory effects of the GA component played a synergistic role in achieving epidural anti-adhesion.

Surgical adhesives with rapid and tough adhesion under wet or aqueous conditions are highly desirable for artery hemostasis yet still extremely challenging. We here explored a kind of protein powder featured with hydration-driven adhesiveness self-reinforcement in water. The protein powder, consisting of corn-derived protein (zein), sodium dodecyl sulfate (SDS), and poly-lysine (PLL), was conveniently produced via sandcastle worm-inspired multivalent ionic crosslinking between zein/SDS colloid and PLL, which showed rapidly water-contacting gelation and tough adhesion on wet surfaces. We revealed that the interfacial water removal and bulk heterogeneity of the hydrated zein/SDS-PLL powder synergistically improved both the interfacial adhesion and the bulk cohesion, resulting in tough wet adhesion within 2 min. The rapid interfacial adhesion of the zein/SDS-PLL powder is attributed to the highly hydrated propensity of the ionic complex and self-gelation via interfacial water removal, while the bulk heterogeneity resulted from the incompletely hydrated ionic domains, which functioned as rigid fillers to improve the cross-density and bulk cohesion of the hydrated adhesive matrix. This bulk heterogeneity mechanism fulfills the existing knowledge gap of adhesiveness enhancement of the hydrated powdery adhesives. The hydrated zein/SDS-PLL powdery adhesive with excellent biocompatibility and biodegradation can resist high bursting pressure (118.2-129.4 mmHg), which can achieve rapid and reliable artery hemostasis on rat, rabbit and pig models.

[This corrects the article DOI: 10.3389/fphar.2025.1619687.].

The supramolecular chemistry of small chiral molecules has attracted widespread attention owing to their similarity to natural assembly codes. Two-component low-molecular-weight (LMW) hydrogels are crucial as they form helical structures via chirality transfer, enabling diverse functions. Herein, we report a pair of two-component chiral LMW hydrogels based on the small molecular drugs baicalin (BA), scutellarin (SCU) and berberine (BBR). The two hydrogels exhibited different helicities and abilities to adhere to methicillin-resistant staphylococcus aureus (MRSA) biofilms. The BA or SCU can each laterally interact with BBR in a tail-to-tail configuration, forming a stable hydrophobic structure, while hydrophilic glucuronide groups are exposed to a water solution to form a hydrogel. However, the tiny variant steric hindrance of the terminal OH moiety of SCU affects pi-pi stacking in the layered assembly, resulting in SCU-BBR having much stronger chirality deviation and supramolecular chirality amplification than BA-BBR. Thereafter, the OH group in SCU-BBR forms more intermolecular hydrogen bonds with MRSA biofilms, enhancing stronger adhesion and better scavenging effects than BA-BBR. This work provides a unique chiral supramolecular assembly pattern, expands the antibacterial application prospect of a two-component LMW hydrogel accompanying chirality amplification, and provides a new perspective and strategy for biofilm removal.

Background: Individuals with atrial fibrillation (AF) are more likely to develop mild cognitive impairment (MCI), but the underlying mechanisms remain unclear. The study aimed to investigate cognitive-related gray matter (GM) volume alterations in stroke-free individuals with AF using voxel-based morphometry (VBM). Methods: 3D-T1-weighted magnetic resonance imaging (MRI) scans were obtained from 40 stroke-free AF individuals with MCI (AF-MCI), 40 stroke-free AF individuals with normal cognition (AF-NC), and 40 healthy controls (HCs). GM atrophy was assessed using VBM. Results: The results revealed widespread GM atrophy in stroke-free individuals with AF, regardless of their cognitive status, with more pronounced GM loss in the AF-MCI group. Significant GM volume reductions were found in several brain regions, including the temporal lobe, parahippocampal gyrus (PHG), cerebellum, and frontal lobe, in the AF-MCI group. Notable reductions in the left PHG and right inferior parietal lobule were observed in the AF-MCI group compared with the AF-NC group. Moreover, decreased GM volume in the left PHG, right superior temporal pole, and right orbital part of the inferior frontal gyrus was positively correlated with cognitive performance. Conclusions: Among AF individuals free of stroke, degeneration of the PHG correlates with a greater probability of developing MCI. Structural alterations in the brain may be related to the transition from normal cognition to MCI in stroke-free individuals with AF. This study highlights the potential for targeted interventions aimed at slowing cognitive decline in stroke-free AF individuals by focusing on these structural alterations.

Background and Aims:Hepatitis B virus (HBV) infection contributes to hepatocellular carcinoma (HCC) tumorigenesis, drug resistance, and recurrence, although the underlying molecular mechanisms remain unclear. Recent studies suggest that HBV infection may be associated with liver cancer stem cells (LCSCs), but the exact mechanisms are yet to be resolved. In this study, we aimed to analyze the role of HBV infection in regulating the stemness of HCCs, which is closely linked to drug resistance. Methods:Sphere formation assay and real-time Polymerase Chain Reaction quantification were used to isolate and confirm liver cancer stem cells. The inhibitory concentration values of sorafenib and regorafenib were calculated and compared using the Cell Counting Kit-8 assay. HBV infection was used to assess the effect of HBV replication on LCSC markers. Co-immunoprecipitation assay was performed to detect the interaction between CD133 and SRC. Furthermore, we utilized the CRISPR-Cas9 system to knockout CD133 expression in HepG2.2.15 cells. Results:LCSCs derived from HCCs exhibited high expression of stem cell markers and demonstrated reduced sensitivity to sorafenib and regorafenib. HBV replication promoted both drug resistance and stemness in hepatoma cells and clinical samples. Overexpression of HBx protein in HepG2 cells upregulated the expression of CD133, EpCAM, and CD24, enhancing resistance to sorafenib and regorafenib. Knockout of CD133 expression using the CRISPR-Cas9 system significantly inhibited drug resistance to both sorafenib and regorafenib in HepG2.2.15 cells. Mechanistically, HBV replication promoted CD133 expression, which in turn interacted with the SRC/STAT3 signaling pathway. Conclusions:Our data suggest that HBV replication enhances the stemness and drug resistance of HCC, providing a strong theoretical foundation for the development of targeted and efficient treatments for HBV-infected HCCs.

In this study, a patient with lung adenocarcinoma harboring an EGFR mutation exhibited primary resistance to the targeted EGFR inhibitor Osimertinib after 2 months of treatment. As the disease advanced, further genetic analysis revealed the emergence of additional mutations in ARID1A, NTRK1, and ZRSR2, alongside the existing EGFR mutation. Subsequent treatment with Pemetrexed resulted in a significant reduction in liver metastases. Protein mass spectrometry sequencing and immunohistochemical analysis collectively indicated that the PI3K/mTOR pathway mediates the mechanism through which these gene mutations confer primary drug resistance. Evidence demonstrates that the co-occurrence of EGFR and ARID1A mutations diminishes the efficacy of EGFR tyrosine kinase inhibitors (EGFR TKIs). Consequently, it is hypothesized that mutations in NTRK1 and ZRSR2, which are implicated in the PI3K/mTOR pathway, contribute to the primary resistance observed with Osimertinib treatment. In this case, the illness was effectively managed through prompt adjustments to the treatment regimen and the rapid administration of chemotherapy drugs. This finding also constitutes the first evidence that mutations in NTRK1 and ZRSR2 are pivotal in the development of primary resistance to Osimertinib. Consequently, it is imperative to conduct genetic testing at the earliest opportunity and modify the treatment plan accordingly.

OBJECTIVE:To investigate the efficacy and potential mechanisms of MGFKP on rabbit atherosclerotic models. METHODS:The left carotid balloon injury surgery were used to establish the rabbit atherosclerotic model, followed by the administration of MGFKP from the second postoperative for 6 weeks. Left carotid ultrasound and histological analysis were determined to evaluate the anti-atherosclerotic efficacy of MGFKP. Additionally, LC-MS and network pharmacology were conducted to identify the active ingredients of MGFKP and their targets, respectively. Lastly, core targets were selected to validate using immunohistochemical staining, western blot or ELISA. RESULTS:The results revealed that the vascular diameters difference, plaque area, plaque thickness, and ratio of vessel lumen to vessel cross-section radius were significantly improved following treatment with MGFKP (P<0.05). 539 ingredients of MGFKP were identified by LC-MS, and 23 ingredients were screened using SwissADME for network pharmacology. After combining the results of PPI and KEGG analyses with published literature, TLR4, NF-κB, IL-1β, and TNF-α were selected for the ensuing analyses. Molecular docking of most compounds showed satisfactory docking energy between TLR4, NF-κB, IL-1β, and TNF-α with their matched compounds. Finally, immunohistochemical analysis of TLR4 and western blot results of NF-κB, TNF-α, and IL-1β demonstrated that these proteins levels were obviously increased in the model group and significantly decreased in MGFKP group (P<0.05). The levels of TNF-α, IL-6, IL-1β were also significantly reduced following MGFKP treatment. CONCLUSIONS:MGFKP is a potential drug for the treatment of atherosclerosis, and might suppress the TLR4/NF-κB inflammatory pathway to alleviate atherosclerotic plaque progression.

The Simoa platform is recognized as a highly sensitive tool for detecting blood-based biomarkers of Alzheimer's disease (AD). It is extensively utilized in the diagnosis and identification of AD, with accuracy emerging as a pivotal metric for assessing assay performance, gradually gaining acceptance and application. The primary objective of this study was to assess the diagnostic efficacy of multiple biomarkers in AD using the Simoa platform. The ultimate goal was to identify the optimal diagnostic biomarkers and further investigate their practical application value in the Chinese population. The study comprised two cohorts: cohort I consisted of 151 healthy controls and 90 AD patients, while cohort II was sourced from a Chinese population cohort, encompassing 123 healthy controls and 126 AD patients, utilizing publicly available data. All patients underwent plasma biomarker concentration measurements using the Simoa platform. The specificity, sensitivity, and accuracy of these biomarkers for AD diagnosis were compared to evaluate their diagnostic efficacy. The findings revealed that plasma P-tau217 exhibited excellent performance in differentiating AD from healthy controls, with a sensitivity of 95.0%, specificity of 96.0%, and accuracy of 95.7% for AD diagnosis. Conversely, other indicators, including Aβ42, Aβ42/40, T-tau/Aβ42, and P-tau181, demonstrated some diagnostic efficacy but fell short of meeting the diagnostic criteria. P-tau217 stands out as a highly effective biomarker for the diagnosis of AD, exhibiting extensive clinical application potential in the Chinese population. It presents a promising array of clinical prospects for the Chinese population. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement All authors acknowledge funding from Tianjin Science and Technology Leading Cultivation Enterprise Project (22YDPYSY0020). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Medical Research Ethics Committee of the General Hospital of Tianjin Medical University gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

Although numerous studies have emphasized the male predominance in autism spectrum disorder (ASD), how sex differences are related to the topological organization of functional networks remains unclear. This study utilized imaging data from 86 ASD (43 females, aged 7-18 years) and 86 typically developing controls (TCs) (43 females, aged 7-18 years) obtained from Autism Brain Imaging Data Exchange databases, constructed individual whole-brain functional networks, used a graph theory analysis to compute topological metrics, and assessed sex-related differences in topological metrics using a 2 × 2 factorial design. At the global level, females with ASD exhibited significantly higher cluster coefficient and local efficiency than female TCs, while no significant difference was observed between males with ASD and male TCs. Meanwhile, the neurotypical sex differences in cluster coefficient and local efficiency observed in TCs were not present in ASD. At the nodal level, ASD exhibited abnormal nodal centrality in the left middle temporal gyrus.

Emerging research suggests a potential association of progression of Alzheimer's disease (AD) with alterations in synaptic currents and mitochondrial dynamics. However, the specific associations between these pathological changes remain unclear. In this study, we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro models. The investigations included behavioural tests, brain magnetic resonance imaging (MRI), liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) analysis, Nissl staining, thioflavin-S staining, enzyme-linked immunosorbent assay, Golgi-Cox staining, transmission electron microscopy (TEM), immunofluorescence staining, proteomics, adenosine triphosphate (ATP) detection, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) assessment, mitochondrial morphology analysis, electrophysiological studies, western blotting, and molecular docking. The results revealed changes in synaptic currents, mitophagy, and mitochondrial dynamics in the AD models. Remarkably, intervention with Dengzhan Shengmai (DZSM) capsules emerged as a pivotal element in this investigation. Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention, which notably amplified the frequency and amplitude of synaptic transmission. The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions, including the hippocampal CA3, primary cingular cortex, prelimbic system, and dysgranular insular cortex. DZSM intervention led to increased IDE levels, augmented LTP amplitude, and enhanced dendritic spine density and length. Moreover, DZSM intervention led to favourable changes in mitochondrial parameters, including ROS expression, MMP and ATP contents, and mitochondrial morphology. In conclusion, our findings delved into the realm of altered synaptic currents, mitophagy, and mitochondrial dynamics in AD, concurrently highlighting the therapeutic potential of DZSM intervention.

Objective To establish a progressive research strategy for “colonic components analysis - efficacy verification and mechanism exploration - gut microbiota”, screen pharmacodynamic substances, and investigate their mechanism via gut microbiota. Methods The pharmacodynamics of Gegen Qinlian decoction (GQD) were assessed using a mouse model of dextran sulfate sodium-induced ulcerative colitis (UC). Ultra-performance liquid chromatography-quadrupole-orbitrap mass spectrometer was used to identify the prototype and metabolic components of GQD in the colon during UC. To analyze the structure and function of characteristic genera of GQD and its active components, 16S rRNA sequencing was performed. Results We identified 67 prototypic and 14 metabolic components of GQD in the UC colon. The primary prototype components are flavonoids and alkaloids, including puerarin (PUE), baicalin (BAI), and berberine (BER). The metabolism was predominantly sulfonation. Efficacy verification showed that the main active components, puerarin, baicalin, and berberine, had good therapeutic effects on UC. The results of 16S rRNA gene sequencing showed that GQD improved UC by regulating the structure and function of the gut microbiota. The abundance of gut microbiota involved in the metabolism of the prototype components was influenced by the corresponding components. The function prediction results showed that PUE was the most comparable to GQD, with 24 consistent pathways. BAI and BER showed comparable gut microbiota regulation pathways. Characteristic pathways of BER include glucometabolic processes. Conclusion This study focused on the key issues in the gut microbiota pathway and developed a progressive research strategy to understand the transformation mechanisms of colonic components. This research systematically analyzed the active components and metabolic transformation of GQD in the colon during the pathological state of UC, as well as changes in the structure and function of the gut microbiota, clarified the mechanism of GQD and its active components in improving UC via the gut microbiota pathway.

IntroductionThe Xihuang Pill (XHP), a venerated traditional Chinese medicine, has demonstrated significant anti-cancer capabilities. Despite its proven efficacy, the scarcity of comprehensive pharmacological studies limits the widespread application of XHP. This research endeavor seeks to demystify the therapeutic underpinnings of XHP, particularly in the realm of colorectal cancer (CRC) therapy.MethodsIn this study, mice harboring CT26 tumors were divided into four groups, each administered with either XHP monotherapy, 5-fluorouracil (5-FU), or a combination of both. The tumor growth trajectory was closely monitored to evaluate the effectiveness of these anti-neoplastic interventions. Advanced techniques, including 16S-rDNA gene sequencing and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), were harnessed to scrutinize the gut microbiota and serum metabolite profiles. Immunohistochemical assays were employed to gauge the expression levels of CD4, CD8, and Foxp3, thereby providing insights into the dynamics of tumor-infiltrating lymphocytes within the tumor microenvironment.ResultsOur findings indicate that XHP effectively suppresses the initiation and progression of colorectal tumors. The combinatorial therapy of XHP with 5-FU exhibited an enhanced inhibitory effect on tumor growth. Metabolic profiling revealed that XHP induced notable metabolic shifts, particularly impacting pathways such as steroid hormone synthesis, arachidonic acid metabolism, purine biosynthesis, and renin secretion. Notably, 17α-ethinyl estradiol and α-ergocryptine were identified as serum metabolites with the most substantial increase following XHP administration. Analysis of the gut microbiome suggested that XHP promoted the expansion of specific bacterial taxa, including Lachnospiraceae_NK4A136_group, Clostridiales, Desulfovibrionaceae, and Anaerotignum_sp., while suppressing the proliferation of others such as Ligilactobacilus, Lactobacillus_taiwanensis, and Candidatus_saccharimonas. Immunohistochemical staining indicated an upregulation of CD4 and CD8 post-XHP treatment.ConclusionThis study delineates a potential mechanism by which XHP inhibits CRC tumorigenesis through modulating the gut microbiota, serum metabolites, and reshaping the tumor immune microenvironment in a murine CRC model. These findings contribute to a more profound understanding and potentially broaden the clinical utility of XHP in oncology.

Background:Trousseau syndrome (TS) is a thromboembolic event in cancer patients caused by abnormalities in coagulation and fibrinolytic mechanisms. Acute multiple cerebral infarction (AMCI) is a rare form of TS. This study aimed to discuss the differentiation of clinical and radiographic characteristics between TS and cardiogenic embolism (CE) with AMCI as the main manifestation.Methods:We retrospectively analyzed 69 patients with TS-AMCI and 105 patients with CE-AMCI who were treated at Shandong Provincial Hospital between August 2018 and October 2022. The clinical baseline data, laboratory indices, and imaging characteristics of the two groups were compared. A logistic regression was used to analyze the risk factors of TS-AMCI, and receiver operating characteristic (ROC) curves were used to analyze the predictive value of the risk factors.Results:In relation to the clinical data, there were statistically significant differences between the two groups of patients in terms of the lipid and coagulation indices. D-dimer [odds ratio (OR) =4.459, 95% confidence interval (CI): 1.871-10.625; P=0.001] and triglyceride (OR =6.001, 95% CI: 2.375-15.165; P<0.001) were independent risk factors for TS-AMCI. In relation to the radiographic characteristics, the infarctions in the TS-AMCI group were widely distributed in multiple arterial supply areas [23 (33.3%) vs. 10 (9.5%); P<0.001]. More importantly, bilateral anterior + posterior circulation was also an independent risk factor for TS-AMCI (OR =15.005, 95% CI: 1.757-128.17; P=0.013).Conclusions:Unexplained AMCI in the cancer-prone age group, abnormalities in the lipid and D-dimer levels, and infarction foci involving multiple arterial blood supply areas suggested a high probability of TS.

70 % of the ulcerative colitis (UC) linked gene loci are associated with other autoimmune or immunodeficient diseases. The phosphatase activity of PTPN22 can regulate the development of T cells and contribute to regulate the level of inflammation in autoimmune diseases. We produced PTPN22-CS thymus-specific transgenic mice, which suppressed PTPN22 enzyme activity in the thymocytes. Overexpressed PTPN22-CS facilitated the development of the thymocytes towards CD4+T cells and resulted in an increased proportion of the Th1 and Treg cells in the UC mesenteric lymph nodes. PTPN22-CS promoted the activation of the JAK/STAT signaling pathway in the Th1 and Treg cells that localized in the colon, resulting in an excessive production of inflammatory mediators such as IL-2 and IFN-γ. Consequently, PTPN22-CS contributes to the inflammatory response of ulcerative colitis. In summary, the tyrosine phosphatase activity of PTPN22 plays a role in modulating UC by regulating T cell differentiation and modulating the JAK/STAT signaling pathway, thereby influencing the inflammatory response in colonic. These findings provide new insight into the association between PTPN22 and the pathogenesis of UC.