Development of a live attenuated vaccine candidate for equid alphaherpesvirus 1 control: a step towards efficient protection.

Equid alphaherpesvirus 1 (EqAHV1) is a viral pathogen known to cause respiratory disease, neurologic syndromes, and abortion storms in horses. Currently, there are no vaccines that provide complete protection against EqAHV1. Marker vaccines and the differentiation of infected and vaccinated animals (DIVA) strategy are effective for preventing and controlling outbreaks but have not been used for the prevention of EqAHV1 infection. Glycoprotein 2 (gp2), located on the envelope of viruses (EqAHV1), exhibits high antigenicity and functions as a molecular marker for DIVA. In this study, a series of EqAHV1 mutants with deletion of gp2 along with other virulence genes (TK, UL24/TK, gI/gE) were engineered. The mutant viruses were studied in vitro and then in an in vivo experiment using Golden Syrian hamsters to assess the extent of viral attenuation and the immune response elicited by the mutant viruses in comparison to the wild-type (WT) virus. Compared with the WT strain, the YM2019 Δgp2, ΔTK/gp2, and ΔUL24/TK/gp2 strains exhibited reduced growth in RK-13 cells, while the ΔgI/gE/gp2 strain exhibited significantly impaired proliferation. The YM2019 Δgp2 strain induced clinical signs and mortality in hamsters. In contrast, the YM2019 ΔTK/gp2 and ΔUL24/TK/gp2 variants displayed diminished pathogenicity, causing no observable clinical signs or fatalities. Immunization with nasal vaccines containing YM2019 ΔTK/gp2 and ΔUL24/TK/gp2 elicited a robust immune response in hamsters. In particular, compared with the vaccine containing the ΔTK/gp2 strain, the vaccine containing the ΔUL24/TK/gp2 strain demonstrated enhanced immune protection upon challenge with the WT virus. Furthermore, an ELISA for gp2 was established and refined to accurately differentiate between infected and vaccinated animals. These results confirm that the ΔUL24/TK/gp2 strain is a safe and effective live attenuated vaccine candidate for controlling EqAHV1 infection.

Research advances in serum chitinase-3-like protein 1 in liver fibrosis.

While liver fibrosis remains a serious, progressive, chronic liver disease, and factors causing damage persist, liver fibrosis may develop into cirrhosis and liver cancer. However, short-term liver fibrosis is reversible. Therefore, an early diagnosis of liver fibrosis in the reversible transition phase is important for effective treatment of liver diseases. Chitinase-3-like protein 1 (CHI3L1), an inflammatory response factor that participates in various biological processes and is abundant in liver tissue, holds promise as a potential biomarker for liver diseases. Here, we aimed to review research developments regarding serum CHI3L1 in relation to the pathophysiology and diagnosis of liver fibrosis of various etiologies, providing a reference for the diagnosis, treatment, and prognosis of liver diseases.

Intraductal photothermal ablation: a noninvasive approach for early breast cancer treatment and prevention.

Background: Innovative treatment strategies for early-stage breast cancer (BC) are urgently needed. Tumors originating from mammary ductal cells present an opportunity for targeted intervention. Methods: We explored intraductal therapy via natural nipple openings as a promising non-invasive approach for early BC. Using functional Near-infrared II (NIR-II) nanomaterials, specifically NIR-IIb quantum dots conjugated with Epep polypeptide for ductal cell targeting, we conducted in situ imaging and photothermal ablation of mammary ducts. Intraductal administration was followed by stimulation with an 808 nm laser. Results: This method achieved precise ductal destruction and heightened immunological responses in the microenvironment. The technique was validated in mouse models of triple-negative BC and a rat model of ductal carcinoma in situ, demonstrating promising therapeutic potential for localized BC treatment and prevention. Conclusion: Our study demonstrated the effectiveness of NIR-II nanoprobes in guiding non-invasive photothermal ablation of mammary ducts, offering a compelling avenue for early-stage BC therapy.

Regulation of IFP in solid tumours through acoustic pressure to enhance infiltration of nanoparticles of various sizes.

Numerous nanomedicines have been developed recently that can accumulate selectively in tumours due to the enhanced permeability and retention (EPR) effect. However, the high interstitial fluid pressure (IFP) in solid tumours limits the targeted delivery of nanomedicines. We were previously able to relieve intra-tumoural IFP by low-frequency non-focused ultrasound (LFNFU) through ultrasonic targeted microbubble destruction (UTMD), improving the targeted delivery of FITC-dextran. However, the accumulation of nanoparticles of different sizes and the optimal acoustic pressure were not evaluated. In this study, we synthesised Cy5.5-conjugated mesoporous silica nanoparticles (Cy5.5-MSNs) of different sizes using a one-pot method. The Cy5.5-MSNs exhibited excellent stability and biosafety regardless of size. MCF7 tumour-bearing mice were subjected to UTMD over a range of acoustic pressures (0.5, 0.8, 1.5 and 2.0 MPa), and injected intravenously with Cy5.5-MSNs. Blood perfusion, tumour IFP and intra-tumoural accumulation of Cy5.5-MSNs were analysed. Blood perfusion and IFP initially rose, and then declined, as acoustic pressure intensified. Furthermore, UTMD significantly enhanced the accumulation of differentially sized Cy5.5-MSNs in tumour tissues compared to that of the control group, and the increase was sevenfold higher at an acoustic pressure of 1.5 MPa. Taken together, UTMD enhanced the infiltration and accumulation of Cy5.5-MSNs of different sizes in solid tumours by reducing intra-tumour IFP.

PET/CT deep learning prognosis for treatment decision support in esophageal squamous cell carcinoma.

OBJECTIVES: The clinical decision-making regarding choosing surgery alone (SA) or surgery followed by postoperative adjuvant chemotherapy (SPOCT) in esophageal squamous cell carcinoma (ESCC) remains controversial. We aim to propose a pre-therapy PET/CT image-based deep learning approach to improve the survival benefit and clinical management of ESCC patients. METHODS: This retrospective multicenter study included 837 ESCC patients from three institutions. Prognostic biomarkers integrating six networks were developed to build an ESCC prognosis (ESCCPro) model and predict the survival probability of ESCC patients treated with SA and SPOCT. Patients who did not undergo surgical resection were in a control group. Overall survival (OS) was the primary end-point event. The expected improvement in survival prognosis with the application of ESCCPro to assign treatment protocols was estimated by comparing the survival of patients in each subgroup. Seven clinicians with varying experience evaluated how ESCCPro performed in assisting clinical decision-making. RESULTS: In this retrospective multicenter study, patients receiving SA had a median OS 9.2 months longer than controls. No significant differences in survival were found between SA patients with predicted poor outcomes and the controls (p > 0.05). It was estimated that if ESCCPro was used to determine SA and SPOCT eligibility, the median OS in the ESCCPro-recommended SA group and SPOCT group would have been 15.3 months and 24.9 months longer, respectively. In addition, ESCCPro also significantly improved prognosis accuracy, certainty, and the efficiency of clinical experts. CONCLUSION: ESCCPro assistance improved the survival benefit of ESCC patients and the clinical decision-making among the two treatment approaches. CRITICAL RELEVANCE STATEMENT: The ESCCPro model for treatment decision-making is promising to improve overall survival in ESCC patients undergoing surgical resection and patients undergoing surgery followed by postoperative adjuvant chemotherapy. KEY POINTS: ESCC is associated with a poor prognosis and unclear ideal treatments. ESCCPro predicts the survival of patients with ESCC and the expected benefit from SA. ESCCPro improves clinicians' stratification of patients' prognoses.

MiR-1909-5p targeting GPX4 affects the progression of aortic dissection by modulating nicotine-induced ferroptosis.

OBJECTIVE: Aortic dissection (AD) is a prevalent and acute clinical catastrophe characterized by abrupt manifestation, swift progression, and elevated fatality rates. Despite smoking being a significant risk factor for AD, the precise pathological process remains elusive. This investigation endeavors to explore the mechanisms by which smoking accelerates AD through ferroptosis induction. METHODOLOGY: In this novel study, we detected considerable endothelial cell death by ferroptosis within the aortic inner lining of both human AD patients with a smoking history and murine AD models induced by ß-aminopropionitrile, angiotensin II, and nicotine. Utilizing bioinformatic approaches, we identified microRNAs regulating the expression of the ferroptosis inhibitor Glutathione peroxidase 4 (GPX4). Nicotine's impact on ferroptosis was further assessed in human umbilical vein endothelial cells (HUVECs) through modulation of miR-1909-5p. Additionally, the therapeutic potential of miR-1909-5p antagomir was evaluated in vivo in nicotine-exposed AD mice. FINDINGS: Our results indicate a predominance of ferroptosis over apoptosis, pyroptosis, and necroptosis in the aortas of AD patients who smoke. Nicotine exposure instigated ferroptosis in HUVECs, where the miR-1909-5p/GPX4 axis was implicated. Modulation of miR-1909-5p in these cells revealed its regulatory role over GPX4 levels and subsequent endothelial ferroptosis. In vivo, miR-1909-5p suppression reduced ferroptosis and mitigated AD progression in the murine model. CONCLUSIONS: Our data underscore the involvement of the miR-1909-5p/GPX4 axis in the pathogenesis of nicotine-induced endothelial ferroptosis in AD.

Effect of Perioperative Blood Transfusion on Prognosis after Radical Resection in Patients with Non-Metastatic Renal Cell Carcinoma: A Retrospective Analysis.

OBJECTIVE: Advancements in medical science have improved non-metastatic renal cell carcinoma (NM-RCC) treatment strategies, but long-term survival is influenced by various factors, including perioperative blood transfusion. This study aims to analyse prognostic factors in patients with NM-RCC after radical nephrectomy. METHODS: From January 2018 to December 2021, a total of 132 patients with NM-RCC after radical nephrectomy were studied. According to 2-year follow-up data, the patients were categorised into case (with poor outcomes, including pneumothorax, renal issues, recurrence or death) and control groups. Data on demographics, clinical characteristics and perioperative blood transfusion were collected, and key prognostic factors were identified through logistic regression. RESULTS: A total of 32 patients with poor prognosis were included in the case group, accounting for 24.24% (32/132), and 100 patients without poor prognosis were included in the control group, accounting for 75.76% (100/132). Tumour stage, tumour size and perioperative blood transfusion were all risk factors for the prognosis of patients, and odds ratio (OR) >1. The above indicators had high predictive value for the prognosis of patients after surgery. CONCLUSIONS: The prognostic factors of patients with NM-RCC after radical nephrectomy include tumour stage, tumour size and perioperative blood transfusion, and each factor had predictive value.

Effect of electroacupuncture stimulation of "Sibai"(ST2) and "Quanliao"(SI18) on excitatory neurons of sensorimotor cortex in mice. / 电针"四白"和"颧髎"æ¿€æ´»å°é¼ èº¯ä½“æ„Ÿè§‰è¿åŠ¨çš®å±‚çš„å ´å¥‹æ€§ç¥žç»å ƒ.

OBJECTIVES: To observe the activation state and neuronal types of somatosensory cortex and the primary motor cortex induced by electroacupuncture (EA) stimulation of "Sibai" (ST2) and "Quanliao" (SI18) acupoints in mice. METHODS: Male C57BL/6J mice were randomly divided into blank control and EA groups, with 6 mice in each group. Rats of the EA group received EA stimulation (2 Hz, 0.6 mA) at ST2 and SI18 for 30 minutes. Samples were collected after EA intervention, and immunofluorescence staining was performed to quantify the expression of the c-Fos gene (proportion of c-Fos positive cells) in the somatosensory cortex and primary motor cortex. The co-labelled cells of calcium/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) and gamma-aminobutyric acid (GABA) in the somatosensory cortex and primary motor cortex were observed and counted by using microscope after immunofluorescence staining. Another 10 mice were used to detect the calcium activity of excitatory neurons in the somatosensory cortex and primary motor cortex by fiber photometry. RESULTS: In comparison with the blank control group, the number of c-Fos positive cells, and the proportion of c-Fos and CaMKⅡ co-labelled cells in both the somatosensory cortex and primary motor cortex were significantly increased after EA stimulation (P<0.05). No significant changes were found in the proportion of c-Fos and GABA co-labeled cells in both the somatosensory cortex and primary motor cortex after EA. Results of fiber optic calcium imaging technology showed that the spontaneous calcium activity of excitatory neurons in both somatosensory cortex and primary motor cortex were obviously increased during EA compared with that before EA (P<0.01), and strikingly reduced after cessation of EA compared with that during EA (P<0.05). CONCLUSIONS: Under physiological conditions, EA of ST2 and SI18 can effectively activate excitatory neurons in the somatosensory cortex and primary motor cortex.

A prospective cohort-based artificial intelligence evaluation system for the protective efficacy and immune response of SARS-CoV-2 inactivated vaccines.

BACKGROUND: Novel coronaviruses constitute a significant health threat, prompting the adoption of vaccination as the primary preventive measure. However, current evaluations of immune response and vaccine efficacy are deemed inadequate. OBJECTIVES: The study sought to explore the evolving dynamics of immune response at various vaccination time points and during breakthrough infections. It aimed to elucidate the synergistic effects of epidemiological factors, humoral immunity, and cellular immunity. Additionally, regression curves were used to determine the correlation between the protective efficacy of the vaccine and the stimulated immune response. METHODS: Employing LASSO for high-dimensional data analysis, the study utilised four machine learning algorithms-logistical regression, random forest, LGBM classifier, and AdaBoost classifier-to comprehensively assess the immune response following booster vaccination. RESULTS: Neutralising antibody levels exhibited a rapid surge post-booster, escalating to 102.38 AU/mL at one week and peaking at 298.02 AU/mL at two weeks. Influential factors such as sex, age, disease history, and smoking status significantly impacted post-booster antibody levels. The study further constructed regression curves for neutralising antibodies, non-switched memory B cells, CD4+T cells, and CD8+T cells using LASSO combined with the random forest algorithm. CONCLUSION: The establishment of an artificial intelligence evaluation system emerges as pivotal for predicting breakthrough infection prognosis after the COVID-19 booster vaccination. This research underscores the intricate interplay between various components of immunity and external factors, elucidating key insights to enhance vaccine effectiveness. 3D modelling discerned distinctive interactions between humoral and cellular immunity within prognostic groups (Class 0-2). This underscores the critical role of the synergistic effect of humoral immunity, cellular immunity, and epidemiological factors in determining the protective efficacy of COVID-19 vaccines post-booster administration.

Dual contrastive learning for synthesizing unpaired fundus fluorescein angiography from retinal fundus images.

Background: Fundus fluorescein angiography (FFA) is an imaging method used to assess retinal vascular structures by injecting exogenous dye. FFA images provide complementary information to that provided by the widely used color fundus (CF) images. However, the injected dye can cause some adverse side effects, and the method is not suitable for all patients. Methods: To meet the demand for high-quality FFA images in the diagnosis of retinopathy without side effects to patients, this study proposed an unsupervised image synthesis framework based on dual contrastive learning that can synthesize FFA images from unpaired CF images by inferring the effective mappings and avoid the shortcoming of generating blurred pathological features caused by cycle-consistency in conventional approaches. By adding class activation mapping (CAM) to the adaptive layer-instance normalization (AdaLIN) function, the generated images are made more realistic. Additionally, the use of CAM improves the discriminative ability of the model. Further, the Coordinate Attention Block was used for better feature extraction, and it was compared with other attention mechanisms to demonstrate its effectiveness. The synthesized images were quantified by the Fréchet inception distance (FID), kernel inception distance (KID), and learned perceptual image patch similarity (LPIPS). Results: The extensive experimental results showed the proposed approach achieved the best results with the lowest overall average FID of 50.490, the lowest overall average KID of 0.01529, and the lowest overall average LPIPS of 0.245 among all the approaches. Conclusions: When compared with several popular image synthesis approaches, our approach not only produced higher-quality FFA images with clearer vascular structures and pathological features, but also achieved the best FID, KID, and LPIPS scores in the quantitative evaluation.

Rapid screening of the novel bioactive peptides with notable α-glucosidase inhibitory activity by UF-LC-MS/MS combined with three-AI-tool from black beans.

This work aimed to propose a rapid method to screen the bioactive peptides with anti-α-glucosidase activity instead of traditional multiple laborious purification and identification procedures. 242 peptides binding to α-glycosidase were quickly screened and identified by bio-affinity ultrafiltration combined with LC-MS/MS from the double enzymatic hydrolysate of black beans. Top three peptides with notable anti-α-glucosidase activity, NNNPFKF, RADLPGVK and FLKEAFGV were further rapidly screened and ranked by the three artificial intelligence tools (three-AI-tool) BIOPEP database, PeptideRanker and molecular docking from the 242 peptides. Their IC50 values were in order as 4.20 ± 0.11 mg/mL, 2.83 ± 0.03 mg/mL, 1.32 ± 0.09 mg/mL, which was opposite to AI ranking, for the hydrophobicity index of the peptides was not included in the screening criteria. According to the kinetics, FT-IR, CD and ITC analyses, the binding of the three peptides to α-glucosidase is a spontaneous and irreversible endothermic reaction that results from hydrogen bonds and hydrophobic interactions, which mainly changes the α-helix structure of α-glucosidase. The peptide-activity can be evaluated vividly by AFM in vitro. In vivo, the screened FLKEAFGV and RADLPGVK can lower blood sugar levels as effectively as acarbose, they are expected to be an alternative to synthetic drugs for the treatment of Type 2 diabetes.

A prognostic model for SARS-CoV-2 breakthrough infection: Analyzing a prospective cellular immunity cohort.

BACKGROUND: Following the COVID-19 pandemic, studies have identified several prevalent characteristics, especially related to lymphocyte subsets. However, limited research is available on the focus of this study, namely, the specific memory cell subsets among individuals who received COVID-19 vaccine boosters and subsequently experienced a SARS-CoV-2 breakthrough infection. METHODS: Flow cytometry (FCM) was employed to investigate the early and longitudinal pattern changes of cellular immunity in patients with SARS-CoV-2 breakthrough infections following COVID-19 vaccine boosters. XGBoost (a machine learning algorithm) was employed to analyze cellular immunity prior to SARS-CoV-2 breakthrough, aiming to establish a prognostic model for SARS-CoV-2 breakthrough infections. RESULTS: Following SARS-CoV-2 breakthrough infection, naïve T cells and TEMRA subsets increased while the percentage of TCM and TEM cells decreased. Naïve and non-switched memory B cells increased while switched and double-negative memory B cells decreased. The XGBoost model achieved an area under the curve (AUC) of 0.78, with an accuracy rate of 81.8 %, a sensitivity of 75 %, and specificity of 85.7 %. TNF-α, CD27-CD19+cells, and TEMRA subsets were identified as high predictors. An increase in TNF-α, cTfh, double-negative memory B cells, IL-6, IL-10, and IFN-γ prior to SARS-CoV-2 infection was associated with enduring clinical symptoms; conversely, an increase in CD3+ T cells, CD4+ T cells, and IL-2 was associated with clinical with non-enduring clinical symptoms. CONCLUSION: SARS-CoV-2 breakthrough infection leads to disturbances in cellular immunity. Assessing cellular immunity prior to breakthrough infection serves as a valuable prognostic tool for SARS-CoV-2 infection, which facilitates clinical decision-making.

Microwave hydrothermal sulfuric acid leaching of spent cathode carbon from aluminum electrolysis for high efficiency removal of insoluble calcium fluoride.

Toxic substances, like fluoride salts present in spent cathode carbon (SCC), have been a great risk to the environment and public health. Our approach involves alkali leaching to eliminate soluble fluoride, followed by microwave hydrothermal acid leaching to efficiently remove insoluble CaF2 from SCC. The optimized conditions, including a temperature of 353 K, a solid-liquid ratio of 1:20, and a 60-minute reaction time, resulted in an impressive 95.6 % removal of fluoride from SCC. Various characterization techniques were employed to analyze the composition, micro-morphology, and elemental content of the materials before and after the leaching process. Furthermore, critical process parameters on the leaching separation of insoluble CaF2 during microwave hydrothermal acid leaching were systematically investigated. The study removal mechanism revealed the transformation of insoluble CaF2 in the process of microwave oxidation insertion-hydrothermal acid leaching for SCC. The kinetic characteristics of the two-stage leaching process of CaF2 at different temperatures were analyzed according to the shrinkage kernel model. The results indicate that the two-stage leaching process of CaF2 is affected by mixing control and by diffusion control, severally. The expansion of the graphite flake layer of SCC through oxidative intercalation was identified as a critical process for the thorough removal of CaF2. Microwave hydrothermal acid leaching demonstrated a 17 % improvement over traditional hydrothermal acid leaching within the same reaction time, showcasing a noteworthy enhancement in fluoride removal. Consequently, the microwave oxidizing intercalation-hydrothermal acid leaching treatment of SCC, as explored in this study, offers an effective approach for achieving deep defluoridation of SCC.

Pectic oligosaccharides: enzymatic preparation, structure, bioactivities and application.

Pectic oligosaccharides have become novel bioactive components. However, the comprehensive preparation methods, structural features, bioactivities and application of them lack a systematic review. Here, we focused on the enzymatic preparation of pectic oligosaccharides, and attempted to outline relationships among the enzymolysis condition, structure, bioactivities and application of pectic oligosaccharides. Pectic oligosaccharides were characterized by the oligosaccharides with units of →4)-α-GalpA-(1→4)-α-GalpA-(1→ or →4)-α-GalpA-(1→2)-α-Rhap-(1→. Enzymatic method was the most suitable approach for pectic oligosaccharides preparation that was significantly affected by the enzyme's type, time and concentration. Besides, pectic oligosaccharides possessed various bioactivities including prebiotic, anti-glycosylation, antioxidant, anticancer and lipid metabolism-regulation activities, which were closely associated with the molecular weight, the structure of side chain and the monosaccharide composition. Especially, many pectic oligosaccharides with low molecular weight demonstrated high prebiotic activities, and those with arabinogalactan side chains exhibited strong anticancer activities. Moreover, pectic oligosaccharides have been used in food preservatives, dairy product additives and food processing aids. Nevertheless, the industrial application, novel technology exploration, and structure-bioactivity relationship of pectic oligosaccharides remain a demanding and significant task for future work.

Acidity-Triggered "Sticky Spotlight": CCK2R-Targeted TME-Sensitive NIR Fluorescent Probes for Tumor Imaging In Vivo.

Cancer which causes high mortality globally threatens public health seriously. There is an urgent need to develop tumor-specific near-infrared (NIR) imaging agents to achieve precise diagnosis and guide effective treatment. In recent years, imaging probes that respond to acidic environments such as endosomes, lysosomes, or acidic tumor microenvironments (TMEs) are being developed. However, because of their nonspecific internalization by both normal and tumor cells, resulting in a poor signal-to-noise ratio in diagnosis, these pH-sensitive probes fail to be applied to in vivo tumor imaging. To address this issue, a cholecystokinin-2 receptor (CCK2R)-targeted TME-sensitive NIR fluorescent probe R2SM was synthesized by coupling pH-sensitive heptamethine cyanine with a CCK2R ligand, minigastrin analogue 11 (MG11) for in vivo imaging, in which MG11 would target overexpressed CCK2Rs in gastrointestinal stromal tumors (GISTs). Cell uptake assay demonstrated that R2SM exhibited a high affinity for CCK2R, leading to receptor-mediated internalization and making probes finally accumulated in the lysosomes of tumor cells, which suggested in the tumor tissues, the probes were distributed in the extracellular acidic TME and intracellular lysosomes. With a pKa of 6.83, R2SM can be activated at the acidic TME (pH = 6.5-6.8) and lysosomes (pH = 4.5-5.0), exhibiting an apparent pH-dependent behavior and generating more intense fluorescence in these acidic environments. In vivo imaging showed that coupling of MG11 with a pH-sensitive NIR probe facilitated the accumulation of probe and enhanced the fluorescence in CCK2R-overexpressed HT-29 tumor cells. A high signal was observed in the tumor region within 0.5 h postinjection, indicating its potential application in intraoperative imaging. Fluorescence imaging of R2SM exhibited higher tumor-to-liver and tumor-to-kidney ratios (2.1:1 and 2.3:1, respectively), compared separately with the probes that are lipophilic, pH-insensitive, or MG11-free. In vitro and in vivo studies demonstrated that the synergistic effect of tumor targeting with pH sensitivity plays a vital role in the high signal-to-noise ratio of the NIR imaging probe. Moreover, different kinds of tumor-targeting vectors could be conjugated simultaneously with the NIR dye, which would further improve the receptor affinity and targeting efficiency.

Electro-acupuncture inhibits HDAC2 via modulating gut microbiota to ameliorate SNI-induced pain and depression-like behavior in rats.

BACKGROUND: Depression and chronic pain frequent co-occur, exacerbating each other's symptoms and hindering treatment. Emerging studies have highlighted abnormal gut microbiota in both conditions. Previous studies have demonstrated the clinical effectiveness of electro-acupuncture (EA) in managing these conditions, yet the underlying mechanisms remain elusive. METHODS: Spared nerve injury (SNI) was employed to induce chronic pain and depression-like behavior. Rats were randomly assigned to sham SNI (SS), SNI, and EA groups. SNI surgery was performed on all rats, except those in SS group, which underwent sham SNI surgery. Then EA group received 5 weeks of EA treatment. Pain and depression-like behavior were assessed through paw withdrawal threshold, sucrose-preference test, and forced swim test. Gut microbiota composition was analyzed via 16S rDNA sequencing. Brain-Derived Neurotrophic Factor (BDNF) and acetylation-related proteins in the medial prefrontal cortex (mPFC) were evaluated through enzyme-linked immunosorbent assay and western blot. RESULTS: EA treatment significantly ameliorated pain and depression-like behavior. The 16S rDNA sequencing showed EA modulated gut microbiota composition, increased short-chain fatty acids (SCFAs)-producing bacteria, including Akkermansi, Ruminococcaceae and Lachnospiraceae family, particularly Akkermansia. Furthermore, EA increased BDNF, AcH3 and decreased HDAC2 in mPFC. Notably, SCFAs-producing bacteria exhibited a negative correlation with HDAC2 levels. LIMITATIONS: This study exclusively investigated microbiota differences resulting from EA stimulation, without delving into the functional variations brought about by these microbial distinctions. CONCLUSIONS: The therapeutic effects of EA on the comorbidity of chronic pain and depression may involve the modulation of the gut microbiota, resulting in histone acetylation changes and upregulation of BDNF.

Effect of a collagen peptide-fish oil high internal phase emulsion on the printability and gelation of 3D-printed surimi gel inks.

The effect of a high internal phase emulsion (HIPE) on three-dimensional-printed surimi gel inks was studied. Increasing the concentration of collagen peptide decreased the particle size of HIPE droplets and improved the viscoelasticity and stability. For example, when the collagen peptide concentration was 5 wt%, the viscoelasticity of the HIPE was high, as indicated by the presence of small and uniform particles, which formed a monolayer in the outer layer of the oil droplets to form stable a HIPE. A HIPE was used as the filling material to fill the surimi gel network, which reduced the porosity of the network. Surimi protein and peptides have dual emulsifying effects on the stabilization of oil. After adding the emulsion, the texture, gel properties and rheological properties of the surimi were reduced, and its printing adaptability was improved. This study provides new ideas for the production of surimi and its application in 3D printing.

MyD88 signaling pathways: role in breast cancer.

MyD88 plays a central role in breast cancer, exerting a multitude of effects that carry substantial implications. Elevated MyD88 expression is closely associated with aggressive tumor characteristics, suggesting its potential as a valuable prognostic marker and therapeutic target. MyD88 exerts influence over several critical aspects of breast cancer, including metastasis, recurrence, drug resistance, and the regulation of cancer stem cell properties. Furthermore, MyD88 modulates the release of inflammatory and chemotactic factors, thereby shaping the tumor's immune microenvironment. Its role in immune response modulation underscores its potential in influencing the dynamic interplay between tumors and the immune system. MyD88 primarily exerts intricate effects on tumor progression through pathways such as Phosphoinositide 3-kinases/Protein kinase B (PI3K/Akt), Toll-like Receptor/Nuclear Factor Kappa B (TLR/NF-κB), and others. Nevertheless, in-depth research is essential to unveil the precise mechanisms underlying the diverse roles of MyD88 in breast cancer. The translation of these findings into clinical applications holds great promise for advancing precision medicine approaches for breast cancer patients, ultimately enhancing prognosis and enabling the development of more effective therapeutic strategies.

Application of Neo-Pancreaticogastrostomy in Total Laparoscopic Pancreaticoduodenectomy.

Objective: To introduce laparoscopic neo-pancreaticogastrostomy (neo-PG) and investigate its application potential in total laparoscopic pancreaticoduodenectomy (TLPD). Materials and Methods: We performed a single-center prospective single-arm trial to evaluate the feasibility and safety of neo-PG for its initial application in TLPD. The first 50 patients who were operated by a single surgeon and who underwent TLPD with neo-PG at our institution were recruited. The pre/intra/postoperation data were collected and analyzed. Results: Twenty-nine male patients and 21 female patients from May 2022 to March 2023 were included. The mean operation time was 272.60 ± 47.30 minutes. The median PG time was 16 (15, 23) minutes. Six patients had delayed gastric emptying (DGE), and all underwent standard LPD. None of the patients had Grade B/C postoperative pancreatic fistula (POPF) or postoperative hemorrhage, or underwent reoperation. The median length of post-LPD hospital stay was 6 (6, 8) days. None of the patients died within 90 days after surgery. Nineteen cases were pathologically classified as pancreatic lesion, 6 cases as bile duct lesion, 18 cases as duodenal lesion, and 7 cases as ampullary lesion. Conclusion: The laparoscopic neo-PG is a simple, safe, and feasible pancreatic anastomosis that can be applied in TLPD. Pylorus-preserving LPD may decrease DGE rate. Further studies involving more surgeons are warranted to prove that our new technique may terminate POPF in TLPD.

Predictive response and outcome of peripheral CD4+ T cell subpopulations to combined immunotherapy and chemotherapy in advanced gastric cancer patients.

BACKGROUND: The identification of predictive biomarkers for patient stratification in immunotherapy is of utmost importance, given the limited benefit observed in certain populations. However, only limited information is so far available on the association between peripheral CD4+ T cell subpopulations and immunotherapy for advanced gastric cancer. Our current report aimed to investigate the predictive value of peripheral CD4+ T cell subpopulations in advanced gastric cancer patients treated with immunotherapy. METHODS: A retrospective cohort analysis of 169 advanced gastric cancer patients treated with sintilimab combined with capecitabine and oxaliplatin in The Affiliated Xinghua People's Hospital, Medical School of Yangzhou University (Xinghua, China) between June 2019 and October 2022 was conducted. Clinical outcomes of peripheral CD4+ T cell subpopulations were analyzed by receiver operating characteristic (ROC) curve, chi-square test, Kaplan-Meier method and the univariate and multivariate Cox proportional hazards regression models. RESULTS: The optimal cutoff values for percentages of CD4+ T cells, naive CD4+ T cells (CD4+ Tn), memory CD4+ T cells (CD4+ Tm), central memory CD4+ T cells (CD4+ Tcm) and effector memory CD4+ T cells (CD4+ Tem) expressing PD-1 were 30.16 %, 17.79 %, 42.49 %, 31.54 % and 74.64 %, respectively. It was found that the percentages of CD4+ T, CD4+ Tn, CD4+ Tm, CD4+ Tcm and CD4+ Tem expressing PD-1 were significantly higher in responder (R) than non-responder (NonR) advanced gastric cancer patients associated with a longer progression free survival (PFS) and overall survival (OS). This correlation was also observed in the PD-L1 combined positive score (CPS) ≥ 5 populations. Univariate and multivariate Cox regression analyses indicated that lower CD4+ T, CD4+ Tn, CD4+ Tm, CD4+ Tcm and CD4+ Tem expressing PD-1 were independent risk factors of PFS and OS in advanced gastric cancer patients treated with combined immunotherapy and chemotherapy. CONCLUSION: The peripheral CD4+ T cell subpopulations demonstrated the high predictive value for therapeutic response and prolonged survival outcomes in advanced gastric cancer patients. CD4+ T cell subpopulations have the potential in predicting and screening benefit populations in advanced gastric cancer patients.