Sex differences in functional and structural alterations of hippocampus region in chronic pain: a DTI and resting-state fMRI study.

Introduction: It is well known that there are significant differences in the prevalence of chronic pain between males and females. Human and animal imaging studies have shown that chronic pain profoundly alters the structure and function of brain regions. However, there is limited research on the sex-specific mechanisms underlying the brain plasticity and adaptive changes associated with chronic pain. In this article, we conducted a multimodal study to evaluate how nerve injury-induced chronic pain affects the brain. Methods: Male and female Sprague-Dawley (SD) rats with spared nerve injury (SNI) model underwent resting-state functional magnetic resonance imaging (rs-fMRI) (male sham group: n = 18; male SNI group: n = 18; female sham group: n = 20; female SNI group: n = 18) and magnetic resonance diffusion tensor imaging (DTI) (male sham group: n = 23; male SNI group: n = 21; female sham group: n = 20; female SNI group: n = 21) scanning. ICA method, Fractional amplitude of low-frequency fluctuations (fALFF), immunofluorescence staining, and graph theory analysis was utilized to extract the rs-fMRI changes of brain regions of each group. Results: Using SNI model, which promotes long-lasting mechanical allodynia, we found that neuropathic pain deeply modified the intrinsic organization of the brain functional network in male and female rats (main effect of operation: F = 298.449, P < 0.001). 64 independent components (ICs) in the brain were divided and assigned to 16 systems. In male rats, we observed significant alterations in the microstructure of the hippocampal cornu ammonis 1 and cornu ammonis 2 (CA1/CA2) region, as indicated by increased mean diffusivity (MD) (CA1_L: P = 0.02; CA1_R: P = 0.031; CA2_L: P = 0.035; CA2_R: P = 0.015) and radial diffusivity (RD) (CA1_L: P = 0.028; CA1_R: P = 0.033; CA2_L: P = 0.037; CA2_R: P = 0.038) values, along with enhanced activating transcription factor 3 (ATF3) expression. Conversely, in female rats, we found significant increases in the fractional amplitude of low frequency fluctuations (fALFF) value within the hippocampal dentate gyrus (DG) (F = 5.419, P = 0.023), accompanied by elevated c-Fos signal (F = 6.269, P = 0.031). Furthermore, graph theory analysis revealed notable differences in the small-world network of the hippocampal system in female rats, characterized by reduced small-world attributes and increased inter-nodal transmission efficiency. Discussion: Our study indicates sex differences in structural and functional alterations in the hippocampal system in rats under chronic pain conditions. The results suggest that the hippocampus system plays an important role in the different mechanisms of chronic pain in different sexes. These findings provide reliable insights to explore the complex mechanisms underlying sex differences in chronic pain.

Protamine cleavage specificity of the avian pathogen Escherichia coli OmpT reveals two substrate-binding sites related to virulence.

The pathogenic nature of bacteria can be increased by cleaving antimicrobial peptides using omptins, to avoid or counter the host's natural immune defenses. Plasmid-encoded OmpT (pOmpT or ArlC) in avian pathogenic Escherichia coli (APEC), like the chromosome-encoded OmpT (cOmpT), belongs to the omptin family and both exhibit highly similar sequences and structures. Through sequence alignment and physiological examinations, pOmpT has been identified as a virulence factor, distinct from cOmpT in terms of substrate specificity. When pOmpT is compared with cOmpT regarding their proteolytic activities and target substrates, Asp267 and Ser276 on loop 5 of cOmpT are found to be binding sites that facilitate substrate anchoring and enhance substrate cleavage (protamine or synthetic peptide) by the catalytic center. Conversely, the characteristics of residues at positions 267 and 276 on loop 5 of pOmpT inhibit protamine cleavage, yet allow the specific cleavage of the human antimicrobial peptide RNase 7, which plays a role in host defense. This finding suggests a relationship between these two binding sites and substrate specificity. Furthermore, the substrate-binding sites (residues 267 and 276, particularly residue 267) of cOmpT and pOmpT are determined to be critical in the virulence of APEC. In summary, residues 267 and 276 of pOmpT are crucial for the pathogenicity of APEC and offer new insights into the determinants of APEC virulence and the development of antimicrobial drugs.

LncRNA HOXB-AS3 promotes proliferation, migration, and invasion of gallbladder cancer cells by activating the MEK/ERK pathway.

Background: LncRNA HOXB-AS3 are associated with tumor progression in several types of carcinomas, yet, its possibly biological role in gallbladder carcinoma(GBC) remains unclear. Therefore, this study aimed to investigate the biological function of HOXB-AS3 in GBC. Methods: To know the potential function of HOXB-AS3 in gallbladder carcinoma, real-time polymerase chain reaction was used to detected the expression of HOXB-AS3 in gallbladder carcinoma cells. The colony formation assay and cell counting kit-8 assay was performed to measured cell viability. Flow cytometry was to analyse cell apoptosis and cell cycle. Cell invasion and migration were determined by the transwell invasion assay and wound-healing assay. A nude mice xenograft tumor model was performed to investigate the biological function of HOXB-AS3 in vivo. Results: The results indicated that HOXB-AS3 was significantly elevated in gallbladder carcinoma tissues and cell lines. We used siHOXB-AS3 to knockdown the expression levels of HOXB-AS3. And knockdown HOXB-AS3 expression depressed gallbladder cancer cell viability and induced cell apoptosis. In addition, the gallbladder carcinoma cell cycle was obviously arrested at the G1 phase. Cell invasion and migration were markedly suppressed following knockdown HOXB-AS3 expression. Furthermore, the features of siHOXB-AS3 in gallbladder cancer cells could be reversed by the ERK1/2 phosphorylation agonist Ro 67-7476. Finally, we confirmed that HOXB-AS3 promoted the growth of transplanted tumors in vivo. Conclusion: HOXB-AS3 promoted gallbladder carcinoma cell proliferation, invasion and migration by activating the MEK/ERK signaling pathway. HOXB-AS3 contributed to gallbladder cancer tumorigenesis and metastasis, making it a viable therapeutic target for gallbladder cancer treatment.

Analysis of the recombination and evolution of the new type mutant pseudorabies virus XJ5 in China.

Pseudorabies have caused enormous economic losses in China's pig industry and have recurred on many large pig farms since late 2011. The disease is caused by highly pathogenic, antigenic variant pseudorabies virus (vPRV) strains. Our laboratory isolated a pseudorabies virus in 2015 and named it XJ5. The pathogenic ability of this mutant strain was much stronger than that of the original isolate. After we sequenced its whole genome (GenBank accession number: OP512542), we found that its overall structure was not greatly changed compared with that of the previous strain Ea (KX423960.1). The whole genome alignment showed that XJ5 had a strong genetic relationship with the strains isolated in China after 2012 reported in GenBank. Based on the isolation time of XJ5 and the mutation and recombination analysis of programs, we found that the whole genome homology of XJ5 and other strains with Chinese isolates was greater than 95%, while the homology with strains outside Asia was less than 94%, which indicated that there may be some recombination and mutation patterns. We found that virulent PRV isolates emerged successively in China in 2011 and formed two different evolutionary clades from foreign isolates. At the same time, this may be due to improper immunization and the presence of wild strains in the field, and recent reports have confirmed that Bartha vaccine strains recombine with wild strains to obtain new pathogenic strains. We performed genetic evolution analysis of XJ5 isolated and sequenced in our laboratory to trace its possible mutations and recombination. We found that XJ5 may be the result of natural mutation of a virus in a branch of mutant strains widely existing in China.

Recent advances in living cell nucleic acid probes based on nanomaterials for early cancer diagnosis.

The early diagnosis of cancer is vital for effective treatment and improved prognosis. Tumor biomarkers, which can be used for the early diagnosis, treatment, and prognostic evaluation of cancer, have emerged as a topic of intense research interest in recent years. Nucleic acid, as a type of tumor biomarker, contains vital genetic information, which is of great significance for the occurrence and development of cancer. Currently, living cell nucleic acid probes, which enable the in situ imaging and dynamic monitoring of nucleic acids, have become a rapidly developing field. This review focuses on living cell nucleic acid probes that can be used for the early diagnosis of tumors. We describe the fundamental design of the probe in terms of three units and focus on the roles of different nanomaterials in probe delivery.

Regulation of TGF-ß2-induced epithelial-mesenchymal transition and autophagy in lens epithelial cells by the miR-492/NPM1 axis.

A cataract is a clinically common blinding disease closely related to the ageing of the eye cells, which has become a major health killer in the elderly. Our research seeks to analyze the primary targets linked to the pathogenesis of cataracts during the ageing process. We performed bioinformatics analyses on the GSE101727 dataset to discover genes linked with ageing and cataracts. To explore the impacts of Nucleophosmin 1 (NPM1) on cell apoptosis, proliferation, as well as epithelial-mesenchymal transition (EMT) processes, in vitro tests such as western blotting, flow cytometry, and MTT were carried out. Additionally, the study incorporated transforming growth factor ß2 (TGF-ß2) to examine its function in cellular responses, chloroquine (CQ) to regulate autophagic flow, and H2O2 therapy to mimic oxidative stress. Our study discovered seven ageing-related genes, including NPM1, that had substantial relationships with cataracts. NPM1 overexpression was shown to boost cell proliferation and prevent apoptosis in SRA01/04 cells. Notably, NPM1 modulated the TGF-ß signalling pathway, influencing cell proliferation and EMT processes. miR-429 was shown to be adversely regulating NPM1 and autophagy-related proteins, as demonstrated by changes in their expression in response to TGF-ß2 treatment. Furthermore, NPM1 knockdown restored autophagy activity suppressed by miR-429 mimics, indicating a complex interaction of miR-429, NPM1, and TGF-ß2 pathways in regulating autophagy and EMT. Lens epithelial cell proliferation and apoptosis were largely regulated by NPM1, as well as autophagy and EMT, which were significantly mediated by TGF-ß2 and the miR-429/NPM1 axis. These results imply new possible targets for prognosis and therapy of cataracts.

The influence of Mn(II) on transformation of Cr-absorbed Schwertmannite: Mineral phase transition and elemental fate.

Schwertmannite (Sch) is considered as an effective remover of Chromium (Cr) due to its strong affinity for toxic Cr species. Since the instability of Sch, the environmental fate of Cr deserves attention during the transformation of Sch into a more stable crystalline phase. The ubiquitous manganese(II) (Mn(II)) probably affects the transformation of Sch and thus the environmental fate of Cr. Therefore, this study investigated the impact of Mn(II) on the transformation of Cr-absorbed Sch (Cr-Sch) and the associated behavior of SO42- and Cr. We revealed that the transformation products of Cr-Sch at pH 3.0 and 7.0 were goethite and Sch, respectively. The presence of Mn(II) weakened the crystallinity of the transformation products, and the trend was positively correlated with the concentration of Mn(II). However, Mn(II) changed the transformation products of Cr-Sch from hematite to goethite at pH 10.0. Mn(II) replaced Fe(III) in the mineral structures or formed Mn-O complexes with surface hydroxyl groups (-OH), thereby affecting the transformation pathways of Sch. The presence of Mn(II) enhanced the immobilization of Cr on minerals at pH 3.0 and 7.0. Sch is likely to provide an channel for electron transfer between Mn(II) and Cr(VI), which promotes the reduction of Cr(VI). Meanwhile, Mn(Ⅱ) induced more -OH production on the surface of secondary minerals, which played an important role in increasing the Cr fixation. In addition, part of the Mn(Ⅱ) was oxidized to Mn(Ⅲ)/Mn(Ⅳ) at pH 3.0 and pH 7.0. This study helps to predict the role of Mn(II) in the transformations of Cr-Sch in environments and design remediation strategies for Cr contamination.

Hyaluronan degradation by HYAL2 is essential for odontoblastic differentiation and migration of mouse dental papilla cells.

The coordination between odontoblastic differentiation and directed cell migration of mesenchymal progenitors is necessary for regular dentin formation. The synthesis and degradation of hyaluronan (HA) in the extracellular matrix create a permissive niche that directly regulates cell behaviors. However, the role and mechanisms of HA degradation in dentin formation remain unknown. In this work, we present that HA digestion promotes odontoblastic differentiation and cell migration of mouse dental papilla cells (mDPCs). Hyaluronidase 2 (HYAL2) is responsible for promoting odontoblastic differentiation through degrading HA, while hyaluronidase 1 (HYAL1) exhibits negligible effect. Silencing Hyal2 generates an extracellular environment rich in HA, which attenuates F-actin and filopodium formation and in turn inhibits cell migration of mDPCs. In addition, activating PI3K/Akt signaling significantly rescues the effects of HA accumulation on cytodifferentiation. Taken together, the results confirm the contribution of HYAL2 to HA degradation in dentinogenesis and uncover the mechanism of the HYAL2-mediated HA degradation in regulating the odontoblastic differentiation and migration of mDPCs.

A Comprehensive Strategy Based on High Clinical Translational Nanosystem for Programmable Immunotherapy of Triple Negative Breast Cancer.

Triple negative breast cancer (TNBCs), known as an immunologically cold tumor, is difficult to completely eliminate with existing monotherapies, let alone metastasis and recurrence. It is urgent to design a rational combination of multiple therapies to programmatically reconstitute tumor microenvironment (TME) and reverse the immune "cold" into "hot" inflammatory tumors to improve the therapeutic effect. Hence, in this work, a multifunctional nanosystem (FeSH NPs) that integrates metal-polyphenol coordination complex as a photothermal agent and polyphenol, salvianolic acid B (SAB) as immunomodulator is designed and fabricated for synergistic photothermal-immunotherapy of TNBCs combined with anti-PD-L1 antibody. Guided by photothermal/photoacoustic dual-mode imaging, photothermal therapy (PTT) caused by FeSH NPs induces immunogenic cell death (ICD) under 808 nm laser irradiation. Subsequently, the loaded SAB is released with the addition of deferoxamine mesylate (DFO) to remodel TME, specifically TGF-ß inhibition and PD-L1 upregulation, and eliminate the primary tumors. The combination of PTT and TME reprogramming by FeSH NPs further synergizes with anti-PD-L1 antibody to eradicate recurrence and inhibit metastasis of TNBCs concurrently. Given the biosafety of FeSH NPs throughout the lifecycle, this work provides a protocol with high clinical translational promise for comprehensive programmed therapeutics of immunologically cold tumors TNBCs.

Exosome-Inhibiting Polymeric Sonosensitizer for Tumor-Specific Sonodynamic Immunotherapy.

Combination cancer immunotherapy based on electromagnetic energy and immunotherapy shows potent anti-cancer efficacy. However, as a factor that mediates tumor metastasis and immune suppression, the impact of tumor exosomes on therapy under electromagnetic energy stimulation remains unclear. Herein, findings indicate that sonodynamic therapy (SDT) increases serum exosome levels by inducing apoptotic exosomes and loosening the tumor extracellular matrix, promoting lung metastasis. To address this problem, an exosome-inhibiting polymeric sonosensitizer (EIPS) selectively inhibiting tumor exosome generation in response to the tumor biomarker is synthesized. EIPS consists of a semiconducting polymer backbone capable of inducing SDT and a poly(ethylene glycol) layer conjugated with a tumor-specific enzyme-responsive exosome inhibitor prodrug. After being cleaved by tumor Cathepsin B, EIPS releases active exosome inhibitors, preventing tumor exosome-mediated immune suppression and lung metastasis. As a result, EIPS elicits robust antitumor effects through the synergistic effect of SDT and tumor exosome inhibition, completely preventing lung metastasis and establishing a long-term immune memory effect. This is the first example showing that combining SDT with tumor-specific exosome inhibition can elicit a potent immune response without the help of typical immune agonists.

A Tandem-Locked Chemiluminescent Probe for Imaging of Tumor-Associated Macrophage Polarization.

Tumor-associated macrophages (TAMs) play a role in both pro- and anti-tumor functions; and the targeted polarization from M2 to M1 TAMs has become an effective therapy option. Although detection of M1 TAMs is imperative to assess cancer immunotherapeutic efficacy, existing optical probes suffer from shallow tissue penetration depth and poor specificity toward M1 TAMs. Herein, we report a tandem-locked NIR chemiluminescent (CL) probe for specific detection of M1 TAMs. Through a combined molecular engineering approach via both atomic alternation and introduction of electron-withdrawing groups, near-infrared (NIR) chemiluminophores are screened out to possess record-long emission (over 800 nm), record-high CL quantum yield (2.7 % einstein/mol), and prolonged half-life (7.7 h). Based on an ideal chemiluminophore, the tandem-locked probe (DPDGN) is developed to only activate CL signal in the presence of both tumour (γ-glutamyl transpeptidase) and M1 macrophage biomarkers (nitric oxide). Such a tandem-lock design ensures its high specificity towards M1 macrophages in the tumor microenvironment over those in normal tissues or peripheral blood. Thus, DPDGN permits noninvasive imaging and tracking of M1 TAM in the tumor of living mice during R837 treatment, showing a good correlation with ex vivo methods. This study not only reports a new molecular approach towards highly efficient chemiluminophores but also reveals the first tandem-locked CL probes for enhanced imaging specificity.

An environmentally friendly strategy for reducing the environmental risks of heavy metals adsorbed by kaolinite.

Plenty of heavy metals (HMs) that are adsorbed on clay minerals (such as kaolinite), in addition to low molecular-weight organic acids (such as oxalic acid (OA)) with high activities, are widespread in the natural environment. In the present study, the effects of OA on the environmental behaviors of Pb2+/Cd2+ adsorbed by kaolinite have been investigated. The effectiveness and mechanisms of calcium silicate (CS) and magnesium silicate (MS) in reducing the environmental risks of the HMs have also been studied. The results showed that the releases of Pb2+/Cd2+ increased with an increasing concentration of OA. When different dosages of CS/MS were added to the aging system, a redistribution of HMs took place and the free form of Pb2+/Cd2+ decreased to very low levels. Also, the unextractable Pb2+/Cd2+ increased to high levels. Furthermore, a series of characterizations showed that the released HMs were re-captured by the CS/MS. In addition, the CS immobilized the OA in the solution during the aging process, which also facilitated an immobilization of the carbon element in the environment. In general, the present study has contributed to a further understanding of the transport behaviors of the HMs in natural environments, and of the interactions between CS (or MS), the environmental media, and the heavy metal contaminants. In addition, this study has also provided an eco-friendly strategy for an effective remediation of heavy metal pollution.

Comparison of the safety and efficacy of the wild-type and lpxL/lpxM mutant inactivated vaccine against the avian pathogenic Escherichia coli O1, O2, and O78 challenge.

Avian pathogenic Escherichia coli (APEC) is primarily responsible for causing septicemia, pneumonitis, peritonitis, swollen head syndrome, and salpingitis in poultry, leading to significant losses in the poultry sector, particularly within the broiler industry. The removal of the lpxL and lpxM genes led to an eightfold decrease in the endotoxin levels of wild APEC strains. In this study, mutant strains of lpxL/lpxM and their O1, O2, and O78 wild-type strains were developed for an inactivated vaccine (referred to as the mutant vaccine and the wild-type vaccine, respectively), and the safety and effectiveness of these two prototype vaccines were assessed in white Leghorn chickens. Findings indicated that chickens immunized with the mutant vaccine showed a return of appetite sooner post-immunization and experienced earlier disappearance of nodules at the injection site compared to those immunized with the wild-type vaccine. Pathological examinations revealed that lesions were still present in the liver, lung, and injection site in chickens vaccinated with the wild-type vaccine 14 days post-vaccination (dpv), whereas no lesions were found in chickens vaccinated with the mutant vaccine at 14 dpv. There were no significant differences in antibody levels on the challenge day or in mortality or lesion scores between challenged birds immunized with either the mutant vaccine or the wild-type vaccine at the same dose. In this study, the safety of a single dose or overdose of the mutant vaccine and its efficacy at one dose were evaluated in broilers, and the results showed that the mutant vaccine had no adverse effects on or protected vaccinated broilers from challenge with the APEC O1, O2, or O78 strains. These results demonstrated that the mutant polyvalent inactivated vaccine is a competitive candidate against APEC O1, O2, and O78 infection compared to the wild-type vaccine.

Artesunate treats obesity in male mice and non-human primates through GDF15/GFRAL signalling axis.

Obesity, a global health challenge, is a major risk factor for multiple life-threatening diseases, including diabetes, fatty liver, and cancer. There is an ongoing need to identify safe and tolerable therapeutics for obesity management. Herein, we show that treatment with artesunate, an artemisinin derivative approved by the FDA for the treatment of severe malaria, effectively reduces body weight and improves metabolic profiles in preclinical models of obesity, including male mice with overnutrition-induced obesity and male cynomolgus macaques with spontaneous obesity, without inducing nausea and malaise. Artesunate promotes weight loss and reduces food intake in obese mice and cynomolgus macaques by increasing circulating levels of Growth Differentiation Factor 15 (GDF15), an appetite-regulating hormone with a brainstem-restricted receptor, the GDNF family receptor α-like (GFRAL). Mechanistically, artesunate induces the expression of GDF15 in multiple organs, especially the liver, in mice through a C/EBP homologous protein (CHOP)-directed integrated stress response. Inhibition of GDF15/GFRAL signalling by genetic ablation of GFRAL or tissue-specific knockdown of GDF15 abrogates the anti-obesity effect of artesunate in mice with diet-induced obesity, suggesting that artesunate controls bodyweight and appetite in a GDF15/GFRAL signalling-dependent manner. These data highlight the therapeutic benefits of artesunate in the treatment of obesity and related comorbidities.

Stabilizing Highly Active Ru Sites by Electron Reservoir in Acidic Oxygen Evolution.

Proton exchange membrane water electrolysis is hindered by the sluggish kinetics of the anodic oxygen evolution reaction. RuO2 is regarded as a promising alternative to IrO2 for the anode catalyst of proton exchange membrane water electrolyzers due to its superior activity and relatively lower cost compared to IrO2. However, the dissolution of Ru induced by its overoxidation under acidic oxygen evolution reaction (OER) conditions greatly hinders its durability. Herein, we developed a strategy for stabilizing RuO2 in acidic OER by the incorporation of high-valence metals with suitable ionic electronegativity. A molten salt method was employed to synthesize a series of high-valence metal-substituted RuO2 with large specific surface areas. The experimental results revealed that a high content of surface Ru4+ species promoted the OER intrinsic activity of high-valence doped RuO2. It was found that there was a linear relationship between the ratio of surface Ru4+/Ru3+ species and the ionic electronegativity of the dopant metals. By regulating the ratio of surface Ru4+/Ru3+ species, incorporating Re, with the highest ionic electronegativity, endowed Re0.1Ru0.9O2 with exceptional OER activity, exhibiting a low overpotential of 199 mV to reach 10 mA cm-2. More importantly, Re0.1Ru0.9O2 demonstrated outstanding stability at both 10 mA cm-2 (over 300 h) and 100 mA cm-2 (over 25 h). The characterization of post-stability Re0.1Ru0.9O2 revealed that Re promoted electron transfer to Ru, serving as an electron reservoir to mitigate excessive oxidation of Ru sites during the OER process and thus enhancing OER stability. We conclude that Re, with the highest ionic electronegativity, attracted a mass of electrons from Ru in the pre-catalyst and replenished electrons to Ru under the operating potential. This work spotlights an effective strategy for stabilizing cost-effective Ru-based catalysts for acidic OER.

Metabolic Nanoregulator Remodels Gut Microenvironment for Treatment of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is strongly related to the occurrence of accumulation of toxic reactive oxygen species (ROS), inflammation of the mucosa, and an imbalance of intestinal microbes. However, current treatments largely focus on a single factor, yielding unsatisfactory clinical outcomes. Herein, we report a biocompatible and IBD-targeted metabolic nanoregulator (TMNR) that synergistically regulates cellular and bacterial metabolism. The TMNR comprises a melanin-gallium complex (MNR) encapsulated within a thermosensitive and colitis-targeting hydrogel, all composed of natural and FDA-approved components. The TMNR confers superior broad-spectrum antioxidant properties, effectively scavenging reactive oxygen species (ROS) and blocking inflammatory signaling pathways. The presence of Ga3+ in TMNR selectively disrupts iron metabolism in pathogenic microorganisms due to its structural resemblance to the iron atom. Additionally, incorporating a thermosensitive injectable hydrogel enables targeted delivery of TMNR to inflammatory regions, prolonging their retention time and providing a physical barrier function for optimizing IBD treatment efficacy. Collectively, TMNR effectively modulates the redox balance of inflamed colonic epithelial tissue and disrupts iron metabolism in pathogenic microorganisms, thereby eliminating inflammation and restoring intestinal homeostasis against IBD. Hence, this work presents a comprehensive approach for precise spatiotemporal regulation of the intestinal microenvironmental metabolism for IBD treatment.

Application of Mid-Pancreatectomy with End-to-End Anastomosis in Pancreatic Benign Tumors.

Mid-pancreatectomy combined with end-to-end anastomosis is a surgical procedure used to treat benign pancreatic tumors. It involves removing the tumor from the middle section of the pancreas and connecting the proximal and distal ends through an anastomosis. The traditional surgical approach for resecting the middle segment of the pancreas involves closing the proximal pancreas and creating a Roux-en-Y anastomosis with the jejunum. However, this approach carries a double risk of pancreatic stump fistula and pancreatico enteric anastomotic leak postoperatively. In this paper, a new procedure is described where stent tubes were placed into the proximal and distal sides of the pancreatic ducts after ensuring sufficient freedom from the proximal distal pancreas. The pancreatic parenchyma was then sutured continuously under direct vision to achieve pancreatic end-to-end anastomosis. This procedure helps preserve pancreatic function, reducing the risk of postoperative pancreatic insufficiency. However, due to the complexity and risks involved, thorough evaluation and preparation are necessary before surgery. We carefully assess the patient's history, serology, and imaging results to determine the feasibility and effectiveness of the procedure. During surgery, we consider the use of a suitable pancreatic duct stent to ensure the flow of pancreatic juice into the intestine through physiological pathways. Our goal is to remove the tumor while preserving as much normal pancreatic tissue as possible for the anastomosis. After the operation, it is crucial to monitor the patient's pancreatic function, paying close attention to blood glucose levels, drainage fluid volume, and amylase value of the pancreatic anastomosis. During the postoperative follow-up visit, the patient's pancreatic function was assessed, and there was no significant change in quality of life compared to before the surgery. This indicates that mid-pancreatectomy combined with end-to-end anastomosis is a safe and effective procedure for treating pancreatic benign neoplasms.

A Versatile Nanovaccine Enhancement Strategy Based on Suction-Inspired Physical Therapy.

Vaccine technology is effective in preventing and treating diseases, including cancers and viruses. The efficiency of vaccines can be improved by increasing the dosage and frequency of injections, but it would bring an extra burden to people. Therefore, it is necessary to develop vaccine-boosting techniques with negligible side effects. Herein, we reported a cupping-inspired noninvasive suction therapy that could enhance the efficacy of cancer/SARS-CoV-2 nanovaccines. Negative pressure caused mechanical immunogenic cell death and released endogenous adjuvants. This created a subcutaneous niche that would recruit and activate antigen-presenting cells. Based on this universal central mechanism, suction therapy was successfully applied in a variety of nanovaccine models, which include prophylactic/therapeutic tumor nanovaccine, photothermal therapy induced in situ tumor nanovaccine, and SARS-CoV-2 nanovaccine. As a well-established physical therapy method, suction therapy may usher in an era of noninvasive and high-safety auxiliary strategies when combined with vaccines.

Leveraging Semiconducting Polymer Nanoparticles for Combination Cancer Immunotherapy.

Cancer immunotherapy has become a promising method for cancer treatment, bringing hope to advanced cancer patients. However, immune-related adverse events caused by immunotherapy also bring heavy burden to patients. Semiconducting polymer nanoparticles (SPNs) as an emerging nanomaterial with high biocompatibility, can eliminate tumors and induce tumor immunogenic cell death through different therapeutic modalities, including photothermal therapy, photodynamic therapy, and sonodynamic therapy. In addition, SPNs can work as a functional nanocarrier to synergize with a variety of immunomodulators to amplify anti-tumor immune responses. In this review, SPNs-based combination cancer immunotherapy is comprehensively summarized according to the SPNs' therapeutic modalities and the type of loaded immunomodulators. The in-depth understanding of existing SPNs-based therapeutic modalities will hopefully inspire the design of more novel nanomaterials with potent anti-tumor immune effects, and ultimately promote their clinical translation.