Targeted multispectral filter array design for the optimization of endoscopic cancer detection in the gastrointestinal tract.

Significance: Color differences between healthy and diseased tissue in the gastrointestinal (GI) tract are detected visually by clinicians during white light endoscopy; however, the earliest signs of cancer are often just a slightly different shade of pink compared to healthy tissue making it hard to detect. Improving contrast in endoscopy is important for early detection of disease in the GI tract during routine screening and surveillance. Aim: We aim to target alternative colors for imaging to improve contrast using custom multispectral filter arrays (MSFAs) that could be deployed in an endoscopic "chip-on-tip" configuration. Approach: Using an open-source toolbox, Opti-MSFA, we examined the optimal design of MSFAs for early cancer detection in the GI tract. The toolbox was first extended to use additional classification models (k-nearest neighbor, support vector machine, and spectral angle mapper). Using input spectral data from published clinical trials examining the esophagus and colon, we optimized the design of MSFAs with three to nine different bands. Results: We examined the variation of the spectral and spatial classification accuracies as a function of the number of bands. The MSFA configurations tested showed good classification accuracies when compared to the full hyperspectral data available from the clinical spectra used in these studies. Conclusion: The ability to retain good classification accuracies with a reduced number of spectral bands could enable the future deployment of multispectral imaging in an endoscopic chip-on-tip configuration using simplified MSFA hardware. Further studies using an expanded clinical dataset are needed to confirm these findings.

Recombinant bivalent subunit vaccine combining truncated VP4 from P[7] and P[23] induces protective immunity against prevalent porcine rotaviruses.

Porcine rotaviruses (PoRVs) cause severe economic losses in the swine industry. P[7] and P[23] are the predominant genotypes circulating on farms, but no vaccine is yet available. Here, we developed a bivalent subunit PoRV vaccine using truncated versions (VP4*) of the VP4 proteins from P[7] and P[23]. The vaccination of mice with the bivalent subunit vaccine elicited more robust neutralizing antibodies (NAbs) and cellular immune responses than its components, even at high doses. The bivalent subunit vaccine and inactivated bivalent vaccine prepared from strains PoRVs G9P[7] and G9P[23] were used to examine their protective efficacy in sows and suckling piglets after passive immunization. The immunized sows showed significantly elevated NAbs in the serum and colostrum, and the suckling piglets acquired high levels of sIgA antibodies from the colostrum. Challenging subunit-vaccinated or inactivated-vaccinated piglets with homologous virulent strains did not induce diarrhea, except in one or two piglets, which had mild diarrhea. Immunization with the bivalent subunit vaccine and inactivated vaccine also alleviated the microscopic lesions in the intestinal tissues caused by the challenge with the corresponding homologous virulent strain. However, all the piglets in the challenged group displayed mild to watery diarrhea and high levels of viral shedding, whereas the feces and intestines of the piglets in the bivalent subunit vaccine and inactivated vaccine groups had lower viral loads. In summary, our data show for the first time that a bivalent subunit vaccine combining VP4*P[7] and VP4*P[23] effectively protects piglets against the diarrhea caused by homologous virulent strains.IMPORTANCEPoRVs are the main causes of diarrhea in piglets worldwide. The multisegmented genome of PoRVs allows the reassortment of VP4 and VP7 genes from different RV species and strains. The P[7] and P[23] are the predominant genotypes circulating in pig farms, but no vaccine is available at present in China. Subunit vaccines, as nonreplicating vaccines, are an option to cope with variable genotypes. Here, we have developed a bivalent subunit candidate vaccine based on a truncated VP4 protein, which induced robust humoral and cellular immune responses and protected piglets against challenge with homologous PoRV. It also appears to be safe. These data show that the truncated VP4-protein-based subunit vaccine is a promising candidate for the prevention of PoRV diarrhea.

Machine learning developed a fibroblast-related signature for predicting clinical outcome and drug sensitivity in ovarian cancer.

Ovarian cancer (OC) is the leading cause of gynecological cancer death. Cancer-associated fibroblasts (CAF) is involved in wound healing and inflammatory processes, tumor occurrence and progression, and chemotherapy resistance in OC. GSE184880 dataset was used to identify CAF-related genes in OC. CAF-related signature (CRS) was constructed using integrative 10 machine learning methods with the datasets from the Cancer Genome Atlas, GSE14764, GSE26193, GSE26712, GSE63885, and GSE140082. The performance of CRS in predicting immunotherapy benefits was verified using 3 immunotherapy datasets (GSE91061, GSE78220, and IMvigor210) and several immune calculating scores. The Lasso + StepCox[forward] method-based predicting model having a highest average C index of 0.69 was referred as the optimal CRS and it had a stable and powerful performance in predicting clinical outcome of OC patients, with the 1-, 3-, and 5-year area under curves were 0.699, 0.708, and 0.767 in the Cancer Genome Atlas cohort. The C index of CRS was higher than that of tumor grade, clinical stage, and many developed signatures. Low CRS score demonstrated lower tumor immune dysfunction and exclusion score, lower immune escape score, higher PD1&CTLA4 immunophenoscore, higher tumor mutation burden score, higher response rate and better prognosis in OC, suggesting a better immunotherapy response. OC patients with low CRS score had a lower half maximal inhibitory concentration value of some drugs (Gemcitabine, Tamoxifen, and Nilotinib, etc) and lower score of some cancer-related hallmarks (Notch signaling, hypoxia, and glycolysis, etc). The current study developed an optimal CRS in OC, which acted as an indicator for the prognosis, stratifying risk and guiding treatment for OC patients.

Research progress on oncoprotein hepatitis B X­interacting protein (Review).

Hepatitis B X­interacting protein (HBXIP) is a membrane protein located on the lysosomal surface and encoded by the Lamtor gene. It is expressed by a wide range of tumor types, including breast cancer, esophageal squamous cell carcinoma and hepatocellular carcinoma, and its expression is associated with certain clinicopathological characteristics. In the past decade, research on the oncogenic mechanisms of HBXIP has increased and the function of HBXIP in normal cells has been gradually elucidated. In the present review, the following was discussed: The normal physiological role of the HBXIP carcinogenic mechanism; the clinical significance of high levels of HBXIP expression in different tumors; HBXIP regulation of transcription, post­transcription and post­translation processes in tumors; the role of HBXIP in improving the antioxidant capacity of tumor cells; the inhibition of ferroptosis of tumor cells and regulating the metabolic reprogramming of tumor cells; and the role of HBXIP in promoting the malignant progression of tumors. In conclusion, the present review summarized the existing knowledge of HBXIP, established its carcinogenic mechanism and discussed future related research on HBXIP.

Boosting the immunogenicity of the CoronaVac SARS-CoV-2 inactivated vaccine with Huoxiang Suling Shuanghua Decoction: a randomized, double-blind, placebo-controlled study.

Introduction: In light of the public health burden of the COVID-19 pandemic, boosting the safety and immunogenicity of COVID-19 vaccines is of great concern. Numerous Traditional Chinese medicine (TCM) preparations have shown to beneficially modulate immunity. Based on pilot experiments in mice that showed that supplementation with Huoxiang Suling Shuanghua Decoction (HSSD) significantly enhances serum anti-RBD IgG titers after inoculation with recombinant SARS-CoV-2 S-RBD protein, we conducted this randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the potential immunogenicity boosting effect of oral HSSD after a third homologous immunization with Sinovac's CoronaVac SARS-CoV-2 (CVS) inactivated vaccine. Methods: A total of 70 participants were randomly assigned (1:1 ratio) to receive a third dose of CVS vaccination and either oral placebo or oral HSSD for 7 days. Safety aspects were assessed by recording local and systemic adverse events, and by blood and urine biochemistry and liver and kidney function tests. Main outcomes evaluated included serum anti-RBD IgG titer, T lymphocyte subsets, serum IgG and IgM levels, complement components (C3 and C4), and serum cytokines (IL-6 and IFN-γ). In addition, metabolomics technology was used to analyze differential metabolite expression after supplementation with HSSD. Results: Following a third CVS vaccination, significantly increased serum anti-RBD IgG titer, reduced serum IL-6 levels, increased serum IgG, IgM, and C3 and C4 levels, and improved cellular immunity, evidenced by reduce balance deviations in the distribution of lymphocyte subsets, was observed in the HSSD group compared with the placebo group. No serious adverse events were recorded in either group. Serum metabolomics results suggested that the mechanisms by which HSSD boosted the immunogenicity of the CVS vaccine are related to differential regulation of purine metabolism, vitamin B6 metabolism, folate biosynthesis, arginine and proline metabolism, and steroid hormone biosynthesis. Conclusion: Oral HSSD boosts the immunogenicity of the CVS vaccine in young and adult individuals. This trial provides clinical reference for evaluation of TCM immunomodulators to improve the immune response to COVID-19 vaccines.

Genetic correlation and causal associations between psychiatric disorders and lung cancer risk.

BACKGROUND: Patients with certain psychiatric disorders have increased lung cancer incidence. However, establishing a causal relationship through traditional epidemiological methods poses challenges. METHODS: Available summary statistics of genome-wide association studies of cigarette smoking, lung cancer, and eight psychiatric disorders, including attention deficit/hyperactivity disorder (ADHD), autism, depression, major depressive disorder, bipolar disorder, insomnia, neuroticism, and schizophrenia (range N: 46,350-1,331,010) were leveraged to estimate genetic correlations using Linkage Disequilibrium Score Regression and assess causal effect of each psychiatric disorder on lung cancer using two-sample Mendelian randomization (MR) models, comprising inverse-variance weighted (IVW), weighted median, MR-Egger, pleiotropy residual sum and outlier testing (MR-PRESSO), and a constrained maximum likelihood approach (cML-MR). RESULTS: Significant positive correlations were observed between each psychiatric disorder and both smoking and lung cancer (all FDR < 0.05), except for the correlation between autism and lung cancer. Both univariable and the cML-MA MR analyses demonstrated that liability to schizophrenia, depression, ADHD, or insomnia was associated with an increased risk of overall lung cancer. Genetic liability to insomnia was linked specifically to squamous cell carcinoma (SCC), while genetic liability to ADHD was associated with an elevated risk of both SCC and small cell lung cancer (all P < 0.05). The later was further supported by multivariable MR analyses, which accounted for smoking. LIMITATIONS: Participants were constrained to European ancestry populations. Causal estimates from binary psychiatric disorders may be biased. CONCLUSION: Our findings suggest appropriate management of several psychiatric disorders, particularly ADHD, may potentially reduce the risk of developing lung cancer.

Distinct Lipidomic Profiles between People Living with HIV Treated with E/C/F/TAF or B/F/TAF: An Open-Label Prospective Cohort Study.

INTRODUCTION: Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) has been increasingly replaced by bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in the treatment of human immunodeficiency virus (HIV) owing to its more favorable pharmacokinetics and fewer drug-drug interactions. However, the effect of this switch on plasma lipids and lipidomic profiles remains poorly characterized. METHODS: HIV infected patients on an E/C/F/TAF regimen were recruited into the study and followed up every 12 weeks. Participants were divided into E/C/F/TAF and B/F/TAF groups depending on whether they were switched to B/F/TAF during follow-up. Clinical information and blood samples were collected at 0, 12, and 24 weeks, and lipidomic analysis was performed using liquid chromatography mass spectrometry. RESULTS: No significant differences were observed between the groups at baseline. At week 24, patients switched to B/F/TAF had lower triglyceride [mmol/L; 1.23 (0.62) versus 2.03 (0.75), P = 0.001] and very low-density lipoprotein cholesterol [mmol/L; 0.64 (0.26) versus 0.84 (0.32), P = 0.037) compared with patients who continued E/C/F/TAF therapy. Small decrease from baseline in Framingham general cardiovascular risk score (FRS) was observed in the B/F/TAF arm [week (W) 0: 2.59 (1.57) versus W24: 2.18 (1.01), P = 0.043]. Lipidomic analysis indicated that E/C/F/TAF treatment increased the levels of several diglycerides (DGs), triacylglycerols (TAGs), and lyso-phosphatidylcholines (LPCs), whereas switching to B/F/TAF led to increased sphingolipids and glycerophospholipids. After adjusting for demographic and clinical parameters, only DG (16:0/18:2), DG (18:2/22:6), DG (18:3/18:2), DG (20:5/18:2), TAG (18:3/18:2/21:5), TAG (20:5/18:2/22:6), and LPC (22:6) were found to be significantly associated with FRS (regression coefficient of 0.17-6.02, P < 0.05). Most of these FRS associate lipid species were significantly elevated in individuals treated with E/C/F/TAF instead of individuals treated with B/F/TAF. CONCLUSION: E/C/F/TAF promotes the accumulation of lipid species closely associated with cardiovascular disease (CVD) risk among people living with HIV, whereas B/F/TAF has a decreased impact on CVD-related lipid profile and is associated with lower CVD risk. A graphical abstract is available with this article. TRIAL REGISTRATION: ClinicalTrials.gov; identifier, NCT06019273.

Migration Inhibition Factor Secreted by Peripheral Blood Memory B Cells Binding to CD74-CD44 Receptor Complex Drives Macrophage Behavior in Alzheimer's Disease.

Dysregulation of the peripheral immune system is be involved in the neuroinflammation in Alzheimer disease (AD) and accelerate the disease progression. The contribution of immune cells, particularly B cells, to AD pathogenesis has gained attention in recent research. In this study, we investigated the role of Peripheral Blood Memory B cells (PBMBs) and their secreted Migration Inhibition Factor (MIF) in driving macrophage behavior in AD based on the scRNA-seq technique, immunofluorescence and flow cytometry. We discovered that MIF binds to the CD74-CD44 receptor complex on macrophages, influencing their behavior. The dysregulated macrophage response hampers the clearance of amyloid-beta (Aß) plaques, exacerbating AD pathology. Targeting the MIF-CD74-CD44 signal pathway may hold therapeutic potential in modulating macrophage activity and mitigating neuroinflammation in AD. This study provides a further understanding of peripheral immune cells dysregulated in AD.

Isolation, identification and whole-genome analysis of an Achromobacter strain with a novel sulfamethazine resistance gene and sulfamethazine degradation gene cluster.

A sulfamethazine (SM2) degrading strain, Achromobacter mucicolens JD417, was isolated from sulfonamide-contaminated sludge using gradient acclimation. Optimal SM2 degradation conditions were pH 7, 36 °C, and 5 % inoculum, achieving a theoretical maximum degradation rate of 48 % at 50 ppm SM2. Cell growth followed the Haldane equation across different SM2 concentrations. Whole-genome sequencing of the strain revealed novel functional annotations, including a sulfonamide resistance gene (sul4) encoding dihydropteroate synthase, two flavin-dependent monooxygenase genes (sadA and sadB) crucial for SM2 degradation, and unique genomic islands related to metabolism, pathogenicity, and resistance. Comparative genomics analysis showed good collinearity and homology with other Achromobacter species exhibiting organics resistance or degradation capabilities. This study reveals the novel molecular resistance and degradation mechanisms and genetic evolution of an SM2-degrading strain, providing insights into the bioremediation of sulfonamide-contaminated environments.

Effects of common dissolved anions on the efficiency of Fe0-based remediation systems.

Quiescent batch experiments were conducted to evaluate the influences of Cl-, F-, HCO3-, HPO42-, and SO42- on the reactivity of metallic iron (Fe0) for water remediation using the methylene blue (MB) method. Strong discoloration of MB indicates high availability of solid iron corrosion products (FeCPs). Tap water was used as an operational reference. Experiments were carried out in graduated test tubes (22 mL) for up to 45 d, using 0.1 g of Fe0 and 0.5 g of sand. Operational parameters investigated were (i) equilibration time (0-45 d), (ii) 4 different types of Fe0, (iii) anion concentration (10 values), and (iv) use of MB and Orange II (O-II). The degree of dye discoloration, the pH, and the iron concentration were monitored in each system. Relative to the reference system, HCO3- enhanced the extent of MB discoloration, while Cl-, F-, HPO42-, and SO42- inhibited it. A different behavior was observed for O-II discoloration: in particular, HCO3- inhibited O-II discoloration. The increased MB discoloration in the HCO3- system was justified by considering the availability of FeCPs as contaminant scavengers, pH increase, and contact time. The addition of any other anion initially delays the availability of FeCPs. Conflicting results in the literature can be attributed to the use of inappropriate experimental conditions. The results indicate that the application of Fe0-based systems for water remediation is a highly site-specific issue which has to include the anion chemistry of the water.

Clinical effectiveness of a multitarget urine DNA test for urothelial carcinoma detection: a double-blinded, multicenter, prospective trial.

Urine-based testing is promising for noninvasive diagnosis of urothelial carcinoma (UC) but has suboptimal sensitivity for early-stage tumors. Herein, we developed a multitarget urine tumor DNA test, UI-Seek, for UC detection and evaluated its clinical feasibility. The prediction model was developed in a retrospective cohort (n = 382), integrating assays for FGFR3 and TERT mutations and aberrant ONECUT2 and VIM methylation to generate a UC-score. The test performance was validated in a double-blinded, multicenter, prospective trial (n = 947; ChiCTR2300076543) and demonstrated a sensitivity of 91.37% and a specificity of 95.09%. The sensitivity reached 75.81% for low-grade Ta tumors and exceeded 93% in high-grade Ta and higher stages (T1 to T4). Simultaneous identification of both bladder and upper urinary tract tumors was enabled with sensitivities exceeding 90%. No significant confounding effects were observed regarding benign urological diseases or non-UC malignancies. The test showed improved sensitivities over urine cytology, the NMP22 test, and UroVysion FISH alongside comparable specificities. The single-target accuracy was greater than 98% as confirmed by Sanger sequencing. Post-surgery UC-score decreased in 97.7% of subjects. Overall, UI-Seek demonstrated robust performance and considerable potential for the early detection of UC.

Transcriptomic analysis of the human habenula in schizophrenia.

Importance: Habenula (Hb) pathophysiology is involved in many neuropsychiatric disorders, including schizophrenia. Deep brain stimulation and pharmacological targeting of the Hb are emerging as promising therapeutic treatments. However, little is known about the cell type-specific transcriptomic organization of the human Hb or how it is altered in schizophrenia. Objective: To define the molecular neuroanatomy of the human habenula and identify transcriptomic changes in individuals with schizophrenia compared to neurotypical controls. Design Setting and Participants: This study utilized Hb-enriched postmortem human brain tissue. Single nucleus RNA-sequencing (snRNA-seq) and single molecule fluorescent in situ hybridization (smFISH) experiments were conducted to identify molecularly defined Hb cell types and map their spatial location (n=3-7 donors). Bulk RNA-sequencing and cell type deconvolution were used to investigate transcriptomic changes in Hb-enriched tissue from 35 individuals with schizophrenia and 33 neurotypical controls. Gene expression changes associated with schizophrenia in the Hb were compared to those previously identified in the dorsolateral prefrontal cortex (DLPFC), hippocampus, and caudate. Main Outcomes and Measures: Semi-supervised snRNA-seq cell type clustering. Transcript visualization and quantification of smFISH probes. Bulk RNA-seq cell type deconvolution using reference snRNA-seq data. Schizophrenia-associated gene differential expression analysis adjusting for Hb and thalamus fractions, RNA degradation-associated quality surrogate variables, and other covariates. Cross-brain region schizophrenia-associated gene expression comparison. Results: snRNA-seq identified 17 cell type clusters across 16,437 nuclei, including 3 medial and 7 lateral Hb populations. Cell types were conserved with those identified in a rodent model. smFISH for cell type marker genes validated snRNA-seq Hb cell types and depicted the spatial organization of subpopulations. Bulk RNA-seq analyses yielded 45 schizophrenia-associated differentially expressed genes (FDR < 0.05), with 32 (71%) unique to Hb-enriched tissue. Conclusions: These results identify topographically organized cell types with distinct molecular signatures in the human Hb. They further demonstrate unique transcriptomic changes in the epithalamus associated with schizophrenia, thereby providing molecular insights into the role of Hb in neuropsychiatric disorders.

Isolation and characterization of a G9P[23] porcine rotavirus strain AHFY2022 in China.

Rotavirus group A (RVA) is a main pathogen causing diarrheal diseases in humans and animals. Various genotypes are prevalent in the Chinese pig herd. The genetic diversity of RVA lead to distinctly characteristics. In the present study, a porcine RVA strain, named AHFY2022, was successfully isolated from the small intestine tissue of piglets with severe diarrhea. The AHFY2022 strain was identified by cytopathic effects (CPE) observation, indirect immunofluorescence assay (IFA), electron microscopy (EM), high-throughput sequencing, and pathogenesis to piglets. The genomic investigation using NGS data revealed that AHFY2022 exhibited the genotypes G9-P[23]-I5-R1-C1-M1-A8-N1-T1-E1-H1, using the online platform the Bacterial and Viral Bioinformatics Resource Center (BV-BRC) (https://www.bv-brc.org/). Moreover, experimental inoculation in 5-day-old and 27-day-old piglets demonstrated that AHFY2022 caused severe diarrhea, fecal shedding, small intestinal villi damage, and colonization in all challenged piglets. Taken together, our results detailed the virological features of the porcine rotavirus G9P[23] from China, including the whole-genome sequences, genotypes, growth kinetics in MA104 cells and the pathogenicity in suckling piglets.

Lipidomics reveals the significance and mechanism of the cellular ceramide metabolism for rotavirus replication.

As one of the most important causative agents of severe gastroenteritis in children, piglets, and other young animals, species A rotaviruses have adversely impacted both human health and the global swine industry. Vaccines against rotaviruses (RVs) are insufficiently effective, and no specific treatment is available. To understand the relationships between porcine RV (PoRV) infection and enterocytes in terms of the cellular lipid metabolism, we performed an untargeted liquid chromatography mass spectrometry (LC-MS) lipidomics analysis of PoRV-infected IPEC-J2 cells. Herein, a total of 451 lipids (263 upregulated lipids and 188 downregulated lipids), spanning sphingolipid, glycerolipid, and glycerophospholipids, were significantly altered compared with the mock-infected group. Interestingly, almost all the ceramides among these lipids were upregulated during PoRV infection. LC-MS analysis was used to validated the lipidomics data and demonstrated that PoRV replication increased the levels of long-chain ceramides (C16-ceramide, C18-ceramide, and C24-ceramide) in cells. Furthermore, we found that these long-chain ceramides markedly inhibited PoRV infection and that their antiviral actions were exerted in the replication stage of PoRV infection. Moreover, downregulation of endogenous ceramides with the ceramide metabolic inhibitors enhanced PoRV propagation. Increasing the levels of ceramides by the addition of C6-ceramide strikingly suppressed the replication of diverse RV strains. We further found that the treatment with an apoptotic inhibitor could reverse the antiviral activity of ceramide against PoRV replication, demonstrating that ceramide restricted RV infection by inducing apoptosis. Altogether, this study revealed that ceramides played an antiviral role against RV infection, providing potential approaches for the development of antiviral therapies.IMPORTANCERotaviruses (RVs) are among the most important zoonosis viruses, which mainly infected enterocytes of the intestinal epithelium causing diarrhea in children and the young of many mammalian and avian species. Lipids play an essential role in viral infection. A comprehensive understanding of the interaction between RV and lipid metabolism in the enterocytes will be helpful to control RV infection. Here, we mapped changes in enterocyte lipids following porcine RV (PoRV) infection using an untargeted lipidomics approach. We found that PoRV infection altered the metabolism of various lipid species, especially ceramides (derivatives of the sphingosine). We further demonstrated that PoRV infection increased the accumulation of ceramides and that ceramides exerted antiviral effects on RV replication by inducing apoptosis. Our findings fill a gap in understanding the alterations of lipid metabolism in RV-infected enterocytes and highlight the antiviral effects of ceramides on RV infection, suggesting potential approaches to control RV infection.

Digitization method for a photonic analog-to-digital converter with phase-shifted optical quantization.

This Letter proposes a novel, to the best of our knowledge, matrix digitization method for a photonic analog-to-digital converter with phase-shifted optical quantization (PSOQ-ADC). This method overcomes the issues of excessive bit width of the output code and the generation of invalid codes encountered by the traditional direct digitization method. A PSOQ-ADC was fabricated on a lithium niobate on insulator (LNOI) platform, and an experimental platform was built. The results show that RF signals at 1/2/5 GHz, which were sampled by a 50GS/s optical pulse train, were digitized successfully with the matrix digitization method, producing 5-bit codes without invalid codes. In comparison, the direct digitization method yields 10-bit codes, and as the optical signal-to-noise ratio (OSNR) decreases, the ratio of invalid codes increases in the direct digitization method; even with Hamming distance correction, its effective number of bits (ENOB) remains smaller than that of the matrix digitization.

A pharynx-to-brain axis controls pharyngeal inflammation-induced anxiety.

Anxiety is a remarkably common condition among patients with pharyngitis, but the relationship between these disorders has received little research attention, and the underlying neural mechanisms remain unknown. Here, we show that the densely innervated pharynx transmits signals induced by pharyngeal inflammation to glossopharyngeal and vagal sensory neurons of the nodose/jugular/petrosal (NJP) superganglia in mice. Specifically, the NJP superganglia project to norepinephrinergic neurons in the nucleus of the solitary tract (NTSNE). These NTSNE neurons project to the ventral bed nucleus of the stria terminalis (vBNST) that induces anxiety-like behaviors in a murine model of pharyngeal inflammation. Inhibiting this pharynx→NJP→NTSNE→vBNST circuit can alleviate anxiety-like behaviors associated with pharyngeal inflammation. This study thus defines a pharynx-to-brain axis that mechanistically links pharyngeal inflammation and emotional response.

Towards a more practical analysis of Newton's rings using deep learning.

As a typical form of optical fringes with a quadratic phase, Newton's ring patterns play an important role in spherical measurements and optical interferometry. A variety of methods have been used to analyze Newton's ring patterns. However, it is still rather challenging to fulfill the analysis. We present a deep-learning-based method to estimate the parameters of Newton's ring patterns and fulfill the analysis accordingly. The experimental results indicate the excellent accuracy, noise robustness, and demodulation efficiency of our method. It provides another applicable approach to analyzing Newton's ring patterns and brings insights into fringe analysis and interferometry-based measurements.

Ketogenic diet mitigates opioid-induced hyperalgesia by restoring short-chain fatty acids-producing bacteria in the gut.

ABSTRACT: Opioids are commonly prescribed to patients with chronic pain. Chronic opioid usage comes with a slew of serious side effects, including opioid-induced hyperalgesia (OIH). The patients with long-term opioid treatment experience paradoxical increases in nociceptive hypersensitivity, namely, OIH. Currently, treatment options for OIH are extremely lacking. In this study, we show that the ketogenic diet recovers the abnormal pain behavior caused by chronic morphine treatment in male mice, and we further show that the therapeutic effect of the ketogenic diet is mediated through gut microbiome. Our 16S rRNA sequencing demonstrates that chronic morphine treatment causes changes in mouse gut microbiota, specifically a decrease in short-chain fatty acids-producing bacteria, and the sequencing data also show that the ketogenic diet rescues those bacteria in the mouse gut. More importantly, we show that supplementation with short-chain fatty acids (butyrate, propionate, and acetate) can delay the onset of OIH, indicating that short-chain fatty acids play a direct role in the development of OIH. Our findings suggest that gut microbiome could be targeted to treat OIH, and the ketogenic diet can be used as a complementary approach for pain relief in patients with chronic opioid treatment. We only used male mice in this study, and thus, our findings cannot be generalized to both sexes.

Enhancing the Gelation Behavior of Transglutaminase-Induced Soy Protein Isolate(SPI) through Ultrasound-Assisted Extraction.

Gelation, as an important functional property of soy protein isolate (SPI), can be improved by some green technologies in food manufacturing, including ultrasound, ultrahigh pressure and microwave treatments. This work investigated the effect of an alkaline solubilisation step in SPI extraction combined with sonication on protein properties. The TGase-induced gel of the modified SPI was prepared to explore the effect of ultrasound on gel properties, including structures, strength, water-holding capacity and rheological properties. Additionally, the differences between traditional ultrasound modification of SPI and current modification methods were analyzed. The results showed that the ultrasonication-assisted extraction method could result in a significant increase in extraction rate from 24.68% to 42.25%. Moreover, ultrasound-assisted modification of SPI gels induced with transglutaminase (TGase) exhibited significant improvement in mechanical properties, such as texture, water-holding capacity and rheological properties, In particular, SPI extracted at 400 W ultrasound intensity for 180 s showed the best overall performance in terms of gel properties. Our method efficiently uniformizes gel structure, enhancing mechanical properties compared to conventional ultrasound methods, which reduced energy consumption and costs. These findings provide insights into the production of high-gelation SPI in food manufacturing.

Machine learning-based cell death signature for predicting the prognosis and immunotherapy benefit in stomach adenocarcinoma.

Stomach adenocarcinoma (STAD) is a one of most common malignancies with high mortality-to-incidence ratio. Programmed cell death (PCD) exerts vital functions in the progression of cancer. The role of PCD-related genes (PRGs) in STAD are not fully clarified. Using TCGA, GSE15459, GSE26253, GSE62254 and GSE84437 datasets, PCD-related signature (PRS) was constructed with an integrative procedure including 10 machine learning methods. The role of PRS in predicting the immunotherapy benefits was evaluated by several predicting score and 3 immunotherapy datasets (GSE91061, GSE78220, and IMvigor210). The model developed by Lasso + CoxBoost algorithm having a highest average C-index of 0.66 was considered as the optimal PRS. As an independent risk factor for STAD patients, PRS had a good performance in predicting the overall survival rate of patients, with an AUC of 1-, 3-, and 5-year ROC curve being 0.771, 0.751 and 0.827 in TCGA cohort. High PRS score demonstrated a lower gene set score of some immune-activated cells and immune-activated activities. Patient with high PRS score had a higher TIDE score, higher immune escape score, lower PD1&CTLA4 immunophenoscore, lower TMB score, lower response rate and poor prognosis, indicating a less immunotherapy response. The IC50 value of some drugs correlated with chemotherapy and targeted therapy was higher in high PRS score group. Our investigation developed an optimal PRS in STAD and it acted as an indicator for predicting the prognosis, stratifying risk and guiding treatment for STAD patients.