Enzymatic preparation of diacylglycerols: lipase screening, immobilization, characterization and glycerolysis performance.

BACKGROUNDS: Glycerolysis, with its advantages of readily available raw materials, simple operation, and mild reaction conditions, is a primary method for producing diacylglycerol (DAG). However, enzymatic glycerolysis faces challenges such as high enzyme costs, low reuse efficiency, and poor stability. The study aims to develop a cost-effective immobilized enzyme by covalently binding lipase to pre-activated carriers through the selection of suitable lipases, carriers, and activating agents. The optimization is intended to improve the glycerolysis reaction for efficient DAG production. RESULTS: Lipase CN-TL (from Thermomyces lanuginosus) was selected through glycerolysis reaction and molecular docking to catalyze the glycerolysis reaction. Optimizing the immobilization method by covalently binding CN-TL to poly(ethylene glycol) diglycidyl ether (PEGDGE)-preactivated resin LX-201A resulted in the preparation of the immobilized enzyme TL-PEGDGE-LX. The immobilized enzyme retained over 90% of its initial activity after five consecutive reactions, demonstrating excellent reusability. The DAG content in the product remained at 84.8% of its initial level, further highlighting the enzyme's potential for reusability and its promising applications in the food and oil industries. CONCLUSIONS: The immobilized lipase TL-PEGDGE-LX, created by covalently immobilizing lipase CN-TL on PEGDGE-preactivated carriers, demonstrated broad applicability and excellent reusability. This approach offers an economical and convenient immobilization strategy for the enzymatic glycerolysis production of DAG. © 2024 Society of Chemical Industry.

Women's perceptions of the use of virtual reality during childbirth: A qualitative systematic review and meta-synthesis.

BACKGROUND: Childbearing women often resort to pharmacotherapies for pain and anxiety management during childbirth, despite their adverse effects. Virtual reality has emerged as an alternative, but a comprehensive synthesis of women's experiences with virtual reality during labor is lacking, hindering validation of its perceived effects. AIM: To synthesize the best available evidence of women's perceptions of the use of virtual reality during childbirth. METHODS: From the beginning until December 31, 2023, a comprehensive search was conducted across nine databases (PubMed, Embase, Cochrane Library, CINAHL, MEDLINE, PsycINFO, Web of Science, Scopus, and ProQuest Dissertations and Theses Global), with no restrictions on publication year but limited to English language only. Qualitative findings focusing on women's experiences with virtual reality during childbirth were included. Two reviewers independently screened studies, extracted data, and appraised quality. Data synthesis followed the Joanna Briggs Institute (JBI) Manual for Evidence Synthesis and thematic analysis framework, with evidence assessed through GRADE-CERQual. RESULTS: Eight studies were included, revealing a central theme: "The Journey of Childbirth through the Lens of Virtual Reality", supported by four themes: collective experiences and sentiments; labor pain and anxiety mitigation; Contentment and enthusiasm for subsequent utilization; and preferences and improvements. CONCLUSION: This qualitative systematic review explored women's unique experiences with virtual reality during childbirth. It highlighted the need for ongoing research and collaborative efforts in healthcare to enhance virtual reality interventions, ensuring their efficacy in obstetrics for competent childbirth management.

AB039. Malignant transformation of intracranial germinoma to non-germinomatous germ cell tumors-incidence, treatment strategy and outcome: a case report and literature review.

BACKGROUND: Intracranial germ cell tumors are rare neoplasms seen mainly in children and adolescents. Compared to non-germinomatous germ cell tumors (NGGCTs), germinomas typically respond well to chemo-radiotherapy and portend a better prognosis. We report here a patient with intracranial germinoma which showed complete remission following chemo-radiotherapy but re-presented with malignant transformation to NGGCT thirteen years later. We then performed a literature review to understand the treatment strategy and outcome of this rare phenomenon. METHODS: Review of the patient's case note, followed by a literature review of the topic. RESULTS: A 13-year-old male presented with 6 weeks of polyuria and polydipsia. Imaging showed bifocal (suprasellar and pineal) lesions. Histology from an open biopsy diagnosed a germinoma. He underwent extended whole ventricular irradiation with local boost and chemotherapy, which led to complete resolution on imaging. Thirteen years later, he re-presented with headaches and diabetes insipidus. Imaging showed a new right frontal lesion with elevated serum beta-human chorionic gonadotropin (ß-hCG) and alpha-fetoprotein (AFP). The tumor was excised with histology confirming a mixed tumor comprising germinoma, yolk sac, and choriocarcinoma. A literature review returned eight case reports of malignant transformation of intracranial germinoma to NGGCTs, covering eight patients (seven males, and one female; aged 5-23 years old). Four had the primary tumor located in the pineal region, three in the suprasellar region, and one at both sites. Recurrence with malignant transformation occurred at a median of 24.5 months after initial diagnosis (range, 5 months to 14 years). Five patients had recurrences intra-abdominally, all of whom had a ventriculoperitoneal shunt (VPS) inserted during the treatment of the initial tumor. Of the remaining three intracranial recurrences, two were at the same site while one at a distant site. The most common histology was yolk sac tumor (five patients), followed by two each of immature teratoma, choriocarcinoma, and embryonal carcinoma (some were mixed germ cell tumors). Of those with intra-abdominal recurrence, four died within 2 months of diagnosis. Those with intracranial recurrences survived longer, with a median survival of 15 months, and one longer than 27 months. CONCLUSIONS: Malignant transformation to NGGCTs is rare. Relapse can occur intracranially, or in cases where VPS was present, intraabdominally. Outcomes following transformation were poor despite aggressive treatment, with those intra-abdominal recurrences faring much worse.

Changes in stability, phytonutrients, 3-chloropropanol esters and glycidyl esters of peanut oil-based diacylglycerols during heat treatment.

Diacylglycerol (DAG) is generally considered one of the precursors of 3-chloropropanol esters (3-MCPDE) and glycidyl esters (GEs). This study aimed to evaluate static heating and stir-frying properties of peanut oil (PO) and PO based 58% and 82% DAG oils (PDAG-58 and PDAG-82). Observations revealed that, phytonutrient levels notably diminished during static heating, with PDAG exhibiting reduced oxidative stability, but maintaining a stability profile similar to PO over a short period. During stir-frying, 3-MCPDE content initially increased and then decreased whereas the opposite was observed for GEs. Furthermore, as temperature, and NaCl concentration increased, there was a corresponding increase in the levels of 3-MCPDE and GEs, although remained within safe limits. When used in suitable concentrations, these findings underscore the potential of DAG, as a nutritionally rich and oxidatively stable alternative to conventional cooking oils, promoting the use of DAG edible oil in heat-cooked food systems.

Immobilization of Lipase from Thermomyces Lanuginosus and Its Glycerolysis Ability in Diacylglycerol Preparation.

In the glycerolysis process for diacylglycerol (DAG) preparation, free lipases suffer from poor stability and the inability to be reused. To address this, a cost-effective immobilized lipase preparation was developed by cross-linking macroporous resin with poly (ethylene glycol) diglycidyl ether (PEGDGE) followed by lipase adsorption. The selected immobilization conditions were identified as pH 7.0, 35 °C, cross-linking agent concentration 2.0%, cross-linking time 4 h, lipase amount 5 mg/g of support, and adsorption time 4 h. Enzymatic properties of the immobilized lipase were analyzed, revealing enhanced pH stability, thermal stability, storage stability, and operational stability post-immobilization. The conditions for immobilized enzyme-catalyzed glycerolysis to produce DAG were selected, demonstrating the broad applicability of the immobilized lipase. The immobilized lipase catalyzed glycerolysis reactions using various oils as substrates, with DAG content in the products ranging between 35 and 45%, demonstrating broad applicability. Additionally, the changes during the repeated use of the immobilized lipase were characterized, showing that mechanical damage, lipase leakage, and alterations in the secondary structure of the lipase protein contributed to the decline in catalytic activity over time. These findings provide valuable insights for the industrial application of lipase.

Pickering Foam Stabilized by Diacylglycerol-Based Solid Lipid Nanoparticles: Effect of Protein Modification.

Pickering foams have great potential for applications in aerated foods, but their foaming ability and physical stability are still far from satisfactory. Herein, solid lipid particles (SLNs) were fabricated by using diacylglycerol of varying acyl chain lengths with modification by a protein. The SLNs showed different crystal polymorphisms and air-water interfacial activity. C14-DAG SLN with a contact angle ∼ 79° formed aqueous foam with supreme stability and high plasticity. Whey protein isolate and sodium caseinate (0.1 wt %) considerably enhanced the foamability and interfacial activity of SLNs and promoted the packing of particles at the bubble surface. However, high protein concentration caused foam destruction due to the competitive adsorption effect. ß-sheet increased in protein after adsorption and changed the polymorphism and thermodynamic properties of SLN. The foam collapsing behaviors varied in the presence of protein. The results gave insights into fabricating ultrastable aqueous foams by using high-melting DAG particles. The obtained foams demonstrated good temperature sensitivity and plasticity, which showed promising application prospects in the food and cosmetic fields.

The correlation between quality of recovery and parturient outcomes after Cesarean delivery: a cohort study.

PURPOSE: Recent studies have reported the use of the obstetric-specific quality of recovery tool (ObsQoR-10) to assess the quality of recovery in parturients after childbirth; however, the correlation between ObsQoR-10 scores and important postpartum outcomes are unclear. The primary aim of the present study was to investigate the correlations between ObsQoR-10 scores at 24 hr after Cesarean delivery and breastfeeding, depressive symptomatology, overall health, and pain at seven days postpartum. METHODS: We recruited parturients who underwent elective Cesarean delivery at KK Hospital in Singapore. Parturients provided responses to post-Cesarean questionnaires at 1) 24 hr (ObsQoR-10, EuroQol EQ-Visual Analogue Scale, Edinburgh Postnatal Depression Scale), 2) 48 hr (ObsQoR-10, EQ-Visual Analogue Scale), and 3) seven days after Cesarean delivery (ObsQoR-10, Breastfeeding Self-Efficacy Scale-Short form, EQ-Visual Analogue Scale, Edinburgh Postnatal Depression Scale, pain survey). RESULTS: We enrolled 222 participants, 200 (90%) of whom completed the seven-day follow-up between September 2022 and April 2023. There was limited correlation between ObsQoR-10 at 24 hr with the Edinburgh Postnatal Depression Scale (r = 0.135), EQ-Visual Analogue Scale (r = 0.158), Breastfeeding Self-Efficacy Scale-Short form (r = 0.225), and averaged pain scores (r = -0.107) at seven days postpartum. ObsQoR-10 breastfeeding sub-score at 24 hr was weakly correlated with Breastfeeding Self-Efficacy Scale-Short form at seven days postpartum (r = 0.307). CONCLUSION: ObsQoR-10 at 24 hr postpartum had limited correlation with breastfeeding, depressive symptomatology, overall health, and pain at seven days. STUDY REGISTRATION: ClinicalTrials.gov ( NCT04989894 ); first submitted 4 July 2021.

RéSUMé: OBJECTIF: Des études récentes ont rapporté l'utilisation de l'outil de qualité de récupération spécifique à l'obstétrique (ObsQoR-10) pour évaluer la qualité de la récupération chez les personnes parturientes après l'accouchement; cependant, la corrélation entre les scores sur l'outil ObsQoR-10 et les devenirs post-partum importants n'est pas claire. L'objectif principal de la présente étude était d'examiner les corrélations entre les scores ObsQoR-10 obtenus 24 heures après l'accouchement par césarienne et l'allaitement, la symptomatologie dépressive, l'état de santé général et la douleur sept jours après l'accouchement. MéTHODE: Nous avons recruté des personnes parturientes qui ont bénéficié d'un accouchement par césarienne programmée à l'Hôpital KK de Singapour. Les personnes parturientes ont répondu aux questionnaires post-césarienne à 1) 24 heures (ObsQoR-10, échelle visuelle analogique EuroQol EQ-Visual Analogue Scale, Échelle de dépression postnatale d'Édimbourg), 2) 48 heures (ObsQoR-10, EQ-Visual Analogue Scale), et 3) sept jours après la césarienne (ObsQoR-10, Échelle abrégée d'auto-efficacité de l'allaitement [Breastfeeding Self-Efficacy Scale-Short form], EQ-Visual Analogue Scale, Échelle de dépression postnatale d'Edimbourg, enquête sur la douleur). RéSULTATS: Nous avons recruté 222 participant·es, dont 200 (90 %) ont terminé le suivi de sept jours entre septembre 2022 et avril 2023. Il y avait une corrélation limitée entre l'ObsQoR-10 à 24 heures et l'Échelle de dépression postnatale d'Édimbourg (r = 0,135), l'échelle EQ-Visual Analogue Scale (r = 0,158), l'échelle d'auto-efficacité de l'allaitement maternel forme courte (r = 0,225) et les scores moyens de douleur (r = -0,107) sept jours après l'accouchement. Le sous-score d'allaitement ObsQoR-10 à 24 heures était faiblement corrélé à l'échelle d'auto-efficacité de l'allaitement maternel à sept jours après l'accouchement (r = 0,307). CONCLUSION: L'ObsQoR-10 à 24 heures après l'accouchement avait une corrélation limitée avec l'allaitement, la symptomatologie dépressive, l'état de santé général et la douleur à sept jours. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov ( NCT04989894 ); première soumission le 4 juillet 2021.

Interplay between particle size and microbial ecology in the gut microbiome.

Physical particles can serve as critical abiotic factors that structure the ecology of microbial communities. For non-human vertebrate gut microbiomes, fecal particle size (FPS) has been known to be shaped by chewing efficiency and diet. However, little is known about what drives FPS in the human gut. Here, we analyzed FPS by laser diffraction across a total of 76 individuals and found FPS to be strongly individualized. Contrary to our initial hypothesis, a behavioral intervention with 41 volunteers designed to increase chewing efficiency did not impact FPS. Dietary patterns could also not be associated with FPS. Instead, we found evidence that human and mouse gut microbiomes shaped FPS. Fecal samples from germ-free and antibiotic-treated mice exhibited increased FPS relative to colonized mice. In humans, markers of longer transit time were correlated with smaller FPS. Gut microbiota diversity and composition were also associated with FPS. Finally, ex vivo culture experiments using human fecal microbiota from distinct donors showed that differences in microbiota community composition can drive variation in particle size. Together, our results support an ecological model in which the human gut microbiome plays a key role in reducing the size of food particles during digestion. This finding has important implications for our understanding of energy extraction and subsequent uptake in gastrointestinal tract. FPS may therefore be viewed as an informative functional readout, providing new insights into the metabolic state of the gut microbiome.

Effects of Tea Seed Oil Extracted by Different Refining Temperatures on the Intestinal Microbiota of High-Fat-Diet-Induced Obese Mice.

Obesity has become one of the most serious chronic diseases threatening human health. Its onset and progression are closely related to the intestinal microbiota, as disruption of the intestinal flora promotes the production of endotoxins and induces an inflammatory response. This study aimed to investigate the variations in the physicochemical properties of various refined tea seed oils and their impact on intestinal microbiota disorders induced by a high-fat diet (HFD) through dietary intervention. In the present study, C57BL/6J mice on a HFD were randomly divided into three groups: HFD, T-TSO, and N-TSO. T-TSO and N-TSO mice were given traditionally refined and optimized tea seed oil for 12 weeks. The data revealed that tea seed oil obtained through degumming at 70 °C, deacidification at 50 °C, decolorization at 90 °C, and deodorization at 180 °C (at 0.06 MPa for 1 h) effectively removed impurities while minimizing the loss of active ingredients. Additionally, the optimized tea seed oil mitigated fat accumulation and inflammatory responses resulting from HFD, and reduced liver tissue damage in comparison to traditional refining methods. More importantly, N-TSO can serve as a dietary supplement to enhance the diversity and abundance of intestinal microbiota, increasing the presence of beneficial bacteria (norank_f__Muribaculaceae, Lactobacillus, and Bacteroides) while reducing pathogenic bacteria (Alistipes and Mucispirillum). Therefore, in HFD-induced obese C57BL/6J mice, N-TSO can better ameliorate obesity compared with a T-TSO diet, which is promising in alleviating HFD-induced intestinal microbiota disorders.

Factors Influencing Mental Well-being Among Older Malaysians.

Older adults are at greater risk of mental health issues. This study examined the factors influencing mental well-being among 2230 Malaysian older adults, using data from the 2018 to 2019 Malaysia Ageing and Retirement Survey. The World Health Organization-Five Well-Being Index (WHO-5) was used to assess mental well-being, and linear regression analysis identified the significant factors. Women had lower mental well-being scores than men (P = .012, ß = -0.016). Chinese (P = .024, ß = -0.020), Indian (P < .001, ß = -0.043), and other ethnicities (P < .001, ß = -0.031) reported lower scores than Malays. The factors associated with better well-being were secondary (P = .001, ß = 0.032) and tertiary education (P < .001, ß = 0.063), and good (P < .001, ß = 0.081) and moderate (P < .001, ß = 0.038) health status. Diseases-limiting activities were associated with poor well-being (P < .001, ß = -0.030). Support from family (P < .001, ß = 0.062) and friends (P < .001, ß = 0.032), social activity participation (P < .001, ß = 0.026), and functional ability (P < .001, ß = 0.043) were significant positive factors. There is a need for targeted interventions to enhance mental health among Malaysian older adults.

Cranioencephalic functional lymphoid units in glioblastoma.

The ecosystem of brain tumors is considered immunosuppressed, but our current knowledge may be incomplete. Here we analyzed clinical cell and tissue specimens derived from patients presenting with glioblastoma or nonmalignant intracranial disease to report that the cranial bone (CB) marrow, in juxtaposition to treatment-naive glioblastoma tumors, harbors active lymphoid populations at the time of initial diagnosis. Clinical and anatomical imaging, single-cell molecular and immune cell profiling and quantification of tumor reactivity identified CD8+ T cell clonotypes in the CB that were also found in the tumor. These were characterized by acute and durable antitumor response rooted in the entire T cell developmental spectrum. In contrast to distal bone marrow, the CB niche proximal to the tumor showed increased frequencies of tumor-reactive CD8+ effector types expressing the lymphoid egress marker S1PR1. In line with this, cranial enhancement of CXCR4 radiolabel may serve as a surrogate marker indicating focal association with improved progression-free survival. The data of this study advocate preservation and further exploitation of these cranioencephalic units for the clinical care of glioblastoma.

Spatial resolution of the head and neck cancer tumor microenvironment to identify tumor and stromal features associated with therapy response.

Head and neck cancer (HNC) is the seventh most common cancer globally, resulting in 440 000 deaths per year. While there have been advancements in chemoradiotherapy and surgery, relapse occurs in more than half of HNCs, and these patients have a median survival of 10 months and a 2-year survival of < 20%. Only a subset of patients displays durable benefits from immunotherapies in metastatic and recurrent HNC, making it critical to understand the tumor microenvironment (TME) underpinning therapy responses in HNC. To recognize biological differences within the TME that may be predictive of immunotherapy response, we applied cutting-edge geospatial whole-transcriptome profiling (NanoString GeoMx Digital Spatial Profiler) and spatial proteomics profiling (Akoya PhenoCycler-Fusion) on a tumor microarray consisting of 25 cores from 12 patients that included 4 immunotherapy-unresponsive (8 cores) and 2 immunotherapy-responsive patients (5 cores), as well as 6 immunotherapy naïve patients (12 cores). Through high-plex, regional-based transcriptomic mapping of the tumor and TME, pathways involved with the complement system and hypoxia were identified to be differentially expressed in patients who went on to experience a poor immunotherapy response. Single-cell, targeted proteomic analysis found that immune cell infiltration of the cancer cell mass and interactions of CD8 T cells with tumor and other immune cells were associated with positive immunotherapy response. The relative abundance of specific tumor phenotypes and their interactions with various immune cells was identified to be different between response groups. This study demonstrates how spatial transcriptomics and proteomics can resolve novel alterations in the TME of HNC that may contribute to therapy sensitivity and resistance.

Thermo-Switchable Enzyme@Metal-Organic Framework for Selective Biocatalysis and Biosensing.

The stimulus-responsive regulation of enzyme catalytic activity and selectivity provides a new opportunity to extend the functionality and efficiency of immobilized enzymes. This work aims to design and synthesize a thermo-switchable enzyme@MOF for size-selective biocatalysis and biosensing through the immobilization of Candida rugosa lipase (CRL) within ZIF-8 functionalized with thermally responsive polymer, poly(N-isopropylacrylamide) (PNIPAM) (CRL@ZIF-8-PNIPAM). Unlike free CRL, which does not demonstrate substrate selectivity, we can reversibly tune the pore size of the ZIF-8-PNIPAM nanostructures (open pores or blocked pores) through temperature stimulus and subsequently modulate the substrate selectivity of CRL@ZIF-8-PNIPAM. CRL@ZIF-8-PNIPAM had the highest hydrolytic activity for small molecules (12 mM p-nitrophenol/mg protein/min, 4-nitrophenyl butyrate (p-NP Be)) and the lowest hydrolytic activity for large molecules (0.16 mM p-nitrophenol/mg protein/min, 4-nitrophenyl palmitate (p-NP P)). In addition, CRL@ZIF-8-PNIPAM demonstrated thermo-switchable behavior for large molecules (p-NP P). The p-NP P hydrolytic activity of CRL@ZIF-8-PNIPAM was significantly lower at 40 °C (blocked pores) than at 27 °C (open pores). However, the transition of blocked pores and open pores is a gradual process that resulted in a delay in the "thermo-switchable" catalytic behavior of CRL@ZIF-8-PNIPAM during thermal cycling. CRL@ZIF-8-PNIPAM was also successfully used for the fabrication of electrochemical biosensors for the selective biosensing of pesticides with different molecular sizes.

Transient inhibition of type I interferon enhances CD8 + T cell stemness and vaccine protection.

Developing vaccines that promote CD8 + T cell memory is a challenge for infectious disease and cancer immunotherapy. TCF-1 + stem cell-like memory T (T SCM ) cells are important determinants of long-lived memory. Yet, the developmental requirements for T SCM formation are unclear. Here, we identify the temporal window for type I interferon (IFN-I) receptor (IFNAR) blockade to drive T SCM cell generation. T SCM cells were transcriptionally distinct and emerged from a transitional precursor of exhausted (T PEX ) cellular state concomitant with viral clearance. T SCM differentiation correlated with T cell retention within the lymph node paracortex, due to increased CXCR3 chemokine abundance which disrupted gradient formation. These affects were due a counterintuitive increase in IFNψ, which controlled cell location. Combining IFNAR inhibition with mRNA-LNP vaccination promoted specific T SCM differentiation and enhanced protection against chronic infection. These finding propose a new approach to vaccine design whereby modulation of inflammation promotes memory formation and function. HIGHLIGHTS: Early, transient inhibition of the type I interferon (IFN) receptor (IFNAR) during acute viral infection promotes stem cell-like memory T (T SCM ) cell differentiation without establishing chronic infection. T SCM and precursor of exhausted (T PEX ) cellular states are distinguished transcriptionally and by cell surface markers. Developmentally, T SCM cell differentiation occurs via a transition from a T PEX state coinciding with viral clearance. Transient IFNAR blockade increases IFNψ production to modulate the ligands of CXCR3 and couple T SCM differentiation to cell retention within the T cell paracortex of the lymph node. Specific promotion of T SCM cell differentiation with nucleoside-modified mRNA-LNP vaccination elicits enhanced protection against chronic viral challenge.

Spatial dynamics of tertiary lymphoid aggregates in head and neck cancer: insights into immunotherapy response.

BACKGROUND: Recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) generally has a poor prognosis for patients with limited treatment options. While incorporating immune checkpoint inhibitors (ICIs) has now become the standard of care, the efficacy is variable, with only a subset of patients responding. The complexity of the tumor microenvironment (TME) and the role of tertiary lymphoid structures (TLS) have emerged as critical determinants for immunotherapeutic response. METHODS: In this study, we analyzed two independently collected R/M HNSCC patient tissue cohorts to better understand the role of TLS in response to ICIs. Utilizing a multi-omics approach, we first performed targeted proteomic profiling using the Nanostring GeoMx Digital Spatial Profiler to quantify immune-related protein expression with spatial resolution. This was further characterized by spatially resolved whole transcriptome profiling of TLSs and germinal centers (GCs). Deeper single-cell resolved proteomic profiling of the TLSs was performed using the Akoya Biosciences Phenocycler Fusion platform. RESULTS: Our proteomic analysis revealed the presence of T lymphocyte markers, including CD3, CD45, and CD8, expressing cells and upregulation of immune checkpoint marker PD-L1 within tumor compartments of patients responsive to ICIs, indicative of 'hot tumor' phenotypes. We also observed the presence of antigen-presenting cells marked by expression of CD40, CD68, CD11c, and CD163 with upregulation of antigen-presentation marker HLA-DR, in patients responding to ICIs. Transcriptome analysis of TLS and GCs uncovered a marked elevation in the expression of genes related to immune modulation, diverse immune cell recruitment, and a potent interferon response within the TLS structure. Notably, the distribution of TLS-tumor distance was found to be significantly different across response groups (H = 9.28, p = 0.026). The proximity of TLSs to tumor cells was found to be a critical indicator of ICI response, implying that patients with TLSs located further from tumor cells have worse outcomes. CONCLUSION: The study underscores the multifaceted role of TLSs in modulating the immunogenic landscape of the TME in R/M HNSCC, likely influencing the efficacy of ICIs. Spatially resolved multi-omics approaches offer valuable insights into potential biomarkers for ICI response and highlight the importance of profiling the TME complexity when developing therapeutic strategies and patient stratification.

Acute toxicity profiling of medicinal herb Ardisia elliptica leaf extract by conventional evaluations and proton nuclear magnetic resonance (NMR) metabolomics.

Background and aim: Interest in the safety of herbal medicine is growing rapidly regarding knowledge and challenges in natural products. Hence, this study aimed to reveal the toxicological profile of Ardisia elliptica, a traditional medicinal plant used in the treatment of various illnesses. Experimental procedure: Acute toxicity study was performed on female and male Sprague Dawley rats with a single oral administration of 2000 mg/kg BW of 70% ethanolic A. elliptica leaf extract, using a combination of conventional investigations and 1H-NMR-based metabolomics approaches. Results: Physical, hematological, biochemical, and histopathological assessments demonstrated the usual rat profile, with no mortality and delayed toxicity 14 days after administration. 1H NMR serum metabolomics depicted similar metabolites between normal and treated groups. Nevertheless, 1H NMR of urinary metabolomics revealed perturbation in carbohydrate, amino acid, and energy metabolism within 24h after extract administration, while no accumulation of toxic biomarkers in the collected biological fluids on Day 14. A minor gender-based difference revealed the influence of sex hormones and different energy expenditure on response to extract treatment. Conclusion: This study suggested that 2000 mg/kg BW of 70% ethanolic A. elliptica leaf extract is considered as safe for consumption and offered a comprehensive overview of the response of physiological and metabolic aspects applicable to food and herbal product development.

Subjective Socioeconomic Status Moderates How Resting Heart Rate Variability Predicts Pain Response.

Higher resting heart rate variability (HRV)-an index of more flexible response to environmental stressors, including noxious stimuli-has been linked to reduced perception of experimentally induced pain. However, as stress responses are adapted to one's chronic environments, we propose that chronic exposure to threats captured by one's subjective socioeconomic status (SSS) may shape different adaptations that produce distinct pain responses linked to higher resting HRV. Specifically, lower SSS individuals with more threat exposures may prioritize threat detection by upregulating sensitivity to stressors, such as acute pain. Therefore, higher HRV would predict greater perceived acute pain among lower SSS individuals. In contrast, higher SSS individuals with less threat exposures may instead prioritize affective regulation by downregulating sensitivity to stressors, producing lower pain perception with higher HRV. We examined this stress response moderation by SSS in 164 healthy young adults exposed to experimental pain via the cold pressor test (CPT). Resting HRV, indexed by the root-mean-square of successive differences in heart rate, and self-reported SSS were measured at rest. Pain perception indexed by self-reported pain and pain tolerance indexed by hand-immersion time during the CPT were assessed. Results revealed that among higher SSS individuals, higher resting HRV predicted lower pain reports and subsequently greater pain tolerance during the CPT. Conversely, among lower SSS individuals, higher resting HRV predicted higher pain reports and subsequently lower pain tolerance. These findings provide preliminary evidence that environmental stress exposures linked to one's SSS may shape unique biological adaptations that predict distinct pain responses. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-023-00234-w.

Sessile serrated lesion prevalence and factors associated with their detection: a post-hoc analysis of a multinational randomized controlled trial from Asia.

BACKGROUND: Sessile serrated lesions (SSLs) are associated with an increased risk of colorectal cancer. Data on the prevalence of SSLs in Asia are limited. We performed this study to estimate the prevalence of SSLs in Asia and to explore endoscopic factors that are associated with SSL detection. METHODS: This is a post-hoc analysis of a multicenter randomized controlled trial from four Asian countries/regions that compared adenoma detection rates using linked-color imaging (LCI) and white-light imaging. Colonoscopies were performed in an average-risk population for screening, diagnostic examination, or polyp surveillance. Patients with SSLs were compared against those without SSLs to evaluate for possible predictors of SSL detection using Firth's logistic regression. RESULTS: 2898 participants (mean age 64.5 years) were included in the analysis. The estimated prevalence of SSLs was 4.0% (95%CI 3.4%-4.8%), with no sex or age group differences. On multivariable analysis, use of LCI (adjusted odds ratio [aOR] 1.63, 95%CI 1.10-2.41), experienced endoscopists (aOR 1.94, 95%CI 1.25-3.00), use of transparent cap (aOR 1.75, 95%CI 1.09-2.81), and longer withdrawal time (aOR 1.06, 95%CI 1.03-1.10) were independently associated with SSL detection. Synchronous adenoma detection (aOR 1.89, 95%CI 1.20-2.99) was also predictive of SSL detection. CONCLUSION: The prevalence of SSLs in Asia is 4.0%. Use of LCI or a transparent cap, greater endoscopist experience, and longer withdrawal time were all associated with increased SSL detection.

A commensal-derived sugar protects against metabolic disease.

Obesity is a worsening global epidemic that is regulated by the microbiota through unknown bacterial factors. We discovered a human-derived commensal bacterium, Clostridium immunis , that protects against metabolic disease by secreting a phosphocholine-modified exopolysaccharide. Genetic interruption of the phosphocholine biosynthesis locus ( licABC ) results in a functionally inactive exopolysaccharide, which demonstrates the critical requirement for this phosphocholine moiety. This C. immunis exopolysaccharide acts via group 3 innate lymphoid cells and modulating IL-22 levels, which results in a reduction in serum triglycerides, body weight, and visceral adiposity. Importantly, phosphocholine biosynthesis genes are less abundant in humans with obesity or hypertriglyceridemia, findings that suggest the role of bacterial phosphocholine is conserved across mice and humans. These results define a bacterial molecule-and its key structural motif-that regulates host metabolism. More broadly, they highlight how small molecules, such as phosphocholine, may help fine-tune microbiome- immune-metabolism interactions.

Consensus statements and guideline for the diagnosis and management of plantar fasciitis in Singapore.

Introduction: Plantar fasciitis (PF) is a common cause of heel pain among the general population. The lack of standard practice guideline in Singapore presents challenges in education and clinical practice for this painful condition. These consensus statements and guideline were developed to streamline and improve the management of PF, covering key aspects such as diagnosis, investigations, risk factors, treatment modalities, monitoring and return to work/play. Method: A multidisciplinary expert panel consisting of 6 sports physicians, 2 orthopaedic surgeons, 2 podiatrists and 1 physiotherapist from SingHealth Duke-NUS Sport & Exercise Medicine Centre (SDSC) was convened based on their clinical and academic experience with PF. The Grading of Recommen-dations, Assessment, Development and Evaluations (GRADE) approach was used to evaluate the quality of the evidence and subsequently prepare a set of clinical recommen-dations pertaining to the manage-ment of PF. A modified Delphi process was used to reach consensus. Results: Eighteen consensus statements were developed to cover key components of PF management, from initial diagnosis to treatment modalities and finally, clinical progression. They were subsequently consolidated under a proposed treatment pathway guideline for PF. Conclusion: The SDSC consensus statements and guideline provide concise recommendations for the management of PF in Singapore.