Encapsulation of Lactiplantibacillus plantarum with casein-gellan gum emulsions to enhance its storage, pasteurization, and gastrointestinal survival.

Probiotics serve a very important role in human health. However, probiotics have poor stability during processing, storage, and gastrointestinal digestion. The gellan gum (GG) is less susceptible to enzymatic degradation and resistant to thermal and acidic environments. This study investigated the effect of casein (CS)-GG emulsions to encapsulate Lactiplantibacillus plantarum CICC 6002 (L. plantarum CICC 6002) on its storage stability, thermal stability, and gastrointestinal digestion. L. plantarum CICC 6002 was suspended in palm oil and emulsions were prepared using CS or CS-GG complexes. We found the CS-GG emulsions improved the viability of L. plantarum CICC 6002 after storage, pasteurization, and digestion compared to the CS emulsions. In addition, we investigated the influence of the gellan gum concentration on emulsion stability, and the optimal stability was observed in the emulsion prepared by CS-0.8% GG complex. This study provided a new strategy for the protection of probiotics based on CS-GG delivery system.

Immunosuppressive tumor microenvironment in gastric signet-ring cell carcinoma.

Gastric signet-ring cell carcinoma (GSRCC) is a subtype of gastric cancer with distinct phenotype and high risk of peritoneal metastasis. Studies have shown that early GSRCC has a good prognosis, while advanced GSRCC is insensitive to radiotherapy, chemotherapy or immune checkpoint blockade therapy. With technological advancement of single-cell RNA sequencing analysis and cytometry by time of flight mass cytometry, more detailed atlas of tumor microenvironment (TME) in GSRCC and its association with prognosis could be investigated extensively. Recently, two single-cell RNA sequencing studies revealed that GSRCC harbored a unique TME, manifested as highly immunosuppressive, leading to high immune escape. The TME of advanced GSRCC was enriched for immunosuppressive factors, including the loss of CXCL13 +-cluster of differentiation 8+-Tex cells and declined clonal crosstalk among populations of T and B cells. In addition, GSRCC was mainly infiltrated by follicular B cells. The increased proportion of SRCC was accompanied by a decrease in mucosa-associated lymphoid tissue-derived B cells and a significant increase in follicular B cells, which may be one of the reasons for the poor prognosis of GSRCC. By understanding the relationship between immunosuppressive TME and poor prognosis in GSRCC and the underlying mechanism, more effective immunotherapy strategies and improved treatment outcomes of GSRCC can be anticipated.

Agrimonolide inhibits glycolysis in ovarian cancer cells by regulating HIF1A.

BACKGROUND: Ovarian cancer is one of the most common tumors affecting females, significantly disrupting their quality of life. Agrimonolide, an extract derived from Agrimony (Agrimonia pilosa Ledeb.), has been shown to exert various regulatory effects on several diseases. Notably, recent studies indicate that Agrimonolide may attenuate the progression of ovarian cancer. However, the detailed regulatory mechanisms of Agrimonolide in this context require further investigation. PURPOSE: To determine the significance of HIF1A as a key target in ovarian cancer and its potential underlying signaling pathway. METHODS: Cell viability and proliferation were assessed using CCK-8 and colony formation assays. Glucose uptake and lactate production were measured using commercial kits, and the extracellular acidification rate (ECAR) was evaluated. Protein expression levels were analyzed through western blotting. RESULTS: Our network pharmacology analysis identified HIF1A as a crucial target and signaling pathway in ovarian cancer. Furthermore, treatment with Agrimonolide (20 µM and 40 µM) inhibited the growth of ovarian cancer cells. Agrimonolide also reduced glycolytic activity in these cells. Additionally, Agrimonolide treatment led to decreased expression levels of HIF1A, HK2, and LDHA in ovarian cancer cells. Rescue assays revealed that glucose uptake and lactate production were diminished following Agrimonolide treatment; however, these effects were reversed upon overexpression of HIF1A. CONCLUSION: This study showed that Agrimonolide can suppress glycolysis in ovarian cancer cells by modulating HIF1A, supporting Agrimonolide as a promising therapeutic agent for ovarian cancer treatment.

The crucial role of NR2A mediating the activation of satellite glial cells in the trigeminal ganglion contributes to orofacial inflammatory pain during TMJ inflammation.

Temporomandibular joint inflammatory diseases are a significant subtype of temporomandibular disorders (TMD) characterized by inflammatory pain in the orofacial area. The N-methyl-D-aspartate receptor (NMDAR), specifically the NR2A subtype, was crucial in neuropathic pain. However, the exact role of NR2A in inflammatory pain in the TMJ and the molecular and cellular mechanisms mediating peripheral sensitization in the trigeminal ganglion (TG) remain unclear. This study utilized male and female mice to induce the TMJOA model by injecting Complete Freund's adjuvant (CFA) into the TMJ and achieve conditional knockout (CKO) of NR2A in the TG using Cre/Loxp technology. The Von-Frey filament test results showed that CFA-induced orofacial pain with reduced mechanical withdrawal threshold (MWT), which was not developed in NR2A CKO mice. Additionally, the up-regulation of interleukin (IL)-1ß, IL-6, and nerve growth factor (NGF) in the TG induced by CFA did not occur by NR2A deficiency. In vitro, NMDA activated satellite glial cells (SGCs) with high expression of glial fibrillary acidic protein (GFAP), and both NMDA and LPS led to increased IL-1ß, IL-6, and NGF in SGCs. NR2A deficiency reduced these stimulating effects of NMDA and LPS. The regulation of IL-1ß involved the p38, Protein Kinase A (PKA), and Protein Kinase C (PKC) pathways, while IL-6 signaling relied on PKA and PKC pathways. NGF regulation was primarily through the p38 pathway. This study highlighted NR2A's crucial role in the TG peripheral sensitization during TMJ inflammation by mediating ILs and NGF, suggesting potential targets for orofacial inflammatory pain management.

A Moderately High-Fat Diet with Proper Nutrient Quality Improves Glucose Homeostasis, Linked to Downregulation of Intestinal CD36 Mediated by the Loss of Desulfovibrio.

The global prevalence of type 2 diabetes mellitus has become a major public health challenge. Dietary intervention is a cornerstone of diabetes management, yet the optimal macronutrient composition remains an open question. In this study, mice were fed a western (W) diet, a moderately high-fat (MHF) diet, a high-protein-high-carbohydrate (HPHC) diet, or a high-protein-low-carbohydrate (HPLC) diet for 22 weeks to compare the effects of different dietary patterns on glucose homeostasis. Our results showed that a MHF diet, under consistent nutrient quality, was most beneficial for glucose metabolism. The MHF diet reduced two key inducers of diabetes─lipid accumulation and inflammation. Downregulation of intestinal CD36 induced by loss of Desulfovibrio colonization restrained lipid absorption and lipopolysaccharide (LPS) transport, which played a crucial role in MHF-mediated resistance to lipid accumulation and inflammation. The findings endorse a dietary pattern featuring MHF of appropriate nutrient quality as an effective strategy for diabetes management.

Maximum standardised uptake value of positron emission tomography as a predictor of oesophageal cancer outcomes.

OBJECTIVES: This study aimed to analyse the value of pre-operative 18F-fluorodeoxyglucose positron emission tomography (PET)-computed tomography that can predict tumour pathological complete response, tumour histology grade, overall survival, and recurrence-free survival in patients with locally advanced oesophageal squamous cell carcinoma who underwent neoadjuvant chemoradiotherapy (NCRT) followed by surgery. METHODS: We retrospectively reviewed the cases of patients with locally advanced oesophageal squamous cell carcinoma undergoing NCRT followed by surgery. Patients who did not undergo PET within 3 months of surgery were excluded. We set a pre-operative PET maximum standardised uptake value (SUVmax) of > 5 as the threshold and classified the patients into two groups. We analysed the tumour response and histology grade, and compared the overall survival and recurrence-free survival between the two groups. RESULTS: This cohort included 92 patients with oesophageal squamous cell carcinoma who underwent NCRT followed by surgery; 49 patients had a pre-operative PET SUVmax < 5, and 43 patients had a pre-operative PET SUVmax > 5. The patients' pre-operative PET SUVmax correlated with tumour histology, ypT stage, and tumour response. Patients with a pre-operative SUVmax < 5 had better 2-year-overall survival (78% vs. 62%, P < 0.05) and 2-year recurrence-free survival (62% vs. 34%, P < 0.05) than those with a pre-operative SUV > 5. CONCLUSIONS: Pre-operative SUVmax may be useful to predict tumour response, survival, and recurrence in patients with locally advanced oesophageal squamous cell carcinoma who undergo NCRT followed by surgery.

Attenuated melanopsin-mediated post-illumination pupillary response (PIPR) is associated with reduced actigraphic amplitude and mesor in older adults.

STUDY OBJECTIVES: This study aimed to explore the relationship between post-illumination pupillary response (PIPR) with sleep and circadian measures in a community sample of healthy older adults. METHODS: Eligible participants were invited to complete a one-week sleep diary, actigraphy and provide an overnight urine sample to measure urinary 6-sulfatoxymelatonin (aMT6s). PIPR was defined as the as the pupil constriction at 6s post-stimulus (PIPR-6s), and ii) for 30s beginning 10s after stimulus (PIPR-30s) normalized as a percentage to the baseline pupil diameter, after 1s of blue and 1s of red-light stimulus, respectively. The Net-PIPRs were reported by subtracting the PIPR to red stimulus from the PIPR to blue stimulus. The relationship between PIPR metrics to aMT6s and actigraphic rest-activity rhythm parameters was examined by generalized linear models. RESULTS: A total of 48 participants were recruited (Mean age: 62.6 ± 7.1 years, Male: 44%). Both Net PIPR-6s and Net PIPR-30s were significantly associated with actigraphic rest-activity amplitude (B=0.03, p=0.001 and B=0.03, p=0.01, respectively), and actigraphic rest-activity mesor (B=0.02, p=0.001 and B=0.03, p=0.004, respectively). Additionally, the Net PIPR-30s were positively associated with overnight aMT6s level (B=0.04, p=0.03), and negatively associated with actigraphic rest-activity acrophase (B=-0.01, p=0.004) in the fully adjusted models. CONCLUSION: Attenuated PIPR is associated with a reduced actigraphic amplitude and mesor. The reduced retinal light responsivity may be a potential pathway contributing to impaired photic input to the circadian clock and resulted in the age-related circadian changes in older adults.

Re-evaluating the necessity of routine laboratory monitoring during isotretinoin therapy for acne.

In this letter, we discuss the topic of necessity of routine laboratory monitoring during isotretinoin treatment for acne. According to Park and colleagues, it is advisable to monitor the levels of triglycerides, alanine aminotransferase, and aspartate aminotransferase every 5 to 6 months. Additionally, the levels of total cholesterol and low-density lipoprotein should be checked within the first two months of treatment. Isotretinoin is a commonly prescribed agent mainly used to treat acne. Despite its high effectiveness, it necessitates regular monitoring of laboratory parameters due to its side effect profile. Currently, there remains a lack of consensus on the appropriate frequency for monitoring these parameters during treatment with isotretinoin. This letter will provide insight into this complex and controversial topic. Based on existing literature, we concluded that the incidence of changes in lipid and liver aminotransferase levels during isotretinoin treatment for acne was low and likely clinically insignificant. For generally healthy people, we recommend testing lipid and liver profiles once at baseline and a second time at the peak dosage. However, frequent testing might still be beneficial in certain populations of patients.

Discovery of Tetrahydro Tanshinone I as a Naturally Occurring Covalent Pan-Inhibitor Against Gut Microbial Bile Salt Hydrolases.

Gut microbial bile salt hydrolases (gmBSHs), an important class of bacteria-produced cysteine hydrolases, play a crucial role in bile acid metabolism. Modulating the total gmBSH activity is a feasible way for ameliorating some metabolic diseases including colorectal cancer, type 2 diabetes, and obesity. This study reported the discovery and characterization of a botanical compound as a covalent pan-inhibitor of gmBSHs. Following the screening of more than 100 botanical compounds, tanshinones were found with strong time-dependent anti-EfBSH effects. After that, a total of 17 naturally occurring tanshinones were collected, and their anti-EfBSH potentials were tested. Among all tested tanshinones, tetrahydro tanshinone I (THTI) exhibited the most potent inhibitory effects against five gmBSHs (EfBSH, LsBSH, BtBSH, CpBSH, and BlBSH), showing the IC50 values ranging from 0.28 ± 0.05 µM to 1.62 ± 0.07 µM. Further investigations showed that THTI could covalently modify the conserved catalytic cysteine (Cys2) of all tested gmBSHs, while this agent could strongly inhibit the total gmBSHs activity in live microorganisms and murine gut luminal content. Collectively, THTI is identified as a naturally occurring covalent pan-inhibitor of gmBSHs, which offers a promising lead compound to develop more efficacious gmBSHs inhibitors for the management of bile acid metabolism and related metabolic disorders.

Effective minimally invasive strategy for mixed-type gynecomastia using vacuum-assisted mastectomy and power-assisted liposuction.

INTRODUCTION: Mixed-type gynecomastia is a benign male breast condition characterized by the proliferation of glandular and adipose tissues. Conventional open surgery has been the main approach for treating gynecomastia. However, this method has been associated with complications, including breast deformity, noticeable scar, nipple necrosis, and hypoesthesia. In contrast, vacuum-assisted biopsy systems and liposuction have demonstrated significant advantages in minimally invasive breast surgery. AIMS: Our study aimed to investigate the effectiveness of combining vacuum-assisted mastectomy with power-assisted liposuction (VAM+PAL) for patients with mixed-type gynecomastia compared to conventional open surgery. METHODS: Sixty patients with mixed-type gynecomastia, treated between January 2019 and June 2023, were included in this study. VAM+PAL was performed on 30 patients (59 breasts), and open excision with periareolar approach was performed on 30 patients (59 breasts). The efficacy, complications, outcomes, scar cosmesis, and patient satisfaction were assessed. RESULTS: Compared to open excision group for gynecomastia, the VAM+PAL group demonstrated a substantial reduction in incision size (4.47 ± 1.21 cm vs. 0.97 ± 0.74 cm, p < 0.001) and lower scores of Vancouver scar scale (3.23 ± 2.27 vs. 1.10 ± 1.47, p < 0.001). No drainage tubes were required for postoperative hematoma/seroma prevention. The patients in the VAM+PAL group had significantly lower complication rates (18.64% vs. 3.39%, p = 0.008), particularly in bruise and hypoesthesia. All VAM+PAL patients reported superior satisfaction with the outcomes in breasts and nipples. CONCLUSION: The combination of vacuum-assisted mastectomy and power-assisted liposuction can be used as an efficient minimally invasive method to treat mixed-type gynecomastia with acceptable complications, superior scar cosmesis, and satisfying outcomes.

ATP-responsive copper(II)-doped ZIF-nanoparticles for synergistic cancer therapy: combining cuproptosis and chemo/chemodynamic therapy.

Cancer, a pressing global health challenge, is characterized by its rapid onset and high mortality rates. Conventional treatment methods prove insufficient in achieving the desired therapeutic outcomes, underscoring the critical need to identify an effective and safe approach for cancer treatment. In this study, a copper-doped nanoparticle known as Cu2+-DOX@ZIF-90 is designed by incorporating copper(II) (Cu(II)) and encapsulating doxorubicin (DOX) within ZIF-90. Leveraging the elevated ATP levels in cancer cells relative to normal cells, Cu2+-DOX@ZIF-90 undergoes intracellular degradation, leading to the release of DOX and Cu(II). DOX, a traditional chemotherapy drug for clinical use, induces apoptosis in cancer cells. Cu(II) interacts with glutathione (GSH) to generate Cu(I), catalyzing H2O2 to produce ˙OH, thereby prompting apoptosis in cancer cells. Concurrently, the reduction of GSH enhances the therapeutic effect of chemodynamic therapy (CDT). Furthermore, Cu(II) triggers the aggregation of lipoylated mitochondrial proteins, leading to the formation of DLAT oligomers and ultimately promoting cuproptosis in cancer cells. In vivo experimental findings demonstrate that Cu2+-DOX@ZIF-90 does not cause damage to normal tissues and organs in tumor-bearing mice, with a notable tumor inhibition rate of 86.18%. This synergistic approach, combining chemotherapy, CDT, and cuproptosis, holds significant promise for the effective and safe treatment of cancer.

Registered Nurses' Attitudes Towards ChatGPT and Self-Directed Learning: A Cross-Sectional Study.

BACKGROUND: Self-directed, lifelong learning is essential for nurses' competence in complex healthcare environments, which are characterised by rapid advancements in medicine and technology and nursing shortages. Previous studies have demonstrated that ChatGPT technology fosters self-directed learning by motivating users to engage with it. OBJECTIVES: To explore the relationships amongst socio-demographic data, attitudes towards ChatGPT use, and self-directed learning amongst registered nurses in Taiwan. METHODS: A cross-sectional study design with an online survey was adopted. Registered nurses from various healthcare settings were recruited through Facebook and LINE, a widely used messaging application in East Asia, reaching over 1000 nurses across five distinct online groups. An online survey was used to collect data, including socio-demographic characteristics, attitudes towards ChatGPT use, and a self-directed learning scale. Data were analysed using descriptive statistical methods, t-tests, Pearson's correlation, one-way analysis of variance, and multiple linear regression analysis. RESULTS: Amongst the 330 participants, 50.6% worked in hospitals, 51.8% had more than 15 years of work experience, and 78.2% did not hold supervisory positions. Of the participants, 46.7% had used ChatGPT. For all nurses, work experience and awareness of ChatGPT statistically significantly predicted self-directed learning, explaining 32.0% of the variance. For those familiar with ChatGPT, work experience in nursing and the technological/social influence of ChatGPT statistically significantly predicted self-directed learning, explaining 35.3% of the variance. CONCLUSIONS: Work experience in nursing provides critical opportunities for professional development and training. Therefore, ChatGPT-supported self-directed learning should be customised for degrees of experience to optimise continuous education. IMPLICATIONS FOR NURSING MANAGEMENT AND HEALTH POLICY: This study explores nurses' diverse use of and attitudes towards ChatGPT for self-directed learning. It suggests that administrators customise support and training when incorporating ChatGPT into professional development, accounting for nurses' varied experiences to enhance learning outcomes. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. REPORTING METHOD: This study adhered to the relevant cross-sectional STROBE guidelines.

The association between serum S100ß levels and prognosis in acute stroke patients after intravenous thrombolysis: a multicenter prospective cohort study.

BACKGROUND: S100ß is a biomarker of astroglial damage, the level of which is significantly increased following brain injury. However, the characteristics of S100ß and its association with prognosis in patients with acute ischemic stroke following intravenous thrombolysis (IVT) remain unclear. METHODS: Patients in this multicenter prospective cohort study were prospectively and consecutively recruited from 16 centers. Serum S100ß levels were measured 24 h after IVT. National Institutes of Health Stroke Scale (NIHSS) and hemorrhagic transformation (HT) were measured simultaneously. NIHSS at 7 days after stroke, final infarct volume, and modified Rankin Scale (mRS) scores at 90 days were also collected. An mRS score ≥ 2 at 90 days was defined as an unfavorable outcome. RESULTS: A total of 1072 patients were included in the analysis. The highest S100ß levels (> 0.20 ng/mL) correlated independently with HT and higher NIHSS at 24 h, higher NIHSS at 7 days, larger final infarct volume, and unfavorable outcome at 3 months. The patients were divided into two groups based on dominant and non-dominant stroke hemispheres. The highest S100ß level was similarly associated with the infarct volume in patients with stroke in either hemisphere (dominant: ß 36.853, 95% confidence interval (CI) 22.659-51.048, P < 0.001; non-dominant: ß 23.645, 95% CI 10.774-36.516, P = 0.007). However, serum S100ß levels at 24 h were more strongly associated with NIHSS scores at 24 h and 3-month unfavorable outcome in patients with dominant hemisphere stroke (NIHSS: ß 3.470, 95% CI 2.392-4.548, P < 0.001; 3-month outcome: odds ratio (OR) 5.436, 95% CI 2.936-10.064, P < 0.001) than in those with non-dominant hemisphere stroke (NIHSS: ß 0.326, 95% CI  - 0.735-1.387, P = 0.547; 3-month outcome: OR 0.882, 95% CI 0.538-1.445, P = 0.619). The association of S100ß levels and HT was not significant in either stroke lateralization group. CONCLUSIONS: Serum S100ß levels 24 h after IVT were independently associated with HT, infarct volume, and prognosis in patients with IVT, which suggests the application value of serum S100ß in judging the degree of disease and predicting prognosis.

Microbiome flexibility enhances the resilience of the potentially invasive coral Tubastraea aurea to abrupt environmental changes: Insights from a shallow water hydrothermal vent transplantation study.

To comprehend the effects of potentially invasive coral Tubastraea aurea on marine ecosystems, it is crucial to understand their adaptive strategies to survive environmental changes and perturbations. Therefore, a cross-transplantation study was conducted to assess the microbiome's role in the resilience of T. aurea to sudden environmental changes.Hydrographic analyses revealed distinct ecological conditions at two sites: a hydrothermal vent (HV) site, characterized by harsh environmental conditions serving as a natural laboratory for future oceanic changes, and a regular coastal site Fulong (FU). Both sites showed significant differences in pH, temperature, and dissolved oxygen. Using Oxford Nanopore Technologies, we examined bacterial dynamics in coral tissue, mucus and ambient sediment samples following cross-transplantation experiments. We observed a rapid shift in dominant bacterial groups post-transplantation with transplanted corals acquiring microbiomes similar to native corals from their respective sites within 16 days. The bacteria Endozoicomonas euniceicola and Ruegeria profundi were dominant in both native and transplanted corals, suggesting their critical role in coral resilience. Furthermore, the enrichment of certain bacterial taxa post-transplantation suggests that opportunistic species also contribute to host acclimatization. Functional profiling data indicated that there was site-specific adaptation because corals had acquired beneficial bacterial assemblages to assist them cope with environmental stressors. More specifically, there was a switch towards sulfur and nitrogen metabolism in corals that moved to high sulfidic environments, while corals transplanted into normal coastal environments showed enriched photoautotrophic processes due to their symbionts. Our study underscored the highly flexible microbiome of T. aurea and its pivotal role in facilitating host resilience to environmental perturbations, particularly in the context of its potential invasiveness. Hence, these findings contribute to the understanding of coral-microbiome dynamics and emphasize the necessity of considering microbially-mediated resilience in managing potentially invasive coral species in marine ecosystems around the world, especially as ocean conditions continue to change.

A nomogram construction and multicenter validation for predicting overall survival after fruquintinib application in patients with metastatic colorectal cancer: a multicenter retrospective study.

Background: Fruquintinib is a third-line and subsequent targeted therapy for patients with metastatic colorectal cancer (mCRC). Identifying survival predictors after fruquintinib is crucial for optimizing the clinical use of this medication. Objectives: We aimed to identify factors influencing the prognosis of patients with mCRC treated with fruquintinib and to leverage these insights to develop a nomogram model for estimating survival rates in this patient population. Design: Multicenter retrospective observational study. Methods: We collected patient data from January 2019 to October 2023, with one healthcare institution's data serving as the training cohort and the other three hospitals' data serving as the multicenter validation cohort. The nomogram for overall survival was calculated from Cox regression models, and variable selection was screened using the univariate Cox regression analysis with additional variables based on clinical experience. Model performance was measured by the concordance index (C-index), calibration curves, decision curve analyses (DCA), and utility (patient stratification into low-risk vs high-risk groups). Results: Data were ultimately collected on 240 patients, with 144 patients included in the training cohort and 96 included in the multicenter validation cohort. Predictors included in the nomogram were CA199, body mass index, T stage, the primary site of the tumor, and other metastatic and pathological differentiation. The C-index of the nomogram in the training set and multicenter validation was 0.714 and 0.729, respectively. The models were fully calibrated and their predictions aligned closely with the observed data. DCA curves indicated the promising clinical benefits of the predictive model. Finally, the reliability of the model was also verified through the risk classification using the nomogram. Conclusions: We constructed a nomogram for mCRC treated with fruquintinib based on six variables that may be used to assist in personalizing the use of the drug.

A nomogram for predicting OS after application of fruquintinib in patients with mCRC The prognostic predictors of fruquintinib as a third-line and subsequent treatment agent for patients with mCRC have not been established. In this study, we explored possible factors influencing its prognosis and developed a nomogram model for estimating survival rates in this patient population. The nomogram, based on six key variables including CA199, BMI, T stage, primary tumor site, other metastatic sites, and pathological differentiation, was validated through a rigorous multicenter validation process. The nomogram has the potential to help clinicians personalize the use of fruquintinib for mCRC patients.

DKK1 as a chemoresistant protein modulates oxaliplatin responses in colorectal cancer.

Oxaliplatin is effective against colorectal cancer (CRC), but resistance hampers treatment. We found upregulated Dickkopf-1 (DKK1, a secreted protein) in oxaliplatin-resistant (OR) CRC cell lines and DKK1 levels increased by more than 2-fold in approximately 50% of oxaliplatin-resistant CRC tumors. DKK1 activates AKT via cytoskeleton-associated protein 4 (CKAP4, a DKK1 receptor), modulating oxaliplatin responses in vitro and in vivo. The leucine zipper (LZ) domain of CKAP4 and cysteine-rich domain 1 (CRD1) of secreted DKK1 are crucial for their interaction and AKT signaling. By utilizing the LZ protein, we disrupted DKK1 signaling, enhancing oxaliplatin sensitivity in OR CRC cells and xenograft tumors. This suggests that DKK1 as a chemoresistant factor in CRC via AKT activation. Targeting DKK1 with the LZ protein offers a promising therapeutic strategy for oxaliplatin-resistant CRC with high DKK1 levels. This study sheds light on oxaliplatin resistance mechanisms and proposes an innovative intervention for managing this challenge.

A Review of Recent Curcumin Analogues and Their Antioxidant, Anti-Inflammatory, and Anticancer Activities.

Curcumin, as the main active component of turmeric (Curcuma longa), has been demonstrated with various bioactivities. However, its potential therapeutic applications are hindered by challenges such as poor solubility and bioavailability, rapid metabolism, and pan-assay interference properties. Recent advancements have aimed to overcome these limitations by developing novel curcumin analogues and modifications. This brief review critically assesses recent studies on synthesising different curcumin analogues, including metal complexes, nano particulates, and other curcumin derivatives, focused on the antioxidant, anti-inflammatory, and anticancer effects of curcumin and its modified analogues. Exploring innovative curcumin derivatives offers promising strategies to address the challenges associated with its bioavailability and efficacy and valuable insights for future research directions.

Lacticaseibacillus jixiensis sp. nov., Isolated from Traditional Chinese Pickle.

A novel lactic acid bacterial strain (designated N163-3-2T), isolated from traditional Chinese pickle ('Suan cai'), was characterized using a polyphasic approach. Strain N163-3-2T was most closely related to the type strains of Lacticaseibacillus baoqingensis, Lacticaseibacillus manihotivorans, and Lacticaseibacillus porcinae, having 97.9-98.4% 16S rRNA gene, 82.0-85.1% pheS, 87.5-87.8% rpoA, and 85.8-86.7% concatenated pheS and rpoA sequence similarities. Strain N163-3-2T had 74.4-81.7% ANI, 22.6-23.9% dDDH, and 74.0-75.1% AAI values with L. baoqingensis 47-3T, L. manihotivorans DSM 13343T and L. porcinae JCM 19617T, less than the threshold for species demarcation (95-96%, 70% and 95-96%, respectively), indicating that strain N163-3-2T represented a novel species of the genus Lacticaseibacillus. Based upon the data obtained in the present study, a novel species, Lacticaseibacillus jixiensis sp. nov., is proposed, and the type strain is N163-3-2T (= CCTCC AB 2024125T = JCM 36999T).

Anion Effect on the CuII-Neocuproine Mediator and Its Electrocatalysts for Dye-Sensitized Solar Cells: Polymeric Chalcogenides of PEDOT-PEDTT and [Ag2(SePh)2]n.

The synthetical methodology for the [Cu(dmp)2]2+/1+ (dmp = 2,9-dimethyl-1,10-phenanthroline; neocuproine) complexes has been systematically investigated by using various copper precursors, including CuCl2, Cu(NO3)2, and Cu(ClO4)2. After an anion exchange to trifluoromethanesulfonimide (TFSI), the tetra-coordinated CuII(dmp)2(TFSI)2-Cu(ClO4)2 (7.43%) outperformed the penta-coordinated CuII(dmp)2(TFSI)(NO3)-Cu(NO3)2 (4.30%) and CuII(dmp)2(TFSI)(Cl)-CuCl2. Polymeric chalcogenides, including a conducting copolymeric electrode of PEDOT-PEDTT [PEDOT = poly(3,4-ethylenedioxythiophene); PEDTT = poly(3,4-ethylenedithiothiophene)] and a coordination polymeric electrode of silver bezeneselenolate ([Ag2(SePh)2]n; mithrene), are introduced as the electrocatalysts for [Cu(dmp)2]2+/1+ for the first time. After optimization, dye-sensitized solar cells (DSSCs) based on carbon cloth (CC)/AgSePh-30 (10.18%) showed superior electrocatalytic ability compared to the benchmark CC/Pt (7.43%) due to numerous active sites provided by electron-donating Se atoms, high film roughness, and bottom-up 2D charge transfer routes. The DSSC based on CC/PEDTT-50 (10.38%) also outperformed CC/Pt due to numerous active sites provided by electron-donating S atoms and proper energy band structure. This work sheds light on the future design and synthesis in Cu-complex mediators and functional polymeric chalcogenides for high-performance DSSCs.