Effect of Fu Zheng Jie Du Formula on outcomes in patients with severe pneumonia receiving prone ventilation: a retrospective cohort study.

Background: The effect of combining prone ventilation with traditional Chinese medicine on severe pneumonia remains unclear. Objective: To evaluate the effect of Fu Zheng Jie Du Formula (FZJDF) combined with prone ventilation on clinical outcomes in patients with severe pneumonia. Methods: This single-center retrospective cohort study included 188 severe pneumonia patients admitted to the ICU from January 2022 to December 2023. Patients were divided into an FZJD group (receiving FZJDF for 7 days plus prone ventilation) and a non-FZJD group (prone ventilation only). Propensity score matching (PSM) was performed to balance baseline characteristics. The primary outcome was the change in PaO2/FiO2 ratio after treatment. Secondary outcomes included 28-day mortality, duration of mechanical ventilation, length of ICU stay, PaCO2, lactic acid levels, APACHE II score, SOFA score, Chinese Medicine Score, inflammatory markers, and time to symptom resolution. Results: After PSM, 32 patients were included in each group. Compared to the non-FZJD group, the FZJD group showed significantly higher PaO2/FiO2 ratios, lower PaCO2, and lower lactic acid levels after treatment (p < 0.05 for all). The FZJD group also had significantly lower APACHE II scores, SOFA scores, Chinese Medicine Scores, and levels of WBC, PCT, hs-CRP, and IL-6 (p < 0.05 for all). Time to symptom resolution, including duration of mechanical ventilation, length of ICU stay, time to fever resolution, time to cough resolution, and time to resolution of pulmonary rales, was significantly shorter in the FZJD group (p < 0.05 for all). There was no significant difference in 28-day mortality between the two groups. Conclusion: FZJDF as an adjuvant therapy to prone ventilation can improve oxygenation and other clinical outcomes in severe pneumonia patients. Prospective studies are warranted to validate these findings.

Female urinary incontinence in China after 15 years' efforts: Results from large-scale nationwide surveys.

Urinary incontinence (UI) is a disease that quietly yet seriously impacts women's health and represents a global health burden that is often neglected. This study aims to systematically assess the prevalence and dynamics of female UI in China, and can inform further policies and have international implications. This study used three nationwide investigations: A national cross-sectional survey in 2021; another nationwide cross-sectional survey in 2006; and data regarding the institutions and physicians providing pelvic floor rehabilitation services from 2005 to 2019. The weighted prevalence of female UI and its subtypes, including stress UI (SUI), urgency UI (UUI), and mixed UI (MUI), were estimated as primary outcomes. Knowledge, attitude and care-seeking behaviors of UI were evaluated. It was found that the weighted prevalence of female UI was 16.0 % (95% CI, 13.3 %-19.1%) with SUI remaining the predominant subtype (7.0%) in 2021, followed by MUI (6.5%) and UUI (1.9%). The estimated absolute number of Chinese adult women with UI was 85.8 million in 2021. 52.7% (95% CI, 45.9%-59.4 %) of women were aware that UI was a medical condition, and only 10.1% of women with UI sought health care. After 15 years of development, there were 8400 pelvic floor rehabilitation institutions and nearly 10,000 relevant physicians in China-they were found to be associated with UI prevalence. The UI prevalence in China was significantly lower in 2021 compared to that in 2006. Despite the achievement, UI remains a public health problem, especially given China's fast aging and three-child policy. More innovations, especially those that can facilitate care seeking, are needed to address this prevalent yet treatable condition.

An oil-in-gel type of organohydrogel loaded with methylprednisolone for the treatment of secondary injuries following spinal cord traumas.

The secondary injuries following traumatic spinal cord injury (SCI) is a multiphasic and complex process that is difficult to treat. Although methylprednisolone (MP) is the only available pharmacological regime for SCI treatment, its efficacy remains controversial due to its very narrow therapeutic time window and safety concerns associated with high dosage. In this study, we have developed an oil-in-gel type of organohydrogel (OHG) in which the binary oleic-water phases coexist, for the local delivery of MP. This new OHG is fabricated by a glycol chitosan/oxidized hyaluronic acid hydrophilic network that is uniformly embedded with a biocompatible oil phase, and it can be effectively loaded with MP or other hydrophobic compounds. In addition to spatiotemporally control MP release, this biodegradable OHG also provides a brain tissue-mimicking scaffold that can promote tissue regeneration. OHG remarkably decreases the therapeutic dose of MP in animals and extends its treatment course over 21 d, thereby timely manipulating microglia/macrophages and their associated with signaling molecules to restore immune homeostasis, leading to a long-term functional improvement in a complete transection SCI rat model. Thus, this OHG represents a new type of gel for clinical treatment of secondary injuries in SCI.

Prognostic Factors Associated with Post-Stroke Dysphagia in Intracerebral Hemorrhage Patients.

Spontaneous intracerebral hemorrhage (ICH) constitutes a significant portion of acute stroke incidents worldwide, often leading to post-stroke dysphagia (PSD), affecting 50-77% of survivors and worsening patient morbidity. This study aimed to identify predictive variables for PSD among patients with spontaneous ICH. A retrospective cohort study was conducted on adult patients with acute spontaneous ICH, confirmed by brain computed tomography, from June 2019 to June 2023. We analyzed demographic, neuroimaging, and stroke-specific characteristics and rehabilitation indicators. PSD was evaluated using nasogastric (NG) tube retention and the Functional Oral Intake Scale (FOIS) levels at 4 and 12 weeks post-ICH. Statistical analyses involved univariate and multivariate logistic regression to identify PSD predictors. A total of 310 ICH patients were included in the study. At 4 weeks, significant predictors for NG tube retention included 24-hour National Institute of Health Stroke Scale (NIHSS) scores, estimated glomerular filtration rate and sitting balance. At 12 weeks, hospital stay duration and ICH score were significant predictors for NG tube retention. Regarding the FOIS, significant predictors at 4 weeks included higher 24-hour NIHSS scores, compromised sitting balance, immobility-related complications, initial hematoma volume and intraventricular hemorrhages. At 12 weeks, older age and higher 24-hour NIHSS scores significantly predicted lower FOIS levels. Our findings demonstrate that PSD in ICH patients is influenced by a complex interplay of factors, including stroke severity, renal function, and physical impairment. The study highlights the importance of early neurological assessment, physical function, and comprehensive management in improving swallowing outcomes, emphasizing a multifaceted approach to enhancing outcomes for ICH survivors.

Analysis of chlordecone and its transformation products in environmental waters by a new SPME-GC-MS method and comparison with LLE-GC-MS/MS and LLE-LC-MS/MS: A case study in the French West Indies.

Among the numerous organochlorines (OCs) applied in the French West Indies (FWI), chlordecone (hydrated form C10Cl10O2H2; CLD) still causes major environmental pollution nowadays. A recent report revealed the unexpected presence in FWI environment of transformation products (TPs) of CLD not routinely monitored due to a lack of commercial standards. Here, we present a method for surface waters and groundwaters to analyze CLD, its main TPs (hydroCLDs, chlordecol (CLDOH), 10-monohydroCLDOH and polychloroindenes) and other OCs. We developed an SPME-GC-SIM/MS method with a PDMS-DVB fiber. Since CLDOH-d commonly used as internal standard (IS) proved unsuitable, we synthesized several IS candidates, and finally identified 10-monohydro-5-methyl-chlordecol as a satisfactory IS for CLDOH and 10-monohydroCLDOH avoiding the use of 13C-labelled analogue. LODs for CLD and its TPs varied from 0.3 to 10 ng/L, equal to or below LODs of the two laboratories, BRGM (the French geological survey) and LDA26 (one of the French Departmental Analytical Laboratories), requested in FWI pollution monitoring that used liquid-liquid extractions and advanced facilities (LLE-GC-MS/MS and LLE-LC-MS/MS methods, respectively). Then, we extended the multi-residue method to 30 OCs (CLD and its TPs, mirex, ß-HCH, lindane, dieldrin, aldrin, HCB, hexachlorobutadiene, TCE, PCE) and applied it to 30 surface and ground waters from FWI. While CLD, 8- and 10-monohydroCLD, CLDOH, 10-monohydroCLDOH, dieldrin, and ß-HCH were detected and quantified, pentachloroindene, another CLD TP, was sporadically found in trace levels. A comparison with BRGM and LDA26 confirmed the interest of the SPME method. Results suggested an underestimation of CLDOH and an overestimation of high CLD concentrations with one of the currently used routine protocol. In light of these findings, previous temporal monitoring of environmental waters in FWI were re-examined and revealed some atypical values, which may indeed be due to analytical bias. These discrepancies call for intensified efforts to reliably quantify CLD and its TPs.

Association of 24-Hour movement behavior and cognitive function in older Taiwanese adults.

OBJECTIVES: This study investigates how 24-hour movement behaviors (physical activity, sedentary time, sleep) relate to cognitive performance in older adults. METHODS: 213 adults (aged 65+) wore accelerometers to track activity. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Isotemporal substitution analysis examined how replacing one behavior with another affected cognition. RESULTS: Increased light physical activity was linked to better cognitive function, whereas longer sleep had a negative impact. Replacing 30 min of sedentary behavior or sleep with light physical activity improved orientation, attention, language, and short-term memory. Substituting moderate-to-vigorous physical activity did not have the same cognitive benefit. CONCLUSION: Encouraging older adults to replace sedentary time or excess sleep with light physical activity could support cognitive health and potentially help prevent dementia. These findings have implications for public health strategies promoting cognitive well-being in aging populations.

Effect of information and communication technology-based smart care services for physical and cognitive functions in older adults living alone: A quasi-experimental study.

BACKGROUND: As the global population ages and the number of older adults living alone increases, societies face the responsibility of building new support systems and providing novel forms of care to ensure the independence and happiness of sick or frail older individuals. This quasi-experimental study examined the association between information and communication technology-based smart care services and the physical and cognitive functions of older individuals living alone. METHODS: This study used a suite of smart technologies (artificial intelligence speaker, radar sensor, and personalized exercise App.) and interventions tailored to the initial physical functional scores of the participants. A total of 176 participants were recruited and assigned, with 88 participants in the intervention group and 88 in the control group. The short physical performance battery (SPPB), the digit span test (DST), and the Korean mini-mental state examination (K-MMSE) were used to assess participants before and after 12 weeks. RESULTS: No significant differences in gender, age, or educational levels were observed between the intervention and control groups. After adjusting for baseline performance, analysis of covariance revealed that the intervention group exhibited better outcomes in the SPPB five-time chair stand score (adjusted score difference: 0.329; P = 0.044) and the backward DST (adjusted score difference: 0.472; P = 0.007), but had lower score of K-MMSE (adjusted score difference: -0.935; P = 0.021), indicating enhanced lower limb muscle strength and cognitive function in working memory. CONCLUSION: ICT-based smart care services, combined with personalized exercise interventions, significantly support the physical and cognitive health of solitary older individuals. This approach highlights the potential of integrating smart technology and targeted physical activity to foster the well-being of the aging population living alone.

[Effect of Intrauterine Perfusion of Granulocyte Colony-Stimulating Factor on Endometrium and Blood Flow Parameters in Patients With Thin Endometrium: A Prospective Controlled Clinical Trial]. / å®«è ”çŒæ³¨ç²’ç»†èƒžé›†è½åˆºæ¿€å› å­æ”¹å–„è–„åž‹å­å®«å† è†œæ‚£è€ å† è†œåŠè¡€æµå‚æ•°çš„å‰çž»æ€§ä¸´åºŠå¯¹ç §è¯•éªŒ.

Objective: To investigate the effects of intrauterine perfusion with granulocyte colony-stimulating factor (G-CSF) on the endometrial thickness, volume, and blood flow parameters of patients with thin endometrium and their clinical outcomes. Methods: We designed a prospective non-randomized synchronous controlled trial and recruited patients with thin endometrium who underwent frozen-thawed embryo transfer (FET) at Mianyang Central Hospital between September 1, 2021 and September 1, 2023. They were divided into two groups, an experimental group of patients who received the experimental treatment of intrauterine perfusion with G-CSF and a control group of patients who did not receive the experimental treatment. The general data and the clinical outcomes of the two groups were analyzed and compared. The endometrial thickness, volume and blood flow parameters of patients in the experimental group before and after intrauterine perfusion with G-CSF were analyzed. Results: The clinical data of 83 patients were included in the study. The experimental group included 51 cases, while the control group included 31 cases. There were no significant differences in the baseline data between the two groups. The clinical pregnancy rate of the experimental group (56.86%) was higher than that of the control group (50.00%) and the rate of spontaneous abortion in the experimental group (27.59%) was lower than that in the control group (37.50%), but the differences were not statistically significant (P>0.05). In the experimental group, the postperfusion endometrial thickness ([0.67±0.1] cm) was greater than the preperfusion endometrial thickness ([0.59±0.09] cm), the postperfusion ([1.84±0.81] cm3) was greater than the preperfusion endometrial volume ([1.54±0.69] cm3), and the postperfusion vascularization flow index (VFI) (1.97±2.82) was greater than the preperfusion VFI (0.99±1.04), with all the differences being statistically significant (P<0.05). Conclusion: Intrauterine perfusion with G-CSF can enhance the endometrial thickness, volume, and some blood flow parameters in patients with thin endometrium.

Leaf on a Film: Mesoporous Silica-Based Epoxy Composites with Superhydrophobic Biomimetic Surface Structure as Anti-Corrosion and Anti-Biofilm Coatings.

In this study, a series of amine-modified mesoporous silica (AMS)-based epoxy composites with superhydrophobic biomimetic structure surface of Xanthosoma sagittifolium leaves (XSLs) were prepared and applied as anti-corrosion and anti-biofilm coatings. Initially, the AMS was synthesized by the base-catalyzed sol-gel reaction of tetraethoxysilane (TEOS) and triethoxysilane (APTES) through a non-surfactant templating route. Subsequently, a series of AMS-based epoxy composites were prepared by performing the ring-opening polymerization of DGEBA with T-403 in the presence of AMS spheres, followed by characterization through FTIR, TEM, and CA. Furthermore, a nano-casting technique with polydimethylsiloxane (PDMS) as the soft template was utilized to transfer the surface pattern of natural XSLs to AMS-based epoxy composites, leading to the formation of AMS-based epoxy composites with biomimetic structure. From a hydrophilic CA of 69°, the surface of non-biomimetic epoxy significantly increased to 152° upon introducing XSL surface structure to the AMS-based epoxy composites. Based on the standard electrochemical anti-corrosion and anti-biofilm measurements, the superhydrophobic BEAMS3 composite was found to exhibit a remarkable anti-corrosion efficiency of ~99% and antimicrobial efficacy of 82% as compared to that of hydrophilic epoxy coatings.

Assessments of polymerization shrinkage by optical coherence tomography-based digital image correlation analysis-Part I: Parameter identification.

OBJECTIVE: To investigate the feasibility of optical coherence tomography (OCT)-based digital image correlation (DIC) analysis and to identify the experimental parameters for measurements of polymerization shrinkage. METHODS: Class I cavities were prepared on bovine incisors and filled with Filtek Z350XT Flowable (Z350F). One OCT image of the polymerized restoration was processed to generate virtually displaced images. In addition, the tooth specimen was physically moved under OCT scanning. A DIC software analyzed these virtual and physical transformation sets and assessed the effects of subset sizes on accuracy. The refractive index of unpolymerized and polymerized Z350F was measured via OCT images. Finally, different particles (70-80 µm glass beads, 150-212 µm glass beads, and 75-150 µm zirconia powder) were added to Z350F to inspect the analyzing quality. RESULTS: The analyses revealed a high correlation (>99.99%) for virtual movements within 131 pixels (639 µm) and low errors (<5.21%) within a 10-µm physical movement. A subset size of 51 × 51 pixels demonstrated the convergence of correlation coefficients and calculation time. The refractive index of Z350F did not change significantly after polymerization. Adding glass beads or zirconia particles caused light reflection or shielding in OCT images, whereas blank Z350F produced the best DIC analysis results. SIGNIFICANCE: The OCT-based DIC analysis with the experimental conditions is feasible in measuring polymerization shrinkage of RBC restorations. The subset size in the DIC analysis should be identified to optimize the analysis conditions and results. Uses of hyper- or hypo-reflective particles is not recommended in this method.

Microbe-Derived Antioxidants Protect IPEC-1 Cells from H2O2-Induced Oxidative Stress, Inflammation and Tight Junction Protein Disruption via Activating the Nrf2 Pathway to Inhibit the ROS/NLRP3/IL-1ß Signaling Pathway.

Oxidative stress can induce inflammation and tight junction disruption in enterocytes. The initiation of inflammation is thought to commence with the activation of the ROS/NLRP3/IL-1ß signaling pathway, marking a crucial starting point in the process. In our previous studies, we found that microbe-derived antioxidants (MAs) showed significant potential in enhancing both antioxidant capabilities and anti-inflammatory effects. The main aim of this research was to investigate the ability of MAs to protect cells from oxidative stress caused by H2O2, to reduce inflammatory responses, and to maintain the integrity of tight junction proteins by modulating the ROS/NLRP3/IL-1ß signaling pathway. IPEC-1 cells (1 × 104 cells/well) were initially exposed to 100 mg/L of MAs for 12 h, after which they were subjected to 1 mM H2O2 treatment for 1 h. We utilized small interfering RNA (siRNA) to inhibit the expression of NLRP3 and Nrf2. Inflammatory factors such as IL-1ß and antioxidant enzyme activity levels were detected by ELISA. Oxidative stress marker ROS was examined by fluorescence analysis. The NLRP3/IL-1ß signaling pathway, Nrf2/HO-1 signaling pathway and tight junction proteins (ZO-1 and Occludin) were detected by RT-qPCR or Western blotting. In our research, it was observed that MA treatment effectively suppressed the notable increase in H2O2-induced inflammatory markers (TNF-α, IL-1ß, and IL-18), decreased ROS accumulation, mitigated the expression of NLRP3, ASC, and caspase-1, and promoted the expression of ZO-1 and Occludin. After silencing the NLRP3 gene with siRNA, the protective influence of MAs was observed to be linked with the NLRP3 inflammasome. Additional investigations demonstrated that the treatment with MAs triggered the activation of Nrf2, facilitating its translocation into the nucleus. This process resulted in a notable upregulation of Nrf2, NQO1, and HO-1 expression, along with the initiation of the Nrf2-HO-1 signaling pathway. Consequently, there was an enhancement in the activities of antioxidant enzymes like SOD, GSH-Px, and CAT, which effectively mitigated the accumulation of ROS, thereby ameliorating the oxidative stress state. The antioxidant effectiveness of MAs was additionally heightened in the presence of SFN, an activator of Nrf2. The antioxidant and anti-inflammatory functions of MAs and their role in regulating intestinal epithelial tight junction protein disruption were significantly affected after siRNA knockdown of the Nrf2 gene. These findings suggest that MAs have the potential to reduce H2O2-triggered oxidative stress, inflammation, and disruption of intestinal epithelial tight junction proteins in IPEC-1 cells. This reduction is achieved by blocking the ROS/NLRP3/IL-1ß signaling pathway through the activation of the Nrf2 pathway.

Syndecan-4 is required for early-stage repair responses during zebrafish heart regeneration.

BACKGROUND: The healing process after a myocardial infarction (MI) in humans involves complex events that replace damaged tissue with a fibrotic scar. The affected cardiac tissue may lose its function permanently. In contrast, zebrafish display a remarkable capacity for scar-free heart regeneration. Previous studies have revealed that syndecan-4 (SDC4) regulates inflammatory response and fibroblast activity following cardiac injury in higher vertebrates. However, whether and how Sdc4 regulates heart regeneration in highly regenerative zebrafish remains unknown. METHODS AND RESULTS: This study showed that sdc4 expression was differentially regulated during zebrafish heart regeneration by transcriptional analysis. Specifically, sdc4 expression increased rapidly and transiently in the early regeneration phase upon ventricular cryoinjury. Moreover, the knockdown of sdc4 led to a significant reduction in extracellular matrix protein deposition, immune cell accumulation, and cell proliferation at the lesion site. The expression of tgfb1a and col1a1a, as well as the protein expression of Fibronectin, were all down-regulated under sdc4 knockdown. In addition, we verified that sdc4 expression was required for cardiac repair in zebrafish via in vivo electrocardiogram analysis. Loss of sdc4 expression caused an apparent pathological Q wave and ST elevation, which are signs of human MI patients. CONCLUSIONS: Our findings support that Sdc4 is required to mediate pleiotropic repair responses in the early stage of zebrafish heart regeneration.

Assessments of polymerization shrinkage by optical coherence tomography-based digital image correlation analysis-Part II: Effects of restorative composites.

OBJECTIVES: To examine the polymerization shrinkage of different resin-based composite (RBC) restorations using optical coherence tomography (OCT) image-based digital image correlation (DIC) analysis. METHODS: The refractive index (RI) of three RBCs, Filtek Z350XT (Z350), Z350Flowable (Z350F), and BulkFill Posterior (Bulkfill), was measured before and after polymerization to calibrate their axial dimensions under OCT. Class I cavities were prepared in bovine incisors and individually filled with these RBCs under nonbonded and bonded conditions. A series of OCT images of these restorations were captured during 20-s light polymerization and then input into DIC software to analyze their shrinkage behaviors. The interfacial adaptation was also examined using these OCT images. RESULTS: The RI of the three composites ranged from 1.52 to 1.53, and photopolymerization caused neglectable increases in the RI values. For nonbonded restorations, Z350F showed maximal vertical displacements on the top surfaces (-16.75 µm), followed by Bulkfill (-8.81 µm) and Z350 (-5.97 µm). In their bonded conditions, all showed increased displacements. High variations were observed in displacement measurements on the bottom surfaces. In the temporal analysis, the shrinkage of nonbonded Z350F and Bulkfill decelerated after 6-10 s. However, Z350 showed a rebounding upward displacement after 8.2 s. Significant interfacial gaps were found in nonbonded Z350 and Z350F restorations. SIGNIFICANCE: The novel OCT image-based DIC analysis provided a comprehensive examination of the shrinkage behaviors and debonding of the composite restorations throughout the polymerization process. The flowable composite showed the highest shrinkage displacements. Changes in the shrinkage direction may occur in nonbonded conventional composite restorations.

Associations between objectively measured overall and intensity-specific physical activity and phase angle in older adults.

Phase angle (PhA) is an indicator of cellular health and is positively associated with overall physical activity (PA). However, varied associations between different intensities of PA and PhA by body segment in older populations remain unexplored. We investigated the associations between overall and different intensities of PA and upper-, lower-, and whole-body PhA in older adults. Overall exposure to light-intensity (LPA), moderate-intensity (MPA), and vigorous-intensity physical activity (VPA) was assessed using a triaxial accelerometer (GT3X + , ActiGraph). The outcome variables were upper-, lower-, and whole-body PhA measured using bioelectrical impedance analysis (MC-780MA, TANITA). Multiple linear regression helped examine the associations between the exposure and outcome variables after adjusting for age, gender, body mass index, and accelerometer wear time. A cross-sectional analysis involved 166 community-dwelling older participants (mean age = 72.1 ± 5.5 years; 78.3% women). Overall PA was associated with larger upper- (B: 0.057, 95% confidence interval [CI] 0.018-0.095) and whole-body PhA (B: 0.044, 95% CI 0.006-0.081). LPA was associated with larger upper-body PhA (B: 0.059, 95% CI 0.017-0.101), and MPA was associated with larger lower- (B: 0.273, 95% CI 0.128-0.419) and whole-body PhA (B: 0.141, 95% CI 0.002-0.280). VPA and PhA were not associated. Future interventions targeting PhA in older adults should consider the differential impact of PA intensity on various body segments of the PhA.

Progesterone in Pregnancy: Evidence-Based Strategies to Reduce Miscarriage and Enhance Assisted Reproductive Technology.

The incidence of miscarriage in early pregnancy, between 5-20 weeks, is common, with a prevalence of between 5-22% of all pregnancies. Miscarriage can have physical, social, and mental health impacts on women and their families. In societies such as Taiwan, where the birth rate is falling and life expectancy is increasing, there is concern that factors that reduce birth rates will have detrimental economic and societal effects. Progesterone has a significant role in maintaining early and successful pregnancy to term. Evidence from preclinical and clinical research on the roles of progesterone has supported recent clinical guidelines in obstetrics and gynecology to reduce rates of early miscarriage and improve methods of assisted reproductive technology (ART). This article aims to present an evidence-based review of current recommendations for the use of progesterone in early pregnancy to reduce miscarriage rates and in luteal phase support for ART, including embryo transfer.

Unraveling the impact of cancer-associated fibroblasts on hypovascular pancreatic neuroendocrine tumors.

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) with low microvessel density and fibrosis often exhibit clinical aggressiveness. Given the contribution of cancer-associated fibroblasts (CAFs) to the hypovascular fibrotic stroma in pancreatic ductal adenocarcinoma, investigating whether CAFs play a similar role in PNETs becomes imperative. In this study, we investigated the involvement of CAFs in PNETs and their effects on clinical outcomes. METHODS: We examined 79 clinical PNET specimens to evaluate the number and spatial distribution of α-smooth muscle actin (SMA)-positive cells, which are indicative of CAFs. Then, the findings were correlated with clinical outcomes. In vitro and in vivo experiments were conducted to assess the effects of CAFs (isolated from clinical specimens) on PNET metastasis and growth. Additionally, the role of the stromal-cell-derived factor 1 (SDF1)-AGR2 axis in mediating communication between CAFs and PNET cells was investigated. RESULTS: αSMA-positive and platelet-derived growth factor-α-positive CAFs were detected in the hypovascular stroma of PNET specimens. A higher abundance of α-SMA-positive CAFs within the PNET stroma was significantly associated with a higher level of clinical aggressiveness. Notably, conditioned medium from PNET cells induced an inflammatory phenotype in isolated CAFs. These CAFs promoted PNET growth and metastasis. Mechanistically, PNET cells secreted interleukin-1, which induced the secretion of SDF1 from CAFs. This cascade subsequently elevated AGR2 expression in PNETs, thereby promoting tumor growth and metastasis. The downregulation of AGR2 in PNET cells effectively suppressed the CAF-mediated promotion of PNET growth and metastasis. CONCLUSION: CAFs drive the growth and metastasis of aggressive PNETs. The CXCR4-SDF1 axis may be a target for antistromal therapy in the treatment of PNET. This study clarifies mechanisms underlying PNET aggressiveness and may guide future therapeutic interventions targeting the tumor microenvironment.

Increased expression of SSEA-4 on TKI-resistant non-small cell lung cancer with EGFR-T790M mutation.

Non-small cell lung cancer (NSCLC), a major life-threatening disease accounting for 85% of all lung cancer cases, has been treated with tyrosine kinase inhibitors (TKIs), but often resulted in drug resistance, and approximately 60% of TKI-resistant cases are due to acquired secondary (epithelial growth factor receptor) EGFR-T790M mutation. To identify alternative targets for TKI-resistant NSCLC with EGFR-T790M mutation, we found that the three globo-series glycosphingolipids are increasingly expressed on this type of NSCLC cell lines, and among them, the increase of stage-specific embryonic antigen-4 (SSEA-4) expression is the most significant. Compared to TKI-sensitive cell lines, SSEA-4 and the key enzyme ß3GalT5 responsible for the synthesis of SSEA3 are more expressed in TKI-resistant NSCLC cell lines with EGFR-T790M mutation, and the expression levels strongly correlate with poor survival in patients with EGFR mutation. In addition, we demonstrated that a SSEA-4 targeted monoclonal antibody, especially the homogeneous glycoform with well-defined Fc glycan designed to improve effective functions, is highly effective against this subpopulation of NSCLC in cell-based and animal studies. These findings provide a direction for the prediction of tumor recurrence and treatment of TKI-resistant NSCLC with EGFR-T790M mutation.

Is overall and timing-specific physical activity associated with depression in older adults?

Objective: Regarding the circadian rhythm regulating an individual's response to external stimulation, it remains unclear whether older adults engaged in physical activity at different times of day may be differently related to depression symptoms. Thus, this study aimed to investigate the association between overall and timing-specific physical activity and depressive symptoms in older Taiwanese adults. Methods: This cross-sectional study was conducted at a medical center in Taipei City, Taiwan, between September 2020 and December 2021. The participants were community-dwelling older adults aged ≥65 who could walk independently and were not at high risk of cognitive dysfunction. Physical activity was measured using a triaxial accelerometer (GT3X+, ActiGraph) and categorized into timing-specific periods (morning: 06:01-12:00; afternoon: 12:01-18:00; evening: 18:01-24:00) as well as overall physical activity, which included both light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA). A 15-item Geriatric Depression Scale was utilized to assess and measure depressive symptoms. Multivariate linear regression models were estimated for data analysis. Results: A total of 180 older adults (55.0% female; 80.5 ± 7.1 years old; 18.3% at risk of depression) were included. On average, the participants spent 237.3 (± 85.7) minutes in LPA per day and 12.8 (± 17.0) minutes in MVPA per day. The results showed that overall MVPA engagement was associated with lower depressive-symptom scores [B = -1.357, 95% CI (-2.561, -0.153)] in older adults. However, no significant associations were observed between overall LPA, timing-specific MVPA and LPA, and depression in older adults. Conclusion: To prevent depression in older adults, it is advisable to accumulate a higher amount of MVPA throughout the entire day rather than engage in LPA. Further studies employing a prospective design are necessary to validate and strengthen our findings.

EUSEDcollab: a network of data from European catchments to monitor net soil erosion by water.

As a network of researchers we release an open-access database (EUSEDcollab) of water discharge and suspended sediment yield time series records collected in small to medium sized catchments in Europe. EUSEDcollab is compiled to overcome the scarcity of open-access data at relevant spatial scales for studies on runoff, soil loss by water erosion and sediment delivery. Multi-source measurement data from numerous researchers and institutions were harmonised into a common time series and metadata structure. Data reuse is facilitated through accompanying metadata descriptors providing background technical information for each monitoring station setup. Across ten European countries, EUSEDcollab covers over 1600 catchment years of data from 245 catchments at event (11 catchments), daily (22 catchments) and monthly (212 catchments) temporal resolution, and is unique in its focus on small to medium catchment drainage areas (median = 43 km2, min = 0.04 km2, max = 817 km2) with applicability for soil erosion research. We release this database with the aim of uniting people, knowledge and data through the European Union Soil Observatory (EUSO).