Gastric Cancer Actively Remodels Mechanical Microenvironment to Promote Chemotherapy Resistance via MSCs-Mediated Mitochondrial Transfer.

Chemotherapy resistance is the main reason of treatment failure in gastric cancer (GC). However, the mechanism of oxaliplatin (OXA) resistance remains unclear. Here, we demonstrate that extracellular mechanical signaling plays crucial roles in OXA resistance within GC. We selected OXA-resistant GC patients and analyzed tumor tissues by single-cell sequencing, and found that the mitochondrial content of GC cells increased in a biosynthesis-independent manner. Moreover, we found that the increased mitochondria of GC cells were mainly derived from mesenchymal stromal cells (MSCs), which could repair the mitochondrial function and reduce the levels of mitophagy in GC cells, thus leading to OXA resistance. Furthermore, we investigated the underlying mechanism and found that mitochondrial transfer was mediated by mechanical signals of the extracellular matrix (ECM). After OXA administration, GC cells actively secreted ECM in the tumor microenvironment (TEM), increasing matrix stiffness of the tumor tissues, which promoted mitochondria to transfer from MSCs to GC cells via microvesicles (MVs). Meanwhile, inhibiting the mechanical-related RhoA/ROCK1 pathway could alleviate OXA resistance in GC cells. In summary, these results indicate that matrix stiffness could be used as an indicator to identify chemotherapy resistance, and targeting mechanical-related pathway could effectively alleviate OXA resistance and improve therapeutic efficacy.

Approximately half of the nursing students confirmed their willingness to participate in caring for older people: a systematic review and meta-analysis.

BACKGROUND: Global population aging poses a significant global challenge, necessitating an increased demand for proficient caregivers specialized in elderly care. In our study, a systematic review and meta-analysis were conducted to synthesize the evidence concerning nursing students' willingness to participate in caring for older people. METHODS: Eligibility criteria focused on cross-sectional studies involving nursing students' willingness to participate in caring for older people and were reported in English or Chinese. PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WANFANG databases were searched from inception until July 24, 2022. The methodological quality assessment in the included studies was evaluated using the AHRQ instrument. The pooled effects of the nursing students' willingness to participate in caring for older people were computed using a random-effects model. Funnel plots and Egger's test were employed to evaluate publication bias. Meta-regression and subgroup analysis were performed to explore the sources of heterogeneity. Sensitivity analysis was conducted to verify the robustness of the meta-analysis findings. All statistical tests were conducted with Stata 16.0 software. RESULTS: A total of 68 studies of medium or high quality met the eligibility criteria, involving 30,328 nursing students. The rate of nursing students' willingness to participate in caring for older people was 49.0% (95% CI = 46-53%, I2 = 98.1%, P = 0.000). The results of meta-regression analysis showed that the following four predictor variables were significantly associated with nursing students' willingness to participate in caring for older people: experience of living with and caring for older people, nursing as their first choice and their year-level in education, respectively. Subgroup analyses for these four predictor variables revealed the following pooled estimates of nursing students' willingness: having experience of living with older people (0.54, 95% CI = 0.46-0.62) vs. no such experience (0.38, 95% CI = 0.30-0.46), having experience of caring for older people (0.55, 95% CI = 0.48-0.63) vs. no such experience (0.38, 95% CI = 0.30-0.46), nursing as their first choice (0.54, 95% CI = 0.51-0.58) vs. not their first choice (0.44, 95% CI = 0.35-0.53), being in the first year of nursing education (0.44, 95% CI = 0.34-0.55), second year (0.45, 95% CI = 0.34-0.56), and third and fourth year (0.62, 95% CI = 0.53-0.71). CONCLUSION: The study found that approximately half of the nursing students confirmed their willingness to participate in caring for older people.The present study can serve as a resource for policymakers to increase the willingness of nursing students to participate in caring for older people.

Assessment of Quality of Reporting in Randomized Controlled Trials of Moxibustion for Chronic Diseases Using the Consolidated Standards of Reporting Trials and Standards for Reporting Interventions in Clinical Trials of Moxibustion Statements.

INTRODUCTION: Moxibustion is clinically used for treating various chronic diseases; however, the reporting quality of current published RCTs of moxibustion is unclear. The objective of this study was to assess the reporting quality of RCTs focusing on moxibustion as a treatment for chronic diseases. METHODS: Seven databases were searched to identify relevant RCTs. Criteria for evaluating the reporting quality of standard RCT elements and moxibustion intervention-related information were developed based on the CONSORT statement and its STRICTOM extension, respectively. Multivariate regression models were used to investigate factors impacting reporting quality. RESULTS: A total of 310 RCTs were included, with 41 (7.6%) published in English journals and 269 (92.4%) in Chinese journals. The median CONSORT and STRICTOM scores of these RCTs, with a maximum score of 100, were 41.2 and 62.9, respectively. RCTs with a later publication year and protocol registration or ethical approval exhibited significantly higher CONSORT and STRICTOM scores. Higher CONSORT scores were also significantly associated with English language publication, funding support, and inclusion of a safety evaluation, while higher STRICTOM scores were additionally associated with an active control design. CONCLUSION: The reporting quality of RCTs focusing on moxibustion treatment for chronic diseases is subpar, with gradual but limited improvement over the last 25 years. To enhance the reporting quality of moxibustion RCTs, researchers should develop a comprehensive study protocol and standardize result reporting based on CONSORT and STRICTOM statements. Registration platforms, ethical approval organizations, funders, and journals can also contribute to this improvement by bolstering structured information reporting in the review process.

High stress during clinical practicum placement is associated with bullying among nursing students: A mixed-method study.

BACKGROUND: Nursing students are often subjected to bullying during their clinical practices, but few study has examined associations of bullying with psychological status among these groups, and how they cope with the bullying. OBJECTIVES: This study aimed to evaluate the experience and psychological status of clinical placement setting bullying among nursing students attending clinical practices, and explore students' coping strategies when bullied. DESIGN: A mixed methods. SETTINGS: Six tertiary hospitals in Northwest China. PARTICIPANTS: A total of 687 nursing students completed the questionnaire survey, of which 18 nursing students participated in the qualitative interview. METHODS: A two-phase hybrid study was produced. During first phase, data were collected by using the Bullying Behavior Scale in Nursing Education (BNEQ) and the Depression, Anxiety and Stress Scale (DASS-21). Subsequently, those who have experienced bullying in the workplace were invited to participate in a face-to-face interview (second phase) which focused on exploring students' deeper insights. RESULTS: Of the 687 students involved, 72.19 % had experienced various types of bullying. Of them, 92.11 % experienced implicit violence. Those with higher education levels and from rural were more likely to experience bullying. Students were prone to greater psychological stress when exposed to bullying. "Pretending not to see" (33.16 %), "reporting to superiors" (30.10 %), and "doing nothing" were the most common ways students responded. Four themes were obtained from the qualitative interviews: (a) impaired self-esteem; (b) career rejection; (c) psychological stress; and (d) the decline of humanistic care. CONCLUSION: Our findings suggest that senior nursing students experience multiple types of bullying during the clinical practices, leading to a high level of psychological stress, which further effect students' professional approval and self-esteem. To prevent such incidents, we need to call on university and hospitals' support to help students successfully cope with bullying.

Associations between traffic-related air pollution and allergic rhinitis outpatient visits in three cities of Gansu Province.

Emerging evidence indicates an increasing prevalence of allergic rhinitis (AR), potentially linked to air quality. The aim of the present study was to assess the relationship between traffic-related air pollutants (TRAPs) and outpatient visits for AR. Daily outpatient data for AR, air pollutant concentrations, and meteorological data were collected from January 2018 to December 2020 in Dingxi, Longnan, and Tianshui. Utilizing a Quasi-Poisson distribution, a generalized additive model (GAM) was employed in conjunction with distributed lag non-linear models (DLNM) to explore the association and lag effects of TRAPs on AR outpatient visits across the three cities. Stratified analyses based on gender, age, and season were conducted. A total of 11 106 outpatient visits for AR were recorded in the three cities. For an increase of 10 µg m-3 in PM2.5, the effect estimates in Dingxi, Longnan, and Tianshui reached their maximum at lag04, lag06, and lag07, respectively, with relative risk (RR) values of 4.696 (95% CI: 1.890, 11.614), 2.842 (95% CI: 2.102, 4.922), and 1.102 (95% CI: 1.066, 1.140). For NO2, the highest associations were exhibited in Dingxi (RR = 1.262, 95% CI: 1.081, 1.473) at lag07, in Longnan (RR = 2.554, 95% CI: 2.100, 4.805) at lag06, and in Tianshui (RR = 1.158, 95% CI: 1.106, 1.213) at lag07. Meanwhile, the strongest effects observed for a 1 mg m-3 increase in CO were 2.786 (95% CI: 1.467, 5.291) for Dingxi at lag07, 1.502 (95% CI: 1.096, 2.059) for Longnan at lag05, and 1.385 (95% CI: 1.137, 1.686) for Tianshui at lag04. Adults aged 15-64 years appeared to be more susceptible to TRAPs, and the associations were stronger in the cold season. The results of the present study indicate that exposure to TRAPs was positively correlated with outpatient visits for AR.

Development of SSR Markers and Evaluation of Genetic Diversity of Endangered Plant Saussurea involucrata.

The conservation biology field underscores the importance of understanding genetic diversity and gene flow within plant populations and the factors that influence them. This study employs Simple Sequence Repeat (SSR) molecular markers to investigate the genetic diversity of the endangered plant species Saussurea involucrata, offering a theoretical foundation for its conservation efforts. Utilizing sequencing results to screen SSR loci, we designed and scrutinized 18 polymorphic microsatellite primers across 112 samples from 11 populations in the Bayinbuluke region. Our findings reveal high genetic diversity (I = 0.837, He = 0.470) and substantial gene flow (Nm = 1.390) among S. involucrata populations (China, Xinjiang), potentially attributed to efficient pollen and seed dispersal mechanisms. Principal Coordinate Analysis (PCoA) indicates a lack of distinct genetic structuring within the Bayinbuluke populations. The cluster analysis using STRUCTURE reflected the genetic structure of S. involucrata to a certain extent compared with PCoA. The results showed that all samples were divided into four groups. To safeguard this species, we advocate for the in situ conservation of all S. involucrata populations in the area. The SSR markers developed in this study provide a valuable resource for future genetic research on S. involucrata.

Efficient elimination of antibiotic resistome in livestock manure by semi-permeable membrane covered hyperthermophilic composting.

Livestock manure is a hotspot for antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs), and an important contributor to antibiotic resistance in non-clinical settings. This study investigated the effectiveness and potential mechanisms of a novel composting technology, semi-permeable membrane covered hyperthermophilic composting (smHTC), in removal of ARGs and MGEs in chicken manure. Results showed that smHTC was more efficient in removal of ARGs and MGEs (92% and 93%) compared to conventional thermophilic composting (cTC) (76% and 92%). The efficient removal in smHTC is attributed to direct or indirect negative effects caused by the high temperature, including reducing the involvement of bio-available heavy metals (HMs) in co-selection processes of antibiotic resistance, decreasing the bacterial abundance and diversity, suppressing the horizontal gene transfer and killing potential ARGs hosts. Overall, smHTC can efficiently remove the resistome in livestock manure, reducing the risk to crops and humans from ARGs residues in compost products.

Ambient temperature and cardiovascular disease-related emergency room visits in Lanzhou, China from 2013 to 2019: A time-series study.

This study assessed the links between daily mean temperature and emergency room (ER) admissions for total and cause-specific cardiovascular diseases (CVD) in Lanzhou, China from 2013 to 2019. A quasi-Poisson Generalized Additive Model (GAM) and a Distributed Lag Non-Linear Model (DLNM) were used to determine the effects of temperature on total and cause-specific cardiovascular emergency visits. The relative risks (RR) at cold (hot) temperatures were calculated by comparing the 5th (95th) centile of temperature with the minimum morbidity temperature (MMT). Exposure-response curves demonstrating an inverted U-shape or an irregular M-shape association were observed between temperature and total and cause-specific CVD. The study found that both cold and hot temperatures had negative impacts on emergency room visits for various cardiovascular diseases. For people with total CVD, heart rhythm disturbances (HRD), or cerebrovascular diseases (CD), females were more sensitive to temperature than males, while for ischemic heart disease (IHD) and heart failure (HF), males were more vulnerable to temperature. The < 65 years old with total CVD, IHD, HRD, or CD was more susceptible to the effects of temperature. The results indicated that the relationship between temperature and total and cause-specific CVD was nonlinear, and susceptibility to temperature varied across disease subtype, gender, and age.

Metalated covalent organic frameworks as efficient catalysts for multicomponent tandem reactions.

Multicomponent tandem reactions have become indispensable synthetic methods due to their economic advantages and efficient usage in natural products and drug synthesis. The emergence of metalated covalent organic frameworks (MCOFs) has opened up new opportunities for the advancement of multicomponent tandem reactions. In contrast to commonly used homogeneous transition metal catalysts, MCOFs possess regular porosity, high crystallinity, and rich metal chelation sites that facilitate the uniform distribution and anchoring of metals within their cavities. Thus, they show extremely high activity and have recently been widely employed as catalysts for multicomponent tandem reactions. It is timely to conduct a review of MCOFs in multicomponent tandem reactions, in order to offer guidance and assistance for the synthesis of MCOF catalysts and their application in multicomponent tandem reactions. This review provides a comprehensive overview of the design and synthesis of MCOFs, their application and progress in multicomponent tandem reactions, and the primary challenges encountered during their current development with the aim of contributing to the promotion of the field.

Lipid Nanoparticular Codelivery System for Enhanced Antitumor Effects by Ferroptosis-Apoptosis Synergistic with Programmed Cell Death-Ligand 1 Downregulation.

Intrinsic or acquired resistance to chemical drugs severely limits their therapeutic efficacy in cancer treatment. Various intracellular antioxidant molecules, particularly glutathione (GSH), play a crucial role in maintaining intracellular redox homeostasis by mitigating the overproduced reactive oxygen species (ROS) due to rapid cell proliferation. Notably, these antioxidants also eliminate chemical-drug-induced ROS, eventually diminishing their cytotoxicity and rendering them less effective. In this study, we combined erastin, a GSH biosynthesis inhibitor, with 2'-deoxy-5-fluorouridine 5'-monophosphate sodium salt (FdUMP), an ROS-based drug, to effectively disrupt intracellular redox homeostasis and reverse chemotherapy resistance. Therefore, efficient ferroptosis and apoptosis were simultaneously induced for enhanced antitumor effects. Additionally, we employed small interfering RNA targeting PD-L1 (siPD-L1) as a third agent to block immune-checkpoint recognition by CD8+ T cells. The highly immunogenic cell peroxidates or damage-associated molecular patterns (DAMPs) induced by erastin acted synergistically with downregulated PD-L1 to enhance the antitumor effects. To codeliver these three drugs simultaneously and efficiently, we designed GE11 peptide-modified lipid nanoparticles (LNPs) containing calcium phosphate cores to achieve high encapsulation efficiencies. In vitro studies verified its enhanced cytotoxicity, efficient intracellular ROS induction and GSH/GPX4 downregulation, substantial lipid peroxidation product accumulation, and mitochondrial depolarization. In vivo, this formulation effectively accumulated at tumor sites and achieved significant tumor inhibition in subcutaneous colon cancer (CRC) mouse models with a maximum tumor inhibition rate of 83.89% at a relatively low dose. Overall, a strategy to overcome clinical drug resistance was verified in this study by depleting GSH and activating adaptive immunity.

Sustainable and ultrafast antibiotics removal, self-cleaning and disinfection with electroactive metal-organic frameworks/carbon nanotubes membrane.

Although conventional nanofiltration (NF) membrane is widely applied in water treatment, it faces the challenges of insufficient selectivity toward emerging contaminants, low permeability and non-sustainable fouling control. Herein, a novel electroactive metal-organic frameworks/carbon nanotubes membrane was constructed by facile and green nanobubbles-mediated non-solvent-induced phase separation (NIPS) strategy for ultrafast antibiotics removal. It presented 3-fold to 100-fold higher permeability (101.3-105.7 L·h-1·m-2·bar-1) without compromising rejection (71.8 %-99.3 %) of common antibiotics (tetracycline, norfloxacin, sulfamethoxazole, sulfamethazine) than most commercial and state-of-the-art NF membranes. The separation mechanism was due to the synergy of loose selective layer with three-dimensional interconnected networks and UiO-66/CNTs with unique pore sieving and charge property. It also presented excellent antibiotics selectivity with high NaCl/tetracycline separation factor of 194 and CuCl2/tetracycline separation factor of 316 for remediation of antibiotics and heavy metal combined pollution. Meanwhile, it possessed efficient anti-fouling, antibacterial and electro-driven self-cleaning ability, which enabled sustainable fouling control and disinfection with short process, low energy and chemical consumption. Furthermore, potential application of UiO-66/CNTs membrane in wastewater reclamation was demonstrated by stable antibiotics rejection, efficient flux recovery and long-term stability over 260 h. This study would provide useful insights into removal of emerging contaminants from water by advanced NF membrane.

Analysis of demand and influencing factors for smart senior care among older adults in underdeveloped regions of western China: a case study of Lanzhou.

Introduction: With the rapid development of artificial intelligence and Internet-of-Things technology, internal support systems among families are gradually weakening, which can no longer satisfy the current demands of older adults. In this context, smart senior care has become a new development direction. However, existing studies on the demand for smart senior care are primarily concentrated in economically developed provinces and mega-cities in eastern China; their research results or conclusions may not apply to underdeveloped areas in the Western region. Therefore, our study selects Lanzhou as a representative city in an underdeveloped western region to investigate the demand of older adults for smart senior care and analyze the influencing factors. Methods: This cross-sectional study included 4,815 older adults from Lanzhou, China. A structured questionnaire was designed to investigate the demands of the older adults for smart senior care and analyze thie influencing factors. The Chi-square test was used for single factor analysis of each variable. The logistic regression model included the statistically significant variables to analyze factors influencing older adults' demand for smart senior care. A significance level of p < 0.05 was considered statistically significant. Results: Among the surveyed older adults, 1,625 (33.75%) expressed a demand for smart senior care. The finding indicated that participants' age, level of education, marital status, monthly income, number of children, type of endowment insurance, and knowledge of smart senior care were significantly associated with their demands for smart senior care (p < 0.05). Notably, medical care emerged as the smart senior care service with the highest demand rate (79.45%). Conclusion: In Lanzhou, older adults show a low level of knowledge but a high demand for smart senior care. Their demand is influenced by personal, family, health conditions, senior care security, and other factors. To advance smart senior care, government departments should accelerate the improvement of the laws and regulations on smart senior care while vigorously enhancing the service's publicity to raise knowledge about it. Additionally, the service contents for smart senior care should be expanded to meet the diversified demands of older adults.

Catalytic infrared radiation dry-peeling Technology for non-Frozen and Frozen Grapes: Effects on temperature, peeling performance, and quality attributes.

This study introduces catalytic infrared radiation (CIR) heating technology as an eco-friendly alternative to conventional grape lye peeling (LP). The effects of heating time and distance on non-frozen and frozen grapes were assessed for temperature, peeling performance, and quality attributes. The findings indicate that CIR heating achieves complete dry-peeling of grapes. Extended heating times and reduced distances improve peeling performance, with more favorable results observed in frozen grapes compared to non-frozen ones. Grapes peeled using CIR demonstrated enhanced hardness, color, sugar-acid ratio, bioactive compounds, and antioxidant capacity, compared to those peeled using LP. Importantly, the frozen samples preserved their quality after CIR dry-peeling treatment. Based on peeling performance and quality attributes, the optimum heating times are established at 160 s for non-frozen grapes and 50 s for frozen grapes, at a heating distance of 5 cm. Therefore, CIR dry-peeling is recommended as an eco-friendly and quality-enhancing sustainable grape processing technology.

Historical spread routes of wild walnuts in Central Asia shaped by man-made and nature.

Walnuts have substantial economic value and are of significant interest being a wild-cultivated species. The study has re-sequenced the entire genome of the wild walnut, aligning it with the walnut reference genome, to identify 2,021,717 single nucleotide polymorphisms (SNPs). These were used to examine the genetics of 130 wild walnut samples collected from three countries. Utilizing structural and principal component analysis, the walnut samples from Central Asia were classified into four populations: Ili ah in Xinjiang (I), Dushanbe region in Tajikistan (II), Sary-Chelek, Arslanbob in Kara-Alma regions of Kyrgyzstan (III), and Kok-Tundy region of Kyrgyzstan (IV). The 4 groups showed large differences in nucleotide diversity, population differentiation, and linkage disequilibrium decay, as well as gene flow among them. The present geographic distribution of these populations does not align with the genetic distribution pattern as the populations of Central Asian wild walnuts have experienced similar population dynamics in the past, i.e., the highest effective population size at ca. 6 Ma, two sharp population declines at 6 and 0.2 Ma, and convergence at ca. 0.2 Ma. The genetic distribution patterns are better explained by human activity, notably through archaeological findings of walnut use and the influence of the Silk Road, rather than by current geographic distributions.

Understanding Salinity-Driven Modulation of Microbial Interactions: Rhizosphere versus Edaphic Microbiome Dynamics.

Soil salinization poses a global threat to terrestrial ecosystems. Soil microorganisms, crucial for maintaining ecosystem services, are sensitive to changes in soil structure and properties, particularly salinity. In this study, contrasting dynamics within the rhizosphere and bulk soil were focused on exploring the effects of heightened salinity on soil microbial communities, evaluating the influences shaping their composition in saline environments. This study observed a general decrease in bacterial alpha diversity with increasing salinity, along with shifts in community structure in terms of taxa relative abundance. The size and stability of bacterial co-occurrence networks declined under salt stress, indicating functional and resilience losses. An increased proportion of heterogeneous selection in bacterial community assembly suggested salinity's critical role in shaping bacterial communities. Stochasticity dominated fungal community assembly, suggesting their relatively lower sensitivity to soil salinity. However, bipartite network analysis revealed that fungi played a more significant role than bacteria in intensified microbial interactions in the rhizosphere under salinity stress compared to the bulk soil. Therefore, microbial cross-domain interactions might play a key role in bacterial resilience under salt stress in the rhizosphere.

Mediterranean diet related to 3-year incidence of cognitive decline: results from a cohort study in Chinese rural elders.

OBJECTIVE: This study aims to examine the effect of the Mediterranean diet (MeDi) on cognitive decline among the Chinese elderly with a 3-year follow-up. METHODS: This study is divided into two waves: wave-1 January 2019 to June 2019 (n = 2313); wave-2 January 2022 to March 2022 (n = 1648). MeDi scores were calculated from the Mediterranean Diet Adherence Screener (MEDAS), with the scoring of low compliance (0-6 points) and high compliance (7-14 points). The Mini-Mental State Examination (MMSE) was used to assess cognitive function. An MMSE score dropping ≥ 2 points from baseline was defined as cognitive decline. The relationships between MeDi score and cognitive decline were analyzed by linear regression models or Binary logistic regression. RESULTS: During the 3-year follow-up, 23.8% of patients exhibited cognitive decline. The study revealed a significant difference in MMSE score changes between low and high MeDi adherence groups (p < 0.001). MeDi score was negatively correlated with cognitive deterioration (ß = -0.020, p = 0.026). MeDi score was only negatively associated with cognitive decline in the female subgroup aged ≥65 years (ß = -0.034, p = 0.033). The food beans (OR = 0.65, 95%CI:0.51, 0.84), fish (OR = 0.72, 95%CI:0.54, 0.97), and cooked vegetables (OR = 0.68, 95%CI:0.53, 0.84) were protective factors for cognitive decline. CONCLUSIONS: This study suggests that greater adherence to the MeDi is linked to a reduced risk of cognitive decline in elderly people. However, this is found only in women who are 65 years old or older. It also found long-term adherence to beans, fish, and vegetables are more effective in improving cognitive function.

MicroRNA-130b Suppresses Malignant Behaviours and Inhibits the Activation of the PI3K/Akt Signaling Pathway by Targeting MET in Pancreatic Cancer.

There has been interested in the microRNAs' roles in pancreatic cancer (PC) cell biology, particularly in regulating pathways related to tumorigenesis. The study aimed to explore the hub miRNAs in PC and underlying mechanisms by bioinformatics and fundamental experiments. RNA datasets collected from the Gene Expression Omnibus were analysed to find out differentially expressed RNAs (DERNAs). The miRNA-mRNA and protein-protein interaction (PPI) networks were built. The clinicopathological features and expressions of hub miRNAs and hub mRNAs were explored. Dual-luciferase reporter gene assay was performed to assess the interaction between microRNA and target gene. RT-qPCR and western blot were employed to explore RNA expression. The roles of RNA were detected by CCK-8 test, wound healing, transwell, and flow cytometry experiment. We verified 40 DEmiRNAs and 1613 DEmRNAs, then detected a total of 69 final functional mRNAs (FmRNAs) and 23 DEmiRNAs. In the miRNA-mRNA networks, microRNA-130b (miR-130b) was the hub RNA with highest degrees. Clinical analysis revealed that miR-130b was considerably lower expressed in cancerous tissues than in healthy ones, and patients with higher-expressed miR-130b had a better prognosis. Mechanically, miR-130b directly targeted MET in PC cells. Cell functional experiments verified that miR-130b suppressed cell proliferation, migration, promoted apoptosis, and inhibited the PI3K/Akt pathway by targeting MET in PC cells. Our findings illustrated the specific molecular mechanism of miR-130b regulating PC progress. The miR-130b/MET axis may be an alternative target in the therapeutic intervention of PC and provide an opportunity to deepen our understanding of the pathogenesis of PC.

Nanomedicines Promote Cartilage Regeneration in Osteoarthritis by Synergistically Enhancing Chondrogenesis of Mesenchymal Stem Cells and Regulating Inflammatory Environment.

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive erosion of the articular cartilage and inflammation. Mesenchymal stem cells' (MSCs) transplantation in OA treatment is emerging, but its clinical application is still limited by the low efficiency in oriented differentiation. In our study, to improve the therapeutic efficiencies of MSCs in OA treatment by carbonic anhydrase IX (CA9) siRNA (siCA9)-based inflammation regulation and Kartogenin (KGN)-based chondrogenic differentiation, the combination strategy of MSCs and the nanomedicine codelivering KGN and siCA9 (AHK-CaP/siCA9 NPs) was used. In vitro results demonstrated that these NPs could improve the inflammatory microenvironment through repolarization of M1 macrophages to the M2 phenotype by downregulating the expression levels of CA9 mRNA. Meanwhile, these NPs could also enhance the chondrogenesis of bone marrow-derived mesenchymal stem cells (BMSCs) by upregulating the pro-chondrogenic TGF-ß1, ACAN, and Col2α1 mRNA levels. Moreover, in an advanced OA mouse model, compared with BMSCs alone group, the lower synovitis score and OARSI score were found in the group of BMSCs plus AHK-CaP/siCA9 NPs, suggesting that this combination approach could effectively inhibit synovitis and promote cartilage regeneration in OA progression. Therefore, the synchronization of regulating the inflammatory microenvironment through macrophage reprogramming (CA9 gene silencing) and promoting MSCs oriented differentiation through a chondrogenic agent (KGN) may be a potential strategy to maximize the therapeutic efficiency of MSCs for OA treatment.

Characterization of Pancreatic Fistula after Post-pancreatectomy Acute Pancreatitis.

OBJECTIVE: This study aimed to investigate the clinical significance and risk factors of postoperative pancreatic fistula (POPF) after post-pancreatectomy acute pancreatitis (PPAP) in patients who underwent pancreaticoduodenectomy (PD). SUMMARY BACKGROUND DATA: PPAP has been recognized as a critical factor in the pathophysiology of POPF after PD. METHODS: A total of 817 consecutive patients who underwent elective PD between January 2020 and June 2022 were included. PPAP and POPF were defined in accordance with the International Study Group for Pancreatic Surgery (ISGPS) definitions. Multivariate logistic analyses were performed to investigate the risk factors for POPF. Comparisons between PPAP-associated POPF and non-PPAP-associated POPF were made to further characterize this intriguing complication. RESULTS: Overall, 159 (19.5%) patients developed POPF after PD, of which 73 (45.9%) occurred following PPAP, and the remaining 86 (54.1%) had non-PPAP-associated POPF. Patients with PPAP-associated POPF experienced significantly higher morbidity than patients without POPF. Multivariate analyses revealed distinct risk factors for each POPF type. For PPAP-associated POPF, independent risk factors included estimated blood loss >200 mL (OR 1.93), MPD ≤3 cm (OR 2.88), and soft pancreatic texture (OR 2.01), largely overlapping with FRS (Fistula Risk Score) elements. On the other hand, non-PPAP-associated POPF was associated with age >65 years (OR 1.95), male (OR 2.10), and MPD ≤3 cm (OR 2.57). Notably, among patients with PPAP, the incidence of POPF consistently hovered around 50% regardless of the FRS stratification. CONCLUSIONS: PPAP-associated POPF presents as a distinct pathophysiology in the development of POPF after PD, potentially opening doors for future prevention strategies targeting the early postoperative period.

Highly Stretchable, Self-Healing, and Sensitive E-Skins at -78 °C for Polar Exploration.

Ultralow temperature-tolerant electronic skins (e-skins) can endow polar robots with tactile feedback for exploring in extremely cold polar environments. However, it remains a challenge to develop e-skins that enable sensitive touch sensation and self-healing at ultralow temperatures. Herein, we describe the development of a sensitive robotic hand e-skin that can stretch, self-heal, and sense at temperatures as low as -78 °C. The elastomeric substrate of this e-skin is based on poly(dimethylsiloxane) supramolecular polymers and multistrength dynamic H-bonds, in particular with quadruple H-bonding motifs (UPy). The structure-performance relationship of the elastomer at ultralow temperatures is investigated. The results show that elastomers with side-chain UPy units exhibit higher stretchability (∼3257%) and self-healing efficiency compared to those with main-chain UPy units. This is attributed to the lower binding energy variation and lower potential well. Based on the elastomer with side-chain UPy and man-made electric ink, a sensitive robotic hand e-skin for usage at -78 °C is constructed to precisely sense the shape of objects and specific symbols, and its sensation can completely self-recover after being damaged. The findings of this study contribute to the concept of using robotic hands with e-skins in polar environments that make human involvement limited, dangerous, or impossible.