A ß-Carboline Derivate PAD4 Inhibitor Reshapes Neutrophil Phenotype and Improves the Tumor Immune Microenvironment against Triple-Negative Breast Cancer.

Triple-negative breast cancer is a highly aggressive and heterogeneous breast cancer subtype characterized by early metastasis, poor prognosis, and high recurrence. Targeting histone citrullination-mediated chromatin dysregulation to induce epigenetic alterations shows great promise in TNBC therapy. We report the synthesis, optimization, and evaluation of a novel series of ß-carboline-derived peptidyl arginine deiminase 4 inhibitors that exhibited potent inhibition of TNBC cell proliferation. The most outstanding PAD4 inhibitor, compound 28, hindered the PAD4-H3cit-NET signaling pathway and inhibited the growth of solid tumors and pulmonary metastatic nodules in the 4T1 in situ mouse model. Furthermore, 28 improved the tumor immune microenvironment by reshaping neutrophil phenotype, upregulating the proportions of dendritic cells and M1 macrophages, and reducing the amount of myeloid-derived suppressor cells. In conclusion, our work offered 28 as an efficacious PAD4 inhibitor that exerts a combination of conventional chemotherapy and immune-boosting effects, which represents a potential therapy strategy for TNBC.

Ligand efficacy shifts a nuclear receptor conformational ensemble between transcriptionally active and repressive states.

Nuclear receptors (NRs) are thought to dynamically alternate between transcriptionally active and repressive conformations, which are stabilized upon ligand binding. Most NR ligand series exhibit limited bias, primarily consisting of transcriptionally active agonists or neutral antagonists, but not repressive inverse agonists-a limitation that restricts understanding of the functional NR conformational ensemble. Here, we report a NR ligand series for peroxisome proliferator-activated receptor gamma (PPARγ) that spans a pharmacological spectrum from repression (inverse agonism) to activation (agonism) where subtle structural modifications switch compound activity. While crystal structures provide snapshots of the fully repressive state, NMR spectroscopy and conformation-activity relationship analysis reveals that compounds within the series shift the PPARγ conformational ensemble between transcriptionally active and repressive conformations that are populated in the apo/ligand-free ensemble. Our findings reveal a molecular framework for minimal chemical modifications that enhance PPARγ inverse agonism and elucidate their influence on the dynamic PPARγ conformational ensemble.

PAD4 Inhibitor-Functionalized Layered Double Hydroxide Nanosheets for Synergistic Sonodynamic Therapy/Immunotherapy Of Tumor Metastasis.

Sonodynamic therapy (SDT) is demonstrated to trigger the systemic immune response of the organism and facilitate the treatment of metastatic tumors. However, SDT-mediated neutrophil extracellular traps (NETs) formation can promote tumor cell spread, thus weakening the therapeutic effectiveness of metastatic tumors. Herein, the amorphous CoW-layered double hydroxide (a-CoW-LDH) nanosheets are functionalized with a peptidyl arginine deiminase 4 (PAD4) inhibitor, i.e., YW3-56, to construct a multifunctional nanoagent (a-LDH@356) for synergistic SDT/immunotherapy. Specifically, a-CoW-LDH nanosheets can act as a sonosensitizer to generate abundant reactive oxygen species (ROS) under US irradiation. After loading with YW3-56, a-LDH@356 plus US irradiation not only effectively induces ROS generation and immunogenic cell death, but also inhibits the elevation of citrullinated histone H3 (H3cit) and the release of NETs, enabling a synergistic enhancement of anti-tumor metastasis effect. Using 4T1 tumor model, it is demonstrated that combining a-CoW-LDH with YW3-56 stimulates an anti-tumor response by upregulating the proportion of immune-activated cells and inducing polarization of M1 macrophages, and inhibits immune escape by downregulating the expression of PD-1 on immune cells under US irradiation, which not only arrests primary tumor progression with a tumor inhibition rate of 69.5% but also prevents tumor metastasis with the least number of lung metastatic nodules.

Features Associated with Visible Lamina Cribrosa Pores in Individuals of African Ancestry with Glaucoma: Primary Open-Angle African Ancestry Glaucoma Genetics (POAAGG) Study.

There are scarce data regarding the rate of the occurrence of primary open-angle glaucoma (POAG) and visible lamina cribrosa pores (LCPs) in the eyes of individuals with African ancestry; the potential impact of these features on disease burden remains unknown. We recruited subjects with POAG to the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. Through regression models, we evaluated the association between the presence of LCPs and various phenotypic features. In a multivariable analysis of 1187 glaucomatous eyes, LCPs were found to be more likely to be present in eyes with cup-to-disc ratios (CDR) of ≥0.9 (adjusted risk ratio (aRR) 1.11, 95%CI: 1.04-1.19, p = 0.005), eyes with cylindrical-shaped (aRR 1.22, 95%CI: 1.11-1.33) and bean pot (aRR 1.24, 95%CI: 1.13-1.36) cups versus conical cups (p < 0.0001), moderate cup depth (aRR 1.24, 95%CI: 1.06-1.46) and deep cups (aRR 1.27, 95%CI: 1.07-1.50) compared to shallow cups (p = 0.01), and the nasalization of central retinal vessels (aRR 1.33, 95%CI: 1.23-1.44), p < 0.0001). Eyes with LCPs were more likely to have a higher degree of African ancestry (q0), determined by means of SNP analysis (aRR 0.96, 95%CI: 0.93-0.99, p = 0.005 for per 0.1 increase in q0). Our large cohort of POAG cases of people with African ancestry showed that LCPs may be an important risk factor in identifying severe disease, potentially warranting closer monitoring by physicians.

Mitosis targeting in non-small lung cancer cells by inhibition of PAD4.

PAD4 expression and activity were significantly up-regulated in lung cancer tissues suggesting that PAD4 could be a possible target for lung cancer treatment. In this study we had demonstrated that PAD4 expression was higher in lung cancer patients whom with lymphnode metastasis and pleural invasion. Inhibiting PAD4 with a small molecular inhibitor could induce apoptosis and suppress growth in lung cancer cells. We used RNA-sequencing to further investigate transcriptional changes that induced by PAD4 inhibition, and results suggested its affected mostly on the cell cycle, mitotic cell cycle process, p53 signaling pathway. By using image flow cytometry analysis, we found that PAD4 inhibited by YW3-56 could accumulate cells in the G1/G0 phases and reducing the fraction of G2/M and S phase cells. Quantification of different phase of mitosis in cells treated with YW3-56 revealed an increasing trend of telophase and prophase cells. Taken together, our data indicated that PAD4 inhibitor could affect cell cycle and mitosis of lung cancer cells, and targeting PAD4 could be a promising strategy for discovery novel anti-NSCLC treatments.

Water and Salt Concentration-Dependent Electrochemical Performance of Hydrogel Electrolytes in Zinc-Ion Batteries.

Zinc-ion batteries (ZIBs) are promising energy storage devices with safe, nonflammable electrolytes and abundant, low-cost electrode materials. Their practical applications are hampered by various water-related undesirable reactions, such as the hydrogen evolution reaction (HER), corrosion of zinc metal, and water-induced decay of cathode materials. Polymer hydrogel electrolytes were used to control these reactions. However, salt, water, and polymeric backbones intervene in polymer hydrogels, and currently, there are no systematic studies on how salt and water concentrations synergistically affect polymer hydrogels' electrochemical performance. Here, we used an in situ polymerization method to synthesize polyacrylamide (PAM) hydrogels with varied Zn(ClO4)2 (0.5 to 2.0 mol kg-1) and water (40 to 90 wt %) concentrations. Their electrochemical performances in Zn||Ti half-cells, Zn||Zn symmetrical cells, and Zn||V2O5 full cells have been comprehensively evaluated. Although the ionic conductivity of electrolytes increases with the salt concentration, a high salt concentration of 2.0 mol kg-1 with more Zn2+ solvated H2O would induce more severe HER and Zn corrosion at the electrolyte/electrode interfaces. A narrow window of the water concentration at 70-80 wt % is optimal to balance needs for achieving a high ionic conductivity and restricting water-related undesirable reactions. The chemically more active water counts roughly 64.1-73.1 wt % of the total water in electrolytes. PAM hydrogel electrolyte with 1.0 mol kg-1 Zn(ClO4)2 and 80 wt % water enables 1200 h of stable cycling in a Zn||Zn symmetric cell and 99.24% of Coulombic efficiency in a Zn||Ti half-cell. Due to the water-induced decay of V2O5, the electrolyte with 70 wt % water delivers the best performance in a Zn||V2O5 full cell, which can retain 73.7% of its initial capacity after 400 charge/discharge cycles. Our results show that achieving precise control of salt and water concentrations of hydrogel electrolytes in their optimal windows to reduce the fraction of chemically more active water while retaining high ionic conductivity is essential to enabling high-performance ZIBs.

Silencing of Jumonji domain-containing 1C inhibits the osteogenic differentiation of bone marrow mesenchymal stem cells via nuclear factor-κB signaling.

BACKGROUND: Osteoporosis is a common metabolic bone disorder induced by an imbalance between osteoclastic activity and osteogenic activity. During osteoporosis, bone mesenchymal stem cells (BMSCs) exhibit an increased ability to differentiate into adipocytes and a decreased ability to differentiate into osteoblasts, resulting in bone loss. Jumonji domain-containing 1C (JMJD1C) has been demonstrated to suppress osteoclastogenesis. AIM: To examine the effect of JMJD1C on the osteogenesis of BMSCs and the potential underlying mechanism. METHODS: BMSCs were isolated from mouse bone marrow tissues. Oil Red O staining, Alizarin red staining, alkaline phosphatase staining and the expression of adipogenic and osteogenic-associated genes were assessed to determine the differentiation of BMSCs. Bone marrow-derived macrophages (BMMs) were incubated with receptor activator of nuclear factor-kappa Β ligand to induce osteoclast differentiation, and osteoclast differentiation was confirmed by tartrate-resistant acid phosphatase staining. Other related genes were measured via reverse transcription coupled to the quantitative polymerase chain reaction and western blotting. Enzyme-linked immunosorbent assays were used to measure the levels of inflammatory cytokines, including tumor necrosis factor alpha, interleukin-6 and interleukin-1 beta. RESULTS: The osteogenic and adipogenic differentiation potential of BMSCs isolated from mouse bone marrow samples was evaluated. JMJD1C mRNA and protein expression was upregulated in BMSCs after osteoblast induction, while p-nuclear factor-κB (NF-κB) and inflammatory cytokines were not significantly altered. Knockdown of JMJD1C repressed osteogenic differentiation and enhanced NF-κB activation and inflammatory cytokine release in BMSCs. Moreover, JMJD1C expression decreased during BMM osteoclast differentiation. CONCLUSION: The JMJD1C/NF-κB signaling pathway is potentially involved in BMSC osteogenic differentiation and may play vital roles in the pathogenesis of osteoporosis.

Effect of 15 days -6° head-down bed rest on microbial communities of supragingival plaque in young men.

Introduction: The microgravity environment astronauts experience during spaceflight can lead to an increased risk of oral diseases and possible changes in oral microecology. In this study, we aimed to assess changes in the microbial community of supragingival plaques to explore the effects of spaceflight microgravity environment on oral microecology. Methods: Sixteen healthy male volunteers were recruited, and supragingival plaque samples were collected under -6° head-down bed rest (HDBR) at five-time points: day 1 before HDBR; days 5, 10, and 15 of HDBR; and day 6 of recovery. Bacterial genomic DNA was sequenced using gene sequencing technology with 16S ribosomal ribonucleic acid V3-V4 hypervariable region amplification and the obtained data were analyzed bioinformatically. Results: Alpha diversity analysis showed a significant increase in species richness in supragingival plaque samples on day 15 of HDBR compared with that at pre-HDBR. Beta diversity analysis revealed that the community composition differed among the groups. Species distribution showed that, compared with those at pre-HDBR, the relative abundances of Corynebacterium and Aggregatibacter increased significantly during HDBR, while those of Veillonella, Streptococcus, and Lautropia decreased significantly. Moreover, compared with those at pre-HDBR, the relative abundance of Leptotrichia increased significantly on day 6 of recovery, whereas the relative abundances of Porphyromonas and Streptococcus decreased significantly. Network analysis showed that the interaction relationship between the dominant genera became simpler during HDBR, and the positive and negative correlations between them showed dynamic changes. Phylogenetic investigation of communities by reconstruction of unobserved states analysis showed that the amino acid metabolism function of plaque microorganisms was more enriched during HDBR. Discussion: In summary, in a 15-day simulated microgravity environment, the diversity, species distribution, interaction relationship, and metabolic function of the supragingival plaque microbial community changed, which suggests that microgravity may affect the oral microecosystem by changing the balance of supragingival plaque microbial communities and further leading to the occurrence and development of oral diseases.

A double-crack structure for bionic wearable strain sensors with ultra-high sensitivity and a wide sensing range.

Flexible strain sensors are crucial in fully monitoring human motion, and they should have a wide sensing range and ultra-high sensitivity. Herein, inspired by lyriform organs, a flexible strain sensor based on the double-crack structure is designed. An MXene layer and an Au layer with cracks are constructed on both sides of the insulated polydimethylsiloxane (PDMS) film, forming an equivalent parallel circuit that guarantees the integrity of the conductive path under a large strain. The rapid disconnection of the crack junctions causes a significant change in the resistance value. Due to the effect of cracks on the conductive path, the sensitivity of the sensor is largely improved. Benefiting from the double-crack structure, the as-obtained sensor shows ultra-high sensitivity (maximum gauge factor of up to 14 373.6), a wide working range (up to 21%), a fast response time (183 ms) and excellent dynamical stability (almost no performance loss after 1000 stretching cycles and different frequency cycles). In practical applications, the sensor is applied to different parts of the human body to sense the deformation of the skin, demonstrating its great potential application value in human physiological detection and the human-machine interaction. This study can provide new ideas for preparing high-performance flexible strain sensors.

Single-cell transcriptomics reveals the role of antigen presentation in liver metastatic breast cancer.

Liver metastasis (LM) is the primary cause of cancer-related mortality in late-stage breast cancer (BC) patients. Here we report an in-depth analysis of the transcriptional landscape of LM of 11 patients with secondary hepatic carcinoma at single-cell resolution. Our study reveals that terminally exhausted CD4+ and dysfunctional CD8+ T cells were enriched in LM along with low antigen presentation. We also found that macrophages were associated with the tumor infiltrating CD4+ T cells, while FCN3+ macrophages, type 1 conventional dendritic cells (cDC1) and LAMP3+ DC regulated T cell functions, probably via antigen processing and presentation. Major histocompatibility complex expression in FCN3+ macrophage, cDC1 and LAMP3+ DC was reduced in LM compared to those in normal tissues and primary BC. Malfunctioned antigen presentation in these cells is linked to a worse prognosis in invasive BC and hepatocellular carcinoma. Our results provide valuable insights into the role of tumor infiltrating T cells in LM.

pH-Responsive, Self-Assembled Ruthenium Nanodrug: Dual Impact on Lysosomes and DNA for Synergistic Chemotherapy and Immunogenic Cell Death.

Several DNA-damaging antitumor agents, including ruthenium complexes, induce immunogenic cell death (ICD). In this study, an arginyl-glycyl-aspartic acid (RGD) peptide-modified carboline ruthenium complex (KS-Ru) is synthesized as a chemotherapeutic nanodrug and an ICD inducer. The RGD peptide, an integrin ligand, provides tumor-specific targeting and promotes self-assembly of the KS-Ru complex. The pH-responsive self-assembly is assessed through transmission and scanning electron microscopy. Additionally, in vitro cytotoxic activity and anti-metastasis ability are evaluated using MTT and Transwell assays, respectively, along with cellular immunofluorescence staining and imaging flow cytometry. The ability of the complex to inhibit primary tumor formation and lung metastasis in vivo is evaluated using Lewis lung cancer and A549 xenograft models. Furthermore, the tumor immune microenvironment is evaluated using single-cell flow mass cytometry. KS-Ru translocates to the nucleus, causing DNA damage and inducing ICD. Within the lysosomes, KS-Ru self-assembled into nanoflowers, leading to lysosomal swelling and apoptosis. Notably, the as-synthesized pH-dependent ruthenium nanomedicine achieves dual functionality-chemotherapy and immunotherapy. Moreover, the pH-responsive self-assembly of KS-Ru enables simultaneous mechanisms in the lysosome and nucleus, thereby lowering the likelihood of drug resistance. This study provides valuable insight for the design of novel ruthenium-based nanoantitumor drugs.

Examining behaviour change techniques (BCTs) in technology-based interventions for enhancing social participation in people with mild cognitive impairment (MCI) or dementia: a scoping review protocol.

INTRODUCTION: Technology-based interventions have improved the social participation of older adults with mild cognitive impairment (MCI) or dementia. Nevertheless, how these interventions modify social participation remains to be seen, and what efficient behaviour change techniques (BCTs) have been used. As such, this study aims to conduct a scoping review, identifying the features and BCTs behind technology-based interventions that improve social participation for individuals with MCI or dementia. METHODS AND ANALYSIS: The scoping review method will be used to search journal articles from electronic databases, such as PsycINFO, PubMed, MEDLINE, Web of Science, Scopus and reference lists. Following the population, concept and context structure, this study focuses on adults over 60 diagnosed with MCI or dementia. It delves into technology-based interventions, specifically focusing on BCTs, features and overall effectiveness for improving social participation. The research considers contextual factors, exploring the diverse settings where these interventions are used, including homes, healthcare facilities and community centres. This approach aims to provide nuanced insights into the impact of technology-based interventions on social participation in the targeted demographic. Two authors will independently screen titles, abstracts and full texts using Covidence software. Disagreements will be resolved through consensus or a third reviewer, and reasons for exclusion will be documented. We will conduct a detailed analysis of BCTs to pinpoint effective strategies applicable to future technology-based intervention designs. Through this scoping review, we aim to provide valuable insights that guide the direction of future research. Specifically, we seek to inform the development of effective technology-based interventions tailored to support social participation for people with MCI or dementia. ETHICS AND DISSEMINATION: Ethical approval is not necessary, as this review will use available articles from electronic databases. The outcome of the study will be published in a peer-reviewed journal. PROTOCOL REGISTRATION NUMBER: https://osf.io/tkzuf/.

The Associations of Two Novel Inflammation Biomarkers, SIRI and SII, with Mortality Risk in Patients with Chronic Heart Failure.

Background: The associations of two novel inflammation biomarkers, systemic inflammation response index (SIRI) and systemic immune inflammation index (SII), with mortality risk in patients with chronic heart failure (CHF) are not well-characterized. Methods: This retrospective cohort study included patients with CHF in two medical centers of Chinese People's Liberation Army General Hospital, Beijing, China. The outcomes of this study included in-hospital mortality and long-term mortality. Associations of SIRI and SII with mortality were assessed using multivariable regressions and receiver operating characteristic (ROC) analyses. Results: A total of 6232 patients with CHF were included in the present study. We documented 97 cases of in-hospital mortality and 1738 cases of long-term mortality during an average 5.01-year follow-up. Compared with patients in the lowest quartile of SIRI, those in the highest quartile exhibited 134% higher risk of in-hospital mortality (adjusted odds ratio, 2.34; 95% confidence interval [CI], 1.16-4.72) and 45% higher risk of long-term mortality (adjusted hazard ratio, 1.45; 95% CI, 1.25-1.67). Compared with patients in the lowest quartile of SII, those in the highest quartile exhibited 27% higher risk of long-term mortality (adjusted hazard ratio, 1.27; 95% CI, 1.11-1.46). In ROC analyses, SIRI showed better prognostic discrimination than C-reactive protein (area under the curve: 69.39 vs 60.91, P = 0.01, for in-hospital mortality; 61.82 vs 58.67, P = 0.03, for 3-year mortality), whereas SII showed similar prognostic value with C-reactive protein. Conclusion: SIRI and SII were significantly associated with mortality risk in patients with CHF. SIRI may provide better prognostic discrimination than C-reactive protein.

Association of Systemic Markers of Inflammation with Signs and Symptoms of Dry Eye Disease and Sjogren's Syndrome in the Dry Eye Assessment and Management (DREAM©) Study.

PURPOSE: To evaluate the possible role of systemic inflammation in dry eye disease (DED) via systemic inflammatory marker associations with DED signs and symptoms, and an analysis of a subgroup with Sjogren's Syndrome (SS). METHODS: Participant serums were analyzed using line immunoassays (LIAs) for the presence of antibodies against 34 systemic inflammatory markers. Using the 2012 American College of Rheumatology definition, the 481 participants were categorized into group 1 (SS; n = 52), group 2 (autoimmune disease not including SS; n = 66), or group 3 (control, i.e. no autoimmune disease; n = 363). RESULTS: 3 markers were positive in ≥10% of participants: Ro52 (19.3%), Scl-70 (15.0%), CN-1A (14.2%). 2 markers were positively associated with symptoms: PM-Scl100 (p = 0.02), Sm (p = 0.009). 5 markers were positively associated with signs: U2SnRNP A', Ro52, La, DNA, Ro60. SS participants showed significantly higher positivity for 4 markers compared to participants with no autoimmune disease: PL-7 (p = 0.02), Ro52 (p < 0.0001), La (p < 0.0001), Ro60 (p < 0.0001). SS participants showed significantly higher positivity for 3 markers compared to participants with another autoimmune disease: Ro52 (p < 0.0001), La (p = 0.002), Ro60 (p < 0.0001). CONCLUSIONS: This study did not show evidence of significant systemic inflammation in participants with moderate-to-severe DED, based on the markers tested. PM-Scl100 and Sm may be associated with more severe DED symptoms. U2SnRNP A', Ro52, La, DNA, and Ro60 may be associated with more severe ocular surface disease. Ro52 and PL-7 may be diagnostic markers for SS. Future research evaluating these relationships and their clinical significance is needed.

High Target Homology Does Not Guarantee Inhibition: Aminothiazoles Emerge as Inhibitors of Plasmodium falciparum.

In this study, we identified three novel compound classes with potent activity against Plasmodium falciparum, the most dangerous human malarial parasite. Resistance of this pathogen to known drugs is increasing, and compounds with different modes of action are urgently needed. One promising drug target is the enzyme 1-deoxy-d-xylulose-5-phosphate synthase (DXPS) of the methylerythritol 4-phosphate (MEP) pathway for which we have previously identified three active compound classes against Mycobacterium tuberculosis. The close structural similarities of the active sites of the DXPS enzymes of P. falciparum and M. tuberculosis prompted investigation of their antiparasitic action, all classes display good cell-based activity. Through structure-activity relationship studies, we increased their antimalarial potency and two classes also show good metabolic stability and low toxicity against human liver cells. The most active compound 1 inhibits the growth of blood-stage P. falciparum with an IC50 of 600 nM. The results from three different methods for target validation of compound 1 suggest no engagement of DXPS. All inhibitor classes are active against chloroquine-resistant strains, confirming a new mode of action that has to be further investigated.

Influence of Blood Pressure on Acute Cervical Spinal Cord Injury Without Fracture and Dislocation: Results From a Retrospective Analysis.

OBJECTIVE: The objective of this study was to investigate the influence of blood pressure on the severity and functional recovery of patients with acute cervical spinal cord injury (SCI) without fracture and dislocation. METHODS: A retrospective case control study analyzed the data of 40 patients admitted to our orthopedics department (Beijing Tiantan Hospital, Capital Medical University) from January 2013 to February 2021. They were diagnosed as acute cervical SCI without fracture and dislocation. Gender, age, height, weight, history of hypertension, postinjury American Spinal Injury Association grade, postinjury modified Japanese Orthopaedic Association (mJOA) score, postoperative mJOA score, 1-year follow-up mJOA score, preoperative mean arterial pressure (MAP), intramedullary T2 hyperintensity, and hyponatremia were collected. The patients were divided into groups and subgroups based on their history of hypertension and preoperative MAP. The effects of history of hypertension and preoperative MAP on the incidence of T2 hyperintensity, hyponatremia, the improvement rate of the postoperative mJOA and 1-year follow-up mJOA scores were analyzed. RESULTS: Patients with history of hypertension had a lower incidence of intramedullary T2 hyperintensity than patients without history of hypertension (P < 0.05). Patients with history of hypertension and patients with a higher preoperative MAP had better neurological recovery at 1 year of follow-up (P < 0.05). CONCLUSIONS: Blood pressure has great influence on acute cervical SCI without fracture and dislocation. Maintaining a higher preoperative MAP is advantageous for better recovery after SCI. Attention should be paid to the dynamic management of blood pressure to avoid the adverse effects of hypotension after SCI.

Seasonal variation of net ecosystem carbon exchange and gross primary production over a Loess Plateau semi-arid grassland of northwest China.

Grassland ecosystems store approximately one-third of the global terrestrial carbon stocks, which play a crucial role in regulating the carbon cycle on regional and global scales, but the current scientific understanding of the variation in net carbon dioxide exchange (NEE) on grassland ecosystems is still limited. Based on the eddy covariance technique, this study investigated the seasonal variation of ecosystem respiration (Reco) and gross primary production (GPP) from 2018 to 2020 in a semi-arid grassland on the Loess Plateau in northwest China. The results indicated that the annual cumulative average NEE value was - 0.778 kg C/m2, the growing season cumulative value accounted for approximately 83.81%, which suggested that the semiarid grassland showed a notable soil carbon sink. The correlation analysis revealed that soil temperature (Ts) (RReco = 0.71, RGPP = 0.61) and soil water content (SWC) (RReco = 0.47, RGPP = 0.44) were the two main driving factors in modulating the variation of daily average GPP and Reco (P < 0.01). Therefore, the monthly average of GPP and Reco increased with the increase in Ts (RGPP = 0.716, P < 0.01; RReco = 0.586, P < 0.05), resulting in an increase in the carbon sequestration capacity of the grass ecosystem. This study also showed that soil moisture has a promoting effect on the response of Reco and GPP to Ts, and the correlation among GPP, Reco, and Ts was much stronger under wet conditions. For instance, the coefficient of determination of Reco and GPP with Ts under wet conditions in 2018 increased by 0.248 and 0.286, respectively, compared to those under droughty conditions. Additionally, the temperature sensitivity of Reco (Q10) increased by 46.13% compared to dry conditions. In addition, carbon exchange models should consider the synergistic effect of Ts and SWC as one of the main driving factors for theoretical interpretation or modeling. Under the potential scenario of future global warming and the frequent extreme weather events, our findings have important implications for predicting future CO2 exchange and establishing an optimal ecological model of carbon flux exchange.

A meta-analysis examining the impact of open surgical therapy versus minimally invasive surgery on wound infection in females with cervical cancer.

A meta-analysis study was executed to measure the effect of minimally invasive surgery (MIS) and open surgical management (OSM) on wound infection (WI) in female's cervical cancer (CC). A comprehensive literature study till February 2023 was applied and 1675 interrelated investigations were reviewed. The 41 chosen investigations enclosed 10 204 females with CC and were in the chosen investigations' starting point, 4294 of them were utilizing MIS, and 5910 were utilizing OSM. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were utilized to compute the value of the effect of MIS and OSM on WI in female's CC and by the dichotomous approaches and a fixed or random model. The MIS had significantly lower WI (OR, 0.23; 95% CI, 0.15-0.35, p < 0.001) with no heterogeneity (I2 = 0%) and postoperative aggregate complications (PACs) (OR, 0.49; 95% CI, 0.37-0.64, p < 0.001) in females with CC and compared OSM. However, MIS compared with OSM in females with CC and had no significant difference in pelvic infection and abscess (PIA) (OR, 0.59; 95% CI, 0.31-1.16, p = 0.13). The MIS had significantly lower WI, and PACs, though, had no significant difference in PIA in females with CC and compared with OSM. However, care must be exercised when dealing with its values because of the low sample size of some of the nominated investigations for the meta-analysis.

Digital Storytelling Intervention for Enhancing the Social Participation of People With Mild Cognitive Impairment: Co-Design and Usability Study.

BACKGROUND: Community-based social participation has shown promise in delaying cognitive decline in older adults with mild cognitive impairment (MCI) who are at risk of developing dementia. Although group storytelling interventions have proven effective, the need for a skilled workforce to support people with MCI can limit broader community implementation. Technology-based interventions may offer a solution to this limitation by replicating the abilities of therapists. OBJECTIVE: This study aims to co-design a digital storytelling intervention and evaluate its usability. METHODS: This co-design process involved 3 stages, engaging people with MCI (n=12), their caregivers (n=4), and therapists (n=5) in Beijing, China. In the first stage, we used card sorting and voting methods to identify potential incentives for social participation and target the specific abilities that people with MCI wanted to enhance. In the second stage, we conducted brainstorming sessions with people with MCI and their caregivers to identify the potential features of a digital storytelling application named Huiyou ("meeting new friends" in Chinese). Finally, we assessed Huiyou's usability with people with MCI and therapists, leading to iterative improvements based on the usability findings. RESULTS: We uncovered a crucial link between boosting the self-confidence of people with MCI and their ability to address social participation challenges. Notably, we identified memory improvement and enhanced language expression as key factors for effective communication with grandchildren. Subsequently, participants suggested features and interfaces to address these challenges, leading to the development of Huiyou, a group-based digital storytelling application featuring functions such as generating story materials, conducting memory retrieval activities, and sharing stories. It received an "excellent" rating in the User Experience Questionnaire benchmark, displaying high levels of attractiveness, dependability, stimulation, and novelty. People with MCI achieved an average task completion rate of 87% (n=19; SD 0.13) of the 22 tasks. However, feedback from people with MCI and therapists highlighted usability issues in navigation, activity management, user interface, and feature optimization, indicating a need for improved accessibility and efficiency. CONCLUSIONS: The co-design approach contributed to developing the Huiyou prototype, supporting community-based social participation. User feedback highlighted the potential of Huiyou to enhance well-being and facilitate meaningful social interactions while maintaining crucial existing relationships.