The synergistic impact of probiotics and dietary fiber on constipation management in chlorpromazine-induced schizophrenia patients: exploring the modulation of intestinal microbiota and neurotrophic factors.

OBJECTIVE: To explore the improvement effect of probiotics combined with dietary fiber on constipation in patients with schizophrenia. METHODS: To compare the improvement scores of constipation, constipation symptoms, quality of life, neurotrophic factors-related indicators, and clinical efficacy between the two groups. RESULTS: There was no statistically significant difference in Cleveland Constipation Scoring System (CCS) scores in the control group before and after treatment (p > 0.05), while the CCS scores in the observation group decreased significantly after treatment (p < 0.05); Patient Assessment of Constipation Symptoms scores significantly decreased in the observation group compared to the control group (p < 0.05), with no significant difference in Patient Assessment of Constipation Quality of Life scores between the two groups pre- and post-treatment; Neuron-specific enolase levels decreased significantly in both groups post-treatment, while brain-derived neurotrophic factor, neuregulin-1, and nerve growth factor levels increased significantly, with a more pronounced rise in the observation group (p < 0.05). Additionally, the total effective rate of clinical treatment in the observation group was higher than that in the control group (p < 0.05). CONCLUSION: Probiotics combined with dietary fiber can improve constipation symptoms in patients with schizophrenia accompanied by constipation, effectively maintain the balance of intestinal microbiota, and improve the quality of life of patients. Additionally, levels of neurotrophic factors associated with bowel function and neurological health increased significantly, with a higher total effective rate of clinical treatment observed in the probiotics and dietary fiber group. These findings suggest the potential efficacy of probiotics and dietary fiber in managing constipation in this patient population.

Temperature Effect on Rhizome Development in Perennial rice.

Traditional agriculture is becoming increasingly not adapted to global climate change. Compared with annual rice, perennial rice has strong environmental adaptation and needs fewer natural resources and labor inputs. Rhizome, a kind of underground stem for rice to achieve perenniallity, can grow underground horizontally and then bend upward, developing into aerial stems. The temperature has a great influence on plant development. To date, the effect of temperature on rhizome development is still unknown. Fine temperature treatment of Oryza longistaminata (OL) proved that compared with higher temperatures (28-30 ℃), lower temperature (17-19 ℃) could promote the sprouting of axillary buds and enhance negative gravitropism of branches, resulting in shorter rhizomes. The upward growth of branches was earlier at low temperature than that at high temperature, leading to a high frequency of shorter rhizomes and smaller branch angles. Comparative transcriptome showed that plant hormones played an essential role in the response of OL to temperature. The expressions of ARF17, ARF25 and FucT were up-regulated at low temperature, resulting in prospectively asymmetric auxin distribution, which subsequently induced asymmetric expression of IAA20 and WOX11 between the upper and lower side of the rhizome, further leading to upward growth of the rhizome. Cytokinin and auxin are phytohormones that can promote and inhibit bud outgrowth, respectively. The auxin biosynthesis gene YUCCA1 and cytokinin oxidase/dehydrogenase gene CKX4 and CKX9 were up-regulated, while cytokinin biosynthesis gene IPT4 was down-regulated at high temperature. Moreover, the D3 and D14 in strigolactones pathways, negatively regulating bud outgrowth, were up-regulated at high temperature. These results indicated that cytokinin, auxins, and strigolactones jointly control bud outgrowth at different temperatures. Our research revealed that the outgrowth of axillary bud and the upward growth of OL rhizome were earlier at lower temperature, providing clues for understanding the rhizome growth habit under different temperatures, which would be helpful for cultivating perennial rice.

The growth and nutrient removal properties of heterotrophic microalgae Chlorella sorokiniana in simulated wastewater containing volatile fatty acids.

To reduce the high cost of organic carbon sources in waste resource utilization in the cultivation of microalgae, volatile fatty acids (VFAs) derived from activated sludge were used as the sole carbon source to culture Chlorella sorokiniana under the heterotrophic cultivation. The addition of VFAs in the heterotrophic condition enhanced the total nitrogen (TN) and phosphorus (TP) removal of C. sorokiniana, which proved the advantageous microalgae in using VFAs in the heterotrophic culture after screening in the previous study. To discover the possible mechanism of nitrogen and phosphorus adsorption in heterotrophic conditions by microalgae, the effect of different ratios of VFAs (acetic acid (AA): propionic acid (PA): butyric acid (BA)) on the nutrient removal and growth properties of C. sorokiniana was studied. In the 8:1:1 group, the highest efficiency (77.19%) of VFAs assimilation, the highest biomass (0.80 g L-1) and lipid content (31.35%) were achieved, with the highest TN and TP removal efficiencies of 97.44 % and 91.02 %, respectively. Moreover, an aerobic denitrifying bacterium, Pseudomonas, was determined to be the dominant genus under this heterotrophic condition. This suggested that besides nitrate uptake and utilization by C. sorokiniana under the heterotrophy, the conduct of the denitrification process was also the main reason for obtaining high nitrogen removal efficiency.

LINC00606 promotes glioblastoma progression through sponge miR-486-3p and interaction with ATP11B.

BACKGROUND: LncRNAs regulate tumorigenesis and development in a variety of cancers. We substantiate for the first time that LINC00606 is considerably expressed in glioblastoma (GBM) patient specimens and is linked with adverse prognosis. This suggests that LINC00606 may have the potential to regulate glioma genesis and progression, and that the biological functions and molecular mechanisms of LINC00606 in GBM remain largely unknown. METHODS: The expression of LINC00606 and ATP11B in glioma and normal brain tissues was evaluated by qPCR, and the biological functions of the LINC00606/miR-486-3p/TCF12/ATP11B axis in GBM were verified through a series of in vitro and in vivo experiments. The molecular mechanism of LINC00606 was elucidated by immunoblotting, FISH, RNA pulldown, CHIP-qPCR, and a dual-luciferase reporter assay. RESULTS: We demonstrated that LINC00606 promotes glioma cell proliferation, clonal expansion and migration, while reducing apoptosis levels. Mechanistically, on the one hand, LINC00606 can sponge miR-486-3p; the target gene TCF12 of miR-486-3p affects the transcriptional initiation of LINC00606, PTEN and KLLN. On the other hand, it can also regulate the PI3K/AKT signaling pathway to mediate glioma cell proliferation, migration and apoptosis by binding to ATP11B protein. CONCLUSIONS: Overall, the LINC00606/miR-486-3p/TCF12/ATP11B axis is involved in the regulation of GBM progression and plays a role in tumor regulation at transcriptional and post-transcriptional levels primarily through LINC00606 sponging miR-486-3p and targeted binding to ATP11B. Therefore, our research on the regulatory network LINC00606 could be a novel therapeutic strategy for the treatment of GBM.

Research in revealing the effects on Cuscuta chinensis to diarrhea type irritable bowel syndrome based on network pharmacology and molecular docking potential mechanism.

To explore the potential mechanism in Cuscuta sinensis on diarrhea-type irritable bowel syndrome using network pharmacology and molecular docking techniques. First, the active components and related targets of Cuscuta were found setting oral utilization >30% and drug-like properties greater than or equal to 0.18 as filter information from TCMSP database. The targets of diarrheal irritable bowel syndrome were compiled by searching DrugBank, GeneCards, OMIM, PharmGkb, and TTD databases. The intersections of drugs and targets related to the disease were taken for gene ontology enrichment and Kyoto encyclopedia of genes and genomes enrichment analyses, to elucidate the potential molecular mechanisms and pathway information of Cuscuta sinensis for the treatment of diarrheal irritable bowel syndrome. The protein-protein interaction network was constructed by using the STRING database and visualized with Cytoscape_v3.10.0 software to find the protein-protein interaction network core At last, molecular docking was performed to validate the combination of active compounds with the core target. The target information of Cuscuta and diarrhea-type irritable bowel syndrome was compiled, which can be resulted in 11 active compounds such as quercetin, kaempferol, isorhamnetin, ß-sitosterol, and another 17 core targets such as TP53, IL6, AKT1, IL1B, TNF, EGFR, etc, whose Kyoto encyclopedia of genes and genomes was enriched in the pathways of lipids and atherosclerosis, chemical carcinogenesis-receptor activation, PI3K-Akt signaling pathway, and fluid shear stress and atherosclerosis, etc. Docking demonstrated that the core targets and the active compounds were able to be better combined. Cuscuta chinensis may exert preventive effects on diarrhea-type irritable bowel syndrome by reducing intestinal inflammation, protecting intestinal mucosa, and playing an important role in antioxidant response through multi-targets and multi-pathways.

An extensive analysis of the prognostic and immune role of FOXO1 in various types of cancer.

Forkhead Box O1 (FOXO1) has been reported to play important roles in many tumors. However, FOXO1 has not been studied in pan-cancer. The purpose of this study was to reveal the roles of FOXO1 in pan-cancer (33 cancers in this study). Through multiple public platforms, a pan-cancer analysis of FOXO1 was conducted to obtained FOXO1 expression profiles in various tumors to explore the relationship between FOXO1 expression and prognosis of these tumors and to disclose the potential mechanism of FOXO1 in these tumors. FOXO1 was associated with the prognosis of multiple tumors, especially LGG (low grade glioma), OV (ovarian carcinoma), and KIRC (kidney renal clear cell carcinoma). FOXO1 might play the role of an oncogenic gene in LGG and OV, while playing the role of a cancer suppressor gene in KIRC. FOXO1 expression had a significant correlation with the infiltration of some immune cells in LGG, OV, and KIRC. By combining FOXO1 expression and immune cell infiltration, we found that FOXO1 might influence the overall survival of LGG through the infiltration of myeloid dendritic cells or CD4+ T cells. Functional enrichment analysis and gene set enrichment analysis showed that FOXO1 might play roles in tumors through immunoregulatory interactions between a lymphoid and a non-lymphoid cell, TGF-beta signaling pathway, and transcriptional misregulation in cancer. FOXO1 was associated with the prognosis of multiple tumors, especially LGG, OV, and KIRC. In these tumors, FOXO1 might play its role via the regulation of the immune microenvironment.

Prophylactic effects of N-acethylcysteine on inflammation-induced depression-like behaviors in mice.

Depression, affecting individuals worldwide, is a prevalent mental disease, with an increasing incidence. Numerous studies have been conducted on depression, yet its pathogenesis remains elusive. Recent advancements in research indicate that disturbances in synaptic transmission, synaptic plasticity, and reduced neurotrophic factor expression significantly contribute to depression's pathogenesis. In our study, we utilized adult male C57BL/6J mice. Lipopolysaccharide (LPS) can induce both chronic and acute depression-like symptoms in mice, a widely used model for studying depression associated with inflammation. N-acetylcysteine (NAC) exhibits anti-inflammatory and ameliorative effects on depressive symptoms. This study sought to determine whether NAC use could mitigate inflammatory depressive behavior through the enhancement of synaptic transmission, synaptic plasticity, and increasing levels of brain-derived neurotrophic factor (BDNF). In this study, we discovered that in mice modeled with depression-like symptoms, the expression levels of dendrites, BDNF, and miniature excitatory postsynaptic potential (mEPSC) in glutamatergic neurons, as well as the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid glutamate receptors (AMPARs) GluA1 and GluA2 subunits, were significantly decreased. These findings suggest an impairment in the synaptic transmission of glutamatergic neurons. Following treatment with NAC, the previously mentioned levels improved, indicating an enhancement in both synaptic transmission and synaptic plasticity. Our results suggest that NAC exerts a protective effect on mouse models of inflammatory depression, potentially through the enhancement of synaptic transmission and plasticity, as well as the restoration of neurotrophic factor expression. These findings offer vital animal experimental evidence supporting NAC's role in mitigating inflammatory depressive behaviors.

Staphylococcus Scalded Skin Syndrome-Induced Thrombosis Leading to Free Flap Complications: A Case Report and Review.

Staphylococcal scalded skin syndrome (SSSS) is a clinical term used for a spectrum of blistering skin conditions induced by the epidermolytic toxins of the Staphylococcus aureus bacteria. The complications of SSSS include thrombosis; however, the pathophysiology of this is still poorly understood. We present a case of free anterolateral thigh (ALT) flap failure in a patient as a result of widespread flap thrombosis associated with staphylococcal scalded skin syndrome (SSSS). This is the first reported case of free flap failure associated with SSSS. Free flap failure due to acquired prothrombotic conditions, such as infection, is a rare and potentially under-reported phenomenon. This article aims to further explore the role of both thrombophilias and provoked thrombotic events in free flap failure. A review of the literature will also be presented, and cases of free flap failure in patients with infection-induced vascular complications will be summarised.

Effects of probiotic supplementation on 12 min run performance, mood management, body composition and gut microbiota in amateur marathon runners: A double-blind controlled trial.

Background: Probiotic supplementation has a positive effect on endurance exercise performance and body composition in athletes, but the underlying mechanisms remain unclear. Gut microbiota can provide measurable markers of immune function in athletes, and microbial composition analysis may be sensitive enough to detect stress and metabolic disorders caused by exercise. Methods: Nineteen healthy active amateur marathon runners (15 male and 4 female) with a mean age of 29.11 years volunteered to participate in this double-blind controlled study. Based on the performance of the Cooper 12-min running test (CRT), the participants were allocated into two groups to receive either a probiotic formulation comprising lactobacillus acidophilus and bifidobacterium longum (n = 10) or placebo containing maltodextrin (n = 9) for five weeks. Consistency of diet and exercise was ensured throughout the experimental period. Before and after the intervention, all participants were assessed for CRT, emotional stability and gastrointestinal symptoms, gut microbiota composition, body composition and magnetic resonance imaging (MRI) indicators of skeletal muscle microcirculation. Results: Compared to before the intervention, the probiotics group showed an increase in CRT score (2.88 ± 0.57 vs 3.01 ± 0.60 km, P＜0.05), significant improvement in GSRS and GIQLI (9.20 ± 4.64 vs 7.40 ± 3.24, 118.90 ± 12.30 vs 127.50 ± 9.85, P＜0.05), while these indicators remained unchanged in the control group, with a significant time-group interaction effect on gastrointestinal symptoms. Additionally, some MRI metabolic cycling indicators of the thigh skeletal muscle also changed in the probiotics group (P＜0.05). Regarding microbiota abundance, the probiotics group exhibited a significant increase in the abundance of beneficial bacteria and a significant decrease in the abundance of harmful bacteria post-intervention (P＜0.05). Conclusion: As a sports nutritional supplement, probiotics have the potential to improve athletic performance by optimizing the balance of gut microbiota, alleviating gastrointestinal symptoms.

Functional mouse hepatocytes derived from interspecies chimeric livers effectively mitigate chronic liver fibrosis.

Liver disease is a major global health challenge. There is a shortage of liver donors worldwide, and hepatocyte transplantation (HT) may be an effective treatment to overcome this problem. However, the present approaches for generation of hepatocytes are associated with challenges, and interspecies chimera-derived hepatocytes produced by interspecies blastocyst complementation (IBC) may be promising donor hepatocytes because of their more comprehensive hepatic functions. In this study, we isolated mouse hepatocytes from mouse-rat chimeric livers using IBC and found that interspecies chimera-derived hepatocytes exhibited mature hepatic functions in terms of lipid accumulation, glycogen storage, and urea synthesis. Meanwhile, they were more similar to endogenous hepatocytes than hepatocytes derived in vitro. Interspecies chimera-derived hepatocytes could relieve chronic liver fibrosis and reside in the injured liver after transplantation. Our results suggest that interspecies chimera-derived hepatocytes are a potentially reliable source of hepatocytes and can be applied as a therapeutic approach for HT.

Structure, spectral properties and antioxidant activity of melanoidins extracted from high temperature sterilized lotus rhizome juice.

Melanoidins are complex macromolecular compounds closely associated with the browning phenomenon in high-temperature sterilized lotus rhizome juice (HTSL). This study aimed to preliminarily investigate the structural properties of melanoidins extracted from HTSL. Results showed that the average molecular weight of HTSL melanoidins ranged from 1.48 to 41.40 kDa. Medium and high molecular weight melanoidins were the main contributors to the brown color of HTSL. Sugars, proteins, and phenolics were present in HTSL, among which sugar was the most abundant, with glucose being the predominant monosaccharide in acid degradation products of melanoidins. Through fluorescence and ultraviolet spectral analysis, we found that the melanoidins contained carboxyl and carbonyl compounds, as well as furan and pyran heterocyclic compounds. The infrared spectra and nuclear magnetic resonance spectra revealed a prominent sugar absorption peak, indicating that sugar was the main component of the melanoidins of HTSL. Furthermore, in vitro antioxidant experiments showed that the antioxidant activity of melanoidins was significantly positively correlated with phenolic compounds. Our results indicated that there were differences in the structural properties of melanoidins fractions with different molecular weights. MW-H fraction significantly impacted the color and antioxidant activity of HTSL.

Synthesis and clinical application of representative small-molecule dipeptidyl Peptidase-4 (DPP-4) inhibitors for the treatment of type 2 diabetes mellitus (T2DM).

Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose levels, which can cause many diseases, including osteoporosis, fractures, arthritis, and foot complications. The inhibitors of dipeptidyl peptidase-4 (DPP-4), an enzyme involved in glucose metabolism regulation, are essential for managing Type 2 Diabetes Mellitus (T2DM). The inhibition of DPP-4 has become a promising treatment approach for T2DM because it can increase levels of active glucagon-like peptide-1 (GLP-1), leading to improved insulin secretion in response to glucose and reduced release of glucagon. The review commences by elucidating the role of DPP-4 in glucose homeostasis and its significance in T2DM pathophysiology. Furthermore, it presents the mechanism of action, preclinical pharmacodynamics, clinical efficacy, and toxicity profiles of small-molecule DPP-4 inhibitors across various clinical stages. This comprehensive review provides valuable insights into the synthesis and clinical application of DPP-4 inhibitors, serving as an invaluable resource for researchers, clinicians, and pharmaceutical professionals interested in diabetes therapeutics and drug development.

Dl-3-n-butylphthalide promotes microglial phagocytosis and inhibits microglial inflammation via regulating AGE-RAGE pathway in APP/PS1 mice.

Alzheimer's disease (AD) stands as the most prevalent neurodegenerative condition worldwide, and its correlation with microglial function is notably significant. Dl-3-n-butylphthalide (NBP), derived from the seeds of Apium graveolens L. (Chinese celery), has demonstrated the capacity to diminish Aß levels in the brain tissue of Alzheimer's transgenic mice. Despite this, its connection to neuroinflammation and microglial phagocytosis, along with the specific molecular mechanism involved, remains undefined. In this study, NBP treatment exhibited a substantial improvement in learning deficits observed in AD transgenic mice (APP/PS1 transgenic mice). Furthermore, NBP treatment significantly mitigated the total cerebral Aß plaque deposition. This effect was attributed to the heightened presence of activated microglia surrounding Aß plaques and an increase in microglial phagocytosis of Aß plaques. Transcriptome sequencing analysis unveiled the potential involvement of the AGE (advanced glycation end products) -RAGE (receptor for AGE) signaling pathway in NBP's impact on APP/PS1 mice. Subsequent investigation disclosed a reduction in the secretion of AGEs, RAGE, and proinflammatory factors within the hippocampus and cortex of NBP-treated APP/PS1 mice. In summary, NBP alleviates cognitive impairment by augmenting the number of activated microglia around Aß plaques and ameliorating AGE-RAGE-mediated neuroinflammation. These findings underscore the related mechanism of the crucial neuroprotective roles of microglial phagocytosis and anti-inflammation in NBP treatment for AD, offering a potential therapeutic target for the disease.

Biomechanical evaluation of various rigid internal fixation modalities for condylar-base-associated multiple mandibular fractures: A finite element analysis.

Condylar-base-associated multiple mandibular fractures are more prevalent than single ones. Direct trauma to mandibular symphysis, body or angle are prone to induce indirect condylar fracture. However, little is known about the effects of various rigid internal fixation modalities in condylar base for relevant multiple mandibular fractures, especially when we are confused in the selection of operative approach. Within the finite element analysis, straight-titanium-plate implanting positions in condylar base contained posterolateral zone (I), anterolateral zone (II), and intermediate zone (III). Von Mises stress (SS) in devices and bone and mandibular displacement (DT) were solved, while maximum values (SSmax and DTmax) were documented. For rigid internal fixation in condylar-base-and-symphysis fractures, I + II modality exhibited least SSmax in screws and cortical bone and least DTmax, I + III modality exhibited least SSmax in plates. For rigid internal fixation in condylar-base-and-contralateral-body fractures, I + III modality exhibited least SSmax in screws and cortical bone, I + II modality exhibited least SSmax in plates and least DTmax. For rigid internal fixation in condylar-base-and-contralateral-angle fractures, I + III modality exhibited least DTmax. The findings suggest that either I + II or I + III modality is a valid guaranty for rigid internal fixation of condylar base fractures concomitant with symphysis, contralateral body or angle fractures.

Base-Promoted Synthesis of Isoquinolines through a Tandem Reaction of 2-Methyl-arylaldehydes and Nitriles.

A convenient method for preparing 3-aryl isoquinolines via a base-promoted tandem reaction is presented. Simply combining commercially available 2-methyl-arylaldehydes, benzonitriles, NaN(SiMe3)2, and Cs2CO3 enabled the synthesis of a variety of isoquinolines (23 examples, ≤90% yield). Among the syntheses of isoquinolines, the transition metal-free method described here is straightforward, practical, and operationally simple.

Illuminating sustainable household well-being and natural resource dependence in the case of disaster resettlement in rural China.

In order to transform rural development, the implementation of disaster resettlement projects should not only reduce environmental hazards, but also improve the sustainability of natural resources and household well-being. This article assesses sustainable household well-being (SHWB) and natural resource dependence using a quantitative survey of rural China. It identifies four classes of relationship between SHWB and natural resource dependence and explores the impact of disaster resettlement on these classes. The result shows that rural households that participate in disaster resettlement as well as in voluntary relocation, centralized relocation, and new-stage relocation are more likely to achieve "high well-being and low dependence." However, the overall SHWB level of the relocated households is lower than that of the non-relocated households, and disaster resettlement also has a significant positive impact on the "low well-being and low dependence" class. It is recommended that governments implement measures to address these issues. The findings in this article could shed light on the impact of resettlement programs on rural households elsewhere.

Analysis of chemoresistance characteristics and prognostic relevance of postoperative gemcitabine adjuvant chemotherapy in pancreatic cancer.

AIM: To investigate the relationship between chemoresistance in pancreatic cancer patients receiving postoperative gemcitabine adjuvant therapy and specific clinical/pathological characteristics, as well as its impact on patient prognosis. METHODS: From June 2018 to June 2021, clinical and pathological data of 148 pancreatic cancer patients were collected, and 101 patients were followed up for tumor recurrence/metastasis and survival status. The correlation between chemoresistance and specific clinical/pathological characteristics or patient prognosis was retrospectively analyzed. RESULTS: Of the 148 patients, 78 were in the chemoresistance group and 70 in the non-chemoresistance group. Univariate analysis showed that the development of chemoresistance may be related to patient age, combined diabetes, preoperative CA19-9 level, tumor size, AJCC stage, vascular invasion, and positive lymph node ratio. Furthermore, subsequent multivariate analysis incorporating these variables indicated that tumor size may be a key factor influencing chemoresistance (p < 0.001, OR = 1.584). Log-rank test showed patients in the chemoresistance group had worse overall survival (OS) (HR = 2.102, p = 0.018) and progression free survival (PFS) (HR = 3.208, p = 0.002) than patients in the non-chemoresistance group; and patients with smaller size tumors (diameter ≤3 cm) had significantly better OS (HR = 2.923, p < 0.001) and PFS (HR = 2.930, p = 0.003) than those with larger size tumors (diameter >3 cm). CONCLUSIONS: Patients with pancreatic cancer receiving postoperative gemcitabine adjuvant therapy are more likely to develop chemoresistance when their tumor sizes are larger (diameter >3 cm). Development of chemoresistance exacerbates the prognosis of patients with pancreatic cancer, and larger tumor size is also a risk factor for poor prognosis in these patients.

Urban-rural differences in the association between occupational physical activity and mortality in Chinese working population: evidence from a nationwide cohort study.

Background: Despite emerging studies suggesting that occupational physical activity (OPA) might be harmful to health, the available evidence is not definitive. Most of these research studies were conducted in high-income Western countries or in urbanized setting. In China, where over one-third of the population resides in rural area, the impact of OPA on health is not well understood. The goal of this study is to investigate how the association between OPA and mortality vary by urban-rural settings. Methods: Baseline data on OPA was gathered using the Global Physical Activity Questionnaire from 30,650 urban and 49,674 rural working adults as part of the 2013-2014 China Chronic Disease and Risk Factor Surveillance. Participants were followed for a median of 6.2 years, and death records were retrieved from the National Mortality Surveillance System until December 31, 2019. The multivariable Cox proportional hazard model was used to examine urban-rural differences in the association between OPA and all-cause and cardiovascular disease (CVD) mortality. Subgroup analyses were performed by sex, socioeconomic status, leisure time, transportation, and non-occupational physical activity. Findings: During the study period, 1342 deaths were recorded, of which 426 were caused by CVD. In rural area, working adults engaging in occupational moderate-to-vigorous physical activity (MVPA) for ≥40 h per week, compared to those without any, had an adjusted hazard ratio of 0.60 (95% CI: 0.49-0.73) for all-cause mortality and 0.55 (95% CI: 0.37-0.83) for CVD mortality. However, no significant association was found in urban area (0.84 [0.61-1.15] for all-cause mortality, Pinteraction = 0.036; and 0.94 [0.53-1.66] for CVD mortality, Pinteraction = 0.098). The negative associations of occupational MVPA with mortality were more pronounced in women, non-smokers, and those with less non-occupational physical activities. Hypertension, heart rate, and diabetes were important contributors to the relationship between occupational MVPA and mortality. Interpretation: The findings from the current study did not support the notion that high levels of OPA would induce harm. On the contrary, in rural setting, higher levels of OPA were associated with lower mortality risks. Furthermore, the observed urban-rural differences in the association between OPA and mortality underscored the need for context-specific public health guidelines on physical activities. Funding: R&D Program of Beijing Municipal Education Commission (KM202210025026),National Key Research and Development Program of China (2021YFC2500201), and Young Elite Scientist Sponsorship Program by BAST (BYESS2023385).

Host-derived Interleukin 1α induces an immunosuppressive tumor microenvironment via regulating monocyte-to-macrophage differentiation.

Tumor-associated macrophages exhibit high heterogeneity and contribute to the establishment of an immunosuppressive tumor microenvironment (TME). Although numerous studies have demonstrated that extracellular factors promote macrophage proliferation and polarization, the regulatory mechanisms governing the differentiation process to generate phenotypically, and functionally diverse macrophage subpopulations remain largely unexplored. In this study, we examined the influence of interleukin 1α (IL-1α) on the development of an immunosuppressive TME using orthotopic transplantation murine models of breast cancer. Deletion of host Il1α led to the rejection of inoculated congenic tumors. Single-cell sequencing analysis revealed that CX3CR1+ macrophage cells were the primary sources of IL-1α in the TME. The absence of IL-1α reprogrammed the monocyte-to-macrophage differentiation process within the TME, characterized by a notable decrease in the subset of CX3CR+ ductal-like macrophages and an increase in iNOS-expressing inflammatory cells. Comparative analysis of gene signatures in both human and mouse macrophage subsets suggested that IL-1α deficiency shifted the macrophage polarization from M2 to M1 phenotypes, leading to enhanced cytotoxic T lymphocyte activity in the TME. Importantly, elevated levels of IL-1α in human cancers were associated with worse prognosis following immunotherapy. These findings underscore the pivotal role of IL-1α in shaping an immune-suppressive TME through the regulation of macrophage differentiation and activity, highlighting IL-1α as a potential target for breast cancer treatment. Teaser: Interleukin 1α dictates macrophage behavior, influencing an immunosuppressive microenvironment in breast cancer, suggesting it as a treatment target.

Tuning the End Alkyl Chain of the Ether Solvent to Stabilize the Electrode/Electrolyte Interfaces in the NCM-Li Battery.

Lithium metal batteries (LMBs) combined with a high-voltage nickel-rich cathode show great potential in meeting the growing need for high energy density. The lack of advanced electrolytes has been a major obstacle in the commercialization of high-voltage lithium metal batteries (LMBs), as these electrolytes need to effectively support both a stable lithium metal anode (LMA) and a high-voltage cathode (>4 V vs Li+/Li). In this work, by extending the two terminal methyl groups in DIGDME and TEGDME to n-butyl groups, we design a new weakly solvating electrolyte (2 M LIFSI+TEGDBE) that enables the stable cycling of NMC83 (LiNi0.83Co0.12Mn0.05O2) cathodes. The NMC83 cell exhibits a high and stable Coulombic efficiency (CE) of over 99%, as well as capacity retention of approximately 99.8% after 100 cycles at 0.3 C. X-ray photoelectron spectroscopy analysis (XPS) and high-resolution transmission electron microscope (HRTEM) images revealed that the anion species decomposed first, resulting in the formation of a cathode-electrolyte interface (CEI) film predominantly consisting of decomposition products from the anions on the positive electrode surface. This work links the functional group of solvents with the solvation structure and electrochemical performance of ether-based electrolytes, providing a distinctive sight to design advanced electrolytes for high-energy-density LMBs.