A thalamic-primary auditory cortex circuit mediates resilience to stress.

Resilience enables mental elasticity in individuals when rebounding from adversity. In this study, we identified a microcircuit and relevant molecular adaptations that play a role in natural resilience. We found that activation of parvalbumin (PV) interneurons in the primary auditory cortex (A1) by thalamic inputs from the ipsilateral medial geniculate body (MG) is essential for resilience in mice exposed to chronic social defeat stress. Early attacks during chronic social defeat stress induced short-term hyperpolarizations of MG neurons projecting to the A1 (MGA1 neurons) in resilient mice. In addition, this temporal neural plasticity of MGA1 neurons initiated synaptogenesis onto thalamic PV neurons via presynaptic BDNF-TrkB signaling in subsequent stress responses. Moreover, optogenetic mimicking of the short-term hyperpolarization of MGA1 neurons, rather than merely activating MGA1 neurons, elicited innate resilience mechanisms in response to stress and achieved sustained antidepressant-like effects in multiple animal models, representing a new strategy for targeted neuromodulation.

The solute carrier SPNS2 recruits PI(4,5)P2 to synergistically regulate transport of sphingosine-1-phosphate.

Solute carrier spinster homolog 2 (SPNS2), one of only four known major facilitator superfamily (MFS) lysolipid transporters in humans, exports sphingosine-1-phosphate (S1P) across cell membranes. Here, we explore the synergistic effects of lipid binding and conformational dynamics on SPNS2's transport mechanism. Using mass spectrometry, we discovered that SPNS2 interacts preferentially with PI(4,5)P2. Together with functional studies and molecular dynamics (MD) simulations, we identified potential PI(4,5)P2 binding sites. Mutagenesis of proposed lipid binding sites and inhibition of PI(4,5)P2 synthesis reduce S1P transport, whereas the absence of the N terminus renders the transporter essentially inactive. Probing the conformational dynamics of SPNS2, we show how synergistic binding of PI(4,5)P2 and S1P facilitates transport, increases dynamics of the extracellular gate, and stabilizes the intracellular gate. Given that SPNS2 transports a key signaling lipid, our results have implications for therapeutic targeting and also illustrate a regulatory mechanism for MFS transporters.

Enhancement of the liver's neuroprotective role ameliorates traumatic brain injury pathology.

Traumatic brain injury (TBI) is a pervasive problem worldwide for which no effective treatment is currently available. Although most studies have focused on the pathology of the injured brain, we have noted that the liver plays an important role in TBI. Using two mouse models of TBI, we found that the enzymatic activity of hepatic soluble epoxide hydrolase (sEH) was rapidly decreased and then returned to normal levels following TBI, whereas such changes were not observed in the kidney, heart, spleen, or lung. Interestingly, genetic downregulation of hepatic Ephx2 (which encodes sEH) ameliorates TBI-induced neurological deficits and promotes neurological function recovery, whereas overexpression of hepatic sEH exacerbates TBI-associated neurological impairments. Furthermore, hepatic sEH ablation was found to promote the generation of A2 phenotype astrocytes and facilitate the production of various neuroprotective factors associated with astrocytes following TBI. We also observed an inverted V-shaped alteration in the plasma levels of four EET (epoxyeicosatrienoic acid) isoforms (5,6-, 8,9-,11,12-, and 14,15-EET) following TBI which were negatively correlated with hepatic sEH activity. However, hepatic sEH manipulation bidirectionally regulates the plasma levels of 14,15-EET, which rapidly crosses the blood-brain barrier. Additionally, we found that the application of 14,15-EET mimicked the neuroprotective effect of hepatic sEH ablation, while 14,15-epoxyeicosa-5(Z)-enoic acid blocked this effect, indicating that the increased plasma levels of 14,15-EET mediated the neuroprotective effect observed after hepatic sEH ablation. These results highlight the neuroprotective role of the liver in TBI and suggest that targeting hepatic EET signaling could represent a promising therapeutic strategy for treating TBI.

Intermittent Hypobaric Hypoxia Ameliorates Autistic-Like Phenotypes in Mice.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by persistent deficits in social communication and stereotyped behaviors. Although major advances in basic research on autism have been achieved in the past decade, and behavioral interventions can mitigate the difficulties that individuals with autism experience, little is known about the many fundamental issues of the interventions, and no specific medication has demonstrated efficiency for the core symptoms of ASD. Intermittent hypobaric hypoxia (IHH) is characterized by repeated exposure to lowered atmospheric pressure and oxygen levels, which triggers multiple physiological adaptations in the body. Here, using two mouse models of ASD, male Shank3B -/- and Fmr1 -/y mice, we found that IHH training at an altitude of 5,000 m for 4 h per day, for 14 consecutive days, ameliorated autistic-like behaviors. Moreover, IHH training enhanced hypoxia inducible factor (HIF) 1α in the dorsal raphe nucleus (DRN) and activated the DRN serotonergic neurons. Infusion of cobalt chloride into the DRN, to mimic IHH in increasing HIF1α expression or genetically knockdown PHD2 to upregulate HIF1α expression in the DRN serotonergic neurons, alleviated autistic-like behaviors in Shank3B -/- mice. In contrast, downregulation of HIF1α in DRN serotonergic neurons induced compulsive behaviors. Furthermore, upregulating HIF1α in DRN serotonergic neurons increased the firing rates of these neurons, whereas downregulation of HIF1α in DRN serotonergic neurons decreased their firing rates. These findings suggest that IHH activated DRN serotonergic neurons via upregulation of HIF1α, and thus ameliorated autistic-like phenotypes, providing a novel therapeutic option for ASD.

Rapid detection of Mycobacterium tuberculosis in sputum using CRISPR-Cas12b combined with cross-priming amplification in a single reaction.

IMPORTANCE: In this study, we successfully established a new One-Pot method, named TB One-Pot, for detecting Mtb in sputum by combining CRISPR-cas12b-mediated trans-cleavage with cross-priming amplification (CPA). Our study evaluated the diagnostic performance of TB One-Pot in clinical sputum samples for tuberculosis. The findings provide evidence for the potential of TB One-Pot as a diagnostic tool for tuberculosis.

Finite element analysis of a customized coronoid prosthesis for traumatic coronoid deficiency.

BACKGROUND: Traumatic coronoid deficiency with persistent elbow instability is a challenging condition. Autologous bone graft reconstruction is often associated with a range of additional clinical problems and the outcome is often unpredictable. The purpose of this study was to design a prosthetic device that can reconstruct coronoid deficiency of any height and to evaluate its mechanical properties using finite element analysis. MATERIALS AND METHODS: A customized coronoid prosthesis was designed based on image registration, automatic measurement, and computer-aided design. After pilot study and sample size calculation, image data collected from 6 patients who underwent bilateral complete upper extremity CT scans were reconstructed. The test was divided into 3 groups: coronoid intact, prosthesis and autograft. Regan-Morrey type II and autologous olecranon osteotomy models were established. The prosthesis and autogenous olecranon were assembled to the coronoid base. Stress was applied axially along the proximal humeral diaphysis and implant micromotion and contact mechanics of the humeroulnar joint were measured at 30°, 45°, 60° and 90° of joint flexion respectively. RESULTS: At all flexion angles, the maximum stress on the coronoid articular surface was significantly reduced in the prosthesis and autograft groups, with the reduction being more significant in the latter (P < .001). With increasing flexion, the maximum stress at the coronoid articular surface increased significantly after autograft reconstruction (7.2 to 68 MPa, P < .001), whereas the humeroulnar joint obtained a similar contact mechanics pattern to that of the control group after prosthetic reconstruction. As the flexion angle increased, the relative micromotion of both the prosthesis and autograft increased significantly (0.5-1.6 vs. 0.2-1.2, Pmeasure time < 0.001, Pgroups < 0.001). Contact pressure and center-of-force paths of the humeroulnar joint experience abrupt stress changes at approximately 60° of flexion. CONCLUSION: The contact stress pattern in the humeroulnar joint is similar in prosthesis and intact coronoid groups. Autograft reconstruction increases contact stresses at the articular surface and alters the joint center-of-force path. The "stress surge phenomenon" in the humeroulnar joint surface before and after 60° of flexion may be one of the mechanisms of traumatic elbow degeneration.

Pan-cancer analysis of TASL: a novel immune infiltration-related biomarker for tumor prognosis and immunotherapy response prediction.

BACKGROUND: New immunotherapeutic strategies based on predictors are urgently needed. Toll-like receptor adaptor interacting with SLC15A4 on the lysosome (TASL) was recently confirmed to fulfill an important role in the innate immune response. However, whether TASL is involved in tumor development and immunotherapy response prediction has not been reported. METHODS: TCGA and GTEx were used to yield transcriptional, genetic, and epigenetic levels of TASL in 33 cancer types. CIBERSORT was used to explore the correlation between TASL expression and multiple immune-related signatures and tumor-infiltrating immune cell content in different cancer types. The ability of TASL to predict tumor immunotherapy response was analyzed in seven datasets. Finally, we tested TASL expression in human glioma cell lines and tissue samples and analyzed its correlation with clinicopathological parameters. RESULTS: TASL is widely heterogeneous at the transcriptional, genetic, and epigenetic levels. High TASL expression is an independent poor prognostic factor for immune "cold" tumor Low-Grade Glioma (LGG) but an opposite factor for "hot" tumors Lung Adenocarcinoma (LUAD) and Skin Cutaneous Melanoma (SKCM). TASL may affect tumor immune infiltration by mediating tumor-infiltrating lymphocytes and tumor-associated macrophages. It may differentially affect the prognosis of the three cancers by regulating the immunosuppressive microenvironment in LGG and the immunostimulatory microenvironment in LUAD and SKCM. High TASL expression is a potential biomarker for the positive response to immunotherapy in cancers such as SKCM and was also experimentally confirmed to be positively associated with adverse clinicopathological features of gliomas. CONCLUSION: TASL expression is an independent prognostic factor for LGG, LUAD, and SKCM. High TASL expression is a potential biomarker for the positive response to immunotherapy in certain cancer types such as SKCM. Further basic studies focusing on TASL expression and tumor immunotherapy are urgently needed.

Melatonin Protects Against Hyperoxia-Induced Apoptosis in Alveolar Epithelial type II Cells by Activating the MT2/PI3K/AKT/ETS1 Signaling Pathway.

PURPOSE: Hyperoxia-induced apoptosis in alveolar epithelial type II cells (AECIIs) plays a critical role in the development of bronchopulmonary dysplasia (BPD). Melatonin has been shown to improve BPD. However, the protective effect of melatonin on hyperoxia-induced apoptosis in AECIIs and the precise mechanisms involved remain unclear. METHODS: Human alveolar epithelial type II A549 cells were treated with hyperoxia as an in vitro model to investigate the antiapoptotic mechanism of melatonin. CCK-8 assays were performed to investigate the viability of A549 cells. Hoechst 33,258 staining was carried out to quantify apoptosis in A549 cells. The protein expression levels of E26 oncogene homolog 1 (ETS1), Bcl-2, Bax, Bim, Wnt, ß-catenin, AKT and phosphorylated AKT were measured by western blotting. LY294002, SC79 and the downregulation of ETS1, melatonin receptor 1 (MT1) and MT2 with specific siRNAs were used to investigate the role of the PI3K/AKT pathway, ETS1, MT1 and MT2 in hyperoxia-induced apoptosis in A549 cells. RESULTS: Melatonin prevented hyperoxia-induced apoptosis in A549 cells, and the upregulation of E26 oncogene homolog 1 (ETS1) contributed to the antiapoptotic effect of melatonin. Melatonin activated the PI3K/AKT axis, which led to ETS1 upregulation and inhibited apoptosis in hyperoxia-exposed A549 cells. Furthermore, melatonin-induced activation of the PI3K/AKT axis, upregulation of ETS1 and inhibition of apoptosis were reversed by melatonin receptor 2 (MT2) siRNA in hyperoxia-exposed A549 cells. CONCLUSION: Melatonin prevents hyperoxia-induced apoptosis by activating the MT2/PI3K/AKT/ETS1 axis in alveolar epithelial cells.

Efficacy and safety of modular versus monoblock stems in revision total hip arthroplasty: a systematic review and meta-analysis.

BACKGROUND: Both modular and monoblock tapered fluted titanium (TFT) stems are increasingly being used for revision total hip arthroplasty (rTHA). However, the differences between the two designs in clinical outcomes and complications are not yet clear. Here, we intend to compare the efficacy and safety of modular versus monoblock TFT stems in rTHA. METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were searched to include studies comparing modular and monoblock implants in rTHA. Data on the survivorship of stems, postoperative hip function, and complications were extracted following inclusion criteria. Inverse variance and Mantel-Haenszel methods in Review Manager (version 5.3 from Cochrane Collaboration) were used to evaluate differences between the two groups. RESULTS: Ten studies with a total of 2188 hips (1430 modular and 758 monoblock stems) were finally included. The main reason for the revision was aseptic loosening. Paprosky type III was the most common type in both groups. Both stems showed similar re-revision rates (modular vs monoblock: 10.3% vs 9.5%, P = 0.80) and Harris Hip Scores (WMD = 0.43, P = 0.46) for hip function. The intraoperative fracture rate was 11.6% and 5.0% (P = 0.0004) for modular and monoblock stems, respectively. The rate of subsidence > 10 mm was significantly higher in the monoblock group (4.5% vs 1.0%, P = 0.003). The application of extended trochanteric osteotomy was more popular in monoblock stems (22.7% vs 17.5%, P = 0.003). The incidence of postoperative complications such as periprosthetic femoral fracture and dislocation was similar between both stems. CONCLUSIONS: No significant difference was found between modular and monoblock tapered stems as regards postoperative hip function, re-revision rates, and complications. Severe subsidence was more frequent in monoblock stems while modular ones were at higher risk of intraoperative fracture. LEVEL OF EVIDENCE: Level III, systematic review of randomized control and non-randomized studies. TRIAL REGISTRATION: We registered our study in the international prospective register of systematic reviews (PROSPERO) (CRD42020213642).

Structural basis of outer membrane protein insertion by the BAM complex.

All Gram-negative bacteria, mitochondria and chloroplasts have outer membrane proteins (OMPs) that perform many fundamental biological processes. The OMPs in Gram-negative bacteria are inserted and folded into the outer membrane by the ß-barrel assembly machinery (BAM). The mechanism involved is poorly understood, owing to the absence of a structure of the entire BAM complex. Here we report two crystal structures of the Escherichia coli BAM complex in two distinct states: an inward-open state and a lateral-open state. Our structures reveal that the five polypeptide transport-associated domains of BamA form a ring architecture with four associated lipoproteins, BamB-BamE, in the periplasm. Our structural, functional studies and molecular dynamics simulations indicate that these subunits rotate with respect to the integral membrane ß-barrel of BamA to induce movement of the ß-strands of the barrel and promote insertion of the nascent OMP.

Optimization Algorithms for Joint Power and Sub-Channel Allocation for NOMA-Based Maritime Communications.

This paper investigates resource optimization schemes in a marine communication scenario based on non-orthogonal multiple access (NOMA). According to the offshore environment of the South China Sea, we first establish a Longley-Rice-based channel model. Then, the weighted achievable rate (WAR) is considered as the optimization objective to weigh the information rate and user fairness effectively. Our work introduces an improved joint power and user allocation scheme (RBPUA) based on a single resource block. Taking RBPUA as a basic module, we propose three joint multi-subchannel power and marine user allocation algorithms. The gradient descent algorithm (GRAD) is used as the reference standard for WAR optimization. The multi-choice knapsack algorithm combined with dynamic programming (MCKP-DP) obtains a WAR optimization result almost equal to that of GRAD. These two NOMA-based solutions are able to improve WAR performance by 7.47% compared with OMA. Due to the high computational complexity of the MCKP-DP, we further propose a DP-based fully polynomial-time approximation algorithm (DP-FPTA). The simulation results show that DP-FPTA can reduce the complexity by 84.3% while achieving an approximate optimized performance of 99.55%. This advantage of realizing the trade-off between performance optimization and complexity meets the requirements of practical low-latency systems.

Antioxidative effect of Lactobacillus plantarum Y44 on 2,2'-azobis(2-methylpropionamidine) dihydrochloride (ABAP)-damaged Caco-2 cells.

Some Lactobacillus strains have been reported to have antioxidative activity. In our previous work, we screened Lactobacillus plantarum Y44 for its antioxidative activity. In this study, we further studied the antioxidative activities of L. plantarum Y44 using chemical antioxidant methods, including the 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) free radical scavenging assays, the ferric reducing antioxidant power test, and oxygen radical absorbance capacity test, and we assessed damage caused by 2,2'-azobis(2-methylpropionamidine) dihydrochloride (ABAP) in a Caco-2 cell model. The results of the chemical antioxidant assays confirmed the antioxidative activity of L. plantarum Y44, which was consistent with the protection of Caco-2 cells against ABAP injury by L. plantarum Y44. We also found that L. plantarum Y44 significantly promoted expression of Nrf2 pathway-associated proteins, downregulated expression of inflammatory-related cytokines IL-8 and tumor necrosis factor-α in ABAP-damaged Caco-2 cells, and enhanced expression of the tight junction proteins ß-catenin and E-cadherin. We determined that L. plantarum Y44 exerted antioxidative effects by quenching oxygen free radicals and activating the Nrf2 signaling pathway in Caco-2 cells.

LncRNA DLEU1 contributes to colorectal cancer progression via activation of KPNA3.

BACKGROUND: Accumulating evidences show that long noncoding RNAs (lncRNA) play essential roles in the development and progression of various malignancies. However, their functions remains poorly understood and many lncRNAs have not been defined in colorectal cancer (CRC). In this study, we investigated the role of DLEU1 in CRC. METHODS: Quantitative real-time PCR was used to detect the expression of DLEU1 and survival analysis was adopted to explore the association between DLEU1 expression and the prognosis of CRC patients. CRC cells were stably transfected with lentivirus approach and cell proliferation, migration, invasion and cell apoptosis, as well as tumorigenesis in nude mice were performed to assess the effects of DLEU1 in BCa. Biotin-coupled probe pull down assay, RNA immunoprecipitation and Fluorescence in situ hybridization assays were conducted to confirm the relationship between DLEU1 and SMARCA1. RESULTS: Here we revealed that DLEU1 was crucial for activation of KPNA3 by recruiting SMARCA1, an essential subunit of the NURF chromatin remodeling complex, in CRC. DLEU1 was indispensible for the deposition of SMARCA1 at the promoter of KPNA3 gene. Increased expression of DLEU1 and KPNA3 was observed in human CRC tissues. And higher expression of DLEU1 or KPNA3 in patients indicates lower survival rate and poorer prognosis. DLEU1 knockdown remarkably inhibited CRC cell proliferation, migration and invasion in vitro and in vivo while overexpressing KPNA3 in the meantime reversed it. CONCLUSIONS: Our results identify DLEU1 as a key regulator by a novel DLEU1/SMARCA1/KPNA3 axis in CRC development and progression, which may provide a potential biomarker and therapeutic target for the management of CRC.

Assessing and comparing antioxidant activities of lactobacilli strains by using different chemical and cellular antioxidant methods.

Some lactobacilli strains had beneficial effects on human beings due to their antioxidant activities. In this study lactobacilli strains stored in our laboratory were screened for potential antioxidant activities by investigating their 1,1-diphenyl-2-picrylhydrazyl free radical scavenging activity, oxygen radical absorbance capacity, resistance to H2O2, and hydroxyl free radical scavenging activity; then the antioxidant activities of the screened strains were evaluated by cellular antioxidant assay and protection for HT-29 cells against H2O2 injury assay. The results showed that Lactobacillus plantarum Y44 could scavenge oxygen free radicals, inhibit the production of intracellular reactive oxygen species without creating obvious cytotoxic effects, and protect HT-29 cells against H2O2 injury evidenced by the significant decrease of the Bcl-2-associated X protein (Bax)/B-cell lymphoma 2 (Bcl-2) ratio and heat shock protein 70 expression, increase of superoxide dismutase and glutathione peroxidase activities, and decrease of malondialdehyde level of HT-29 cells damaged by H2O2. It was speculated that L. plantarum Y44 protect HT-29 cells against oxygen radical injury through scavenging reactive oxygen species and activating intracellular antioxidant enzymes. A significant correlation was observed among the results of the hydroxyl radical scavenging assay, protection assay for HT-29 cells against H2O2 injury, and the cellular antioxidant assay. The findings indicated that L. plantarum Y44 could be a probiotic candidate with antioxidant properties and combining several chemical antioxidant methods and antioxidant cellular models could be an effective procedure to screen lactobacilli strains with antioxidant activity.

Ancestral state reconstruction infers phytopathogenic origins of sooty blotch and flyspeck fungi on apple.

Members of the sooty blotch and flyspeck (SBFS) complex are epiphytic fungi in the Ascomycota that cause economically damaging blemishes of apples worldwide. SBFS fungi are polyphyletic, but approx. 96% of SBFS species are in the Capnodiales. Evolutionary origins of SBFS fungi remain unclear, so we attempted to infer their origins by means of ancestral state reconstruction on a phylogenetic tree built utilizing genes for the nuc 28S rDNA (approx. 830 bp from near the 59 end) and the second largest subunit of RNA polymerase II (RPB2). The analyzed taxa included the well-known genera of SBFS as well as non-SBFS fungi from seven families within the Capnodiales. The non-SBFS taxa were selected based on their distinct ecological niches, including plant-parasitic and saprophytic species. The phylogenetic analyses revealed that most SBFS species in the Capnodiales are closely related to plant-parasitic fungi. Ancestral state reconstruction provided strong evidence that plant-parasitic fungi were the ancestors of the major SBFS lineages. Knowledge gained from this study may help to better understand the ecology and evolution of epiphytic fungi.

A Novel Method for Vertical Acceleration Noise Suppression of a Thrust-Vectored VTOL UAV.

Acceleration is of great importance in motion control for unmanned aerial vehicles (UAVs), especially during the takeoff and landing stages. However, the measured acceleration is inevitably polluted by severe noise. Therefore, a proper noise suppression procedure is required. This paper presents a novel method to reduce the noise in the measured vertical acceleration for a thrust-vectored tail-sitter vertical takeoff and landing (VTOL) UAV. In the new procedure, a Kalman filter is first applied to estimate the UAV mass by using the information in the vertical thrust and measured acceleration. The UAV mass is then used to compute an estimate of UAV vertical acceleration. The estimated acceleration is finally fused with the measured acceleration to obtain the minimum variance estimate of vertical acceleration. By doing this, the new approach incorporates the thrust information into the acceleration estimate. The method is applied to the data measured in a VTOL UAV takeoff experiment. Two other denoising approaches developed by former researchers are also tested for comparison. The results demonstrate that the new method is able to suppress the acceleration noise substantially. It also maintains the real-time performance in the final estimated acceleration, which is not seen in the former denoising approaches. The acceleration treated with the new method can be readily used in the motion control applications for UAVs to achieve improved accuracy.

A New Target for Hepatic Fibrosis Prevention and Treatment: The Warburg Effect.

Hepatic fibrosis is a major public health problem that endangers human wellbeing. In recent years, a number of studies have revealed the important impact of metabolic reprogramming on the occurrence and development of hepatic fibrosis. Among them, the Warburg effect, as an intracellular glucose metabolism reprogramming, can promote the occurrence and development of hepatic fibrosis by promoting the activation of hepatic stellate cells (HSCs) and inducing the polarization of liver macrophages (KC). Understanding the Warburg effect and its important role in the progression of hepatic fibrosis will assist in developing new strategies for the prevention and treatment of hepatic fibrosis. This review focuses on the Warburg effect and the specific mechanism by which it affects the progression of hepatic fibrosis by regulating HSCs activation and KC polarization. In addition, we also summarize and discuss the related experimental drugs and their mechanisms that inhibit the Warburg effect by targeting key proteins of glycolysis in order to improve hepatic fibrosis in the hope of providing more effective strategies for the clinical treatment of hepatic fibrosis.

The effect of physical activity on the subjective well-being of rural left-behind children: the mediating role of discrimination perceptions and loneliness.

OBJECTIVE: This study explored the mediating role of perceptions of discrimination and loneliness on the relationship between physical exercise and subjective well-being in rural left-behind children. METHODS: A package of surveys were administered to junior high school students and senior primary school students (n = 592) in the countryside, which including the scale of the Physical Activity Behavior Scale, Subjective Well-Being Scale, Perceived Discrimination Scale, and Loneliness Scale. Structural Equation Modeling and Bootstrap were used to analyze the data to investigate the chain mediating effect of perceived discrimination and loneliness. RESULTS: (1) There was a positive correlation between physical activity and subjective well-being, and the direct prediction of subjective well-being was significant. (2) Physical activity negatively predicted perceptions of discrimination, and perceptions of discrimination positively predicted loneliness and negatively predicted subjective well-being, and loneliness could negatively predict subjective well-being. (3) Perception of discrimination and loneliness significantly mediated the relationship between physical activity and subjective well-being. The mediating effect consisted of indirect effects generated by 2 paths, one was that physical exercise indirectly affected subjective well-being by affecting discrimination perception, and the other was that physical exercise further acted on subjective well-being through the chain mediating effect from discrimination perception to loneliness. CONCLUSION: Physical exercise can directly affect the subjective well-being of rural left-behind children. Physical exercise can indirectly affect left-behind children's subjective well-being through discrimination perceptions, and it can also indirectly affect left-behind children's subjective well-being through the chain mediating effect of discrimination perceptions and loneliness.

Bibliometric analysis of global research on human organoids.

The emergence and rapid development of human organoids have provided the possibility to replace animal models in treating human diseases. Intelligence studies help focus on research hotspots and address key mechanistic issues. Currently, few comprehensive studies describe the characteristics of human organoid research. In this study, we extracted 8,591 original articles on organoids from the Web of Science core collection database over the past two decades and conducted intelligence analysis using CiteSpace. The number of publications in this field has experienced rapid growth in the last ten years (almost 70-fold increase since 2009). The United States, China, Germany, Netherlands, and UK have strong collaborations in publishing articles. Clevers Hans, Van Der Laan, Jason R Spence, and Sato Toshiro have made significant contributions to advancing progress in this field. Clustering and burst analysis categorized research hotspots into tissue model and functional construction, intercellular signaling, immune mechanisms, and tumor metastasis. Organoid research in highly cited articles covers four major areas: basic research (38%), involving stem cell developmental processes and cell-cell interactions; biobanking (10%), with a focus on organoid cultivation; precision medicine (16%), emphasizing cell therapy and drug development; and disease modeling (36%), including pathogen analysis and screening for disease-related genetic variations. The main obstacles currently faced in organoid research include cost and technology, vascularization of cells, immune system establishment, international standard protocols, and limited availability of high-quality clinical trial data. Future research will focus on cost-saving measures, technology sharing, development of international standards, and conducting high-level clinical trials.

Interaction of Exosomal MicroRNA and Oxidative Stress in the Pathogenesis of Colitis-Associated Cancer.

Colitis-associated cancer (CAC) is the most serious complication of inflammatory bowel disease. In recent years, the incidence of CAC has increased worldwide. Oxidative stress (OS) is involved in the development of CAC through oxidative damage to biomolecules or activation of inflammatory signaling pathways. Exosomes are extracellular vesicles that act as messengers to deliver signals and macromolecules to target cells, making them important mediators of intercellular communication and exchange of biologically active molecules between cells. MicroRNAs (miRNAs) carried by exosomes regulate the pro- and anti-inflammatory pathways of OS and play a key role in communication between OS and cancer cells. This review describes the correlation between OS and exosomal miRNAs with the goal of identifying a novel therapeutic method for CAC.