Hematopoietic stem cell niche generation and maintenance are distinguishable by an epitranscriptomic program.

The niche is typically considered as a pre-established structure sustaining stem cells. Therefore, the regulation of its formation remains largely unexplored. Whether distinct molecular mechanisms control the establishment versus maintenance of a stem cell niche is unknown. To address this, we compared perinatal and adult bone marrow mesenchymal stromal cells (MSCs), a key component of the hematopoietic stem cell (HSC) niche. MSCs exhibited enrichment in genes mediating m6A mRNA methylation at the perinatal stage and downregulated the expression of Mettl3, the m6A methyltransferase, shortly after birth. Deletion of Mettl3 from developing MSCs but not osteoblasts led to excessive osteogenic differentiation and a severe HSC niche formation defect, which was significantly rescued by deletion of Klf2, an m6A target. In contrast, deletion of Mettl3 from MSCs postnatally did not affect HSC niche. Stem cell niche generation and maintenance thus depend on divergent molecular mechanisms, which may be exploited for regenerative medicine.

The crucial role of transient tri-coordinated oxygen in the flow of silicate melts.

The transport properties of high-temperature silicate melts control magma flow and are crucial for a wide variety of industrial processes involving minerals. However, anomalous melt properties have been observed that cannot be explained by the traditional polymerization degree theory, which was derived based on quenched melts. Ab initio molecular dynamics (AIMD) simulations were conducted to investigate the flow mechanism of CaO-Al2O3-SiO2 melts under high temperature atmospheric conditions. By analyzing the dynamic structure of melted silicates and employing molecular orbital theory, we gained a fundamental understanding of the flow mechanism from a chemistry perspective. Transient tri-coordinated oxygen (TO) bonded with one Si and two Al atoms (SiOAl2) was found to be a pivotal intermediate in melt flow and atomic diffusion processes. Frequent chemical transition between TO in SiOAl2 and bridging oxygen (BO) dominated the fluidity of melted silicates. The presence of such transitions is facilitated by the unstable nature of [SiAlO2] 4-membered rings, which are susceptible to instability due to the intense repulsion between the O 2p lone pairs and the excessively bent O-Al-O angle. Additionally, the density of SiOAl2 type TO motif could serve as an indicator to determine the relationship between structure and fluidity. Our results challenge the traditional polymerization degree theory and suggest the need to reassess high-temperature liquid properties that govern processes in the Earth and industry by monitoring transient motifs.

Dishevelled Associated Activator Of Morphogenesis (DAAM) Facilitates Invasion of Hepatocellular Carcinoma by Upregulating Hypoxia-Inducible Factor 1α (HIF-1α) Expression.

BACKGROUND The dishevelled associated activator of morphogenesis (DAAM) family, consisting of DAAM1 and DAAM2, is an important component of the Wnt signal pathway. Previous studies have suggested that DAAM2 reduces Von Hippel-Lindau (VHL) expression by promoting its ubiquitination, but the correlation between DAAM and HIF-1alpha in hepatocellular carcinoma (HCC) has not been studied. MATERIAL AND METHODS In our study, expression of DAAM1 and DAAM2 in HCCs and tumor-adjacent liver tissues was assessed with qRT-PCR and immunohistochemistry. Correlations between DAAM1/2 and the clinicopathologic variables were evaluated with the Chi-square test. With univariate and multivariate analysis, we further evaluated the prognostic significance of DAAM1 and DAAM2. Using in vitro experiments, we assessed the functions of DAAM1 and DAAM2 in invasion and proliferation in different HCC cell lines and investigated their underlying mechanisms. RESULTS DAAM1 and 2 overexpression were 18.8% and 48.7%, respectively, of the whole cohort. mRNAs of DAAM2 in HCCs were substantially higher than mRNAs in liver tissues, while DAAM1 mRNA had no marked difference. High DAAM2 expression was notably associated with advanced T stage (P=0.032), TNM stage (P=0.032), and overall survival (OS) rate (P=0.004). DAAM 2 knockdown promoted VHL accumulation and subsequent HIF-1alpha down-regulation in HCC cells. In HCC specimens, DAAM2 expression was also negatively correlated with VHL and positively associated with HIF-1alpha. Moreover, HIF-1alpha was required in DAAM2-induced invasion of HCC cells. CONCLUSIONS DAAM2, rather than DAAM1, was able to predict prognosis of HCC. DAAM2 decreased VHL expression and consequently upregulated HIF-1alpha, eventually facilitating invasion of HCC.

Critical regulation of miR-200/ZEB2 pathway in Oct4/Sox2-induced mesenchymal-to-epithelial transition and induced pluripotent stem cell generation.

Fibroblasts can be reprogrammed to induced pluripotent stem cells (iPSCs) by application of transcription factors octamer-binding protein 4 (Oct4), SRY-box containing gene 2 (Sox2), Kruppel-like factor 4 (Klf4), and c-Myelocytomatosis oncogene (c-Myc) (OSKM), but the underlying mechanisms remain unclear. Here, we report that exogenous Oct4 and Sox2 can bind at the promoter regions of mir-141/200c and mir-200a/b/429 cluster, respectively, and induce the transcription activation of miR-200 family during the OSKM-induced reprogramming. Functional suppression of miR-200s with specific inhibitors significantly represses the OSKM-caused mesenchymal-to-epithelial transition (MET, an early event in reprogramming of fibroblasts to iPSCs) and iPSC generation, whereas overexpression of miR-200s promotes the MET and iPSC generation. Mechanistic studies showed that miR-200s significantly repress the expression of zinc finger E-box binding homeobox 2 (ZEB2) through directly targeting its 3' UTR and direct inhibition of ZEB2 can mimic the effects of miR-200s on iPSC generation and MET process. Moreover, the effects of miR-200s during iPSC generation can be blocked by ZEB2 overexpression. Collectively, our findings not only reveal that members of the miR-200 family are unique mediators of the reprogramming factors Oct4/Sox2, but also demonstrate that the miR-200/ZEB2 pathway as one critical mechanism of Oct4/Sox2 to induce somatic cell reprogramming at the early stage.

The independent impact of newborn hepatitis B vaccination on reducing HBV prevalence in China, 1992-2006: A mathematical model analysis.

OBJECTIVE: To evaluate the independent impact of newborn hepatitis B vaccination on reducing HBV prevalence in China, from its introduction in 1992 to 2006. METHODS: An age- and time-dependent discrete dynamic model was developed to simulate HBV transmission in China under the assumptions of no any change in interventions and only with newborn vaccination introduction, respectively. The initial conditions of the model were determined according to the national serosurvey in 1992. The simulated results were compared with the observed results of the national serosurvey in 2006, and the contribution rate of newborn vaccination on reducing HBV prevalence was calculated overall and by birth cohort. RESULTS: The total HBV prevalence would remain stable through the 14-year period if no any change in interventions, but decrease year by year if only with newborn vaccination introduction. Newborn vaccination could account for more than 50% of the reduction of the total HBV prevalence, although the full 3-dose and timely birth dose vaccination coverage rates were low in the early years. The results by birth cohort showed that the higher the two coverage rates, the higher contribution rate on reducing HBV prevalence. For the 2005 birth cohort which had high levels in the two coverage rates, the contribution rate could reach more than 95%. CONCLUSION: Newborn hepatitis B vaccination from 1992 to 2006 in China had played the most important role in reducing HBV prevalence. Newborn vaccination with high full 3-dose and timely birth dose coverage rates is the decisive factor in controlling hepatitis B in China.

METTL3: Melting the tumor microenvironment for improved immunotherapy.

The tumor microenvironment (TME) dictates the outcome of cancer immunotherapy. In this issue of Cell Chemical Biology, Yu et al.1 report that targeting Mettl3 leads to a more inflamed, "hot" TME and effective anti-PD-1 therapy. This study points to a new target in remodeling the TME for improved immunotherapy.

miR-99b-3p/Mmp13 axis regulates NLRP3 inflammasome-dependent microglial pyroptosis and alleviates neuropathic pain via the promotion of autophagy.

BACKGROUND: Neuropathic pain significantly impairs quality of life, and effective interventions are limited. NOD-like receptor thermal protein domain associated protein 3 (NLRP3)-mediated microglial pyroptosis and the subsequent proinflammatory cytokine production are critical in exacerbating pain. Considering microglial pyroptosis as a potential target for developing specific analgesic interventions for neuropathic pain, our study investigated the pathogenesis and therapeutic targets in this condition. METHODS: In vitro experiments involved the co-culture of the immortalized BV-2 microglia cell line with lipopolysaccharide (LPS) to induce microglial pyroptosis. Differentially expressed microRNAs (miRNAs) were identified using high-throughput sequencing analysis. The downstream target genes of these miRNAs were determined through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, and the downstream target genes, combined with miRNAs, were predicted and verified through dual luciferase reporter gene assays. In vivo experiments were conducted to construct a chronic constriction injury (CCI) neuropathic pain model in rats and evaluate the analgesic effects of intrathecal injection of an adeno-associated virus vector (AAV) carrying miR-99b-3p. Gene expression was modulated through mimic or siRNA transfection. Western blot analysis assessed the expression of microglial pyroptosis and autophagy-related proteins, whereas RT-qPCR measured changes in proinflammatory cytokines expression. RESULTS: LPS-stimulated up-regulation of proinflammatory cytokines in microglia, accompanied by NLRP3-dependent pyroptosis, including increased NLRP3, GSDMD-N, Caspase1-p20, and mature-IL-1ß expression. High-throughput sequencing analysis revealed 16 upregulated and 10 downregulated miRNAs in LPS-stimulated microglia, with miR-99b-3p being the most downregulated. KEGG analysis revealed that the target genes of these miRNAs are primarily enriched in calcium, FoxO, and mitogen-activated protein kinase (MAPK) signal pathways. Furthermore, overexpression of miR-99b-3p through mimic transfection significantly inhibited the inflammatory response and NLRP3-mediated pyroptosis by promoting autophagy levels in activated microglia. In addition, we predicted that the 3' untranslated region (UTR) of matrix metalloproteinase-13 (Mmp13) could bind to miR-99b-3p, and knockdown of Mmp13 expression through siRNA transfection similarly ameliorated enhanced proinflammatory cytokines expression and microglial pyroptosis by enhancing autophagy. In vivo, Mmp13 was co-localized with spinal dorsal horn microglia and was suppressed by intrathecal injection of the AAV-miR-99b-3p vector. Moreover, overpressed miR-99b-3p alleviated CCI-induced mechanical allodynia and neuroinflammation while suppressing pyroptosis by enhancing autophagy in the spinal cord of CCI rats. CONCLUSION: miR-99b-3p exerts analgesic effects on neuropathic pain by targeting Mmp13. These antinociceptive effects are, at least in part, attributed to the promotion of autophagy, thereby inhibiting neuroinflammation and NLRP3-mediated pyroptosis in activated microglia.

Exosomes from umbilical cord mesenchymal stem cells ameliorate intervertebral disc degeneration via repairing mitochondrial dysfunction.

Background: Reactive oxygen species (ROS), predominantly generated by mitochondria, play a crucial role in the pathogenesis of intervertebral disc degeneration (IVDD). Reduction of ROS levels may be an effective strategy to delay IVDD. In this study, we assessed whether umbilical cord mesenchymal stem cell-exosomes (UCMSC-exos) can be used to treat IVDD by suppressing ROS production caused by mitochondrial dysfunction. Materials and methods: Human UCMSC-exos were isolated and identified. Nucleus pulposus cells (NPCs) were stimulated with H2O2 in the presence or absence of exosomes. Then, 4D label free quantitative (4D-LFQ) proteomics were used to analyze the differentially expressed (DE) proteins. Mitochondrial membrane potential (MMP), mitochondrial ROS and protein levels were determined via immunofluorescence staining, flow cytometry and western blotting respectively. Additionally, high-throughput sequencing was performed to identify the DE miRNAs in NPCs. Finally, therapeutic effects of UCMSC-exos were investigated in a puncture-induced IVDD rat model. Degenerative grades of rat IVDs were assessed using magnetic resonance imaging and histochemical staining. Results: UCMSC-exos effectively improved the viability of NPCs and restored the expression of the extracellular matrix (ECM) proteins, collagen type II alpha-1 (COL2A1) and matrix metalloproteinase-13 induced by H2O2. Additionally, UCMSC-exos not only reduced the total intracellular ROS and mitochondrial superoxide levels, but also increased MMP in pathological NPCs. 4D-LFQ proteomics and western blotting further revealed that UCMSC-exos up-regulated the levels of the mitochondrial protein, mitochondrial transcription factor A (TFAM), in H2O2-induced NPCs. High-throughput sequencing and qRT-PCR uncovered that UCMSC-exos down-regulated the levels of miR-194-5p, a potential negative regulator of TFAM, induced by H2O2. Finally, in vivo results showed that UCMSC-exos injection improved the histopathological structure and enhanced the expression levels of COL2A1 and TFAM in the rat IVDD model. Conclusions: Our findings suggest that UCMSC-exos promote ECM synthesis, relieve mitochondrial oxidative stress, and attenuate mitochondrial dysfunction in vitro and in vivo, thereby effectively treating IVDD. The translational potential of this article: This study provides solid experimental data support for the therapeutic effects of UCMSC-exos on IVDD, suggesting that UCMSC-exos will be a promising nanotherapy for IVDD.

Research on the Roundness Approximation Search Algorithm of Si3N4 Ceramic Balls Based on Least Square and EMD Methods.

This paper aims to obtain the best shape accuracy evaluation algorithm for silicon nitride ceramic balls after lapping, and to extract the initial signal of the ball surface to improve the accuracy and reliability of the algorithm. The research methods of this paper are as follows: Firstly, an analysis of the uniform envelope of the lapping trajectory of ceramic balls is carried out to verify whether the lapping trajectory after processing can achieve a consistent envelope on the balls' surface. On this basis, it is found through experiments that the standard deviation SD between the roundness deviations of different contour sections is small. The value is maintained at approximately 0.03 µm, and the roundness deviation can approximately replace the spherical deviation. Then the different contour sections of the sphere are sampled by the Taylor roundness instrument. Considering the uncertainty, the sampling points of different contour sections are averaged and used as the original signal of the sphere surface. Then the EMD method is used to process the signal to be detected on the sphere surface. The initial signal of the sphere surface is extracted by judging whether the number of ripples Kc obtained by decomposition is greater than the critical value. Then the initial signal is used as the input value of the approximation algorithm. Through the roundness deviation approximation algorithm based on the least square method, the given minimum approximation domain range is finely processed. The divided fine points are used as the center of the circle to intersect with the initial signal. The maximum, minimum, and range of each circle are calculated to obtain the roundness error based on the minimum circumscribed circle, the maximum inscribed circle, and the minimum region method. Finally, the calculated values are compared with those obtained by the traditional algorithm. The experimental results of this paper show that the algorithm is consistent with the roundness error measured by the instrument, compared with the mainstream evaluation criteria. In summary, the conclusions can be drawn as follows: Through a large number of experimental cases and comparative experiments, the algorithm has high accuracy and reliability. The research results of this paper have essential reference significance for accurately evaluating the shape accuracy of ceramic balls in actual production.

Cellular plasticity of the bone marrow niche promotes hematopoietic stem cell regeneration.

Hematopoietic stem cells (HSCs) regenerate after myeloablation, a procedure that adversely disrupts the bone marrow and drives leptin receptor-expressing cells, a key niche component, to differentiate extensively into adipocytes. Regeneration of the bone marrow niche is associated with the resolution of adipocytes, but the mechanisms remain poorly understood. Using Plin1-creER knock-in mice, we followed the fate of adipocytes in the regenerating niche in vivo. We found that bone marrow adipocytes were highly dynamic and dedifferentiated to leptin receptor-expressing cells during regeneration after myeloablation. Bone marrow adipocytes could give rise to osteolineage cells after skeletal injury. The cellular fate of steady-state bone marrow adipocytes was also plastic. Deletion of adipose triglyceride lipase (Atgl) from bone marrow stromal cells, including adipocytes, obstructed adipocyte dedifferentiation and led to severely compromised regeneration of HSCs as well as impaired B lymphopoiesis after myeloablation, but not in the steady state. Thus, the regeneration of HSCs and their niche depends on the cellular plasticity of bone marrow adipocytes.

Huc-MSCs-derived exosomes attenuate neuropathic pain by inhibiting activation of the TLR2/MyD88/NF-κB signaling pathway in the spinal microglia by targeting Rsad2.

BACKGROUND: Mesenchymal stem cells (MSCs)-derived exosomes have shown promise as a cell-free therapeutic strategy for neuropathic pain. This study was conducted to explore the potential mechanisms underlying the analgesic effects of MSC-derived exosomes in treating neuropathic pain. METHODS: Human umbilical cord MSCs (huc-MSCs)-derived exosomes were isolated and identified. BV-2 microglia were stimulated with lipopolysaccharide (LPS) in the presence or absence of exosomes. Differentially expressed proteins were identified by tandem mass tag (TMT)-based proteomic analysis. The analgesic effects of huc-MSCs-derived exosomes were evaluated in a rat model of chronic constriction injury (CCI). The underlying mechanism was investigated by flow cytometry, RT-qPCR, Western blotting, immunofluorescent staining, and small interfering RNA transfection. RESULTS: In vitro, huc-MSCs-derived exosomes suppressed LPS-induced microglial activation and inhibited activation of the TLR2/MyD88/NF-κB signaling pathway. Based on the proteomic analysis, Rsad2 was identified and confirmed to be down-regulated by huc-MSCs-derived exosomes. Importantly, knockdown of Rsad2 also inhibited microglial activation and restrained activation of the TLR2/MyD88/NF-κB signaling pathway. In vivo, intrathecal injection of exosomes ameliorated CCI-induced mechanical allodynia, down-regulated Rsad2 expression and restrained TLR2/MyD88/NF-κB signaling activation in the spinal microglia. CONCLUSION: Huc-MSCs-derived exosomes exerted analgesic effects on neuropathic pain by inhibiting activation of the TLR2/MyD88/NF-κB signaling pathway in the spinal microglia. The mechanism underlying these antinociceptive effects involved exosome-mediated interference with Rsad2 expression, thereby inhibiting microglial activation.

Mesenchymal stem cell-derived extracellular vesicles carrying miR-99b-3p restrain microglial activation and neuropathic pain by stimulating autophagy.

Neuropathic pain is a complex condition that seriously affects human quality of life. This study aimed to investigate the therapeutic mechanism of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) and try to discover new targets for alleviating neuropathic pain. Extracellular vesicles were isolated and identified via ultracentrifugation. BV-2 microglial cells were stimulated with lipopolysaccharide (LPS) in the presence or absence of MSC-EVs. Further, microglial activation and neuroinflammation were evaluated by flow cytometry, RT-qPCR, and ELISA. High-throughput sequencing analysis was performed to reveal the differentially expressed (DE) miRNAs in BV-2 microglia. Autophagy-related regulators were assessed by Western blotting and Immunofluorescence staining. Chronic constriction injury (CCI) model was used to induce neuropathic pain in rats, and the mechanical withdrawal threshold (MWT) was measured. High-throughput sequencing analysis identified 17 DE miRNAs, which were mainly enriched in PI3K-AKT and mTOR signaling pathways. MSC-EVs inhibited the activation of PI3K/AKT/mTOR signaling pathway in LPS-stimulated microglia. Moreover, MSC-EVs treatment enhanced the autophagy level in activated microglia, whereas autophagy inhibitor 3-MA reversed the suppressing effects of MSC-EVs on microglial activation and neuroinflammation. The MSC-EV-mediated transfer of miR-99b-3p was verified to promote microglial autophagy, and miR-99b-3p overexpression suppressed the expression of pro-inflammatory factors in activated microglia. During in vivo studies, intrathecal injection of MSC-EVs significantly up-regulated the expression of miR-99b-3p, and alleviated mechanical allodynia caused by activated microglia in the spinal cord dorsal horn of CCI rats. Moreover, MSC-EVs treatment repaired CCI-induced autophagic impairment by stimulating autophagy in the spinal cord. Collectively, our findings demonstrated that MSC-EVs had an analgesic effect on neuropathic pain via promoting autophagy, and these antinociceptive effects were at least in part caused by MSC-EV-mediated transfer of miR-99b-3p, thereby inhibiting microglial activation and pro-inflammatory cytokines expression.

The physical encapsulation and chemical fixation of Zn during thermal treatment process of municipal solid waste incineration (MSWI) fly ash.

Thermal treatment is a promising treatment technology of municipal solid waste incineration (MSWI) fly ash because of its detoxication and volume reduction. However, the relationship between immobilization of heavy metals and mineral transformation during thermal treatment remains unclear. In this study, the immobilization mechanism of Zn during thermal treatment process of MSWI fly ash was investigated by experiment and calculation. The results show that addition of SiO2 facilitates transition of dominant minerals from melilite to anorthite during sintering, increases liquid content during melting and improves liquid polymerization degree during vitrification. ZnCl2 tends to be physically encapsulated by liquid phase, and ZnO is mainly chemically fixed into minerals at high temperature. Increase in both liquid content and liquid polymerization degree favors the physical encapsulation of ZnCl2. The decreasing order of chemical fixation ability of minerals to ZnO is spinel > melilite > liquid > anorthite. To better immobilize Zn during sintering and vitrification process chemical composition of MSWI fly ash should be located in melilite and anorthite primary phases of pseudo-ternary phase diagram, respectively. The results are helpful to understand immobilization mechanism of heavy metals and avoid volatilization of heavy metals during thermal treatment process of MSWI fly ash.

Changes in Levels of Homocysteine and C-Reactive Protein in Patients with Alzheimer's Disease and Their Correlation with Cognitive and UPDRS Functions.

Objective: To investigate the changes in the levels of homocysteine (Hcy) and C-reactive protein (CRP) in patients with Alzheimer's disease (AD) and analyze their correlation with cognitive and UPDRS functions. Methods: A total of 50 patients with AD admitted to our hospital from January 2020 to March 2022 were selected into the research group, and 50 healthy subjects were selected as the control group. The levels of Hcy and CRP of the two groups were analyzed, and the patients' cognitive functions were evaluated with the Mini-Mental State Examination (MMSE) score and UPDRS function scoring. The correlation between the changes in levels of Hcy and CRP, and cognitive and UPDRS functions in the two groups was compared and analyzed. Results: The levels of Hcy and CRP of the research group were higher than those of the control group, with statistical significance (P < 0.05). The following were evaluated for the scoring of patients' cognitive functions in the research group: orientation, attentional computation, short-term memory, language ability, visuospatial ability, instant memory, and MMSE total score, all of which were lower than those in the control group, with statistical significance (P < 0.05). UPDRS I, UPDRS, UPDRS, and total UPDRS score in the research group were higher than those in the control group, with statistical significance (P < 0.05). In the research group, the higher the Hcy level, the lower the MMSE score, with a negative correlation (P < 0.05), and the higher the Hcy level, the higher the UPDRS score, with a positive correlation (P < 0.05). And, the higher the CRP level, the lower the MMSE score, with a negative correlation (P < 0.05); the higher the CRP level, the higher the UPDRS score, with a positive correlation (P < 0.05). Conclusion: Compared with the health subject group, the levels of Hcy and CRP were higher in patients with AD, and their changes had a negative correlation with cognitive functions in patients with AD, and a positive correlation with UPDRS in patients with AD, with high clinical values in evaluating cognitive and UPDRS functions.

Differences in the Impact of Heart Rate Variability on the Surgical Approach in Patients With Early Cervical Cancer: Laparoscopic versus Open Surgery.

Background: Evidence suggests that the risk of recurrence and death in patients with early cervical cancer (ECC) undergoing minimally invasive surgery is significantly higher than that in patients undergoing open surgery. However, the mechanisms underlying such a difference remain unclear. Heart rate variability (HRV) represents autonomic nerve activity, which is related to tumorgenesis and can be used as a prognostic indicator for various cancers. The main purpose of this study was to explore the difference in the effects of laparoscopic and open surgery on HRV in ECC patients. Methods: A total of 68 ECC (FIGO IA1 with lymphovascular space invasion -IIA2) patients undergoing radical hysterectomy for the first time (84% open group vs. 16% laparoscopic group) were included. A single-lead micro-ECG recorder was used to collect 5 min electrocardiograms 1 day before the operation and 3 days after the operation, and then HRV time domain and frequency domain indices were analyzed, including mean heart rate (MeanHR), maximum heart rate (MaxHR), minimum heart rate (MinHR), the standard deviation of all normal-to-normal intervals (SDNN), the root mean square of successive interval differences (RMSSD), very low-frequency power (VLF), low-frequency power (LF), high-frequency power (HF), total power (TP), and the ratio of LF to HF (LF/HF). Results: Heart rate (i.e., MeanHR, MaxHR, and MinHR) were significantly higher, and HRV (i.e., SDNN, RMSSD, LF, HF, and TP) were significantly lower after the operation than before the operation in both the laparoscopic and open groups (P < 0.05). The postoperative reduction in RMSSD and HF was significantly higher in the laparoscopic group than in the open group (P < 0.05). Conclusions: These data suggest that radical hysterectomy can lead to increased heart rate and decreased HRV in patients with ECC, which can negatively affect cardiac autonomic regulation. Compared with open surgery, laparoscopic surgery has a greater negative impact on the HRV of ECC patients.

Thrombopoietin from hepatocytes promotes hematopoietic stem cell regeneration after myeloablation.

The bone marrow niche plays critical roles in hematopoietic recovery and hematopoietic stem cell (HSC) regeneration after myeloablative stress. However, it is not clear whether systemic factors beyond the local niche are required for these essential processes in vivo. Thrombopoietin (THPO) is a key cytokine promoting hematopoietic rebound after myeloablation and its transcripts are expressed by multiple cellular sources. The upregulation of bone marrow-derived THPO has been proposed to be crucial for hematopoietic recovery and HSC regeneration after stress. Nonetheless, the cellular source of THPO in myeloablative stress has never been investigated genetically. We assessed the functional sources of THPO following two common myeloablative perturbations: 5-fluorouracil (5-FU) administration and irradiation. Using a Thpo translational reporter, we found that the liver but not the bone marrow is the major source of THPO protein after myeloablation. Mice with conditional Thpo deletion from osteoblasts and/or bone marrow stromal cells showed normal recovery of HSCs and hematopoiesis after myeloablation. In contrast, mice with conditional Thpo deletion from hepatocytes showed significant defects in HSC regeneration and hematopoietic rebound after myeloablation. Thus, systemic THPO from the liver is necessary for HSC regeneration and hematopoietic recovery in myeloablative stress conditions.

Synergistic Effect of Hydrogen Bonds and Chemical Bonds to Construct a Starch-Based Water-Absorbing/Retaining Hydrogel Composite Reinforced with Cellulose and Poly(ethylene glycol).

The hydrogel prepared by graft copolymerization of starch (ST) and acrylamide (AM) is a commonly used absorbent material; however, due to their irregular network structure and a limited number of hydrophilic groups, starch-based hydrogels have poor water absorption and water retention. To overcome this, here, we provide a new preparation method for starch-based hydrogels. Using cerium ammonium nitrate (CAN) as an initiator, the starch-acrylamide-cellulose (CMC)/poly(ethylene glycol) (S-A-M/PEG) superabsorbent hydrogel was prepared by graft copolymerization. The starch-acrylamide-cellulose/poly(ethylene glycol) hydrogel network is constructed through the synergistic effect of hydrogen bonds and chemical bonds. The experimental results showed that the starch-acrylamide-cellulose/poly(ethylene glycol) superabsorbent hydrogel has a complete network structure that does not easily collapse due to its superior mechanical properties. The water swelling rate reached 80.24 times, and it reached 50.61% water retention after 16 days. This hydrogel has excellent water-absorbing and water-retaining properties, biocompatibility, and degradability, making it useful for further studies in medical, agricultural, and other fields.

Heart Rate Variability is an Independent Predictor of Lymph Node Metastasis in Patients with Cervical Cancer.

PURPOSE: Heart rate variability (HRV) has been reported as a useful biomarker for prognostic factors in a variety of cancers. The purpose of this study was to explore the predictive value of preoperative HRV for lymph node metastasis (LNM) in patients with cervical cancer (CC). PATIENTS AND METHODS: A total of 77 patients with CC were included, including 18 LNM and 59 non-LNM patients. A five-minute resting electrocardiogram (ECG) was collected before surgery for the analysis of HRV time domain, frequency domain and Poincaré plot parameters (ie, SDNN, RMSSD, LF, HF, LF/HF, SD1, SD2 and SD2/SD1). Student's t-tests and logistic regression were performed to determine the relationship between HRV and LNM. RESULTS: The LNM group had significantly lower SDNN, LF, and SD2 than the non-LNM group (all p < 0.05; all Cohen's d > 0.5). Binary logistic regression analysis indicated that SDNN, LF and SD2 were still significantly associated with LNM. Specifically, for each 1 ms decrease in SDNN and SD2 and each 1 logarithmic unit decrease in ln (LF), the odds of LNM increased by 12%, 9%, and 86%, respectively (all p < 0.05). CONCLUSION: These findings suggest an association between HRV and CC LNM, and HRV could be a potential noninvasive biomarker for the prediction of LNM in CC patients.

Predicting Post-operative Blood Inflammatory Biomarkers Using Pre-operative Heart Rate Variability in Patients With Cervical Cancer.

Blood inflammatory biomarkers, including the neutrophil-to-lymphocyte ratio (NLR), the lymphocyte-to-monocyte ratio (LMR), and the platelet-to-lymphocyte ratio (PLR), play a significant role in determining the prognosis of patients with cervical cancer (CC). Currently, no methods are available to predict these indexes pre-operatively. Cardiac autonomic function is determined based on the heart rate variability (HRV), which is also associated with a progressive inflammatory response and cancer. Thus, the main aim of this study was to evaluate the feasibility of using pre-operative HRV parameters in CC patients to predict post-operative blood inflammation biomarkers as a means of determining prognosis. Between 2020 and 2021, 56 patients who were diagnosed with CC and then underwent hysterectomy surgery at the Department of Gynecologic Oncology, First Affiliated Hospital, Bengbu Medical College were enrolled in this study. Five-minute electrocardiogram data were collected 1 day before the operation for analysis of HRV parameters, including frequency domain parameters (LF, HF, and LF/HF) and Poincaré plot parameters (SD1, SD2, and SD2/SD1). Venous blood was collected 2 days post-operatively and inflammatory biomarkers were evaluated, with the NLR, LMR, and PLR determined. Pre-operative SD2 was significantly associated with post-operative PLR, with each 1-unit increase in SD2 decreasing the PLR value by 2.4 ± 0.9 (P < 0.05). Besides, LF/HF was significantly correlated with NLR, with each 1-unit increase in LF/HF increasing the NLR value by 1.1 ± 0.5 (P < 0.05). This association was independent of patient age and body mass index. These results suggest that the pre-operative autonomic nervous system plays a role in the regulation of post-operative cancer inflammation and that pre-operative HRV parameters can potentially predict post-operative inflammation and facilitate clinical treatment decisions.

Open total dislocation of ankle joint without fractures: A case report.

RATIONALE: Open total dislocation of ankle joint is rare and often caused by high-energy injury. The present study describes a patient with open total lateral dislocation of ankle joint without fractures and obtained a satisfactory clinical result following early debridement and irrigation, one-stage repairment of ligaments, and plaster external fixation. PATIENT CONCERNS: The patient, a 45-year-old male, complained of right foot pain with bleeding and limited motion. Physical examination showed a 15-cm open wound at the medial ankle region, with soft tissues impaired and ankle bones exposed. The 3 dimensional reconstruction computed tomography (CT) examination showed an open total dislocation of ankle joint without concomitant fractures. DIAGNOSES: open total lateral dislocation of ankle joint without fractures. INTERVENTIONS: Early modern wound care including thorough debridement and irrigation on the wound was performed to remove contaminated soft tissues. Subsequently, the dislocated ankle joint was reduced by hand and the medial and lateral collateral ligaments were repaired using wire anchors. OUTCOMES: The medial wound healed at 2 weeks after surgery, and several common complications such as infection and skin necrosis did not occur. The last follow-up showed a good range of metatarsal flexion and extension of the injured foot, and obvious signs of traumatic arthritis were not observed. According to Kaikkonen ankle function score, the patient was assessed with 90 points. LESSONS: For open total dislocation of ankle joint, early treatment should focus on debridement and irrigation, reduction and fixation of the dislocated ankle, protection of the weak soft tissues, and stable external fixation to promote wound healing and reduce the incidence of related complications.