A slow-releasing donor of hydrogen sulfide inhibits neuronal cell death via anti-PANoptosis in rats with spinal cord ischemia‒reperfusion injury.

BACKGROUND: Spinal cord ischemia‒reperfusion injury (SCIRI) can lead to paraplegia, which leads to permanent motor function loss. It is a disastrous complication of surgery and causes tremendous socioeconomic burden. However, effective treatments for SCIRI are still lacking. PANoptosis consists of three kinds of programmed cell death, pyroptosis, apoptosis, and necroptosis, and may contribute to ischemia‒reperfusion-induced neuron death. Previous studies have demonstrated that hydrogen sulfide (H2S) exerts a neuroprotective effect in many neurodegenerative diseases. However, whether H2S is anti-PANoptosis and neuroprotective in the progression of acute SCIRI remains unclear. Thus, in this study we aimed to explore the role of H2S in SCIRI and its underlying mechanisms. METHODS: Measurements of lower limb function, neuronal activity, microglia/macrophage function histopathological examinations, and biochemical levels were performed to examine the efficacy of H2S and to further demonstrate the mechanism and treatment of SCIRI. RESULTS: The results showed that GYY4137 (a slow-releasing H2S donor) treatment attenuated the loss of Nissl bodies after SCIRI and improved the BBB score. Additionally, the number of TUNEL-positive and cleaved caspase-3-positive cells was decreased, and the upregulation of expression of cleaved caspase-8, cleaved caspase-3, Bax, and Bad and downregulation of Bcl-2 expression were reversed after GYY4137 administration. Meanwhile, both the expression and activation of p-MLKL, p-RIP1, and p-RIP3, along with the number of PI-positive and RIP3-positive neurons, were decreased in GYY4137-treated rats. Furthermore, GYY4137 administration reduced the expression of NLRP3, cleaved caspase-1 and cleaved GSDMD, decreased the colocalization NeuN/NLRP3 and Iba1/interleukin-1ß-expressing cells, and inhibited proinflammatory factors and microglia/macrophage polarization. CONCLUSIONS: H2S ameliorated spinal cord neuron loss, prevented motor dysfunction after SCIRI, and exerted a neuroprotective effect via the inhibition of PANoptosis and overactivated microglia-mediated neuroinflammation in SCIRI.

[Relationship between dietary nutrients and hypertension, overweight and obesity in pupil grades 3 to 6 in Wuhan City].

OBJECTIVE: To explore the relationship between children's dietary nutrient intakes and hypertension, overweight and obesity. METHODS: In April 2016, 1033 children aged 9 to 12 from grades 3 to 6 in two primary schools in Hongshan District of Wuhan City were selected by cluster sampling method, with an average age of(10.55±1.10) years, including 545 boys(52.8%) and 488 girls(47.2%), for physical examination and dietary survey. Physical examination included height, weight, blood pressure, etc. Dietary survey was conducted using a 3-day 24 h retrospective method. Principal component factor analysis was used to explore the dietary nutrient patterns of children, and logistic regression was used to analyze the effects of different dietary nutrient patterns on children's hypertension, overweight and obesity. RESULTS: In terms of M(P25, P75), compared with normal blood pressure group, hypertensive group had higher energy intake(1761.97(1617.17, 1940.43)kcal vs.1730.95(1556.06, 1905.71)kcal, P=0.011). Compared with normal weight group, overweight and obese group had higher carbohydrate(250.65(226.55, 281.29)g vs.244.41(220.04, 273.01)g, P=0.011), vitamin B_1(0.29(0.22, 0.36)mg vs.0.27(0.22, 0.34)mg, P=0.022), vitamin B_2(0.45(0.33, 0.60)mg vs.0.39(0.32, 0.51)mg, P=0.001), iron(12.64(11.06, 14.48)mg vs.12.39(10.57, 14.21)mg, P=0.033), zinc(5.11(4.00, 6.77)mg vs.4.60(3.87, 5.84)mg, P<0.001)intakes, lower calcium intake(185.52(136.92, 264.73)mg vs.207.39(141.25, 300.92)mg, P=0.007). Low cholesterol, low vitamin, high calcium pattern(OR=0.644, 95%CI 0.421-0.985) and Q2 of low protein, low fat and low cholesterol(OR=0.626, 95%CI 0.412-0.951) were protective factors for overweight and obesity. CONCLUSION: High carbohydrate may be a risk factor for overweight and obesity, while high calcium, low fat and low cholesterol may be protective factors for overweight and obesity.

Preparation of modified MFI-type/PDMS composite membranes for the separation of dichlorobenzene isomers via pervaporation.

Zeolite-polymer composite membranes have become promising and effective materials for the pervaporative separation of liquids, especially for isomeric mixtures. In this paper, silicalite-1/PDMS composite membranes have been used to investigate the separation of dichlorobenzene (DCB) isomers via pervaporation for the first time. Silicalite-1 zeolites modified by the silane coupling agent, NH3-C3H6-Si(OC2H5)3, have been incorporated into polydimethylsiloxane (PDMS). Then, the silicalite-1/PDMS composite membranes have been successfully prepared on porous polyvinylidene fluoride (PVDF) supports. The morphology and structure of the silicalite-1 zeolites and silicalite-1/PDMS composite membranes have been characterized by XRD, FTIR, SEM and BET techniques. The results show that the modified silicalite-1 zeolite particles have smaller pore sizes dispersed more uniformly in the active layers of the silicalite-1/PDMS composite membranes and present fewer aggregation and pinholes formed by the accumulation of zeolite particles. The silicalite-1/PDMS composite membranes are all dense and continuous with good homogeneity. To evaluate the pervaporative separation performance of the DCB isomers, the unmodified and modified silicalite-1/PDMS composite membranes have been further tested in single-isomer and binary-isomer systems at 60 °C. The modified silicalite-1/PDMS composite membranes present higher DCB isomer separation factors. The separation factors of the modified silicalite-1/PDMS composite membranes in the binary-isomer systems for p-/o-DCB and p-/m-DCB are 3.53 and 5.63, respectively. The permeate flux of p-DCB through the modified silicalite-1/PDMS composite membranes in the p-/o-DCB binary-isomer system is 116.7 g m-2 h-1 and in the p-/m-DCB binary-isomer system, it is 93.5 g m-2 h-1. The result provides a new approach towards the pervaporative separation of DCB isomers from their mixture for future industrialization applications.

Silicalite-1/PDMS Hybrid Membranes on Porous PVDF Supports: Preparation, Structure and Pervaporation Separation of Dichlorobenzene Isomers.

Separation of dichlorobenzene (DCB) isomers with high purity by time− and energy−saving methods from their mixtures is still a great challenge in the fine chemical industry. Herein, silicalite-1 zeolites/polydimethylsiloxane (PDMS) hybrid membranes (silicalite-1/PDMS) have been successfully fabricated on the porous polyvinylidene fluoride (PVDF) supports to first investigate the pervaporation separation properties of DCB isomers. The morphology and structure of the silicalite-1 zeolites and the silicalite-1/PDMS/PVDF hybrid membranes were characterized by XRD, FTIR, SEM and BET. The results showed that the active silicalite-1/PDMS layers were dense and continuous without any longitudinal cracks and other defects with the silicalite-1 zeolites content no more than 10%. When the silicalite-1 zeolites content exceeded 10%, the surfaces of the active silicalite-1/PDMS layers became rougher, and silicalite-1 zeolites aggregated to form pile pores. The pervaporation experiments both in single-isomer and binary−isomer systems for the separation of DCB isomers was further carried out at 60 °C. The results showed that the silicalite-1/PDMS/PVDF hybrid membranes with 10% silicalite-1 zeolites content had better DCB selective separation performance than the silicalite-1/α−Al2O3 membranes prepared by template method. The permeate fluxes of the DCB isomers increased in the order of m−DCB < o−DCB < p−DCB both in single-isomer and binary-isomers solutions for the silicalite-1/PDMS/PVDF hybrid membranes. The separation factor of the silicalite-1/PDMS/PVDF hybrid membranes for p/o−DCB was 2.9 and for p/m−DCB was 4.6 in binary system. The permeate fluxes of the silicalite-1/PDMS/PVDF hybrid membranes for p−DCB in p/o−DCB and p/m−DCB binary−isomers solutions were 126.2 g∙m−2∙h−1 and 104.3 g∙m−2∙h−1, respectively. The thickness−normalized pervaporation separation index in p/o−DCB binary−isomers solutions was 4.20 µm∙kg∙m−2∙h−1 and in p/m−DCB binary−isomers solutions was 6.57 µm∙kg∙m−2∙h−1. The results demonstrated that the silicalite-1/PDMS/PVDF hybrid membranes had great potential for pervaporation separation of DCB from their mixtures.

Protein C receptor maintains cancer stem cell properties via activating lipid synthesis in nasopharyngeal carcinoma.

Metastasis and recurrence account for 95% of deaths from nasopharyngeal carcinoma (NPC). Cancer stem cells (CSCs) are regarded as one of the main reasons for tumor cell resistance to clinical therapy, and cancer metastasis or recurrence, while little is known about CSCs in NPC. The present study uncovers a subpopulation of cells labeled as CD45-EPCAM+PROCR+ in NPC biopsy samples that exhibit stem cell-like characteristics. A relatively low number of these cells initiate xenograft tumors in mice. Functional analysis reveals that protein C receptor (PROCR) not only serves as a stem cell marker in NPC, but also maintains tumor cells' stemness potential through regulating lipid metabolism and mitochondrial fission. Epistatic studies reveal that cAMP-protein kinase A stimulates Ca2+ release to manipulate lipid metabolism related genes' expression. Finally, in a cohort of 207 NPC samples, PROCR expression is correlated with tumor metastasis or recurrence, and predicts poor prognosis. These novel findings link PROCR labeled CSCs with lipid metabolism and mitochondrial plasticity, and provides new clinical target against metastatic or recurrent NPC.

Adsorption of Phosphate in Aqueous Phase by Biochar Prepared from Sheep Manure and Modified by Oyster Shells.

Sheep manure and oyster shells as C and Ca sources, respectively, were used to obtain Ca-enriched biochar materials with a high dephosphorization efficiency. This approach is helpful for the utilization of livestock manure and shell solid waste as well as for creating highly adsorbent materials. The results show that as the Ca content in biochar was increased, the material's phosphate adsorption capacity increased. The maximum adsorption efficiency reached 94%. The highest adsorption capacity (calculated using Langmuir fitting) of the material containing 1:1 biochar/oyster shell weight ratio reached 146.3 mg P/g. With the increase of the pH value of phosphate solution, the adsorption capacity of the sample gradually increased to 89.5-93.3 mg P/g. The adsorption occurred mainly by complexation. The results of this work provide insights into livestock manure and shell solid waste utilization, which yields a material with useful adsorption properties that can be applied for the removal of phosphate and other inorganics from water.

Synthesis of silicalite-1 zeolite membranes for vapor-permeation separation of dichlorobenzene Isomers.

Silicalite-1 zeolitic membranes have been successfully fabricated on the porousα-Al2O3support by templated and template-free protocol, respectively, for vapor permeation separation of dichlorobenzene (DCB) isomers. After proving the high quality of the membranes by single gas permeation (He and SF6) performance, the vapor-permeation of DCB isomers over two types of the silicalite-1 membrane was then investigated. The separation results clearly indicated that under the lower partial pressure and higher temperature, the effect of DCB isomer adsorption on the permeance could be kept at a sufficiently low level and sharp selectivity become more important. Thus, highp-DCB selectivity could be achieved. Comparatively, the template-free silicalite-1 zeolite has a much higher p-DCB selectivity due to the relatively fewer inter-crystalline gaps. Under certain separation conditions, the highest selectivity ofp-DCB forp-/m-DCB andp-/o-DCB binary systems could reach 165 and 113, respectively.

Enhanced adsorption of phosphorus in soil by lanthanum-modified biochar: improving phosphorus retention and storage capacity.

Use of soil adsorbent is an effective method for the promotion of phosphorus adsorption capacity of soil, though most of the soil adsorbents have weak phosphorus retention ability. Herein, we compared the traditional gypsum (GP) and zeolite (ZP) adsorbents to explore the phosphorus retention ability of lanthanum modified walnut shell biochar (La-BC) in soil. The results showed that with the increase of exogenous phosphorus concentration, the adsorption amount of phosphorus by adsorbents in soil increased at first and then tended to be stable. The maximum adsorption capacity of soil to phosphorus is gypsum, lanthanum-modified biochar > zeolite, and the addition of lanthanum-modified biochar can improve the adsorption capacity of soil to phosphorus, enhance the binding strength of soil and phosphorus, improve the ability of soil to store phosphorus, reducing phosphorus adsorption saturation, and is beneficial to control the leaching of soil phosphorus. FTIR and XRD analysis showed that the adsorption of phosphorus by each adsorbent in soil was mainly chemical precipitation. The response surface analysis showed that the adsorption performance of La-BC+S was the best when the concentration of exogenous phosphorus was 50.0 mg/L, pH was 6.47, and the reaction time was 436.98 min. This study provides a reference for soil adsorbents to hold phosphorus and reduce the risk of phosphorus leaching to avoid groundwater pollution.

MFI-Type Zeolite Membranes for Pervaporation Separation of Dichlorobenzene Isomers.

MFI-type zeolitic membranes were prepared on the porous α-A2O3 support to investigate the separation properties of dichlorobenzene isomers. The pervaporation tests were performed with unary and binary isomer mixtures at 333 K. The results indicate that the silicalite membranes, irrespective of being synthesized by the templated or template-free method, are permeable for all dichlorobenzene isomers. The pervaporation fluxes of the pure dichlorobenzene isomers decrease in the order p-DCB > o-DCB > m-DCB. For the binary pervaporation system, the dichlorobenzene fluxes are all less than those with a single component due to the binary interactions between DCB isomers and between the DCB isomer and the zeolite membrane. Comparatively, the template-free MFI-type zeolite exhibits higher selectivity for dichlorobenzene isomers due to less inter-crystalline gaps. The separation factors for p-/o-DCB and p-/m-DCB can reach 16.7 and 22.0, respectively.

Chromatin remodeler Znhit1 preserves hematopoietic stem cell quiescence by determining the accessibility of distal enhancers.

Hematopoietic stem cell (HSC) utilizes its quiescence feature to combat exhaustion for lifetime blood cell supply. To date, how certain chromatin architecture and subsequent transcription profile permit HSC quiescence remains unclear. Here, we show an essential role of chromatin remodeler zinc finger HIT-type containing 1 (Znhit1) in maintaining HSC quiescence. We find that loss of Znhit1 leads to exhaustion of stem cell pool and impairment of hematopoietic function. Mechanically, Znhit1 determines the chromatin accessibility at distal enhancers of HSC quiescence genes, including Pten, Fstl1, and Klf4, for sustained transcription and consequent PI3K-Akt signaling inhibition. Moreover, Znhit1-Pten-PI3K-Akt axis also participates in controlling myeloid expansion and B-lymphoid specification. Our findings therefore identify a dominant role of Znhit1-mediated chromatin remodeling in preserving HSC function for hematopoietic homeostasis.

TRIM21-SERPINB5 aids GMPS repression to protect nasopharyngeal carcinoma cells from radiation-induced apoptosis.

BACKGROUND: The main strategy against nasopharyngeal carcinoma (NPC) is radiotherapy. However, radioresistance mediated recurrence is a leading clinical bottleneck in NPC. Revealing the mechanism of NPC radioresistance will help improve the therapeutic effect. METHODS: In this study, the role of TRIM21 (tripartite motif-containing 21) in NPC receiving ionizing radiation was firstly examined both in vivo and in vitro. Mass spectrometry analysis was performed to identify the downstream targets of TRIM21. NPC cells with TRIM21 or SERPINB5 (serpin family B member 5) overexpression or knockout were used to determine the epistatic relationship among SERPINB5, GMPS (guanine monophosphate synthase) and TRIM21. Flow cytometry, co-immunoprecipitation, western blot and immunofluorescence were employed to strengthen the results. Finally, immunohistochemistry using 4 radiosensitive and 8 radioresistent NPC patient samples was perform to examine the association between SERPINB5 or GMPS expression and patient radio-sensitivity. RESULTS: As an E3 ligase, TRIM21 was highly expressed in NPC. After ionizing radiation, TRIM21 repressed TP53 expression by mediating GMPS ubiquitination and degradation. Overexpression of TRIM21 protected NPC cells from radiation mediated cell apoptosis in vitro and in vivo. Further analysis revealed that TRIM21 mediated GMPS repression was dependent on SERPINB5, and SERPINB5 served as an adaptor which prevented GMPS from entering into the nucleus and introduced TRIM21 for GMPS ubiquitination. Moreover, the in vitro and in vivo results validated the finding that SERPINB5 promoted NPC cell radioresistance, and the radioresistant patients had higher SERPINB5 expression. CONCLUSIONS: Overall, our data showed that TRIM21-SERPINB5-mediated GMPS degradation facilitated TP53 repression, which promoted the radioresistance of NPC cells. This novel working model related to TP53 suppression provided new insight into NPC radioresistence clinically.

Reliability and validity of short Beck Hopelessness Scale in psychological autopsy study among Chinese rural elderly.

BACKGROUND: Older adults represent the segment of population most exposed to the risk of suicide nearly everywhere in the world. Previous studies showed that hopelessness was an important risk factor for suicide. AIMS: This study aimed to evaluate the reliability and validity of the four-item Beck Hopelessness Scale (BHS-4) in psychological autopsy study among Chinese rural elderly. METHOD: Two-stage stratified cluster sampling method was used to select research sites. Using case-control psychological autopsy study, face-to-face interviews were conducted to collected information. RESULTS: A total of 242 elderly suicide deaths and 242 matched living comparisons were investigated, including 135 males and 107 females for each group. Intraclass Correlation Coefficients (ICC) of the controls were 0.682-0.713. The median score of BHS-4 among suicides was significantly higher than that among controls. The corrected correlation coefficient between items and total score were 0.184-0.723. Cronbach's Alphas coefficient was 0.834. Only one common factor was precipitated by exploratory factor analysis and the cumulative variance contribution rates were 59.558% for suicides and 52.722% for living controls. The correlation coefficient between hopelessness and depression were 0.481 among suicide death and 0.617 among living controls. CONCLUSION: The information provided by the informants through psychological autopsy method had high reliability to reflect the actual situation of suicides and controls. BHS-4 has good reliability and validity among Chinese rural elderly suicides. It is suitable for psychological autopsy study among Chinese rural elderly.

Isoform-specific involvement of Brpf1 in expansion of adult hematopoietic stem and progenitor cells.

Bromodomain-containing proteins are known readers of histone acetylation that regulate chromatin structure and transcription. Although the functions of bromodomain-containing proteins in development, homeostasis, and disease states have been well studied, their role in self-renewal of hematopoietic stem and progenitor cells (HSPCs) remains poorly understood. Here, we performed a chemical screen using nine bromodomain inhibitors and found that the bromodomain and PHD finger-containing protein 1 (Brpf1) inhibitor OF-1 enhanced the expansion of Lin-Sca-1+c-Kit+ HSPCs ex vivo without skewing their lineage differentiation potential. Importantly, our results also revealed distinct functions of Brpf1 isoforms in HSPCs. Brpf1b promoted the expansion of HSPCs. By contrast, Brpf1a is the most abundant isoform in adult HSPCs but enhanced HSPC quiescence and decreased the HSPC expansion. Furthermore, inhibition of Brpf1a by OF-1 promoted histone acetylation and chromatin accessibility leading to increased expression of self-renewal-related genes (e.g. Mn1). The phenotypes produced by OF-1 treatment can be rescued by suppression of Mn1 in HSPCs. Our findings demonstrate that this novel bromodomain inhibitor OF-1 can promote the clinical application of HSPCs in transplantation.

Validating the Life Events Scale for the Elderly with proxy-based data: A case-control psychological autopsy study in rural China.

AIM: The present study aimed to evaluate the validity of proxy informants' reports on Life Event Scale for the Elderly (LESE) by using psychological autopsy method among rural older adults in China. METHODS: A multistage stratified cluster sampling method was used to select research sites. Using a case-control psychological autopsy study, face-to-face interviews were carried out to collect information from 242 suicide cases and 242 living controls. We compared the intensity and number of life events to assess the validity and reliability of LESE with proxy data reported by different informants. Data from proxy respondents of the living controls were compared with data reported by the targets (gold standards). Intraclass correlation coefficients were computed to evaluate the consistency of informants. Spearman's correlation analysis was used to analyze the convergent validity and discriminate validity of the LESE. RESULTS: The number of life events between different informants showed higher intraclass correlation coefficients values than the intensity of life events, but the results of correlation analysis was similar. The LESE was positively correlated with depression, loneliness and hopelessness, and negatively correlated with quality of life, family function and social support both in suicide cases and living controls. CONCLUSIONS: The LESE has good convergent validity and discriminant validity. LESE is a valid instrument for measuring life events in psychological autopsy studies. We suggest using the number of life events to assess the validity and reliability with proxy data in a psychological autopsy study, which is more reliable than using the intensity of life events. Geriatr Gerontol Int 2019; 19: 547-551.

m6A-mediated ZNF750 repression facilitates nasopharyngeal carcinoma progression.

Nasopharyngeal carcinoma (NPC) progression is regulated by genetic, epigenetic, and epitranscript modulation. As one of the epitranscript modifications, the role of N6-Methyladenosine (m6A) has not been elucidated in NPC. In the present study, we found that the poorly methylated gene ZNF750 (encoding zinc finger protein 750) was downregulated in NPC tumor tissues and cell lines. Ectopic expression of ZNF750 blocked NPC growth in vitro and in vivo. Further studies revealed that m6A modifications maintained the low expression level of ZNF750 in NPC. Chromatin immunoprecipitation sequencing identified that ZNF750 directly regulated FGF14 (encoding fibroblast growth factor 14), ablation of which reversed ZNF750's tumor repressor effect. Moreover, the ZNF750-FGF14 signaling axis inhibited NPC growth by promoting cell apoptosis. These findings uncovered the critical role of m6A in NPC, and stressed the regulatory function of the ZNF750-FGF14 signaling axis in modulating NPC progression, which provides theoretical guidance for the clinical treatment of NPC.

BLOS2 maintains hematopoietic stem cells in the fetal liver via repressing Notch signaling.

During development, hematopoietic stem cells (HSCs) undergo a rapid expansion in the fetal liver (FL) after their emergence in the aorta-gonad-mesonephros (AGM) region. We recently reported that the endolysosomal trafficking factor BLOS2, encoded by the Bloc1s2 gene, regulates HSC/hematopoietic progenitor cell emergence in the AGM region; however, whether it plays a role in the FL remains unknown. Here, we show that BLOS2 plays an essential role in the regulation of HSC proliferation and differentiation in the FL. Bloc1s2 depletion leads to elevated Notch signaling, with an increased frequency but weakened self-renewal ability of FL HSCs. Functional assays show that Bloc1s2-/- FL HSCs harbor impaired lymphoid and myeloid differentiation abilities. These findings reveal that balanced control of Notch signaling by BLOS2 is required for HSC homeostasis during FL hematopoiesis.

BLOS2 negatively regulates Notch signaling during neural and hematopoietic stem and progenitor cell development.

Notch signaling plays a crucial role in controling the proliferation and differentiation of stem and progenitor cells during embryogenesis or organogenesis, but its regulation is incompletely understood. BLOS2, encoded by the Bloc1s2 gene, is a shared subunit of two lysosomal trafficking complexes, biogenesis of lysosome-related organelles complex-1 (BLOC-1) and BLOC-1-related complex (BORC). Bloc1s2-/- mice were embryonic lethal and exhibited defects in cortical development and hematopoiesis. Loss of BLOS2 resulted in elevated Notch signaling, which consequently increased the proliferation of neural progenitor cells and inhibited neuronal differentiation in cortices. Likewise, ablation of bloc1s2 in zebrafish or mice led to increased hematopoietic stem and progenitor cell production in the aorta-gonad-mesonephros region. BLOS2 physically interacted with Notch1 in endo-lysosomal trafficking of Notch1. Our findings suggest that BLOS2 is a novel negative player in regulating Notch signaling through lysosomal trafficking to control multiple stem and progenitor cell homeostasis in vertebrates.