C1Q labels a highly aggressive macrophage-like leukemia population indicating extramedullary infiltration and relapse.

Extramedullary infiltration (EMI) is a concomitant manifestation that may indicate poor outcome of acute myeloid leukemia (AML). The underlying mechanism remains poorly understood and therapeutic options are limited. Here, we employed single-cell RNA sequencing on bone marrow (BM) and EMI samples from a patient with AML presenting pervasive leukemia cutis. A complement C1Q+ macrophage-like leukemia subset, which was enriched within cutis and existed in BM before EMI manifestations, was identified and further verified in multiple patients with AML. Genomic and transcriptional profiling disclosed mutation and gene expression signatures of patients with EMI that expressed high levels of C1Q. RNA sequencing and quantitative proteomic analysis revealed expression dynamics of C1Q from primary to relapse. Univariate and multivariate analysis demonstrated adverse prognosis significance of C1Q expression. Mechanistically, C1Q expression, which was modulated by transcription factor MAF BZIP transcription factor B, endowed leukemia cells with tissue infiltration ability, which could establish prominent cutaneous or gastrointestinal EMI nodules in patient-derived xenograft and cell line-derived xenograft models. Fibroblasts attracted migration of the C1Q+ leukemia cells through C1Q-globular C1Q receptor recognition and subsequent stimulation of transforming growth factor ß1. This cell-to-cell communication also contributed to survival of C1Q+ leukemia cells under chemotherapy stress. Thus, C1Q served as a marker for AML with adverse prognosis, orchestrating cancer infiltration pathways through communicating with fibroblasts and represents a compelling therapeutic target for EMI.

LncRNA FOXD1-AS1 regulates pancreatic cancer stem cell properties and 5-FU resistance by regulating the miR-570-3p/SPP1 axis as a ceRNA.

Cancer stem cells (CSCs) play a pivotal role in the pathogenesis of human cancers. Previous studies have highlighted the role of long non-coding RNA (lncRNA) in modulating the stemness of CSCs. In our investigation, we identified an upregulation of lncRNA FOXD1-AS1 in CSCs. The enforced expression of lncRNA FOXD1-AS1 promotes tumorigenesis and self-renewal in pancreatic cancer CSCs. Conversely, the knockdown of lncRNA FOXD1-AS1 inhibits tumorigenesis and self-renewal in pancreatic cancer CSCs. Furthermore, our findings reveal that lncRNA FOXD1-AS1 enhances self-renewal and tumorigenesis in pancreatic cancer CSCs by up-regulating osteopontin/secreted phosphoprotein 1(SPP1) and acting as a ceRNA to sponge miR-570-3p in pancreatic cancer (PC) CSCs. Additionally, lncRNA FOXD1-AS1 depleted pancreatic cancer cells exhibit heightened sensitivity to 5-FU-indued cell growth inhibition and apoptosis. Analysis of patient-derived xenografts (PDX) indicates that a low level of lncRNA FOXD1-AS1 may serve as a predictor of 5-FU benefits in PC patients. Moreover, the introduction of SPP1 can reverse the sensitivity of lncRNA FOXD1-AS1-knockdown PC cells to 5-FU-induced cell apoptosis. Importantly, molecular studies have indicated that the elevated levels of lncRNAFOXD1-AS1 in PC are facilitated through METTL3 and YTHDF1-dependent m6A methylation. In summary, our results underscore the critical functions of lncRNA FOXD1-AS1 in the self-renewal and tumorigenesis of pancreatic cancer CSCs, positioning lncRNA FOXD1-AS1 as a promising therapeutic target for PC.

[Pay attention to the mental health of children with short stature]. / å ³æ³¨çŸ®èº«æå„¿ç«¥å¿ƒç†å¥åº·.

In the clinical diagnosis and treatment of children with short stature, mental health issues merit special attention. It is widely acknowledged that the psychological well-being of children with short stature is lower than that of their peers with normal height. Therefore, during the diagnosis, treatment, and care of short stature, it is crucial to actively monitor the mental health of these children, promptly identify potential psychological and behavioral issues, and intervene accordingly. Such measures play a positive role in enhancing the quality of life of these children and improving their physical and mental health. This article analyses and discusses the current state of psychological assessment and psycho-behavioral interventions for children with short stature, aiming to provide insights for improving their mental health.

[Diagnostic value of baseline serum luteinizing hormone level for central precocious puberty in girls].

OBJECTIVE: To evaluate the diagnostic value of baseline serum luteinizing hormone (LH) level for central precocious puberty (CPP) in girls. METHODS: A total of 279 girls with precocious puberty were subjected to assessment of growth and development, bone age determination, baseline LH test, and follicle-stimulating hormone (FSH) test, gonadotropin-releasing hormone stimulation test, and other related examinations. Of the 279 patients, 175 were diagnosed with CPP and 104 with premature thelarche (PT). The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of baseline LH and FSH levels and their peak levels for CPP, and the correlation between the baseline LH level and the peak LH level was analyzed. RESULTS: The CPP group had significantly higher bone age, baseline LH and FSH levels, peak LH and FSH levels, and ratio of peak LH level to peak FSH level than the PT group (P<0.01). The ROC curve proved that baseline LH level and peak LH level had good diagnostic values for CPP. Among the three bone age subgroups in the CPP group (7.0-9.0 years, 9.0-11.0 years, and >11.0 years), baseline LH level showed the best diagnostic value in the >11.0 years subgroup, with the largest area under the ROC curve. At a baseline LH level of 0.45 IU/L, the Youden index reached the peak value, and the sensitivity and specificity were 66.7% and 80% respectively, for the diagnosis of CPP. At a peak LH level of 9.935 IU/L, the Youden index reached the peak value, and the sensitivity and specificity were 74.8% and 100% respectively, for the diagnosis of CPP. The baseline LH level was positively correlated with the peak LH level (r=0.440, P<0.01). CONCLUSIONS: Baseline LH level can be used as an primary screening index for the diagnosis of CPP. It has a certain diagnostic value for CPP at different bone ages, and may be used as a monitoring index during the treatment and follow-uP.

Mitochondrial oxidative phosphorylation is dispensable for survival of CD34+ chronic myeloid leukemia stem and progenitor cells.

Chronic myeloid leukemia (CML) are initiated and sustained by self-renewing malignant CD34+ stem cells. Extensive efforts have been made to reveal the metabolic signature of the leukemia stem/progenitor cells in genomic, transcriptomic, and metabolomic studies. However, very little proteomic investigation has been conducted and the mechanism regarding at what level the metabolic program was rewired remains poorly understood. Here, using label-free quantitative proteomic profiling, we compared the signature of CD34+ stem/progenitor cells collected from CML individuals with that of healthy donors and observed significant changes in the abundance of enzymes associated with aerobic central carbonate metabolic pathways. Specifically, CML stem/progenitor cells expressed increased tricarboxylic acid cycle (TCA) with decreased glycolytic proteins, accompanying by increased oxidative phosphorylation (OXPHOS) and decreased glycolysis activity. Administration of the well-known OXPHOS inhibitor metformin eradicated CML stem/progenitor cells and re-sensitized CD34+ CML cells to imatinib in vitro and in patient-derived tumor xenograft murine model. However, different from normal CD34+ cells, the abundance and activity of OXPHOS protein were both unexpectedly elevated with endoplasmic reticulum stress induced by metformin in CML CD34+ cells. The four major aberrantly expressed protein sets, in contrast, were downregulated by metformin in CML CD34+ cells. These data challenged the dependency of OXPHOS for CML CD34+ cell survival and underlined the novel mechanism of metformin. More importantly, it suggested a strong rationale for the use of tyrosine kinase inhibitors in combination with metformin in treating CML.

Incidence of bifid pancreatic duct in pancreaticoduodenectomy and its impact on clinically relevant postoperative pancreatic fistula.

Objectives: This study aimed to examine the incidence of bifid pancreatic duct (BPD) in pancreaticoduodenectomy (PD) and clarify its impact on clinically relevant postoperative pancreatic fistula (CR-POPF). Background: Until now, all the literature about BPD during PD are published as case reports, and the incidence of BPD in PD and its impact on CR-POPF remain unknown. Results: A total of 438 consecutive PDs were divided into two groups: the former year group and the latter year group. The former year group included 215 consecutive PDs, while the latter year group included 223. In the latter year group, we found 16 BPDs during PD (O-BPD); the incidence of O-BPD is 7.17%. Of them, there were eight patients who had BPD in the preoperative imaging (I-BPD). All the I-BPDs are O-BPDs; which means that 50% of O-BPDs were a single pancreatic duct in the preoperative imaging (I-SPD). There were 17 I-BPDs in the 438 consecutive PDs; the incidence of I-BPD is 3.88%. In the former year group, the rate of severe complications of I-BPD and I-SPD is 77.78% and 27.18%, respectively (p = 0.003); the rate of CR-POPF of I-BPD is higher than I-SPD, 55.56% vs. 27.18%, but there were no statistically significant differences. In the latter year group, the rate of severe complications of O-BPD and O-SPD is 50% and 18.36%, and the rate of CR-POPF of O-BPD and O-SPD is 37.5% and 22.22%, respectively; both of them have statistically significant differences, and the p-value is 0.003 and 0.006, respectively. In the subgroup analysis, both the rate of severe complications and the rate of CR-POPF of I-BPD were higher than O-BPD, 77.78% vs. 50%, and 55.56% vs. 37.5%, but there were no statistically significant differences in both of them; the p-value is 0.174 and 0.434, respectively. Univariate and multivariate analyses showed that BPD was an independent risk factor of CR-POPF. Conclusions: The incidence of O-BPD in PD is 7.17%, 50% of O-BPDs were I-SPD, and the incidence of I-BPD is 3.88%. BPD is an independent risk factor of CR-POPF. The suture closure method may be a simple, safe, and effective method in dealing with BPD in PD.

[Effects of selective cutting on the distribution pattern and inter-specific association of arbor seedlings in Tilia amurensis secondary forest]. / æ‹©ä¼å¯¹ç´«æ¤´æ¬¡ç”Ÿæž—ä¹”æœ¨å¹¼è‹—åˆ†å¸ƒæ ¼å±€åŠç§é—´å ³è”æ€§çš„å½±å“.

The distribution pattern and interspecific associations of arbor seedlings were examined in two Tilia amurensis forest stands in Zhangguangcailing, with one without man-made interference (natural recovery secondary forest) and the other one being 20-year-old after selective cutting (selective cutting secondary forest). The results showed that the importance value of the seedlings of the soft broad-leaved (heliophile) and tolerant tree species was 7.9 and 64.5 in natural recovery secondary forest, and was 3.9 and 68.9 in selective cutting secondary forest, respectively. The spatial distribution pattern of arbor seedlings in natural recovery and selective cutting secondary forests showed clustered distribution at the scale of 0-18 m and 0-15 m, respectively. Most of tree species pairs were negatively correlated at large scale (14-45 m) in the natural recovery secondary forest, whereas tree species pairs at all the scales were mostly uncorrelated in the selective cutting secon-dary forest. Most of the tree pairs of T. amurensis seedlings (57%) with other tree species showed negatively correlation at large scale (31-45 m). In the natural recovery secondary forest, the proportion of negatively correlated tree pairs was higher than 60%. In selective cutting secondary forest, Acer mono seedlings were negatively correlated with other tree species at more scales (6-45 m). In the natural recovery secondary forest, the pairs of A. mono and other arbor seedlings were positively correlated at small scale (0-5 m), but not at large scale (31-45 m). Therefore, selective cutting accelerated the succession of the secondary forest of T. amurensis, which induced random distribution of the arbor seedlings at the large scale (31-45 m), promoted a more coordinated inter-specific relationship, and adjusted the spatial competition between T. amurensis seedlings. Both stands were under succession, and thus suitable artificial management should be carried out to promote tree regeneration and community restoration.

[Stoichiometry of soil extracellular enzymes and its seasonal variation in natural forests with different altitudes in northern Greater Khingan Mountains, China]. / å¤§å ´å®‰å²­åŒ—éƒ¨ä¸åŒæµ·æ‹”å¤©ç„¶æž—åœŸå£¤èƒžå¤–é ¶åŒ–å­¦è®¡é‡ç‰¹å¾åŠå ¶å­£èŠ‚åŠ¨æ€.

In this study, we examined the characteristics and influence mechanism of soil extracellular enzyme activity (EEA) and enzymatic stoichiometry in different soils in forests at different altitudes (750-1420 m) in Aokelidui Mountains in the north of the Greater Khingan Mountains. The results showed that altitude, season and their interactions significantly affected the activities of ß-glucosidase (BG), ß-1,4-N-acetylglucosaminidase (NAG), L-leucine aminopeptidase (LAP), and acid phosphatase (AP). In May, BG and NAG activities gradually increased with increasing altitude, while AP activities increased first and then decreased with increasing altitude. In July, NAG activity increased with altitude, while AP activity increased first and then decreased. In September, NAG activity changed significantly in different altitudes, with the highest activity at 1420 m (124.22 nmol·h-1·g-1). With the increases of altitude, ln(BG): ln(NAG+LAP) showed a decreasing trend. Except for the altitude of 830 m, stoichiometric ratio in all altitudes was the highest in July. The ratio of logarithmic conversion of soil C, N, and P invertase activity was 1:1.25:0.82. Altitude and soil temperature were the main factors affecting soil extracellular enzyme activities. There was a significant positive correlation between soil temperature and BG, NAG, and AP. Enzymatic stoichiometry ln(BG):ln(NAG+LAP) and ln(NAG+LAP):ln(AP) showed significant positive and negative correlations with soil pH, and had a negative and positive relationship with DOC. The ratio of ln(BG):ln(AP) was greatly affected by soil bulk density.

Effects of soil in larch plantations on the growth of Picea koraiensis and P. crassifolia seedlings.

In addition to soil fertility decline, larch plantation had difficulty in natural regeneration, which challenges the healthy development and sustainable management. A greenhouse experiment was conducted with two kinds of shade-tolerant conifer species (Picea koraiensis and P. crassifolia) to examine the responses of seedling growth of two spruce species on sterilization treatment of larch plantation soils (except spruce biological characteristics), which would provide scientific basis for the transformation, regeneration and multi-storied forest cultivation of larch. The results showed that soil sterilization did not significantly affect the biomass of P. koraiensis and P. crassifolia seedlings. The biomass of P. koraiensis (75.6 and 72.2 mg, respectively) was significantly higher than that of P. crassifolia (55.6 and 60.0 mg, respectively) in both unsterilized and sterilized soils. The root diameter, cortical thickness, stele diameter and stele to root diameter ratio of the first-order roots of P. koraiensis were not affected by soil sterilization. In contrast, the root diameter, stele diameter and stele to root diameter ratio of the first-order roots except cortical thickness of P. crassifolia in sterilized soil (331.30 µm, 143.23 µm and 43.3%, respectively) were significantly higher than those in unsterilized soil (276.50 µm, 99.35 µm and 36.0%), showing a more positive response to sterilized soil. It indicated that P. koraiensis had better adaptability in larch plantation. Because the microbial community function was dominated by ectomycorrhiza which displayed some antagonisms for soil pathogen, seedlings of two spruce species could escape from soil pathogens accumulated in larch plantation and grow normally, with P. koraiensis having more advantages than the P. crassifolia.

Effect of real-world sounds on protein crystallization.

Protein crystallization is sensitive to the environment, while audible sound, as a physical and environmental factor during the entire process, is always ignored. We have previously reported that protein crystallization can be affected by a computer-generated monotonous sound with fixed frequency and amplitude. However, real-world sounds are not so simple but are complicated by parameters (frequency, amplitude, timbre, etc.) that vary over time. In this work, from three sound categories (music, speech, and environmental sound), we selected 26 different sounds and evaluated their effects on protein crystallization. The correlation between the sound parameters and the crystallization success rate was studied mathematically. The results showed that the real-world sounds, similar to the artificial monotonous sounds, could not only affect protein crystallization, but also improve crystal quality. Crystallization was dependent not only on the frequency, amplitude, volume, irradiation time, and overall energy of the sounds but also on their spectral characteristics. Based on these results, we suggest that intentionally applying environmental sound may be a simple and useful tool to promote protein crystallization.

[Effect of soil phenolic acids on soil microbe of coal-mining depressed land after afforestation restoration by different tree species]. / é‡‡ç ¤æ²‰é™·åŒºä¸åŒé€ æž—æ ‘ç§æ¢å¤åœŸå£¤é šé ¸ç‰©è´¨å¯¹åœŸå£¤å¾®ç”Ÿç‰©çš„å½±å“.

Phenolic acids are one of the most important factors that influence microbial community structure. Investigating the dynamic changes of phenolic acids and their relationship with the microbial community structure in plantation soils with different tree species could contribute to better understanding and revealing the mechanisms of microbial community changes under afforestation restoration in coal-mining subsidence areas. In this study, plantations of three conifer and one deciduous species (Pinus koraiensis, Larix gmelinii, Pinus sylvestris var. mongolica, and Populus ussuriensis) were established on abandoned coal-mining subsidence areas in Baoshan District, Shuangyashan City. The contents of soil phenols, 11 types of phenolic acids, and microbial communities in all plots were determined. The results showed that the contents of soil complex phenol in plantations were significantly higher than that of abandoned land overall. Specifically, soils in larch and poplar plantations had higher contents of complex phenol, while soils in larch and Korean pine plantations had greater contents of total phenol. Moreover, soil in the P. koraiensis plantation had a higher content of water-soluble phenol compared with abandoned lands. The determination of 11 phenolic acids indicated that the contents of ferulic acid, abietic acid, ß-sitosterol, oleanolic acid, shikimic acid, linoleic acid, and stearic acid were higher in plantation soils. Although soil phenol contents were not related with soil microbial biomass, the individual phenolic acids showed a significant relationship with soil microbes. Ferulic acid, abietic acid, and ß-sitosterol showed significant promoting effects on soil microbial biomass, and they showed positive correlations with fungi and fungi/bacteria ratio. These three phenolic acids had higher contents in the poplar plantation, suggesting that poplar affo-restation had a beneficial effect on soil quality in coal-mining subsidence areas.

[Effect of electro-acupuncture combined with olfactory ensheathing cell transplantation on spinal cord injury axonal regeneration and direction].

OBJECTIVE: To explore the impact and mechanism of electro-acupuncture (EA) on olfactory ensheathing cells (OECs) transplantation of spinal cord injury (SCI) axonal regeneration. METHODS: In the experiment, 72 adult Sprague Dawley male rats weighted (220±20) g underwent contusion and transection method to cause the T9 model of spinal cord injury, were randomly divided into four groups involving model group, EA group,OECs group,and EA+OECs group. 5% fluorescein gold (FG) solution of 0.5 µl was injected into rats' spinal cord at 4 weeks and 8 weeks after SCI, a series of tests were performed including fluorescein gold(FG) retrograde tagging, BBB scores. RESULTS: (1)The BBB scores level among four groups had no differences from the 1st day to the 1st week after the SCI (P>0.05). From the 3rd week after the SCI, the BBB scores level in EA+ OECs group were obviously higher than that of other groups (P<0.05). (2)The result of the fluorescein gold (FG) retrograde tagging showed at 4 weeks and 8 weeks after treatment FG positive nerve fibers were observed in SCI region. In EA+OECs group the number of FG positive nerve fibers was more than other three groups, and the fibers were more regularly arranged than other three groups. CONCLUSION: The combination of electro-acupuncture and OECs transplantation can recover the pathway of nerve conduction and promote nerve fibers regeneration and hind limb function recovery for SCI rat, and can guide the trend of the axonal regeneration.

LC-MS/MS determination of acrylamide in instant noodles from supermarkets in the Hebei province of China.

Acrylamide (AA) concentrations in instant noodles (90 samples, covering 10 different brands) from Hebei Province of China were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The instant noodles were sampled from the southern and northern areas of Hebei Province (Shijiazhuang and Tangshan, respectively). The average content of AA for all 10 instant noodle brands was 6-145 µg/kg. The average content of AA in fried instant noodles was 4.47 times of those in non-fried ones, indicating the influence of the frying process. The average content of AA in instant noodles from Shijiazhuang was 1.64 times that of the samples from Tangshan (56 µg/kg). Eighty-four percent of the instant noodle samples in Hebei were contaminated with AA, with an average content of 80 µg/kg. These observations will be helpful for evaluating individual exposure to AA from instant noodles in China.

Determination of aflatoxins in edible oil from markets in Hebei Province of China by liquid chromatography-tandem mass spectrometry.

Analysis of aflatoxin B1 (AFB1), B2 (AFB2), G1 (AFG1) and G2 (AFG2) in 76 edible oil samples (peanut oil, soybean oil, corn embryo oil and blended oil) was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The oils were sampled from three areas (Shijiazhuang, Baoding and Tangshan) of Hebei Province of China. AFB1 was detected in 22 samples representing 28.9%, followed by AFB2 (7.89%) and AFG1 (3.95%), while no AFG2 contamination was detected in any samples. AFB1 levels in oil samples ranged 0.14-2.72 µg kg(-1) and AFB2 ranged 0.15-0.36 µg kg(-1), while lower levels of 0.01-0.02 µg kg(-1) for AFG1 were recorded. The paper is part of an on-going investigation of aflatoxin contamination in Chinese edible oils.