Mechanical activation is a solution to the problem of low reactivity of ferrous extraction tailing of nickel slag (FETNS). In this paper, FETNS was treated with different ball milling times (5 min, ...10 min, 20 min). The effects of mechanical ball milling on the microstructure, mineral phase composition, and particle size distribution of FETNS were analyzed. The effects of mechanical ball milling on the properties, reaction products, and pore structure of the FETNS-OPC composite cementitious system were studied. The experimental results show that mechanical ball milling increases the fineness of FETNS and the amorphous phase content. The compressive strength of the composite cementitious system increases with the increase of ball milling time. The compressive strength of 3d, 7d, 28d, 60d, and 90d increases by 65.96%, 22.3%, 14.97%, 23.43%, and 9.12%, respectively. X-ray diffraction test and simultaneous thermal analysis show that the increase in ball milling time promotes the formation of reaction products. The hydration heat test shows that the increase in ball milling time increases the heat release rate of the early hydration reaction. N2 adsorption-desorption experiments show that the increase in ball milling time increases the number of fine pores in the slurry, reduces the number of coarse pores, and improves the compactness of the internal structure. Mechanical activation can stimulate the reactivity of FETNS, which is conducive to the application of FETNS in building materials.
•The effect of ball milling on the physical properties of FETNS was studied.•The effect of ball milling on the reactivity of FETNS was investigated.•The effect of ball milling on the properties of cementitious system was studied.
Treatment of severe Coronavirus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to ...treat severe COVID-19 patients with lung damage, based on our phase 1 data. In this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 10
cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test (6-MWT), maximum vital capacity, diffusing capacity, and adverse events were recorded and analyzed. In all, 100 COVID-19 patients were finally received either UC-MSCs (n = 65) or placebo (n = 35). UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was -13.31%, 95% CI -29.14%, 2.13%, P = 0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: -15.45%; 95% CI -30.82%, -0.39%; P = 0.043). The 6-MWT showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m; 95% CI 0.00, 57.00; P = 0.057). The incidence of adverse events was similar in the two groups. These results suggest that UC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. A phase 3 trial is required to evaluate effects on reducing mortality and preventing long-term pulmonary disability. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.
Abstract
Background
The pathophysiological mechanisms of aggression are manifold and they may closely interconnect. Current study aimed to determine the gut microbiota and its metabolites, and ...clarify their correlations with inflammation, oxidation, leaky gut and clinical profiles underlying aggression in schizophrenia (ScZ).
Methods
Serum and stool specimens from ScZ inpatients with (ScZ-Ag, 25 cases) and without aggression (NScZ-Ag, 25 cases) were collected. Systemic inflammation, oxidation and leaky gut biomarkers were determined by ELISA, gut microbiota by 16S rRNA sequencing, short-chain fatty acids (SCFAs) by gas chromatography-mass spectrometry analysis and neurotransmitters by liquid chromatograph mass spectrometry analysis.
Results
Significantly higher systemic pro-inflammation, pro-oxidation and leaky gut biomarkers were observed in ScZ-Ag than NScZ-Ag group (all
P
<0.001). Compared to NScZ-Ag group, the alpha-diversity and evenness of fecal bacterial community were much lower, the abundance of fecal genera
Prevotella
was significantly increased, while that
Bacteroides
,
Faecalibacterium
,
Blautia
,
Bifidobacterium
,
Collinsella
and
Eubacterium_coprostanoligenes
were remarkably reduced in ScZ-Ag group (all corrected
P
<0.001). Meanwhile, 6 SCFAs and 6 neurotransmitters were much lower in ScZ-Ag group (all
P
<0.05). Finally, a few strongly positive or negative correlations among altered gut microbiota, SCFAs, systemic pro-inflammation, leaky gut, pro-oxidation and aggression severity were detected.
Conclusions
These results demonstrate that pro-inflammation, pro-oxidation and leaky gut phenotypes relating to enteric dysbacteriosis and microbial SCFAs feature the aggression onset or severity in ScZ individuals.
An increasing number of studies have found that SOX2 mutations can cause variable extraocular symptoms, including growth retardation, sensorineural hearing loss, mental retardation, no pubertal ...signs, and male genitourinary tract malformations (micropenis, cryptorchidism, and hypospadias). The LHRH stimulation test was performed in our hospital when the patient was 3.5 years old, and the results were as follows: basic luteinizing hormone (LH) 1.89 IU/L, follicle stimulating hormone (FSH) 5.48 IU/L, T <20 ng/dl, and peak LH/FSH = 3.47/5.48 = 0.63>0.60, suggesting a normal pituitary response. The basic hormone levels of patient 3 at 5 months were as follows: LH 1.40 IU/L, FSH 7.90 IU/L, T < 20 ng/dL, T 116 ng/dL after hCG stimulation test, AMH > 23.00 ng/mL, INHB 74.50 pg/mL, insulin-like growth factor-1 (IGF-1) 50.9 ng/mL, and peak LH/FSH = 2.59/7.90 = 0.33<0.60 after the LHRH stimulation test, which suggested the pituitary gland could have a response. Patients 1 and 2 carry the same reported heterozygous pathogenic site mutation (p.T232N) in the SOX2 gene, which is located in the carboxy terminal transcription activation region, and patient 3 carries a de novo nonsense heterozygous mutation (p.Y110X) that has not been reported in the literature, but a missense mutation (p.Y110C) at the same site has been reported to cause non-syndromic HH in a male patient.
Antley-Bixler syndrome (ABS) caused by P450 oxidoreductase deficiency (PORD) is a congenital adrenal hyperplasia with skeletal malformations and disordered sex development in both sexes. There have ...been no reports of ABS caused by PORD in Chinese children.
We described the clinical and genetic characteristics of eight Chinese children with ABS caused by PORD and compared them with those of subjects in previous studies.
Eight patients, aged 6 months-17.8 years, showed strikingly similar craniofacial malformations. We first described four unreported features: lower eyelid fat pads (4/8), prominent lower eyelid-zygoma transverse line (4/8), underdeveloped or absent antihelix (5/8) and single earlobe crease (5/8). Five 46, XY patients presented various degrees of undervirilization, while three 46, XX cases showed masculinization. Basal endocrine measurements revealed the following consistent results: normal cortisol; elevated adrenocorticotropic hormone, progesterone, pregnenolone, 17-hydroxypropgesterone, and corticosterone; and decreased or normal testosterone/oestradiol. We identified three previously reported variants and four novel variants (c.51719_51710delGGCCCCTGTGinsC, p.D210G, p.Y248X and p.R554X) of POR. The most prevalent variant was p.R457H (8/16). The hydrocortisone dosages of patients differed because of variable degrees of adrenal insufficiency.
We described novel phenotypes and genotypes of ABS caused by PORD. The variant p.R457H was the most prevalent in this cohort. All subjects had combined characteristics of 17-hydroxylase and 21-hydroxylase deficiency. Steroid replacement therapy for patients with PORD requires individually tailored dosing.
Patients harboring
mutations have a wide spectrum of phenotypes.
To investigate the phenotype of patients with
gene mutations from a 30 Chinese patient cohort.
We reported the clinical features of ...children with
gene mutations and compared them between two groups of patients with social genders of male (boys group) and female (girls group).
Thirty patients with
mutations ranging from 2 months to 17 years of age were studied. There were 11 boys and 19 girls who were identified when they visited the hospital. The patients were verified as having testes without a uterus and ovaries by B-mode ultrasound. There was no difference between boys and girls in terms of the Prader stage (
= 0.086), but the position of the testes was higher in girls than in boys (
= 0.013). The patients' average height is -0.43 SDS according to the normal boys' height with SDS (while their average target height was 0.07 SDS). However, there was no such difference between boys and girls (
> 0.05). Although the basal LH and post-hCG testosterone (T) levels were not different (
> 0.05), but the basal FSH level, LH/FSH ratio, and INHB level were decreased in girls (
= 0.002;
= 0.001;
= 0.006). All of the mothers of the patients reported to have normal pregnancies. We found 24 patients (80%) with
mutations in the
gene; 5 patients had inherited mutations from their mothers, and one inherited from the father. Only the mothers of patients 16 and 18 showed premature ovarian failure at the time of reporting. Among 26 disease associated mutations, 14 novel mutations that have been reported the first time and p.R87C is the most common Among the other 12 had had been reported,the p.R313C is the most common.
Patients with 46, XY
mutations presented a wide spectrum of external genitalia characteristics and severe Sertoli cell impairment. The p.R87C and p.R313C mutations appeared to be common (10%) in this group, and 14 new mutations were identified, improving our understanding the genotype phenotype correlations.
Background
Patients with steroid 5α‐reductase 2 deficiency (5α‐RD) caused by SRD5A2 (OMIM #607306) variants present variable genotypes and phenotypes. The genotype‐phenotype correlations remain ...unclear.
Methods
We investigated genotype‐phenotype correlations of SRD5A2 variants in a large Chinese single‐center cohort. Phenotypes were categorized using the external masculinization score (EMS), urethral meatus and gonad position, and penile length‐standard deviation score.
Results
Of the 130 included patients, 113 had hypospadias, and 17 had a normal urethral meatus position. Testosterone/dihydrotestosterone (T/DHT) values were not significantly associated with phenotypic severity (p = 0.539–0.989). Of the 31 SRD5A2 variants, including 10 novel variants, p.R227Q was the most prevalent (39.62%), followed by p.Q6* (16.92%), p.R246Q (13.46%), and p.G203S (10.38%). Compared to biallelic missense mutations, biallelic nonsense mutations were associated with a lower EMS and urethral meatus score (p = 0.009 and p = 0.024, respectively). Patients homozygous for p.R227Q exhibited mild and variable phenotypes, while those homozygous for p.Q6*, p.R246Q, or p.G203S showed consistently severe phenotypes. The phenotypes were variable and milder in patients with compound heterozygosity for p.R227Q and these mutations.
Conclusion
T/DHT does not predict phenotype severity. The most prevalent SRD5A2 variant in Han Chinese is p.R227Q, which is associated with milder phenotypes and greater phenotypic variability. SRD5A2 variants may significantly influence phenotypic variation.
Patients homozygous for p.R227Q exhibited mild and variable phenotypes while those with homozygous p.Q6*, p.R246Q, and p.G203S showed consistently severe phenotypes. When those mutations were compound heterozygotes for p.R227Q, the genotypes were variable and milder.
LiFePO
4 is a potential cathode candidate for the next generation of secondary lithium batteries. Its reactivity and thermodynamic stability have been determined. At low potentials it can be reduced ...to lithium phosphate and iron. The fully charged state, orthorhombic FePO
4, is metastable relative to the trigonal all tetrahedral form; however, the massive structural rearrangement necessary makes the structural change kinetically unfavorable at room temperature. LiFePO
4 has been prepared by a variety of routes. When synthesized at elevated temperatures in the presence of a carbon gel, only LiFePO
4 was detected by X-ray diffraction even when the starting material was LiFePO
4(OH). At a
C/2 discharge/charge rate, LiFePO
4 retained about 80% of the theoretical capacity cycling at room temperature. The hydrothermal form shows some iron disorder, which impacts its electrochemical and chemical reactions.
Congenital growth hormone deficiency (GHD) is a rare and etiologically heterogeneous disease. We aim to screen disease-causing mutations of GHD in a relatively sizable cohort and discover underlying ...mechanisms
a candidate gene-based mutational burden analysis.
We retrospectively analyzed 109 short stature patients associated with hormone deficiency. All patients were classified into two groups: Group I (n=45) with definitive GHD and Group II (n=64) with possible GHD. We analyzed correlation consistency between clinical criteria and molecular findings by whole exome sequencing (WES) in two groups. The patients without a molecular diagnosis (n=90) were compared with 942 in-house controls for the mutational burden of rare mutations in 259 genes biologically related with the GH axis.
In 19 patients with molecular diagnosis, we found 5 possible GHD patients received known molecular diagnosis associated with GHD (
c.2329T>A, c.7131C>G,
c.731G>A,
c.1102delC,
c.187_207dup). By mutational burden analysis of predicted deleterious variants in 90 patients without molecular diagnosis, we found that
(
= 0.005),
(
= 0.006),
(
= 0.021) and
(
= 0.040) represented top genes enriched in GHD patients.
Our study revealed the discrepancies between the laboratory testing and molecular diagnosis of GHD. These differences should be considered when for an accurate diagnosis of GHD. We also identified four candidate genes that might be associated with GHD.
5α-reductase type 2 deficiency (5αRD) is an autosomal recessive hereditary disease of the group of 46, XY disorders of sex development (DSD).
To study the growth pattern in Chinese pediatric patients ...with 5αRD.
Data were obtained from 141 patients with 5αRD (age: 0-16 years old) who visited eight pediatric endocrine centers from January 2010 to December 2017.
In this retrospective cohort study, height, weight, and other relevant data were collected from the multicenter hospital registration database. Baseline luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T), and dihydrotestosterone (DHT) after human chorionic gonadotropin (HCG) stimulation test were measured by enzyme enhanced chemiluminescence assay. Bone age (BA) was assessed using the Greulich-Pyle (G-P) atlas. Growth curve was constructed based on λ-median-coefficient of variation method (LMS).
The height standard deviation scores (HtSDS) and weight standard deviation scores (WtSDS) in 5αRD children were in the normal range as compared to normal boys. Significantly higher HtSDS was observed in patients with 5αRD who were <1 year old (
= 3.658, 2.103,
= 0.002, 0.048, respectively), and higher WtSDS in those <6 months old (
= 2.756,
= 0.012). Then HtSDS and WtSDS decreased gradually and fluctuated near the median of the same age until 13 years. WtSDS in 5αRD children from northern China were significantly higher than those from the south (
= -2.670,
= 0.008). The variation tendency of HtSDS in Chinese 5αRDs was consistent with the trend of stimulating T. HtSDS and stimulating T in the external masculinization score (EMS) <7 group were slightly higher than those in EMS ≥ 7 group without significant difference. Additionally, the ratio of BA over chronological age (BA/CA) was significantly <1 in children with 5αRD.
Children with 5αRD had a special growth pattern that was affected by high levels of T, while DHT played a very small role in it. Their growth accelerated at age <1 year, followed by slowing growth and fluctuating height near normal median boys' height. The BA was delayed in 5αRD children. Androgen treatment, which may be considered anyway for male 5αRD patients with a micropenis, may also be beneficial for growth.
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