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Alkaptonuria (AKU) is a rare tyrosine metabolism disorder caused by homogentisate 1,2-dioxygenase (HGD) mutations and homogentisic acid (HGA) accumulation. In this study, we investigated the genotype-phenotype relationship in AKU patients with a novel HGD gene mutation from a Chinese Hani family.Routine clinical examination and laboratory evaluation were performed, urine alkalinization test and urinary gas chromatography-mass spectrometry were used to assess HGA. Gene sequencing was utilized to study the defining features of AKU. NetGene2-2.42 and BDGP software was used to predict protein structure online. Flow cytometry and RT-PCR were used to analyze HGD proteins and HGD mRNA, respectively.Two pediatric patients fulfilled diagnostic criteria for AKU with eddish-brown or black diapers and urine HGA testing. Sequencing testing revealed that all members of this family had a novel samesense mutation c.15G A at the edge of exon 1 of the HGD. By flow cytometry, the expression of HGD protein in the pediatric patients' peripheral blood mononuclear cells was barely expressed. NetGene2-2.42 and BDGP software showed that the mutation reduced the score of the 5' splice donor site and disrupted its normal splicing, and the RT-PCR product also demonstrated that the defect in the HGD protein was due to the lack of the first exon containing the start codon ATG after the mutation.The novel mutation c.15G A in HGD is associated with the AKU phenotype. It may affect the splicing of exon 1, leading to exon skipping, which impairs the structure and function of the protein.

X-linked lymphoproliferative syndrome (XLP) is a rare X-linked recessive inborn errors of immunity. The pathogenesis of XLP might be related to phophatidylinositol-3-kinase (PI3K)-associated pathways but insight details remain unclear. This study was to study an infant XLP-1 case caused by a mutation in SH2D1A gene, investigate the structural and functional alteration of mutant SAP protein, and explore the potential role of PI3K-associated pathways in the progression of XLP-1.The proband's condition was monitored by laboratory and imagological examinations. Whole exome sequencing and Sanger sequencing were performed to detect the genetic disorder. Bioinformatics tools including PolyPhen-2, SWISS-MODEL and SWISS-PDB Viewer were used to predict the pathogenicity and estimate structural change of mutant protein. Flow cytometry was used to investigate expression of SAP and PI3K-associated proteins.The proband was diagnosed with XLP-1 caused by a hemizygous mutation c.96GT in SH2D1A gene resulting in a missense substitution of Arginine to Serine at the site of amino acid 32 (p.R32S). The mutant protein contained a hydrogen bond turnover at the site of mutation and was predicted to be highly pathogenic. Expression of SH2D1A encoded protein SAP was downregulated in proband. The PI3K-AKT-mTOR signaling pathway was fully activated in XLP-1 patients, but it was inactive or only partially activated in healthy people or HLH patients.The mutation c.96GT in SH2D1A gene caused structural and functional changes in the SAP protein, resulting in XLP-1. The PI3K-AKT-mTOR signaling pathway may play a role in XLP-1 pathogenesis.

WXGEN, a weather generator model based on stochastic process theory and mathematical statistics, was widely used in hydrological monitoring models, crop yield estimation models and derived fields of meteorological data. In this study, we used WXGEN to evaluate the simulation accuracy of hydrothermal conditions in the highlands of the Qinghai–Tibet Plateau. Results showed that: (1) The Markovian chain transfer parameters P(W|D) and P(W|W) of each station were between 0.03–0.30 and 0.12–0.74, which was basically consistent with the temporal and spatial distribution of actual precipitation; (2) In the thermal data simulation, more than 96% of the meteorological stations passed the 0.05 level in three different significance tests of monthly mean minimum and maximum temperature and solar radiation, and the measured deviations of simulated annual mean temperature and solar radiation were 0.686 °C and 1.65 MJ/m2, respectively. In all, 94% of the stations in the hydrological simulation passed the monthly precipitation significance test; (3) The simulated vs. measured deviations of annual precipitation, heavy rain days and wet days were 8.04 mm, 1.023 d and 8.374 d, respectively; (4) The simulation of extreme hydrothermal conditions that may affect the yield of highland barley was very close to the measured situation, and the R2 of simulation and measured value was all above 0.85. The simulation of freezing damage was less accurate, but also higher than 0.85.

Magnetic biochar was successfully synthesized via a one-step method through simultaneous activation and magnetization with alkali-acid modified citrus peel as the raw material, which could effectively penetrate interfering substances. The characterization analysis showed that the magnetic biochar exhibited high graphitic degree, higher specific surface area and smaller pore diameter, which resulted in superior adsorption performance. The magnetic biochar was used as an adsorbent for the cleanup and extraction of 22 pesticides (consisting of insecticides, fungicides and herbicides) from vegetables and the quantitative detection was completed by gas chromatography-mass spectrometry (GC-MS). The Plackett-Burman experimental design (PBD), central composite design (CCD) and response surface methodology (RSM) were employed to identify significant factors and optimal experimental conditions. Under optimal conditions, the methodological linearity was in the range of 1-100 μg kg-1 with the coefficients of determination ranging from 0.9969-0.9999, while the limits of detection (LODs) and limits of quantification (LOQs) were 0.31-0.91 μg kg-1 and 1.03-3.05 μg kg-1, respectively. The recoveries of the analytes from spiked samples were in the range of 78.1-112.5%. It was confirmed that the method established by using magnetic graphitic biochar as the adsorbent is an efficient pretreatment procedure and could be successfully applied for analysis of food safety.

The latest special report from the Intergovernmental Panel on Climate Change (IPCC), published in 2018 (Anandhi et al. 2016), estimates a 1.5 °C increase in global temperature in 2040 at the current rate of global warming. Such a rise has serious implications for major cereal crop cultivation: unless crop varieties adapted to higher temperatures become available, the areas suitable for cropping are bound to shift in the future. Therefore, to safeguard food security, we need to predict such changes in spatial and temporal terms, which can intuitively reflect the potential distribution of crops under different climate change scenarios and for different time periods, helping to reduce losses according to local conditions (Deng et al. 2009).

The increasing temperature with global warming will have great impacts on major cereal crop cultivation (Peng et al. 2004; Fahad et al. 2019). Among various impacts, the crop exposure to extremely high temperature, which is based on the land suitability for crop cultivation, may ultimately pose a great threat to food security.

Background Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a rare autosomal recessive disorder characterized by severe pre‐ and postnatal growth restrictions, microcephaly, skeletal dysplasia, severe teeth deformities, and typical facial features. Previous studies have shown that MOPD II is associated with mutations in the pericentrin (PCNT) gene. Methods We evaluated the clinical features of a 10‐year and 7‐month‐old Chinese girl with MOPD II. Subsequently, next‐generation sequencing and flow cytometry were performed to investigate genetic characteristics and the expression of PCNT protein respectively. Results The patient presented with short stature, microcephaly, typical craniofacial features, teeth deformity, thrombocytosis, and a delayed bone age (approximately 7 years). No abnormality in growth hormone or insulin‐like growth factor 1 was detected. Notably, the patient was found to carry a novel homozygous PCNT mutation (c.6157G>T, p.Glu2053Ter), which was inherited from her healthy heterozygous parents. Meanwhile, significant deficiency of PCNT expression was identified in the patient. Conclusion Our study identified a novel PCNT mutation associated with MOPD II, expanded the mutation spectrum of the PCNT gene and improved our understanding of the molecular basis of MOPD II., We describe a rare case of MOPD II in a 10‐year and 7‐month old Chinese female. A novel homozygous mutation was identified in exon 30 of the PCNT gene (c.6157G>T, p.Glu2053Ter) by next‐generation sequencing. Meanwhile, flow cytometry revealed a deficiency in the PCNT protein expression of the patient. This is the first report of a Chinese MOPD II patient with a homozygous PCNT gene mutation.

Waardenburg syndrome (WS) is a congenital hereditary disease, attributed to the most common symptoms of sensorineural deafness and iris hypopigmentation. It is also known as the hearing-pigmentation deficient syndrome. Mutations on SOXl0 gene often lead to congenital deafness and has been shown to play an important role in the pathogenesis of WS. We investigated one family of five members, with four patients exhibiting the classic form of WS2, whose DNA samples were analyzed by the technique of Whole-exome sequencing (WES). From analysis of WES data, we found that both the mother and all three children in the family have a heterozygous mutation on the Sex Determining Region Y - Box 10 (SOX10) gene. The mutation was c.298_300delinsGG in exon 2 of SOX10 (NM_006941), which leads to a frameshift of nine nucleotides, hence the amino acids (p. S100Rfs*9) are altered and the protein translation may be terminated prematurely. Further flow cytometry confirmed significant down-regulation of SOX10 protein, which indicated the SOX10 gene mutation was responsible for the pathogenesis of WS2 patients. In addition, we speculated that some other mutated genes might be related to disease phenotype in this family, which might also participate in promoting the progression of WS2.

Global climate change, mainly characterized by warming, has resulted in significant migration of temperature-sensitive crops from traditional planting areas, making crops more vulnerable to climate change and natural disasters, increasing yield losses caused by disasters. Based on the MaxEnt model, combining Representative Concentration Pathways 4.5 and 8.5, the potential suitable areas for highland barley planting on the Qinghai-Tibet Plateau were estimated, and the results showed that: (1) Over 30% of the Qinghai-Tibet Plateau is unsuitable for highland barley cultivation, the area of moderately suitable area for highland barley planting is close to 50%, and the marginally suitable and highly suitable area is less than 20%; (2) From the past distribution to the near and medium-term distributions, the unsuitable area for highland barley planting is gradually shrinking. In the moderately suitable area for highland barley planting, some of the area with relatively low suitability was transformed from unsuitable area, and some of the area with relatively high suitability was transformed into marginally suitable area, so that the total area remained basically unchanged. A small part of the marginally suitable area was converted into high-suitability area, which increased the highly suitable area; (3) From the perspective of different scenarios, in the near and medium term, the area with a slight decrease or no change in suitability under RCP 8.5 was smaller than under RCP 4.5, but the area with a significant increase was larger than under RCP 4.5. The areas with a small decrease or no change in suitability accounted for 23.66–33.77% of the total plateau area and were concentrated in the northwestern Qinghai-Tibet Plateau and the Qaidam Basin. Areas with a large increase in suitability accounted for 3.47–15.64% of the total area and were located in the southern, central, and eastern parts of the Qinghai-Tibet Plateau, this area increased significantly with time; (4) Judging from the average altitude change in highland barley planting, the average altitude of the highly suitable area will rise from 3759 m to 3937 m (RCP 4.5) and 3959 m (RCP 8.5) in the near term. By the medium term, the average elevation of the highly suitable area will increase from 3759 m to 4017 m (RCP 4.5) and 4090 m (RCP 8.5). The trend of rising average altitude continues to strengthen.

The aim of this study was to investigate the clinical features and genetic causes of two family cases with familial chylomicronemia syndrome (FCS). Clinical manifestations of proband 1 and her families, and also proband 2 showed severe hypertriglyceridemia, especially the triglycerides levels of two probands were extremely high. Gene sequencing results showed that the LPL genes in each of the two probands had a new mutation site. For the proband 1, a compound heterozygous mutation at c.429 (c.429 + 1G > T) was detected in the LPL gene, which was splicing mutation and inherited from her mother. Homozygous mutation was detected in the LPL gene of proband 2, the nucleotide mutation at c.802 (c.802C > T) exhibited missense mutation, his parents and brother had a heterozygous mutation at the same site. It was confirmed that the conservative lipoprotein lipase superfamily domain changed an amino acid from histidine to tyrosine at p. 268 (p. His268Tyr). Flow cytometry confirmed the deficient expression of LPL protein in two families. These results indicated that the mutation in LPL gene might be the cause of familial chylomicronemia syndrome.

Rationale: Norrie disease (ND) is a rare X-linked recessive disease characterized by bilateral congenital blindness and auditory impairments. According to the previous studies, Norrin cystine knot growth factor (NDP) gene have been found to be responsible for ND. Herein, we report a case of ND with a novel mutation in NDP and elucidate the clinical and molecular characteristics of this patient. Patient concerns: A 2-month-old Chinese male infant presented with gray-white opacification in the bilateral cornea. Vitreous opacity and retinal detachment were observed on ocular ultrasound. Furthermore, a novel de novo hemizygous mutation (c.22_25dupGCAT, p.S9Cfs∗18) in exon 2 of the NDP gene was identified by next-generation sequencing. SWISS-MODEL predicted that the c.22_25dupGCAT mutation truncated the NDP protein. Diagnosis: Based on the above clinical and genetic evidence, this patient was eventually diagnosed with ND. Interventions: Currently, no clinical therapy is available for ND. Outcomes: In addition to the typical ocular symptoms, no other abnormalities were observed. The patient's vital signs remained stable and normal. Lesson: A novel causative mutation of NDP was identified using next-generation sequencing. Our report expands the pathogenic mutation spectrum of NDP and facilitates genetic counseling and prenatal diagnosis. Additionally, we emphasize the importance of molecular genetic testing in the diagnosis of ND.

A magnetic solid-phase extraction adsorbent that consisted of citrus peel-derived nanoporous carbon and silica-coated Fe3 O4 microspheres (C/SiO2 @Fe3 O4 ) was successfully fabricated by co-precipitation. As a modifier for magnetic microspheres, citrus peel-derived nanoporous carbon was not only economical and renewable for its raw material, but exerted enormous nanosized pore structure, which could directly influence the type of adsorbed analytes. The C/SiO2 @Fe3 O4 also possessed the advantages of Fe3 O4 microspheres like superparamagnetism, which could be easily separated magnetically after adsorption. Integrating the superior of biomass-derived nanoporous carbon and Fe3 O4 microspheres, the as-prepared C/SiO2 @Fe3 O4 showed high extraction efficiency for target analytes. The obtained material was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and the Brunauer-Emmett-Teller method, which demonstrated that C/SiO2 @Fe3 O4 was successfully synthesized. Under the optimal conditions, the adsorbent was selected for the selective adsorption of seven insecticides before gas chromatography with mass spectrometry detection, and good linearity was obtained in the concentration range of 2-200 μg/kg with the correlation coefficient ranging from 0.9952 to 0.9997. The limits of detection were in the range of 0.03-0.39 μg/kg. The proposed method has been successfully applied to the enrichment and detection of seven insecticides in real vegetable samples.

Polyphylla gracilicornis is one of the important underground pest species that damage agricultural and forestry plants and often requires chemical control during outbreak. Here, we determined the c...

Rationale Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive disease characterized by thrombocytopenia, small platelets, eczema, immunodeficiency, and an increased risk of autoimmunity and malignancies. X-linked thrombocytopenia (XLT), the milder phenotype of WAS, is always limited to thrombocytopenia with absent or slight infections and eczema. Here, we illustrated the clinical and molecular characteristics of 2 unrelated patients with WAS from Chinese minorities. Patient concerns Patient 1, a 13-day-old male newborn of the Chinese Lahu minority, showed a classic WAS phenotype, including thrombocytopenia, small platelets, buttock eczema, and recurrent infections. Patient 2, an 8-year-and 8-month-old boy of the Chinese Zhuang minority, presented an XLT phenotype without eczema and repeated infections. Diagnosis Next-generation sequencing was performed to investigate the genetic variations. Flow cytometry was used to quantify the expression of WAS protein and analyze the lymphocyte subsets. A novel frameshift WAS mutation (c.927delC, p.Q310Rfs∗135) and a known nonsense WAS mutation (c.1090C>T, p.R364X) were identified in Patient 1 and Patient 2, respectively. Both patients were confirmed to have WAS protein deficiency, which was more severe in Patient 1. Meanwhile, the analysis of lymphocyte subsets revealed an abnormality in Patient 1, but not in Patient 2. Combined with the above clinical data and genetic characteristics, Patient 1 and Patient 2 were diagnosed as classic WAS and XLT, respectively. In addition, many miliary nodules were accidentally found in abdominal cavity of Patient 2 during appendectomy. Subsequently, Patient 2 was confirmed with pulmonary and abdominal tuberculosis through further laboratory and imaging examinations. To our knowledge, there have been only a few reports about WAS/XLT with tuberculosis. Interventions Both patients received anti-infection therapy, platelet transfusions, and intravenous immunoglobulins. Moreover, Patient 2 also received antituberculosis treatment with ethambutol and amoxicillin-clavulanate. Outcomes The clinical symptoms and hematological parameters of these 2 patients were significantly improved. Regrettably, both patients discontinued the treatment for financial reasons. Lessons Our report expands the pathogenic mutation spectrum of WAS gene and emphasizes the importance of molecular genetic testing in diagnosing WAS. Furthermore, researching and reporting rare cases of WAS from different populations will facilitate diagnosis and treatment of this disease.

Cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) have always been two research hotpots in emergency medicine. Problems such as optimizing animal CA models and promoting CPR efficiency are to be explored. Establishing animal CA models is the precondition of CPR study. Previous studies usually use electric shock or intravenous drug administration to induce CA in animals. Nevertheless, as electric shock is complicated to operate and the dosage for drug administration is difficult to control, many published animal CA models are not ideally stable and operable. In order to establish a stable and operable CA model for cardiac arrest- cardiopulmonary resuscitation (CA-CPR) research, this study established different pig CA models via intravenous administration of KCI, MgSO 4 and ketamine respectively, and subsequently performed CRP with a self-designed inspiratory impedance threshold device (SIITD). The success rate of CRP in different CA models was evaluated according to hemodynamic and biochemical parameters of pigs. Results demonstrated that in the CA model established by intravenous administration of MgSO 4 , cardiac output of pigs were significantly elevated and reached the normal range at 10-min after CPR, and other vital signs and biochemical parameters in this model exhibited recovery trends throughout CPR. This study provides a more effective CA model and new ideas in methodology of future CA-CPR research.

Highly graphitic nanoporous carbon (NPC) was obtained from an agricultural waste—citrus peel at optimum condition. Then, a low-cost and pore size-controlled magnetic graphitic nanoporous carbon (MNPC) with ultrahigh specific surface area (1064 m2 g−1) was successfully fabricated by coprecipitation of Fe3O4 particles onto NPC. The prepared MNPC was characterized by Brunauer-Emmett-Teller (BET), Raman spectrum, scanning electron microscope (SEM) and Fourier transform infrared spectrometry (FT-IR). BET results showed a significant increase in the micropores volume and specific surface area of MNPCs following the increase of carbonization temperature, which implied that highly efficient carbonization made NPC an excellent active phase for MNPC. Besides, the adsorption mechanism was investigated and turned out that π-π interactions between interfering substances and MNPC were considered to be the major driving force for the adsorption process. The experimental parameters affecting the cleanup efficiency was optimized through Response surface methodology (RSM) in detail. Under the optimal cleanup condition, the MNPC was applied for determination of 16 insecticides in vegetables coupled with gas chromatography-mass spectrometry (GC-MS), a satisfactory performance was obtained. Good linearity was observed in the investigated concentration range of 1–100 μg kg−1 with correlation coefficients (r2) between 0.9963 and 0.9999. The limits of detection (LODs) were in the range of 0.03–0.33 μg kg−1. The recoveries ranged from 81.9 to 112.3% with relative standard deviations (RSDs) less than 10.9%. To summary up, the MNPC could potentially be used as a super adsorbent to efficiently remove pigments from vegetables, so that the proposed method was an efficient cleanup and enrichment procedure.

An adsorbent, consisting of silica-coated Fe3O4 grafted graphene oxide and β-cyclodextrin (Fe3O4@SiO2/GO/β-CD), which possessed the merits of antioxidation, superparamagnetism, high surface area, high supramolecular recognition and environment friendly, was successfully fabricated. Considering the synergy between β-CD and graphene oxide in adsorption mechanism, the synthesized adsorbent could grasp compounds especially with aromatic structures through π-π interaction, hydrophobic interaction and host-guest inclusion complex forming. Based on the advantages, a magnetic solid phase extraction (MSPE) method for 9 PGRs using Fe3O4@SiO2/GO/β-CD as adsorbents was developed in this study. The characterizations of Fe3O4@SiO2/GO/β-CD were performed on Fourier transform infrared spectrometry (FT-IR), X-ray photoelectron spectroscopy (XPS), CHNS/O elemental analyzer, scanning electron microscopy (SEM) and vibrating sample magnetometry (VSM). Under the optimal MSPE condition, the Fe3O4@SiO2/GO/β-CD exhibited selectivity capability toward 9 PGRs when compared with Fe3O4@SiO2/GO. Meanwhile, the selectivity capability of Fe3O4@SiO2/GO/β-CD was higher than that of Fe3O4@SiO2/GO/α-CD except for 4-FPA. When the developed MSPE procedure was coupled with ultra-high performance liquid chromatography-triple quadrupole linear ion trap mass spectrometry (UHPLC-QTrap-MS/MS) to quantitative analysis of 9 PGRs, linearities ranging from 2 to 50 μg/kg were achieved for 9 PGRs with the correlation coefficients (r2) in the range of 0.9975-0.9999. The limits of detection (LODs) for 9 analytes varied from 0.04 to 0.29 μg/kg. Finally, the proposed technique was applied to analyze PGRs residues in mutiple vegetable samples.