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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.

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.

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.

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...

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.

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.